Sample records for acute immune-mediated thrombocytopenia

  1. Acute immune-mediated thrombocytopenia due to oxaliplatin administration: a case report.

    Pietrantonio, Filippo; Di Bartolomeo, Maria; Buzzoni, Roberto; Bajetta, Emilio


    Drug-induced acute thrombocytopenia is an extremely rare side effect that may occur immediately after oxaliplatin infusion. This potentially fatal reaction is immune mediated and can be anticipated by mild hemorrhagic signs during previous administrations. This is the first report of acute thrombocytopenia occurring during adjuvant treatment of colorectal cancer with oxaliplatin. Clinicians should be aware of this adverse event in order to prevent possible serious consequences and stop further oxaliplatin administration.

  2. New insights and therapeutics for immune-mediated thrombocytopenia.

    Metjian, Ara; Abrams, Charles S


    In recent years, great advances have been made in elucidating the pathogenesis of thrombocytopenia and the mechanisms of thrombopoiesis. Drawing upon decades of basic science and clinical research, the pathways behind the immune-mediated destruction of platelets have opened new avenues. This has led to the application of safer and more efficacious immunosuppressive agents, such as the anti-CD20 monoclonal antibody rituximab, or potentially altering the co-stimulatory pathways of the immune system with an anti-CD40L (CD154) monoclonal antibody. This has been coupled with the discoveries of the genetic and molecular pathways in thrombopoiesis, including the identification and cloning of thrombopoietin (TPO) and its receptor. The use of recombinant TPO, such as PEG-rHuMGDF and rhTPO, to treat thrombocytopenia have paved the way for alternative peptidyl and nonpeptidyl thrombopoietic agents that are considered to be nonimmunogenic. Those that have undergone evaluation in humans include the Amgen megakaryopoiesis protein (AMG) 531 compound, eltrombopag, and AKR-501. Additional TPO mimetics show promise in vitro and await future development.

  3. Immune-mediated thrombocytopenia associated with angiostrongylus vasorum infection in a jack russell terrier

    JO'Neill Emma


    Full Text Available Abstract A twenty-month-old Jack Russell terrier was presented with a four-day history of thrombocytopenia, echymotic inguinal haemorrhages, coughing and reduced exercise tolerance. Clinical examination revealed several petechial haemorrhages on the gingivae and small echymotic haemorrhages in the inguinal region, along with mild bilateral epistaxis. Haematology confirmed a platelet count of 1.0 × 10/L. Thoracic radiographs revealed a wide-spread mixed alveolar-interstitial lung pattern, apparent throughout the entire lungfield, but particularly marked within the left lung lobes. A presumptive diagnosis of immune-mediated thrombocytopenia was made and the dog was treated with vincristine and immunosuppressive doses of prednisolone. Initially anaemia developed following gastrointestinal haemorrhage; however, after symptomatic treatment the dog showed a marked clinical improvement. Evaluation for an underlying cause of the disease revealed Angiostrongylus vasorum L1 larvae on faecal analysis and treatment with fenbendazole was commenced. The dog made a full clinical recovery with all treatment was withdrawn within five weeks of diagnosis. This is the second report of immune-mediated thrombocytopenia associated with Angiostrongylus vasorum infection and it is the first to be successfully managed. The report highlights that Angiostrongylus vasorum should be considered in young dogs presented with thrombocytopenia.

  4. Immune-mediated thrombocytopenia associated with angiostrongylus vasorum infection in a Jack Russell terrier.

    Jo'neill, Emma; Acke, Els; Tobin, Emma; McCarthy, Grainne


    A twenty-month-old Jack Russell terrier was presented with a four-day history of thrombocytopenia, echymotic inguinal haemorrhages, coughing and reduced exercise tolerance. Clinical examination revealed several petechial haemorrhages on the gingivae and small echymotic haemorrhages in the inguinal region, along with mild bilateral epistaxis. Haematology confirmed a platelet count of 1.0 × 10/L. Thoracic radiographs revealed a wide-spread mixed alveolar-interstitial lung pattern, apparent throughout the entire lungfield, but particularly marked within the left lung lobes. A presumptive diagnosis of immune-mediated thrombocytopenia was made and the dog was treated with vincristine and immunosuppressive doses of prednisolone. Initially anaemia developed following gastrointestinal haemorrhage; however, after symptomatic treatment the dog showed a marked clinical improvement. Evaluation for an underlying cause of the disease revealed Angiostrongylus vasorum L1 larvae on faecal analysis and treatment with fenbendazole was commenced. The dog made a full clinical recovery with all treatment was withdrawn within five weeks of diagnosis. This is the second report of immune-mediated thrombocytopenia associated with Angiostrongylus vasorum infection and it is the first to be successfully managed. The report highlights that Angiostrongylus vasorum should be considered in young dogs presented with thrombocytopenia.

  5. Immune-mediated thrombocytopenia associated with angiostrongylus vasorum infection in a Jack Russell terrier

    JO'Neill Emma; Acke Els; Tobin Emma; McCarthy Grainne


    Abstract A twenty-month-old Jack Russell terrier was presented with a four-day history of thrombocytopenia, echymotic inguinal haemorrhages, coughing and reduced exercise tolerance. Clinical examination revealed several petechial haemorrhages on the gingivae and small echymotic haemorrhages in the inguinal region, along with mild bilateral epistaxis. Haematology confirmed a platelet count of 1.0 × 10/L. Thoracic radiographs revealed a wide-spread mixed alveolar-interstitial lung pattern, appa...

  6. Acute renal failure and severe thrombocytopenia associated with metamizole

    Maria Dolores Redondo-Pachon


    Full Text Available Metamizole or dipyrone is a pyrazolone derivative that belongs to the non-steroidal anti-inflammatory drugs. Its main side-effect is hematological toxicity. Thrombocytopenia due to metamizole is rare and is usually associated with the involvement of the two other blood series. Drug-induced thrombocytopenia is more frequently related to immune mechanisms, and the diag-nosis is still largely made by exclusion of other causes and by correlation of timing of thrombocytopenia with the administration of drug. Metamizole may cause acute renal failure due to hemodynamic renal failure/acute tubular necrosis and/or acute tubulointerstitial nephritis. We report a case of acute renal failure and severe thrombocytopenia after metamizole. As far as we know, this combination of adverse effects from this drug has not been reported previously.

  7. CFU-MK assay for acute thrombocytopenia.

    Parent-Massin, Dominique; Sibiril, Yann


    In this unit, protocols to culture human platelet progenitors (Colony Forming Unit-Megakaryocyte; CFU-M) with or without toxicants are described. Platelet progenitors are obtained from human umbilical cord blood. After separation of mononuclear cells, the cell suspension can be cryopreserved or plated immediately. Megakaryocytes are identified by immunocytochemistry. Test chemicals are added to the culture medium before cells are plated. Megakaryocytes are scored after 12 days of culture. IC(10), IC(50) and IC(90) can be calculated by comparison to control cultures. A predictive model is proposed to evaluate the hazard of thrombocytopenia induced by chemicals. When IC(50) and IC(90) are below C(max) in humans, the likelihood of thrombocytopenia is strong.

  8. Prevention of non-immune mediated transfusion-related acute lung injury; from blood bank to patient.

    van Bruggen, Robin; de Korte, Dirk


    Transfusion-related acute lung injury (TRALI) is a severe form of pulmonary insufficiency induced by transfusion. TRALI is the leading cause of transfusion-related death, and is caused by the infusion of either anti-leukocyte antibodies in plasma containing blood products or neutrophil priming substances that accumulate during storage of cellular blood products. Among these neutrophil priming substances are bioactive lipids, such as lyso-phosphatidylcholines (lysoPCs) and arachidonic acid, soluble CD40L (sCD40L) and possibly other, as yet unidentified substances. The accumulation of these substances during cellular blood product storage and their role in the induction of "non-immune mediated" TRALI pathogenesis are highly relevant for the current debate of the use of longer vs. shorter stored blood products. In this review, the accumulation of these different substances during storage, as well as their mode of action in inducing TRALI are discussed. In addition, different improvements in current blood banking procedures to prevent TRALI due to these non-immune mediators will be proposed.

  9. Acute profound thrombocytopenia secondary to local abciximab infusion

    Press, Christopher D.; Moscona, John C.; Syed, Rashad H. Khazi; Katz, Morgan J.; Egan, Alison A.; Bisharat, Mohannad B.; Nijjar, Vikram S.; Anwar, Asif H.


    Glycoprotein (GP) IIb/IIIa receptor antagonists are powerful antiplatelet agents that are typically used in percutaneous coronary intervention. All three GP IIb/IIIa agents currently approved for use in the United States cause thrombocytopenia as a rare side effect. Abciximab is unique to the class in that it is a modified monoclonal antibody to the GP IIb/IIIa receptor, a property that can lead to increased platelet destruction. Presented herein is a patient who received a local infusion of abciximab for a lower-extremity thrombus and within 2 hours developed an acute profound thrombocytopenia that likely caused a large retroperitoneal hematoma. This case demonstrates the importance of checking platelet count within 2 to 4 hours after local (in addition to systemic) abciximab administration. Additionally, this report outlines how other causes of acute precipitous platelet drops, such as heparin-induced thrombocytopenia and pseudothrombocytopenia, can be rapidly excluded and allow for the prompt initiation of optimal therapy to minimize bleeding. PMID:23077384

  10. Acute Severe Thrombocytopenia Following Non-Ionic Low-Osmolarity Intravenous Contrast Medium Injection

    Bata Pal; Domonkos, Adam; Tamoki, David Laszio; Horvath, Evelin; Berczi, Viktor; Szalay, Ferenc [Semmelweis University, Budapest (Hungary)


    Intravenous contrast medium (ICM) rarely induces anaphylactic reactions, including urticaria, hypotension and respiratory failure. Even the most modern ICM may cause such adverse events. Thrombocytopenia has been reported as an extreme rare consequence of ICM. Here we report on a case of a 72-year-old male patient with a self-limiting severe acute thrombocytopenia following administration of intravenous non-ionic low-osmolarity contrast medium. No such low platelet count has ever been reported. We also present a review of the literature.

  11. Human Herpesvirus 6 Infection Presenting as an Acute Febrile Illness Associated with Thrombocytopenia and Leukopenia

    Maja Arnež


    Full Text Available We present an infant with acute fever, thrombocytopenia, and leukopenia, coming from an endemic region for tick-borne encephalitis, human granulocytic anaplasmosis, and hantavirus infection. The primary human herpesvirus 6 infection was diagnosed by seroconversion of specific IgM and IgG and by identification of viral DNA in the acute patient’s serum. The patient did not show skin rash suggestive of exanthema subitum during the course of illness.

  12. Transient leucopenia, thrombocytopenia and anaemia associated with severe acute phenobarbital intoxication in a dog.

    Khoutorsky, A; Bruchim, Y


    A nine-year-old Labrador retriever dog was admitted to the emergency unit of the Hebrew University Veterinary Teaching Hospital with acute-onset tremors and coma. It had recently ingested a large quantity of phenobarbital and had a high serum phenobarbital concentration. On this basis, a diagnosis of acute phenobarbital intoxication was made. Significant leucopenia, thrombocytopenia and mild anaemia developed on the third day after admission. The leucopenia resolved on day 6 and the thrombocytopenia on day 13. The red blood cell count remained low for the next month. The dog was discharged on day 13 at which time it was ambulatory but weak. It was completely recovered clinically eight days later. In summary, high levels of serum phenobarbital as a result of acute intoxication induced pancytopenia, which improved when the serum phenobarbital level was normalised.

  13. Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia.

    Sabine Topka


    Full Text Available Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL, the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A second ETV6 p. N385fs mutation was identified in an unrelated kindred characterized by thrombocytopenia, ALL and secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from the proband in the second kindred showed deletion of wild type ETV6 with retention of the ETV6 p. N385fs. Enforced expression of the ETV6 mutants revealed normal transcript and protein levels, but impaired nuclear localization. Accordingly, these mutants exhibited significantly reduced ability to regulate the transcription of ETV6 target genes. Our findings highlight a novel role for ETV6 in leukemia predisposition.

  14. Oral exposure to Phytomonas serpens attenuates thrombocytopenia and leukopenia during acute infection with Trypanosoma cruzi.

    Rosiane V da Silva

    Full Text Available Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS, which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease.

  15. Thrombocytopenia is associated with acute respiratory distress syndrome mortality: an international study.

    Tiehua Wang

    Full Text Available BACKGROUND: Early detection of the Acute Respiratory Distress Syndrome (ARDS has the potential to improve the prognosis of critically ill patients admitted to the intensive care unit (ICU. However, no reliable biomarkers are currently available for accurate early detection of ARDS in patients with predisposing conditions. OBJECTIVES: This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies. METHODS: We examined clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who were admitted to the ICU and were at high risk for ARDS. Identified biomarkers were then replicated in a second cohort of1,878 patients in Boston, USA. RESULTS: Of 178 patients recruited from participating hospitals in Beijing, 75 developed ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70-18.3, pulmonary injury (OR: 3.22; 95% CI: 1.60-6.47, and thrombocytopenia, defined as platelet count <80×10(3/µL, (OR: 2.67; 95% CI: 1.27-5.62were significantly associated with increased risk of developing ARDS. Thrombocytopenia was also associated with increased mortality in patients who developed ARDS (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07-1.57 but not in those who did not develop ARDS(AHR: 1.25, 95% CI: 0.96-1.62. The presence of both thrombocytopenia and ARDS substantially increased 60-day mortality. Sensitivity analyses showed that a platelet count of <100×10(3/µL in combination with ARDS provide the highest prognostic value for mortality. These associations were replicated in the cohort of US patients. CONCLUSIONS: This study of ICU patients in both China and US showed that thrombocytopenia is associated with an increased risk of ARDS and platelet count in combination with ARDS had a high predictive value for patient mortality.

  16. Severe Thrombocytopenia after Zika Virus Infection, Guadeloupe, 2016

    Boyer Chammard, Timothée; Schepers, Kinda; Breurec, Sébastien; Messiaen, Thierry; Destrem, Anne-Laure; Mahevas, Matthieu; Soulillou, Adrien; Janaud, Ludovic; Curlier, Elodie; Herrmann-Storck, Cécile


    Severe thrombocytopenia during or after the course of Zika virus infection has been rarely reported. We report 7 cases of severe thrombocytopenia and hemorrhagic signs and symptoms in Guadeloupe after infection with this virus. Clinical course and laboratory findings strongly suggest a causal link between Zika virus infection and immune-mediated thrombocytopenia. PMID:27997330

  17. Immune mediated liver failure

    Wang, Xiaojing; Ning, Qin


    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capac...

  18. Acute Thrombocytopenia, Leucopenia, and Multiorgan Dysfunction: The First Case of SFTS Bunyavirus outside China?

    Srdjan Denic


    Full Text Available We report a 57-year-old man with acute thrombocytopenia, leucopenia, and multiorgan dysfunction. Patient was from North Korea and was temporarily working in Dubai, United Arab Emirates, when he fell ill in March 2009. At the same time and unknown to us, many patients with similar clinical manifestations were admitted to hospitals in China. The Chinese cases—identified between March and July 2009—were recently reported to have been infected with a tick-born strain of bunyavirus, a new disease. The virus infection was documented in patients from central China and the region that shares the border with North Korea. The clinical manifestations, the time of disease onset, and geographical link of the patient with the region in which the disease is endemic suggest that the patient had SFTS bunyavirus infection.

  19. [Diagnosis of immune-mediated neuropathies].

    Diószeghy, Péter


    Separate discussion of immune-mediated neuropathies from other neuropathies is justified by the serious consequences of the natural course of these diseases, like disability and sometimes even life threatening conditions. On the other hand nowadays effective treatments already exist, and with timely and correct diagnosis an appropriately chosen treatment may result in significant improvement of quality of life, occasionally even complete recovery. These are rare diseases, and the increasing number of different variants makes it more difficult to recognize them. Their diagnosis is based on the precise knowledge of clinical signs and symptoms, and it is verified by the help of neurophysiologic and laboratory, first of all CSF examinations. Description of clinical features of the classic acute immune-mediated neuropathy, characterized by ascending paresis and demyelination is followed by a summary of characteristics of newly recognized axonal, regional and functional variants. Chronic immune-mediated demyelinating polyneuropathies are not diagnosed in due number even today. This paper does not only present the classic form but it also introduces the ever increasing special variants, like distal acquired demyelinating sensory neuropathy, Lewis-Sumner syndrome, multifocal motor neuropathy and paraproteinemic neuropathies. Vasculitic neuropathies can be divided into two groups: systemic and non-systemic ones. The first sign of a vasculitic neuropathy is a progressive, painful mononeuropathy; the classic clinical presentation is the mononeuritis multiplex. It is characterized by general signs like fever, loss of weight, fatigue. In systemic vasculitis organ specific symptoms are also present. From the paraneoplastic diseases the subacute sensory neuropathy and the sensory neuronopathy are members of the immune-mediated neuropathies, being most frequently associated with small cell lung cancer.

  20. Meloxicam-induced thrombocytopenia.

    Ranieri, Melissa M; Bradley, Elizabeth F; Simon, Allison B


    Immune thrombocytopenia can have several causes including the use of certain drugs. Thrombocytopenia has been documented as a rare adverse effect of some nonsteroidal antiinflammatory drugs (NSAIDs) including diclofenac, naproxen, and ibuprofen. However, only one previously documented case of meloxicam-associated thrombocytopenia has been reported in the literature. We describe an 84-year-old woman who developed a case of immune-mediated thrombocytopenia that was attributed to meloxicam therapy. The patient's platelet count decreased from a baseline of 267 × 10(3) /mm(3) to 2 × 10(3) /mm(3) 1 week after she received her first lifetime dose of meloxicam. She also experienced black stools and bruising that coincided with the meloxicam administration. The almost immediate onset of thrombocytopenia and symptoms after initiation of meloxicam, as well as the marked reduction in her platelet count, suggest an idiosyncratic reaction. According to the Hill criteria for assessing causality of adverse drug events, it is plausible that this reaction was due to meloxicam. Health care providers should be aware of the possibility of thrombocytopenia secondary to NSAID therapy including meloxicam. Immune thrombocytopenia can be life threatening if it is not identified and treated promptly. A thorough medication history is particularly important when patients present with unusual symptoms, with a focus on those drugs that have been recently initiated. Although thrombocytopenia is a rare adverse effect of NSAID therapy, it should be considered a potential cause in patients receiving these drugs who have signs and symptoms consistent with this blood dyscrasia.

  1. Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs.

    Friedenberg, Steven G; Buhrman, Greg; Chdid, Lhoucine; Olby, Natasha J; Olivry, Thierry; Guillaumin, Julien; O'Toole, Theresa; Goggs, Robert; Kennedy, Lorna J; Rose, Robert B; Meurs, Kathryn M


    Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes, we conducted a candidate gene study of 15 of these genes across four immune-mediated diseases (immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis (IMPA), and atopic dermatitis) in 195 affected and 206 unaffected dogs to assess whether causative or predictive polymorphisms might exist in similar genes in dogs. We demonstrate a strong association (Fisher's exact p = 0.0004 for allelic association, p = 0.0035 for genotypic association) between two polymorphic positions (10 bp apart) in exon 2 of one allele in DLA-79, DLA-79*001:02, and multiple immune-mediated diseases. The frequency of this allele was significantly higher in dogs with immune-mediated disease than in control dogs (0.21 vs. 0.12) and ranged from 0.28 in dogs with IMPA to 0.15 in dogs with atopic dermatitis. This allele has two non-synonymous substitutions (compared with the reference allele, DLA-79*001:01), resulting in F33L and N37D amino acid changes. These mutations occur in the peptide-binding pocket of the protein, and based upon our computational modeling studies, are likely to affect critical interactions with the peptide N-terminus. Further studies are warranted to confirm these findings more broadly and to determine the specific mechanism by which the identified variants alter canine immune system function.

  2. Acute brucellosis as unusual cause of immune thrombocytopenia: a case report and review of the literature

    Tajeldin Mohammedien Abdallah


    Full Text Available A 25 year-old male patient was admitted to the causality with complaints of fever, joints pain, epistaxis and gingival bleeding, for the last week, the complete blood count revealed pancytopenia. Serological test for brucella was reported positive as 1/320, but the patient failed to respond to brucella treatment for 4 d. On day 5th the diagnosis of immune thrombocytopenia was confirmed after bone marrow aspiration. Steroid was initiated on 6th day after admission and on the 3rd day of steroid therapy thrombocytes count was raised to 55×109/L and came up to 180×109/L on 12th day after admission. Brucella-induced immune thrombocytopenia should be considered in patient presenting with bleeding and febrile illness especially in endemic region.

  3. Treatment of immune-mediated, dysimmune neuropathies.

    Finsterer, J


    This review focuses on the actual status and recent advances in the treatment of immune-mediated neuropathies, including: Guillain-Barre syndrome (GBS) with its subtypes acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, Miller Fisher syndrome, and acute pandysautonomia; chronic inflammatory demyelinating polyneuropathy (CIDP) with its subtypes classical CIDP, CIDP with diabetes, CIDP/monoclonal gammopathy of undetermined significance (MGUS), sensory CIDP, multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy or Lewis-Sumner syndrome, multifocal acquired sensory and motor neuropathy, and distal acquired demyelinating sensory neuropathy; IgM monoclonal gammopathies with its subtypes Waldenstrom's macroglobulinemia, myelin-associated glycoprotein-associated gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome, mixed cryoglobulinemia, gait ataxia, late-onset polyneuropathy syndrome, and MGUS. Concerning the treatment of GBS, there is no significant difference between intravenous immunoglobulins (IVIG), plasma exchange or plasma exchange followed by IVIG. Because of convenience and absent invasiveness, IVIG are usually preferred. In treating CIDP corticosteroids, IVIG, or plasma exchange are equally effective. Despite the high costs and relative lack of availability, IVIG are preferentially used. For the one-third of patients, who does not respond, other immunosuppressive options are available. In MMN IVIG are the treatment of choice. Inadequate response in 20% of the patients requires adjunctive immunosuppressive therapies. Neuropathies with IgM monoclonal gammopathy may respond to various chemotherapeutic agents, although the long-term effects are unknown. In addition, such treatment may be associated with serious side effects. Recent data support the use of rituximab, a monoclonal antibody against the B

  4. Interferon-α induced severe thrombocytopenia:A case report and review of the literature


    We report a case of severe thrombocytopenia following pegylated interferon-α 2a(Peg-IFN-α 2a)treatment of hepatitis C virus infection and summarize the clinical characteristics of 16 cases of IFN-α induced severe thrombocytopenia and its immune-mediated mechanism.Discontinuation of IFN-α and early administration of immunosuppressants are the effective therapy for IFN-αinduced severe thrombocytopenia.

  5. Immune-Mediated Vascular Injury and Dysfunction in Transplant Arteriosclerosis

    Anna evon Rossum


    Full Text Available Solid organ transplantation is the only treatment for end-stage organ failure but this life-saving procedure is limited by immune-mediated rejection of most grafts. Blood vessels within transplanted organs are targeted by the immune system and the resultant vascular damage is a main contributor to acute and chronic graft failure. The vasculature is a unique tissue with specific immunological properties. This review discusses the interactions of the immune system with blood vessels in transplanted organs and how these interactions lead to the development of transplant arteriosclerosis, a leading cause of heart transplant failure.

  6. Congenital Thrombocytopenia



    @@ Platelets are essential for normal hemostasis.Platelets adhere to damaged blood vessels, and then aggregate and promote activation of coagulation factors, resulting to ceasing bleeding.Both quantitative and qualitative abnormalities of platelets can cause bleeding problems.Among them, immune thrombocytopenias are the most common conditions.However, congenital thrombocytopenias are often neglected because of their relative rarity and complex laboratory tests.That causes misdiagnosis and unnecessary and potentially harmful treatments for many patients.

  7. Acute Kidney Injury, Recurrent Seizures, and Thrombocytopenia in a Young Patient with Lupus Nephritis: A Diagnostic Dilemma

    Hector Alvarado Verduzco


    Full Text Available Introduction. Posterior reversible encephalopathy syndrome (PRES is a constellation of clinical and radiologic findings. Fluctuations in blood pressure, seizures, and reversible brain MRI findings mainly in posterior cerebral white matter are the main manifestations. PRES has been associated with multiple conditions such as autoimmune disorders, pregnancy, organ transplant, and thrombotic microangiopathy (TMA. Case Presentation. A 22-year-old woman with history of Systemic Lupus Erythematous complicated with chronic kidney disease secondary to lupus nephritis class IV presented with recurrent seizures and uncontrolled hypertension. She was found to have acute kidney injury and thrombocytopenia. Repeat kidney biopsy showed diffuse endocapillary and extracapillary proliferative and membranous lupus nephritis (ISN-RPS class IV-G+V and endothelial swelling secondary to severe hypertension but no evidence of TMA. Brain MRI showed reversible left frontal and parietal lesions that resolved after controlling the blood pressure, making PRES the diagnosis. Conclusion. PRES is an important entity that must be recognized and treated early due to the potential reversibility in the early stages. Physicians must have high suspicion for these unusual presentations. We present a case where performing kidney biopsy clinched the diagnosis in our patient with multiple confounding factors.

  8. Immune-mediated canine and feline keratitis.

    Andrew, Stacy E


    Although the normal cornea is devoid of vasculature and lymphatics, there are still several immune-mediated corneal conditions that can occur in dogs and cats. An overview of corneal immunology is presented. Diseases of dogs, including chronic superficial keratitis, superficial punctate keratitis, and canine adenovirus endotheliitis, as well as feline diseases, including eosinophilic keratitis and herpesvirus-related conditions, are discussed.

  9. C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia.

    Kapur, Rick; Heitink-Pollé, Katja M J; Porcelijn, Leendert; Bentlage, Arthur E H; Bruin, Marrie C A; Visser, Remco; Roos, Dirk; Schasfoort, Richard B M; de Haas, Masja; van der Schoot, C Ellen; Vidarsson, Gestur


    Immune-mediated platelet destruction is most frequently caused by allo- or autoantibodies via Fcγ receptor-dependent phagocytosis. Disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors play a role. Here we show that the acute phase protein C-reactive protein (CRP), a ligand for Fc receptors on phagocytes, enhances antibody-mediated platelet destruction by human phagocytes in vitro and in vivo in mice. Without antiplatelet antibodies, CRP was found to be inert toward platelets, but it bound to phosphorylcholine exposed after oxidation triggered by antiplatelet antibodies, thereby enhancing platelet phagocytosis. CRP levels were significantly elevated in patients with allo- and autoantibody-mediated thrombocytopenias compared with healthy controls. Within a week, intravenous immunoglobulin treatment in children with newly diagnosed immune thrombocytopenia led to significant decrease of CRP levels, increased platelet numbers, and clinically decreased bleeding severity. Furthermore, the higher the level of CRP at diagnosis, the longer it took before stable platelet counts were reached. These data suggest that CRP amplifies antibody-mediated platelet destruction and may in part explain the aggravation of thrombocytopenia on infections. Hence, targeting CRP could offer new therapeutic opportunities for these patients.

  10. Immune-Mediated Therapies for Liver Cancer

    Aravalli, Rajagopal N.; Steer, Clifford J.


    In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion have enhanced our understanding on the immunology of liver cancer. Preclinical and clinical studies with immune-mediated therapies have shown potential benefits in patients with liver cancer. In this review, we summarize current knowledge and recent developments in tumor immunology by focusing on two main primary liver cancers: hepatocellular carcinoma and cholangiocarcinoma. PMID:28218682

  11. Immune-Mediated Therapies for Liver Cancer

    Aravalli, Rajagopal N; Steer, Clifford J.


    In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion ...

  12. 间充质干细胞治疗提升免疫性血小板减少症小鼠的血小板数并影响其外周血单核细胞中 T-bet 和 GATA-3基因表达%Mesenchymal stem cells increase platelet counts in mice with immune-mediated thrombocytopenia and affect T-bet and GATA-3 gene expression

    徐敏; 王椋; 刘国强; 鲁光; 丁慧芳; 邢健; 赵霞; 韩芳; 尚应辉


    目的:探讨间充质干细胞( MSC)对原发免疫性血小板减少症( ITP)小鼠血小板数目的影响及其机制。方法采用腹腔注射大鼠抗小鼠CD41抗体( MWReg30单抗)的方法诱导BALB/c小鼠产生ITP后,取20只作为实验组,20只作为对照组。之后通过鼠尾静脉给实验组小鼠注射MSC 2×107个/只。注射后5 d、7 d、14 d,测定实验组与对照组小鼠外周血血小板数;14 d时应用逆转录聚合酶链反应( RT-PCR)检测小鼠外周血单个核细胞( PBMC)中转录因子T-bet和GATA-3 mRNA的表达;应用酶联免疫法测定Th1类细胞因子IFN-γ、IL-2及Th2类细胞因子IL-4、IL-10的水平。结果7 d、14 d后,注射MSC实验组小鼠血小板值[(588.0±81.6)×109/L、(623.0±78.9)×109/L]明显高于未注射MSC对照组[(317.0±90.1)×109/L、(288.0±87.8)×109/L](P<0.05);14 d时,实验组PBMC中T-bet mRNA表达水平低于对照组[(0.04±0.03) vs (0.27±0.05)](P<0.05);GATA-3 mRNA的表达水平高于对照组[(0.14±0.04) vs (0.07±0.05)](P<0.05);实验组Th1类细胞因子IFN-γ、IL-2水平[(3.1±1.7) pg/ml、(3.2±2.1) pg/ml]明显低于对照组[(10.3±4.8) pg/ml、(16.3±5.7) pg/ml](P<0.05);实验组外周血 Th2类细胞因子 IL-4、IL-10水平[(88.6±15.2) pg/ml、(38.3±11.8) pg/ml]明显高于对照组[(32.7±5.7) pg/ml、(22.1±3.4) pg/ml](P<0.05)。结论 MSC可以有效提升ITP小鼠的血小板数,机制可能与抑制了T-bet和GATA-3的表达失常导致的Th1细胞极化有关。%Objective To explore the effects of mesenchymal stem cells ( MSC ) treatment on platelet counts in mice with immune-mediated thrombocytopenia ( ITP) and the possible mechanism .Meth-ods ITP was induced by daily intraperitoneal injection of anti-platelet membrane CD 41 antibody (MWReg30) into

  13. Acute brucellosis as unusual cause of immune thrombocytopenia:a case report and review of the literature

    Tajeldin Mohammedien Abdallah; Omer Mohammed Abd elbagi; Abuelgasim OsmanKaroum; Abdel Aziem Abdallah Ali


    A 25 year-old male patient was admitted to the causality with complaints of fever, joints pain, epistaxis and gingival bleeding, for the last week, the complete blood count revealed pancytopenia. Serological test for brucella was reported positive as 1/320, but the patient failed to respond to brucella treatment for 4 d. On day 5th the diagnosis of immune thrombocytopenia was confirmed after bone marrow aspiration. Steroid was initiated on 6th day after admission and on the 3rd day of steroid therapy thrombocytes count was raised to 55í109/L and came up to 180í109/L on 12th day after admission. Brucella-induced immune thrombocytopenia should be considered in patient presenting with bleeding and febrile illness especially in endemic region.

  14. Acute brucellosis as unusual cause of immune thrombocytopenia:a case report and review of the literature

    Tajeldin; Mohammedien; Abdallah; Omer; Mohammed; Abd; elbagi; Abuelgasim; OsmanKaroum; Abdel; Aziem; Abdallah; Ali


    A 25 year-old male patient was admitted to the causality with complaints of fever,joints pain,epislaxis and gingival bleeding,for the last week,the complete blood count revealed pancytopenia.Serological test for brucella was reported positive as 1/320,but the patient failed to respond lo brucella treatment for 4 d.On day 5th the diagnosis of immune thrombocytopenia was confirmed after bone marrow aspiration.Steroid was initiated on 6th day after admission and on the 3rd day of steroid therapy thrombocytes count was raised to 55×10~9/L and came up to 180×10~9/L on 12 th day after admission.Brucella-induced immune thrombocytopenia should be considered in patient presenting with bleeding and febrile illness especially in endemic region.

  15. [Heparin-induced thrombocytopenia. New therapeutical options].

    Seculini Patiño, Carina E; Tabares, Aldo H


    Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.

  16. Multiple sclerosis and fatigue: A review on the contribution of inflammation and immune-mediated neurodegeneration.

    Patejdl, Robert; Penner, Iris K; Noack, Thomas K; Zettl, Uwe K


    Multiple sclerosis (MS) is an immune mediated disease of the central nervous system (CNS) and the leading cause of non-traumatic disability among young and middle-aged adults in the western world. One of its most prevalent and debilitating symptoms is fatigue. Despite the general acceptance of the idea of an immune pathogenesis of MS itself, the role of autoimmunity in the course of MS-fatigue is a matter of debate. Both immune-related processes (acute inflammation, chronic inflammation, immune-mediated neurodegeneration, immune-mediated alterations of endocrine functions related to fatigue) and presumably non-immune-mediated disturbances and factors (sleep disturbances, depression, cognitive alterations, chronic infections, adverse effects of medications) contribute to the clinical picture. Data from in vitro and animal experiments has provided evidence for a role of cytokines as IL-1 and TNF-alpha. This association could not be verified directly in blood samples from humans whereas whole blood stimulation protocols gave some indirect evidence for a role of cytokines in MS-fatigue. MRI being able to detect acute and chronic immune mediated damage to the CNS could depict that global atrophy of gray or white matter does not correlate with fatigue. Rather, distinctive clusters of lesions and atrophy at different locations, mostly bifrontal or in subcortical structures, correlate specifically with fatigue. Regardless of the difficulties in pinpointing the immunogenesis of MS-fatigue, an important role of autoimmunity is strongly supported by an indirect route: A growing amount of data shows that the highly effective immunotherapeutics which have been introduced to MS-treatment over the last years effectively and sustainably stabilize and ameliorate fatigue in parallel to their dampening effects on the neuroinflammatory process. This review summarizes the existing data on the relation between inflammation, patterns of CNS-lesions and the effects of immunotherapeutics

  17. Prevalencia de trombocitopenia en niños con HIV/sida Prevalence of thrombocytopenia in HIV infected children

    Graciela Barboni


    Full Text Available La trombocitopenia es una de las múltiples alteraciones hematológicas presentes en pacientes infectados con el virus de la inmunodeficiencia humana (HIV. Puede ser de curso crónico, en la cual la destrucción inmune, el secuestro esplénico o el daño en la producción son los mecanismos primariamente involucrados, o aguda, acompañando a otra intercurrencia. En este trabajo se evaluó la prevalencia de trombocitopenia en un lapso de 14 años, en una población pediátrica con HIV/sida, analizando las características clínicas y la relación con el estado inmuno-virológico. La prevalencia de trombocitopenia fue de 8.5%, (29 de los 339 niños en seguimiento. En 22 fue de curso crónico y en 7 aguda. Los pacientes evaluados presentaron niveles porcentuales de TCD4+ variables y la presencia de trombocitopenia no estuvo en relación con el compromiso inmunitario. Los pacientes trombocitopénicos tuvieron niveles de carga viral significativamente mayores que los que no la presentaron. En 10 de los 29 niños con recuentos plaquetarios disminuidos, la trombocitopenia fue la manifestación inicial de la infección por HIV. Las manifestaciones hemorrágicas de las trombocitopenias crónicas fueron leves, presentes en el 23% de los niños y no se asociaron al deterioro inmunológico, mientras que en las agudas fueron más graves y condicionadas a la evolución de la enfermedad coexistente. El desarrollo de trombocitopenias se ve favorecido por la continua actividad viral y la falla en la implementación del tratamiento antirretroviral adecuado.Thrombocytopenia is a common hematologic finding in patients infected with the human immunodeficiency virus. Multiple mechanisms may contribute to the development of chronic thrombocytopenia as immune-mediated platelet destruction, enhanced platelet splenic sequestration and impaired platelet production. Acute thrombocytopenia is frequently associated with coexisting disorders. In this study, the prevalence of

  18. Nitrofurantoin-induced immune-mediated lung and liver disease

    Milić Rade


    Full Text Available Introduction. Nitrofurantoin, a furan derivative, introduced in the fifties has widely been used as an effective agent for the treatment and prevention of urinary tract infections (UTI. Spectrum of adverse reactions to nitrofurantoin is wide, ranging from eosinophilic interstitial lung disease, acute hepatitis and granulomatous reaction, to the chronic active hepatitis, a very rare adverse effect, that can lead to cirrhosis and death. Case report. We presented a 55-year-old female patient with eosinophilic interstitial lung disease, severe chronic active hepatitis and several other immune- mediated multisystemic manifestations of prolonged exposure to nitrofurantoin because of the recurrent UTI caused by Escherichia coli. We estimated typical radiographic and laboratory disturbances, also restrictive ventilatory changes, severe reduction of carbon monoxide diffusion capacity and abnormal liver function tests. Lymphocytic-eosinophylic alveolitis was consistent with druginduced reaction. Hepatitis was confirmed by liver biopsy. After withdrawal of nitrofurantoin and application of high dose of glicocorticosteroids, prompt clinical and laboratory recovery was achieved. Conclusion. Adverse drug reactions should be considered in patients with concomitant lung and liver disease. The mainstay of treatment is drug withdrawal and the use of immunosuppressive drugs in severe cases. Consideration should be given to monitor lung and liver function tests during long term nitrofurantoin therapy.

  19. Thrombocytopenia in Pregnancy

    Mehmet Ozsurmeli


    Full Text Available Thrombocytopenia, which is encountered in 7-10% of pregnancies is characterized with decreased number of thrombocytes. The most frequent cause of thrombocytopenia during pregnancy is gestational thrombocytopenia. These patients usually do not have symptoms due to mild thrombocytopenia. The diagnosis is usually established by excluding connective tissue disorders, drug effects and obstetric causes. The etiology of thrombocytopenia during early pregnancy is most frequently due to autoimmune causes. Thrombocytopenia secondary to obstetric causes like preeclampsia, HELLP syndrome should always be kept in mind. Under these circumstances the thrombocytopenia will not resolve unless pregnancy is terminated. The clinician should be able to distinguish between thrombocytopenia that does not require treatment and the causes that require emergent and serious medical interventions. [Archives Medical Review Journal 2016; 25(3.000: 420-432

  20. Acute thrombocytopenia caused by ceftizoxime sodium%头孢唑肟钠引起急性血小板减少



    1例32岁女性患者,因发热腰痛4d入院,诊断为急性肾孟肾炎,予静脉点滴头孢唑肟钠(2g,bid)治疗.用药第2天患者出现血小板急剧下降,无出血,立即停用头孢唑肟钠,患者血小板在1周内逐渐恢复正常.本文分析并总结头孢菌素类药物引起血小板减少的可能发生机制及血小板变化特点,以引起临床关注.%One 32-year-old female patient who was hospitalized as a result of fever and waist pain for 4 days, was diagnosed as acute pyelonephritis. Ceftizoxime sodium injection 2 g twice daily was administered to control the infection. After 2 days, the platelet count of this patient decreased sharply. There was no sign of bleeding in this patient. Ceftizoxime sodium was discontinued immediately. Platelet count of the patient gradually increased to normal within a week. The possible pathogenesis and change characteristics of platelet count in thrombocytopenia caused by cephalosporins were analyzed and summarized, which should be paid more attention to in clinical practice.

  1. Heparin-induced thrombocytopenia

    Shaikh Nissar


    Full Text Available In the last 7 decades heparin has remained the most commonly used anticoagulant. Its use is increasing, mainly due to the increase in the number of vascular interventions and aging population. The most feared complication of heparin use is heparin-induced thrombocytopenia (HIT. HIT is a clinicopathologic hypercoagulable, procoagulant prothrombotic condition in patients on heparin therapy, and decrease in platelet count by 50% or to less than 100,000, from 5 to 14 days of therapy. This prothrombotic hypercoagulable state in HIT patient is due to the combined effect of various factors, such as platelet activation, mainly the formation of PF4/heparin/IgG complex, stimulation of the intrinsic factor, and loss of anticoagulant effect of heparin. Diagnosis of HIT is done by clinical condition, heparin use, and timing of thrombocytopenia, and it is confirmed by either serotonin release assay or ELISA assay. Complications of HIT are venous/arterial thrombosis, skin gangrene, and acute platelet activation syndrome. Stopping heparin is the basic initial treatment, and Direct Thrombin Inhibitors (DTI are medication of choice in these patients. A few routine but essential procedures performed by using heparin are hemodialysis, Percutaneous Coronary Intervention, and Cardiopulmonary Bypass; but it cannot be used if a patient develops HIT. HIT patients with unstable angina, thromboembolism, or indwelling devices, such as valve replacement or intraaortic balloon pump, will require alternative anticoagulation therapy. HIT can be prevented significantly by keeping heparin therapy shorter, avoiding bovine heparin, using low-molecular weight heparin, and stopping heparin use for flush and heparin lock.

  2. Immune-Mediated Muscle Diseases of the Horse.

    Durward-Akhurst, S A; Valberg, S J


    In horses, immune-mediated muscle disorders can arise from an overzealous immune response to concurrent infections or potentially from an inherent immune response to host muscle antigens. Streptococcus equi ss. equi infection or vaccination can result in infarctive purpura hemorrhagica (IPH) in which vascular deposition of IgA-streptococcal M protein complexes produces ischemia and complete focal infarction of skeletal muscle and internal organs. In Quarter Horse-related breeds with immune-mediated myositis, an apparent abnormal immune response to muscle antigens results in upregulation of major histocompatibility complex class (MHC) I and II on muscle cell membranes, lymphocytic infiltration of lumbar and gluteal myofibers, and subsequent gross muscle atrophy. Rarely, an inflammatory event results in myositis with subsequent systemic calcinosis characterized by a pathognomonic hyperphosphatemia and high fatality rate. This review presents an overview of these immune-mediated myopathies and highlights clinical and pathological features as well as the suspected pathophysiology.

  3. Relapsing anemia with thrombocytopenia and acute kidney injury%反复发作贫血、血小板减少伴急性肾损伤



    青年女性,分别先后因少年时不洁饮食及青年期妊娠7月发生急性肾功能不全、微血管病性溶血、血小板减少、癫痫反复发作.第一次肾活检为典型的急性血栓性微血管病变,经甲泼尼龙1.5g冲击、血浆置换2次后血小板升至正常,透析治疗半年后肾功能恢复;第二次发病重复肾活检见肾小球及血管呈慢性化病变,但存在急性肾小管-间质损伤,静脉滴注甲泼尼龙40 mg/d、输注血浆治疗3d后血小板即升至正常,1月后肾功能恢复.两次发病查血管性血友病因子裂解酶13(ADAMTS13)活性均正常、抗ADAMTS13抗体低滴度阳性.最终诊断为获得性血栓性血小板减少性紫癜.%A female patient was admitted for both presenting as acute renal dysfunction, microangiopathic hemolysis, thrombocytopenia ,epilepsia and transient fever separately when she was 14 and 22 years old. In her first onset, renal histoiogiral showed classic acute thrombotic microangiopathies(TMA) .platelet increased to the normal after treatment of Prednisolone 0. 5 g/d for 3 days and plasma exchange twice, her renal function recovered after half-year hemodialysis. Her Second renal biopsy showed that glomcrulus and blood vessel displayed mainly chronic pathological changes, meanwhile obviously acute tubulointerstial injury. Platelet increased and renal function recovered quickly. ADAMTS13 activities were normal,and anti-ADAMTS13 antibodies were positive at her two episodes. Finally,TTP was diagnosed.

  4. Pyrazinamide induced thrombocytopenia

    Kant Surya


    Full Text Available Thrombocytopenia is an uncommon but potentially life-threatening complication of certain antitubercular drugs and is characterized by rapid destruction of platelets whenever offending drug is taken by a susceptible person. We report a case of pyrazinamide-induced thrombocytopenia in a patient receiving anti tubercular drugs.

  5. Mechanisms of conduction block in immune-mediated polyneuropathies

    Straver, D.C.G.


    Multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated neuropathies. Despite treatment being available, patients suffer from disabling weakness of arm and leg muscles and fatigue. Pathogenesis of MMN and CIDP is unclear, but the development

  6. Immune-mediated diseases in primary sclerosing cholangitis

    Lamberts, Laetitia E.; Janse, Marcel; Haagsma, Elizabeth B.; van den Berg, Arie P.; Weersma, Rinse K.


    Background: Primary sclerosing cholangitis is a chronic cholestatic liver disease. An immune aetiology is suggested by associations between PSC and inflammatory bowel disease. Data on concomitant prevalence of other immune-mediated diseases is limited. Aim: To assess the prevalence of concomitant im

  7. Advances in alloimmune thrombocytopenia: perspectives on current concepts of human platelet antigens, antibody detection strategies, and genotyping.

    Hayashi, Tomoya; Hirayama, Fumiya


    Alloimmunisation to platelets leads to the production of antibodies against platelet antigens and consequently to thrombocytopenia. Numerous molecules located on the platelet surface are antigenic and induce immune-mediated platelet destruction with symptoms that can be serious. Human platelet antigens (HPA) cause thrombocytopenias, such as neonatal alloimmune thrombocytopenia, post-transfusion purpura, and platelet transfusion refractoriness. Thirty-four HPA are classified into 28 systems. Assays to identify HPA and anti-HPA antibodies are critically important for preventing and treating thrombocytopenia caused by anti-HPA antibodies. Significant progress in furthering our understanding of HPA has been made in the last decade: new HPA have been discovered, antibody-detection methods have improved, and new genotyping methods have been developed. We review these advances and discuss issues that remain to be resolved as well as future prospects for preventing and treating immune thrombocytopenia.

  8. Treatment of immune thrombocytopenia after allogeneic cord blood stem cell transplantation with rituximab: a case report

    Mengxing Li; Jishi Wang; Yan Zhang; Zhiqiang Sun; Yanju Li; Xiaoli Zhou


    Immune thrombocytopenia (ITP) is a chronic disease resulting from increased platelet destruction and impaired platelet production. Secondary ITP can be a manifestation of chronic graft-versus-host disease (GVHD) and represent a lymphoproliferative disorder. A boy with chronic graft-versus-host disease after cord blood stem cell transplantation who had severe refractory immune-mediated thrombocytopenia received infusion of rituximab weekly, 375 mg/m2, for 4 weeks. Platelets count of the patient was recovered, and rituximab was well tolerated with no severe toxicity observed during treatment.

  9. Neonatal alloimmune thrombocytopenia

    Mella MT


    Full Text Available Maria Teresa Mella, Keith A Eddleman Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Mount Sinai School of Medicine, New York, NY, USA Abstract: Neonatal alloimmune thrombocytopenia occurs in one in 1,000–1,500 live births and is the most common cause of severe thrombocytopenia and intracranial hemorrhage in term infants. It is the equivalent of red blood cell alloimmunization and is due to transplacental passage of maternal antibodies against paternally derived fetal platelet antigens. A diagnosis of neonatal alloimmune thrombocytopenia should be considered for any neonate with unexplained thrombocytopenia. Once the diagnosis is made, it is known that all subsequent pregnancies are at risk for severe disease. In order to prevent the devastating and potentially life-threatening manifestations of the disease, the goal is to initiate treatment early with serial percutaneous umbilical blood sampling, intravenous immunoglobulin administration, prednisone, and/or fetal platelet transfusions. Timing of delivery is variable with delivery for severe disease recommended at an earlier gestational age. Vaginal delivery can be considered if the fetal platelet count is greater than 50,000–100,000 µL. Thrombocytopenia due to neonatal alloimmune thrombocytopenia usually resolves spontaneously within 1–2 weeks after delivery, but a platelet transfusion may be necessary to prevent a serious hemorrhagic event. In all cases, a multidisciplinary approach to care should be undertaken with delivery at a tertiary care center. Keywords: neonatal thrombocytopenia, fetal therapy, intracranial hemorrhage, intravenous immunoglobulin, alloimmunization

  10. Eltrombopag for the Treatment of Immune Thrombocytopenia: The Aegean Region of Turkey Experience

    Füsun Özdemirkıran


    Full Text Available INTRODUCTION: OBJECTIVE: Immune thrombocytopenia (ITP is an immune mediated disease characterized by transient or persistent decrease of the platelet count to less than 100 × 109/l. Although it is included in a benign disease group, bleeding complications may be mortal. With a better understanding of the pathophysiology of the disease, thrombopoietin receptor agonists which came into use in recent years, seem to be an effective option in the treatment of resistant patients. METHODS: In this study, retrospective data of 40 patients who were treated with Eltrombopag due to the diagnosis of refractory ITP in the Aegean region were examined and evaluated. RESULTS: In the study total rate of response was 87%, and in the cases with response the median period that number of platelets reached over 50. × 109/l was determined as 19.5 (5-60 days. DISCUSSION AND CONCLUSION: CONCLUSION: In one patient venous sinus thrombosis was observed and showed no other additional risk factor due to/ related to thrombosis. The other patient with complete response and irregular follow-up for 12 months was lost due to sudden death as the result of propable acute myocardial infarction.

  11. Incidence, severity, prognostic significance of thrombocytopenia in malaria

    Bezwada Srinivasa Rao


    Full Text Available Background: Malaria is an infectious disease caused by plasmodium parasite. P. falciparum account for majority of morbidity and mortality. Thrombocytopenia and anaemia are the most frequently associated hematological complications in malaria. The low platelet count together with acute febrile syndrome emerged as the strongest predictor of malaria a finding that is frequent and present even before anemia and splenomegaly sets in. Severe thrombocytopenia is a good predictor of poor prognosis than mild and moderate thrombocytopenia. The aim is to study the incidence, severity, prognostic significance of thrombocytopenia in malaria. Methods: This was an observational and prospective study. The study enrolled 100 patients with thrombocytopenia and fever who were proven to have malaria either by peripheral smear or Quantitative Buffy Coat (QBC test or malarial antigen assay were included in the study and patients with thrombocytopenia due to other causes were excluded from the study. Platelet count was estimated on a fully automated quantitative analyzer. All the 100 patients were followed during the hospital stay and upto discharge or till the outcome. Results: The incidence of thrombocytopenia was 73% indicating a common association in malaria. Complicated malaria was observed in 58.80% of P. falciparum infection whereas 66% of P. vivax infection was associated with uncomplicated malaria. Severe thrombocytopenia showed positive correlation with severity of malaria. Thrombocytopenic patients with effective anti-malarial treatment showed 95.90% recovery and 3 patients 4.10% had mortality. Patients with severe thrombocytopenia were 8.5 times more likely to have complicated malaria with P <0.001 according to student and lsquo;t' test. Conclusion: Thrombocytopenia is the most common hematological finding in malaria. Severe thrombocytopenia showed positive correlation with complicated malaria and a good predictor of poor prognosis. Patients with classical

  12. Urine metabolome profiling of immune-mediated inflammatory diseases

    Alonso, Arnald; Julià, Antonio; Vinaixa, Maria; Domènech, Eugeni; Fernández-Nebro, Antonio; Cañete, Juan D.; Ferrándiz, Carlos; Tornero, Jesús; Gisbert, Javier P; Nos, Pilar; Casbas, Ana Gutiérrez; Puig, Lluís; González-Álvaro, Isidoro; Pinto-Tasende, José A.; Blanco, Ricardo


    Background Immune-mediated inflammatory diseases (IMIDs) are a group of complex and prevalent diseases where disease diagnostic and activity monitoring is highly challenging. The determination of the metabolite profiles of biological samples is becoming a powerful approach to identify new biomarkers of clinical utility. In order to identify new metabolite biomarkers of diagnosis and disease activity, we have performed the first large-scale profiling of the urine metabolome of the six most pre...

  13. Infection and immune-mediated meningococcal-associated arthritis: combination features in the same patient

    Karim Yaqub Ibrahim


    Full Text Available We present a case of a 16-year-old male patient with sudden-onset, rash, arthritis and meningitis by Neisseria meningitidis one week after an acute upper respiratory infection. On the 10th day of treatment followed by neurological and arthritis clinical improvement, he presented once again a tender and swollen left knee with a moderate effusion, and active and passive range of motion was severely limited secondary to pain, and when he was submitted to surgical drainage and synovial fluid analysis he showed inflammatory characteristics. A non-steroidal anti-inflammatory drug was taken for five days with complete improvement of symptoms. The case is notable for its combination of features of septic and immune-mediated arthritis, which has rarely been reported in the same patient.

  14. Maternal and fetal outcome among pregnant women presenting with thrombocytopenia

    Vikrant Chauhan


    Conclusions: In pregnancy with thrombocytopenia, gestational thrombocytopenia is the commonest and benign condition which does not alter the obstetrical management. Still a vigil should be kept on maternal platelet count in antenatal period to prevent unfavorable outcome in serious conditions that may require specific and urgent management (HELLP syndrome, severe pre-eclampsia, TTP, HUS and acute fatty liver of pregnancy. [Int J Reprod Contracept Obstet Gynecol 2016; 5(8.000: 2736-2743

  15. Inflammatory Bowel Disease: Autoimmune or Immune-mediated Pathogenesis?

    Zhonghui Wen


    Full Text Available The pathogenesis of Crohn's disease (CD and ulcerative colitis (UC, the two main forms of inflammatory bowel disease (IBD, is still unclear, but both autoimmune and immune-mediated phenomena are involved. Autoimmune phenomena include the presence of serum and mucosal autoantibodies against intestinal epithelial cells in either form of IBD, and against human tropomyosin fraction five selectively in UC. In addition, perinuclear antineutrophil cytoplasmic antibodies (pANCA are common in UC, whereas antibodies against Saccharomyces cerevisiae (ASCA are frequently found in CD. Immune-mediate phenomena include a variety of abnormalities of humoral and cell-mediated immunity, and a generalized enhanced reactivity against intestinal bacterial antigens in both CD and UC. It is currently believed that loss of tolerance against the indigenous enteric flora is the central event in IBD pathogenesis. Various complementary factors probably contribute to the loss of tolerance to commensal bacteria in IBD. They include defects in regulatory T-cell function, excessive stimulation of mucosal dendritic cells, infections or variants of proteins critically involved in bacterial antigen recognition, such as the products of CD-associated NOD2/CARD15 mutations.

  16. Dermatomyositis, polymyositis and immune-mediated necrotising myopathies.

    Luo, Yue-Bei; Mastaglia, Frank L


    Dermatomyositis, polymyositis and immune-mediated necrotising myopathy are major forms of idiopathic inflammatory myopathy. We review here recent developments in understanding the pathology and pathogenesis of these diseases, and characterisation of autoantibody biomarkers. Dermatomyositis is traditionally considered to be due to a complement-mediated microangiopathy but the factors responsible for complement activation remain uncertain. Recent studies have emphasised the importance of the type I interferon pathway in the pathogenesis of the disease and have identified autoantibodies with specificities for different clinical subgroups of patients. Polymyositis is characterised by a cytotoxic T cell response targeting as yet unidentified muscle antigens presented by MHC Class I molecules, and can occur in isolation but is more often part of a multi-systemic overlap syndrome. The immune-mediated necrotising myopathies are heterogeneous and are distinguished from polymyositis by the sparseness of inflammatory infiltrates and recognition of an association with specific autoantibodies such as anti-SRP and anti-HMGCR in many cases. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

  17. Thalidomide-associated thrombocytopenia

    Duyvendak, M; Naunton, M.; Kingma, B.J; Brouwers, J.R.B.J.


    OBJECTIVE: To report thrombocytopenia in a patient prescribed thalidomide for multiple myeloma (MM). CASE SUMMARY: A 70-year-old woman was diagnosed in 2003 with MM. At diagnosis, melphalan 0.25 mg/kg/day and prednisolone 2 mg/kg/day were started; however, the patient became refractory to therapy. M

  18. Acute Compressive Ulnar Neuropathy in a Patient of Dengue Fever: An Unusual Presentation

    Anil K Mehtani


    Full Text Available Introduction: Dengue haemorrhagic fever is known for its haemorrhagic and neurologic complications. Neurologic complications are caused by three mechanism namely neurotropism, systemic complications causing encephalopathy and postinfectious immune-mediated mechanisms. However acute compressive neuropathy due to haemorrhage is not frequent and we could find no literature describing this Case Report: We report a case of acute compressive ulnar neuropathy due to peri neural hematoma, following an attempt at intravenous cannulation in the cubital fossa in a patient of dengue haemorrhagic fever with thrombocytopenia. Immediate fasciotomy and removal of haematoma was performed to relieve the symptoms. Conclusion: Compression neuropathies can be seen in dengue hemorrhagic fever and removal of compressing hematoma relieves symptoms. Keywords: Dengue haemmorrhagic fever; coagulopathy; peri neural haematoma.

  19. Recurrent Acute Myocardial Infarction in Patients with Immune Thrombocytopenic Purpura

    Fengyi Shen


    Full Text Available Immune thrombocytopenic purpura (ITP, also known as idiopathic thrombocytopenic purpura, is an acquired immune-mediated disease of adults and children characterized by a transient or persistent decrease of platelets and, depending upon the degree of thrombocytopenia, an increased risk of bleeding. The use of standard treatments for acute myocardial infarction (AMI, such as antiplatelet agents and anticoagulants, pose serious problems in patients with ITP due to the potential higher risk of bleeding complications. There are no current guidelines available for management of ITP patients with AMI. In this brief review of the limited available literature, we discuss the proposed pathophysiological link between ITP and arterial thrombosis and the challenging medical and interventional treatment of these patients.

  20. Immune-mediated diseases and microbial exposure in early life

    Bisgaard, H; Bønnelykke, K; Stokholm, Jacob


    colonization patterns in neonates drive both short-term and long-term asthma symptoms, while, on the other hand, the composition of the microbiome in early life may protect against asthma and allergy in later life. This apparent contradiction may be explained by a deeper disease heterogeneity than we...... are currently able to discriminate, and in particular, the indiscriminate lumping together of different diseases into one atopic disease category. Also, the microbiome needs a differentiated understanding, considering balance between microbial groups, diversity and microbial genetic capability. Furthermore......The non-communicable disease pandemic includes immune-mediated diseases such as asthma and allergy, which are likely originating in early life where the immature immune system is prone to alterations caused by the exposome. The timing of exposure seems critical for the developing immune system...

  1. Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology.

    Benedict D Michael

    Full Text Available Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause.We measured 38 mediators in serum and cerebrospinal fluid (CSF of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology.Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006. Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03. Multivariate analysis selected serum MPO; classifying 31 (91% as infectious (p = 0.008 and 17 (85% as unknown (p = 0.009 as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85% as infectious as opposed to immune-mediated (p = 0.036. CSF neutrophils were detected in eight (62% infective and one (14% immune-mediated cases (p = 0.004; CSF MPO correlated with neutrophils (p<0.0001.Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.

  2. Dabigatran approaching the realm of heparin-induced thrombocytopenia

    Ho, Patricia J


    Heparin-induced thrombocytopenia (HIT) is a serious, immune mediated complication of exposure to unfractionated or low-molecular-weight heparin. Though rare, it is a condition associated with high morbidity and mortality that requires immediate change to alternative anticoagulants for the prevention of life-threatening thrombosis. The direct thrombin inhibitors lepirudin and argatroban are currently licensed for the treatment of HIT. Dabigatran, a novel oral anticoagulant (NOAC) with a similar mechanism of action and effective use in other indications, has recently been proposed as another therapeutic option in cases of HIT. This review serves as an introduction to using dabigatran for this purpose, detailing the clinical aspects of its administration, evidence of its performance compared to other anticoagulants, and the preliminary reports of HIT successfully treated with dabigatran. As the literature on this develops, it will need to include clinical trials that directly evaluate dabigatran against the other NOACs and current treatment options. PMID:27382551

  3. Delayed profound thrombocytopenia presenting 7 days after use of abciximab (ReoPro).

    Sharma, Sanjiv; Bhambi, Brijesh; Nyitray, William; Sharma, Geetanjali; Shambaugh, Shawn; Antonescu, Adrian; Shukla, Pankaj; Denny, Eileen


    A case of a 65-year-old woman presenting with delayed profound thrombocytopenia 7 days after the use of abciximab (ReoPro) in the setting of percutaneous coronary intervention is described. The patient had normal platelet counts for the first 24 hours after the use of abciximab (ReoPro). She presented with petechiae and profound thrombocytopenia 1 week later. The patient was treated successfully with a platelet transfusion and recovered uneventfully. Profound thrombocytopenia occurs acutely within the first few hours after abciximab (ReoPro) use, so this case was unique in that the profound thrombocytopenia presented 1 week after use of abciximab (ReoPro).

  4. Refractory primary immune thrombocytopenia with subsequent del(5q) MDS: complete remission of both after lenalidomide.

    Mortensen, Thomas Bech; Frederiksen, Henrik; Marcher, Claus Werenberg; Preiss, Birgitte


    A patient with refractory primary immune thrombocytopenia (ITP) characterised by severe skin and mucosal bleedings was treated with several ITP-directed therapies including cyclophosphamide. He later developed therapy-related del(5q) myelodysplastic syndrome with no dysplastic morphological features in bone marrow. He remained severely thrombocytopenic, which suggests ongoing immune mediated platelet destruction. After two 3 week cycles of low-dose lenalidomide, complete cytogenetic remission and complete normalisation of platelet count were observed. This suggests that lenalidomide may be a viable treatment option for ITP in the presence of del(5q) not responding to standard treatments.

  5. [Thrombocytopenia induced by heparin. Diagnosis, treatment, physiopathology: current concepts].

    Gruel, Y; Drouet, L


    Iatrogenic thrombocytopenia is a rare, but severe complication of treatments with heparin and heparinoids. Mean temporary thrombocytopenia failing to show any complications are usually diagnosed as quite different from acute and delayed thrombocytopenia of which severity depends mainly on thrombotic symptoms demonstrated in 65 p. 100 of cases; the initial evolution of an average thrombocytopenia is not easy to diagnose; it may as well exist a connection between the two diseases, from a physiopathogenic point of view. The diagnosis of severe thrombocytopenia depends:--clinically, on the initial data, delayed as compared with the heparin treatment beginning and existence of arterial and/or venous thrombosis;--biologically, by demonstrating an aggregating activity for platelets in presence of heparin, in the patient plasma. Such an activity requires the suppression of standard heparinotherapy as well as the choice of substitutive anticoagulant treatment in case of evolutive thrombosis. Low molecular weight heparins are prescribed only if in vitro tests of platelet aggregation with the patient's plasma are negative. Antivitamins K are to be used as soon as possible alone or combined with heparin fractions. Antiaggregants are prescribed alone, above all in case of isolated thrombocytopenia and combined with AVK. Treatment of thrombotic complications depends on surgical disobstruction if arterial thrombosis, and use of fibrinolytics if pulmonary embolisms. The acute reaction of some thrombocytopenia to heparin as well as therapeutic difficulties demonstrate the efficiency of an early diagnosis performed thanks to systematic platelet numerations during the first 15 days of a treatment with heparin, as well as to the prevention along with systematic association with aspirin, especially if replaced with AVK.

  6. Significance of Anti-cyclic Citrullinated Peptide Autoantibodies in Immune-mediated Inflammatory Skin Disorders with and without Arthritis

    Grover, Chander; Kashyap, Bineeta; Daulatabad, Deepashree; Dhawan, Amit; Kaur, Iqbal R


    Background: Anti-cyclic citrullinated peptides (CCPs) are autoantibodies directed against citrullinated peptides. Rheumatoid factor (RF), an antibody against the Fc portion of IgG, is known to form immune complexes and contribute to the etiopathogenesis of various skin disorders. C-reactive protein (CRP), an acute-phase protein, increases following secretion of interleukin-6 from macrophages and T cells. Anti-CCP, RF, and CRP are well-established immune-markers, their diagnostic potential in immune-mediated skin disorders remains less widely studied. Aims and Objectives: To determine the correlation between anti-CCP, RF, and CRP in immune-mediated inflammatory skin diseases. Materials and Methods: About 61 clinically diagnosed cases of various immune-mediated skin diseases (psoriasis [n = 38], connective tissue diseases such as systemic lupus erythematosus and systemic sclerosis [n = 14], and immunobullous disorders including pemphigus vulgaris and pemphigus foliaceus [n = 9]) were included in the study. These patients were subclassified on the basis of presence or absence of arthritis. Arthritis was present in nine cases of psoriasis and seven connective tissue disorder patients. Detection of serum anti-CCP was done using enzyme-linked immunosorbent assay, whereas CRP and RF levels were detected using latex agglutination technique. Results: Of the 61 specimens, 14.75% had elevated serum anti-CCP levels. RF and CRP levels were elevated in 18.03% and 39.34% specimens, respectively. RF was elevated in 13.16% of inflammatory and 42.88% of connective tissue disorders, whereas anti-CCP was raised in 10.53% of inflammatory and 35.71% of connective tissue disorders. CRP positivity was highest in connective tissue disorders (50%), followed by 39.47% in inflammatory and 22.22% in immunobullous conditions. In none of the immunobullous patients, anti-CCP or RF levels were found to be elevated. Association of the presence of arthritis with elevated anti-CCP was found to be

  7. Romiplostim as a treatment for immune thrombocytopenia: a review

    Chalmers S


    Full Text Available Sarah Chalmers,1,2 Michael D Tarantino1–31University of Illinois College of Medicine – Peoria, 2The Children's Hospital of Illinois, 3The Bleeding and Clotting Disorders Institute, Peoria, Illinois, USAAbstract: “Immune thrombocytopenia” (ITP is an autoimmune disorder that leads to peripheral destruction, as well as a decreased production of platelets. ITP most commonly presents as mild mucocutaneous bleeding. Though it is rare, the leading cause of mortality in persons with ITP is intracranial hemorrhage and those that do not respond to therapy are at increased risk. Our understanding of the pathophysiology of ITP has evolved immensely, especially over the last 60 years. The discovery of the platelet-production stimulator, thrombopoietin (TPO, lent clarity to an earlier hypothesis that inhibition of platelet production at the level of the megakaryocyte, at least in part, accounts for thrombocytopenia in adults with ITP. This facilitated the development of TPO-based therapies to treat ITP. Thrombopoietin receptor agonists are one of the most recent treatments to enter the landscape. Original production of a recombinant human TPO was halted after clinical trials revealed the untoward effect of autoantibodies to the recombinant human TPO with cross-reactivity to endogenous TPO. Next-step development focused on stimulation of the TPO receptor with fewer immunogenic agents. Currently, two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are licensed in the USA to treat thrombocytopenia in adults with persistent or chronic ITP. Ongoing research will assess their efficacy in other immune-mediated and nonimmune-mediated primary and secondary thrombocytopenias.Keywords: thrombopoietin, thrombopoietin receptor agonist, megakaryocyte, peptibody

  8. Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms.

    Ole A Andreassen

    Full Text Available Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS to investigate shared single nucleotide polymorphisms (SNPs between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals, applying new False Discovery Rate (FDR methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG, low density lipoproteins (LDL, high density lipoproteins (HDL] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis. We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88, LDL (n = 87 and HDL (n = 52. Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2 and intestinal host-microbe interactions (e.g. ATG16L1. We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.

  9. Fetal/neonatal alloimmune thrombocytopenia.

    Sachs, Ulrich J


    In fetal/neonatal alloimmune thrombocytopenia (FNAIT), antibodies against paternal antigens present on fetal platelets are produced by the mother. These antibodies will cross the placenta and can cause thrombocytopenia of the unborn. One severe consequence of thrombocytopenia is intracranial bleeding which may lead to death or severe sequelae. FNAIT index cases in one family are usually detected at birth only since antenatal screening programmes have not been installed so far. Subsequent pregnancies of immunized mothers may require special diagnostic and prophylactic interventions, and interdisciplinary counselling and treatment involving obstetricians, pediatricians and immunohematologists may prove useful for optimized care. This short review covers pathogenesis, clinical presentation, diagnostic, and therapeutic options in FNAIT.




    Full Text Available OBJECTIVE: To determine etiology, onset, clinical features and outcome of neonates with thrombocytopenia. METHODS: 140 neonates having bleeding or having platelet count (<1.5lakhs/µl were selected from those admitted to NICU’S attached to MR Medical College, Gulbarga. Initial platelet count was done on admission and counts were repeated 12 hours after any therapeutic intervention. OBSERVATION AND RESULTS: Severe thrombocytopenia (<50000/µl was present in 8.5%, moderate (50, 000-1, 00, 000/µl in 17%. Majority (45.33% were preterm and the major cause was sepsis in 51.3%.Mucosal bleed was the most common presentation. Mortality was 37% in severe and 3.9% in moderate thrombocytopenia group. CONCLUSION: Significant association is observed with maternal PIH, Late onset sepsis, NEC and sepsis with DIC .Prematurity, IUGR, Birth asphyxia were common associated morbidities. Severe thrombocytopenia in sick neonates, in NICU, is a poor prognostic indicator.

  11. Diagnosis and management of neonatal thrombocytopenia.

    Holzhauer, Susanne; Zieger, Barbara


    Thrombocytopenia is the most common haematological abnormality in newborns admitted to neonatal care units and serves as an important indicator of underlying pathological processes of mother or child. In most cases thrombocytopenia is mild to moderate and resolves within the first weeks of life without any intervention. However, in some neonates thrombocytopenia is severe or may reflect an inborn platelet disorder. As clinical course and outcome of thrombocytopenia depend on the aetiology of thrombocytopenia, an appropriate work-up is essential to guide therapy in neonates with thrombocytopenia and to avoid severe bleeding.

  12. Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies

    Leussink, Verena I.; Hartung, Hans-Peter; Kieseier, Bernd C.; Stettner, Mark


    Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients. PMID:27366241

  13. Genetics of immune-mediated disorders: from genome-wide association to molecular mechanism

    Kumar, Vinod; Wijmenga, Cisca; Xavier, Ramnik J.


    Genetic association studies have identified not only hundreds of susceptibility loci to immune-mediated diseases but also pinpointed causal amino-acid variants of HLA genes that contribute to many autoimmune reactions. Majority of non-HLA genetic variants are located within non-coding regulatory region. Expression QTL studies have shown that these variants affect disease mainly by regulating gene expression. We discuss recent findings on shared genetic loci between infectious and immune-mediated diseases and provide potential clues to explore genetic associations in the context of these infectious agents. We propose that the interdisciplinary studies (genetics-genomics-immunology-infection-bioinformatics) are the future post-GWAS approaches to advance our understanding of the pathogenesis of immune-mediated diseases. PMID:25458995

  14. Romiplostim in thrombocytopenia treatment after allogeneic bone marrow transplantation

    I. A. Lisukov


    Full Text Available Persistent thrombocytopenia is a frequent complication after allogeneic bone marrow transplantation (BMT. The major causes of thrombocytopenia include accelerated platelet destruction by antiplatelet antibodies, microangiopathy, viral infection, drug toxicity,graft`s hypofunction with insufficient production of platelets from megakaryocytes. We have evaluated an efficacy of TPO-receptor agonistromiplostim in treatment of 3 patients with refractory thrombocytopenia after allogeneic BMT. The first 30 years old patient received haploidentical allogeneic stem cell transplantation for refractory AML relapse. He developed graft hypofunction due to CMV infection, acute GVHD and thrombotic thrombocytopenic purpura (TTP with platelet counts 5 × 109/l and bleeding complications. After bone marrow “boost” the patient received romiplostim 1 mkg/kg weekly during 2 weeks and 4 mkg/kg during another 2 weeks. Upon reaching platelet counts 50 × 109/l the romiplostim was stopped, but platelet count decreased to 5–7 × 109/l and romiplostim was administered in dose of 4 mkg/kg weekly during 5 weeks. Platelet counts have achieved 150 × 109/l and thrombocytopenia during further follow-up was not revealed. The second 19 years old AML patient received haploidentical allogeneic stem cell transplantation for second remission consolidation. He developed thrombocytopenia (10 × 109/l due to CMV infection and severe TTP. He received romiplostim 4 mkg/kg weekly and 5 weeks later platelet counts was 50 × 109/l. The administration of romiplostim was allowed to avoid bleeding complications and transfusion dependency. The third 18 years old ALL patient received MUD allogeneic stem cell transplantation for second remission consolidation. He developed profound thrombocytopenia (5 × 109/l with severe hemorrhagic complications and platelet transfusions refractory due to TTP and acute GVHD. He received one dose of romiplostim 1 mkg/kg and two doses of 3 mkg

  15. Romiplostim in thrombocytopenia treatment after allogeneic bone marrow transplantation

    I. A. Lisukov


    Full Text Available Persistent thrombocytopenia is a frequent complication after allogeneic bone marrow transplantation (BMT. The major causes of thrombocytopenia include accelerated platelet destruction by antiplatelet antibodies, microangiopathy, viral infection, drug toxicity,graft`s hypofunction with insufficient production of platelets from megakaryocytes. We have evaluated an efficacy of TPO-receptor agonistromiplostim in treatment of 3 patients with refractory thrombocytopenia after allogeneic BMT. The first 30 years old patient received haploidentical allogeneic stem cell transplantation for refractory AML relapse. He developed graft hypofunction due to CMV infection, acute GVHD and thrombotic thrombocytopenic purpura (TTP with platelet counts 5 × 109/l and bleeding complications. After bone marrow “boost” the patient received romiplostim 1 mkg/kg weekly during 2 weeks and 4 mkg/kg during another 2 weeks. Upon reaching platelet counts 50 × 109/l the romiplostim was stopped, but platelet count decreased to 5–7 × 109/l and romiplostim was administered in dose of 4 mkg/kg weekly during 5 weeks. Platelet counts have achieved 150 × 109/l and thrombocytopenia during further follow-up was not revealed. The second 19 years old AML patient received haploidentical allogeneic stem cell transplantation for second remission consolidation. He developed thrombocytopenia (10 × 109/l due to CMV infection and severe TTP. He received romiplostim 4 mkg/kg weekly and 5 weeks later platelet counts was 50 × 109/l. The administration of romiplostim was allowed to avoid bleeding complications and transfusion dependency. The third 18 years old ALL patient received MUD allogeneic stem cell transplantation for second remission consolidation. He developed profound thrombocytopenia (5 × 109/l with severe hemorrhagic complications and platelet transfusions refractory due to TTP and acute GVHD. He received one dose of romiplostim 1 mkg/kg and two doses of 3 mkg

  16. Assessment of Equine Autoimmune Thrombocytopenia (EAT by flow cytometry

    Schwarzwald Colin


    Full Text Available Abstract Rationale Thrombocytopenia is a platelet associated process that occurs in human and animals as result of i decreased production; ii increased utilization; iii increased destruction coupled to the presence of antibodies, within a process know as immune-mediated thrombocytopenia (IMT; or iv platelet sequestration. Thus, the differentiation of the origin of IMT and the development of reliable diagnostic approaches and methodologies are important in the clarification of IMT pathogenesis. Therefore, there is a growing need in the field for easy to perform assays for assessing platelet morphological characteristics paired with detection of platelet-bound IgG. Objectives This study is aimed to develop and characterize a single color flow cytometric assay for detection of platelet-bound IgG in horses, in combination with flow cytometric assessment of platelet morphological characteristics. Findings The FSC and SSC evaluation of the platelets obtained from the thrombocytopenic animals shows several distinctive features in comparison to the flow cytometric profile of platelets from healthy animals. The thrombocytopenic animals displayed i increased number of platelets with high FSC and high SSC, ii a significant number of those gigantic platelets had strong fluorescent signal (IgG bound, iii very small platelets or platelet derived microparticles were found significantly enhanced in one of the thrombocytopenic horses, iv significant numbers of these microplatelet/microparticles/platelet-fragments still carry very high fluorescence. Conclusions This study describes the development and characterization of an easy to perform, inexpensive, and noninvasive single color flow cytometric assay for detection of platelet-bound IgG, in combination with flow cytometric assessment of platelet morphological characteristics in horses.

  17. Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts

    Larsen, Ole H; Stentoft, Jesper; Radia, Deepti


    Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole b...

  18. Thrombocytopenia and leptospirosis Trombocitopenia e leptospirose

    Antonio Carlos Nicodemo


    Full Text Available The present study has intended to contribute to the elucidation of the pathogenic mechanisms, involved in the thrombocytopenia and in the bleeding diathesis seen in the course of Leptospirosis. The group of cases included in the present prospective study consisted of 30 patients with Leptospirosis, admitted to the Infectious and Parasitic Diseases Ward, Hospital das Clínicas, Faculty of Medicine, University of São Paulo. The following possible mechanisms of thrombocytopenia have been considered and therefore investigated: platelet consumption, due to disseminated intravascular coagulation; immune-mediated platelet destruction, due to platelet-associated antibodies and an inhibited platelet production in the bone marrow. Thrombocytopenia occurred in 86.6% of 30 patients and did not seem to be immune-mediated by platelet-associated antibodies. Furthermore it did not seem to be due to a disseminated intravascular coagulation consumption. Although there was a statistically-significant correlation between bone marrow platelet production and platelet counts we think that the static microscopic examination of a bone marrow aspirate cannot accurately depict the dynamic mechanisms of platelet production when these cells are being consumed in peripheral blood. Vasculitis should be considered as the most important factor for the pathogenesis of the bleeding disturbances in Leptospirosis. However, we believe that thrombocytopenia, uremia and coagulation disorders, individually or as a group, should be included among the contributing factors that lead to and worsen bleeding episodes, which represent the leading cause of death in this disease.O propósito do presente trabalho é colaborar para o estudo da patogenia da plaquetopenia que ocorre na Leptospirose. A pesquisa foi feita de maneira prospectiva e o grupo de casos foi constituído por 30 pacientes internados com hipótese diagnostica de Leptospirose na Clínica de Doenças Infecciosas e Parasit

  19. Autoimmunity : Break-through in the diagnosis and treatment of immune-mediated inflammatory diseases

    Kroese, Frans G. M.; Baeten, Dominique; Huizinga, Tom W. J.


    The study of fundamental mechanisms of autoimmunity has been instrumental to clinical progress in the diagnosis and treatment of a range of immune-mediated inflammatory disorders. Dutch immunology has made major contributions to these developments, ranging from fundamental studies on immune cells, a

  20. Immune-mediated hemolytic anemia associated with trimethoprim-sulphamethoxazole administration in a horse.

    Thomas, H L; Livesey, M A


    A 10-year-old, thoroughbred gelding was administered sulphonamide drugs during surgical treatment of guttural pouch mycosis. The horse became anemic and a diagnosis of immune-mediated hemolytic anemia was made after other causes of anemia had been ruled out. The anemia resolved after the drugs were withdrawn.

  1. Three cases of immune-mediated adnexal skin disease treated with cyclosporin.

    Noli, Chiara; Toma, Stefano


    Cyclosporin is currently considered a new and interesting drug in veterinary dermatology for the treatment of immune-mediated skin diseases, and a safe and effective alternative to immunosuppressive therapy with glucocorticoids. The authors report a case of granulomatous folliculitis and furunculosis and of sebaceous adenitis in two cats and a case of alopecia areata in a dog, successfully controlled with cyclosporin.

  2. Early intervention in psoriasis and immune-mediated inflammatory diseases: A hypothesis paper

    Girolomoni, G.; Griffiths, C.E.; Krueger, J.; Nestle, F.O.; Nicolas, J.F.; Prinz, J.C.; Puig, L.; Stahle, M.; Kerkhof, P.C.M. van de; Allez, M.; Emery, P.; Paul, C.


    Psoriasis is an immune-mediated inflammatory disease (IMID) which may have a major impact on a patient's life, especially when the disease is moderate to severe. There is evidence that treatment of psoriasis during the first years is conservative and frequently based on topical agents which rarely c

  3. Eptifibatide-induced thrombocytopenia: with thrombosis and disseminated intravascular coagulation immediately after left main coronary artery percutaneous coronary angioplasty.

    Tempelhof, Michael W; Benzuly, Keith H; Fintel, Dan; Krichavsky, Marc Z


    Early clinical trials of eptifibatide did not show a significant association between eptifibatide and the development of thrombocytopenia, thrombosis, or disseminated intravascular coagulation. However, more recent literature has suggested a significant association between eptifibatide and the development of thrombocytopenia and thrombosis. Although the true incidence and the pathophysiology of these associations are unknown, the development of these events can be life-threatening. Herein, we describe the case of a patient who experienced acute onset of profound thrombocytopenia, developing thrombosis, pulmonary emboli, and disseminated intravascular coagulation. This paper adds to the few previous reports of cases that suggested an association between thrombocytopenia, thrombosis, and the administration of eptifibatide. To the best of our knowledge, this is the first case report in the medical literature that associates the new onset of thrombocytopenia, thrombosis, and disseminated intravascular coagulation with the administration of eptifibatide. We also provide a subject review.

  4. 急性心力衰竭应用主动脉内球囊反搏患者血小板减少因素分析%Cause analysis of thrombocytopenia in acute heart failure implanted with intra-aortic balloon pump

    房芳; 李宇


    Objective To explore the causes of thrombocytopenia in acute heart failure (AHF) implanted with intra-aortic balloon pump (IABP).Methods Totally 50 cases with AHF implanted with IABP from November 2011 to November 2013 were retrospective enrolled.The time duration of IABP implantion and change of thrombocyte were recorded;the correlations of thrombocytopenia with disease type,size of ballon,gender were analyzed,the influence of thrombocytopenia on hospital mortality rate were assessed.Results The time duration of IABP implantion was (181 ±34) h (32.4-1 136.5 h).There was 27 patients with thrombocytopenia (mild:15 cases,moderate:9 cases,severe:3 cases),the time of the least platelet count was(100 ± 10) h.The incidence of thrombocytopenia in patients with acute myocardial infarction induced AHF was not significantly different from that in patients with other causes induced AHF [51.6% (16/31) vs 57.9% (11/19)] (P > 0.05).The incidence of thrombocytopenia was significantly lower in patients applied with 30 CC balloon than that in patients applied with 40 CC balloon [31.3% (5/16) vs 64.7% (22/34)],was significantly lower in males than that in femals [46.2% (18/39) vs 81.8% (9/11)] (P < 0.05).In 50 patients,17 cases was dead in hospital;the mortality rate in patients with thrombocytopenia was significantly higher than that in patients without thrombocytopenia [48.1% (13/27) vs 17.4% (4/23)] (P <0.05).Conclusion Thrombocytopenia can increase the morality rate in acute heartfailure patients implanted with IABP,which is correlated with the size of implanted balloon and gender.%目的 探讨急性心力衰竭应用主动脉内球囊反搏(IABP)患者血小板减少的原因.方法 回顾性选取首都医科大学附属北京安贞医院2011年11月至2013年11月收治的应用IABP的急性心力衰竭患者50例,记录应用IABP的时间以及应用后患者的血小板变化情况;分析血小板减少和疾病类型、球囊大小、性别的关

  5. Childhood immune thrombocytopenia: Clinical presentation and management

    Faki Osman, Mohamed El


    Immune thrombocytopenia (ITP) is an acquired hematological disorder that is developed secondary to the production of auto-antibodies against platelets leading to isolated thrombocytopenia, in the absence of other causes of thrombocytopenia such as drugs, infections, malignancy, or other autoimmune diseases [1–6]. ITP commonly affects children between one and seven years of age. Severe life threatening bleeding is rare (0.2–0.9%) [7–12]. Childhood primary ITP usually runs a benign, self-limiti...

  6. PPARγ antagonist attenuates mouse immune-mediated bone marrow failure by inhibition of T cell function.

    Sato, Kazuya; Feng, Xingmin; Chen, Jichun; Li, Jungang; Muranski, Pawel; Desierto, Marie J; Keyvanfar, Keyvan; Malide, Daniela; Kajigaya, Sachiko; Young, Neal S


    Acquired aplastic anemia is an immune-mediated disease, in which T cells target hematopoietic cells; at presentation, the bone marrow is replaced by fat. It was reported that bone marrow adipocytes were negative regulators of hematopoietic microenvironment. To examine the role of adipocytes in bone marrow failure, we investigated peroxisomal proliferator-activated receptor gamma, a key transcription factor in adipogenesis, utilizing an antagonist of this factor called bisphenol-A-diglycidyl-ether. While bisphenol-A-diglycidyl-ether inhibited adipogenesis as expected, it also suppressed T cell infiltration of bone marrow, reduced plasma inflammatory cytokines, decreased expression of multiple inflammasome genes, and ameliorated marrow failure. In vitro, bisphenol-A-diglycidyl-ether suppressed activation and proliferation, and reduced phospholipase C gamma 1 and nuclear factor of activated T-cells 1 expression, as well as inhibiting calcium flux in T cells. The in vivo effect of bisphenol-A-diglycidyl-ether on T cells was confirmed in a second immune-mediated bone marrow failure model, using different strains and non-major histocompatibility antigen mismatched: bisphenol-A-diglycidyl-ether ameliorated marrow failure by inhibition of T cell infiltration of bone marrow. Our data indicate that peroxisomal proliferator-activated receptor gamma antagonists may attenuate murine immune-mediated bone marrow failure, at least in part, by suppression of T cell activation, which might hold implications in the application of peroxisomal proliferator-activated receptor gamma antagonists in immune-mediated pathophysiologies, both in the laboratory and in the clinic. Genetically "fatless" mice developed bone marrow failure with accumulation of marrow adipocytes in our model, even in the absence of body fat, suggesting different mechanisms of systematic and marrow adipogenesis and physiologic versus pathophysiologic fat accumulation.

  7. Activation and Regulation of Hemostasis in Acute Liver Failure and Acute Pancreatitis

    Lisman, Ton; Porte, Robert J.


    Acute liver failure and acute pancreatitis are accompanied by substantial changes in the hemostatic system. In acute liver failure, defective synthesis of coagulation factors and intravascular activation of coagulation results in thrombocytopenia and reduced levels of proteins involved in coagulatio

  8. The diagnostic and prognostic value of neurofilament heavy chain levels in immune-mediated optic neuropathies.

    Petzold, Axel; Plant, Gordon T


    Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH) in three immune-mediated optic neuropathies. Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON, n = 20), chronic relapsing inflammatory optic neuritis (CRION, n = 19), neuromyelitis optica (NMO, n = 9), and healthy controls (n = 28). Serum NfH-SMI35 levels were quantified by ELISA. Findings. Serum NfH-SMI35 levels were highest in patients with NMO (mean 0.79 ± 1.51 ng/mL) compared to patients with CRION (0.13 ± 0.16 ng/mL, P = 0.007), MSON (0.09 ± 0.09, P = 0.008), and healthy controls (0.01 ± 0.02 ng/mL, P = 0.001). High serum NfH-SMI35 levels were related to poor visual outcome. Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions.

  9. Early childhood poverty, immune-mediated disease processes, and adult productivity.

    Ziol-Guest, Kathleen M; Duncan, Greg J; Kalil, Ariel; Boyce, W Thomas


    This study seeks to understand whether poverty very early in life is associated with early-onset adult conditions related to immune-mediated chronic diseases. It also tests the role that these immune-mediated chronic diseases may play in accounting for the associations between early poverty and adult productivity. Data (n = 1,070) come from the US Panel Study of Income Dynamics and include economic conditions in utero and throughout childhood and adolescence coupled with adult (age 30-41 y) self-reports of health and economic productivity. Results show that low income, particularly in very early childhood (between the prenatal and second year of life), is associated with increases in early-adult hypertension, arthritis, and limitations on activities of daily living. Moreover, these relationships and particularly arthritis partially account for the associations between early childhood poverty and adult productivity as measured by adult work hours and earnings. The results suggest that the associations between early childhood poverty and these adult disease states may be immune-mediated.

  10. The Diagnostic and Prognostic Value of Neurofilament Heavy Chain Levels in Immune-Mediated Optic Neuropathies

    Axel Petzold


    Full Text Available Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH in three immune-mediated optic neuropathies. Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON, n=20, chronic relapsing inflammatory optic neuritis (CRION, n=19, neuromyelitis optica (NMO, n=9, and healthy controls (n=28. Serum NfH-SMI35 levels were quantified by ELISA. Findings. Serum NfH-SMI35 levels were highest in patients with NMO (mean 0.79±1.51 ng/mL compared to patients with CRION (0.13±0.16 ng/mL, P=0.007, MSON (0.09±0.09, P=0.008, and healthy controls (0.01±0.02 ng/mL, P=0.001. High serum NfH-SMI35 levels were related to poor visual outcome. Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions.

  11. Application of the 2012 revised diagnostic definitions for paediatric multiple sclerosis and immune-mediated central nervous system demyelination disorders

    van Pelt, E. Danielle; Neuteboom, Rinze F.; Ketelslegers, Immy A.; Boon, Maartje; Catsman-Berrevoets, Coriene E.; Hintzen, Rogier Q.


    Background Recently, the International Paediatric Multiple Sclerosis Study Group (IPMSSG) definitions for the diagnosis of immune-mediated acquired demyelinating syndromes (ADS) of the central nervous system, including paediatric multiple sclerosis (MS), have been revised. Objective To evaluate the

  12. Refractory heparin induced thrombocytopenia with thrombosis (HITT) treated with therapeutic plasma exchange and rituximab as adjuvant therapy.

    Schell, Amy M; Petras, Melissa; Szczepiorkowski, Zbigniew M; Ornstein, Deborah L


    We report a case of refractory heparin-induced thrombocytopenia with thrombosis (HITT) with prolonged thrombocytopenia and multiple thrombotic complications that failed to improve despite aggressive treatment. A 60 year old female with a prior history of venous thromboembolism was admitted with an acute pulmonary embolism, and developed HITT after several days on heparin therapy. She suffered multiple complications including bilateral venous limb gangrene, acute renal failure, and refractory thrombocytopenia, leading us to use multimodality therapy including therapeutic plasma exchange (TPE) and rituximab immunosuppression. The patient had transient improvements in her thrombocytopenia with TPE, and rituximab was added in an attempt to reduce antibody production. She eventually required bilateral limb amputation, and only after removal of the gangrenous limbs did her platelet count show sustained improvement. We discuss the possible contribution of infection to her prolonged course.

  13. A study of cytological changes in the bone marrow of patients with severe fever with thrombocytopenia syndrome.

    Xing QuanTai

    Full Text Available BACKGROUND: Peripheral blood leucopenia and thrombocytopenia are the main manifestations in severe fever with thrombocytopenia syndrome (SFTS patients. However, the underlying causes are poorly understood. Therefore, we aimed to investigate cytology of bone marrow samples collected from SFTS patients. METHODS: 10 SFTS patients were identified by typical clinical manifestations, detection of peripheral blood leucopenia and thrombocytopenia, and nucleic acid-based detection of the newly identified bunyavirus. SFTS patients, along with 10 participants with acute aplastic anemia and 10 healthy volunteers were enrolled in this study after written informed consent to undergo bone marrow cytological examination. RESULTS: We observed similar bone marrow properties in SFTS patients and healthy volunteers, significantly different from the characteristics observed in acute aplastic anemia patients. CONCLUSION: Similarities between bone marrow samples collected from SFTS patients and healthy volunteers suggest that peripheral blood leucopenia and thrombocytopenia do not result from bone marrow cell plasticity.

  14. 2, 3, 7, 8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury

    Fullerton, Aaron M.; Roth, Robert A.; Ganey, Patricia E.


    Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30µg/kg TCDD or vehicle cont...

  15. Venous Thromboembolism in Patients With Thrombocytopenia

    Baelum, Jens Kristian; Moe, Espen Ellingsen; Nybo, Mads


    . OBJECTIVES: To identify VTE risk factors and describe treatment and outcome (bleeding episodes and mortality) in patients with thrombocytopenia. PATIENTS/METHODS: Patients with thrombocytopenia (platelet count ... with anticoagulants. There was no difference in bleeding incidence between cases and controls. CONCLUSIONS: Several known VTE risk factors also seems to apply in patients with thrombocytopenia. Also, patients with thrombocytopenia may be VTE risk stratified based on platelet count and comorbidities. Finally, patients......BACKGROUND: Venous thromboembolism (VTE) is a frequent and potentially lethal condition. Venous thrombi are mainly constituted of fibrin and red blood cells, but platelets also play an important role in VTE formation. Information about VTE in patients with thrombocytopenia is, however, missing...

  16. Bleeding complications in immune thrombocytopenia.

    Arnold, Donald M


    Bleeding manifestations in patients with immune thrombocytopenia (ITP) range from mild skin bruises to life-threatening intracranial hemorrhage (ICH). Severe bleeding is distinctly uncommon when the platelet count is >30 × 10(9)/L and usually only occurs when the platelet count falls administrative databases, the frequency of ICH in patients with ITP is ~0.5% in children and 1.5% in adults. Estimates of severe (non-ICH) bleeding are difficult to obtain because of the lack of standardized case definitions; the lack of a universally accepted, ITP-specific bleeding assessment tool; and the omission of reporting bleeding outcomes in many clinical studies. In practice, the presence of bleeding should dictate whether or not treatment is needed because many patients, especially children, can be safely managed with observation alone. Guiding principles for the management of ITP, based on the bleeding risk are: (1) Decide when treatment is needed and when it can safely be withheld; (2) for patients with chronic ITP, use the least toxic treatment at the lowest dose; (3) emergency treatment of severe thrombocytopenia-associated bleeding requires combination therapy; and (4) early aggressive therapy may result in durable platelet count responses.

  17. Systemic Lupus Erythematosus Presenting as Thrombotic Thrombocytopenia Purpura: How Close Is Close Enough?

    Cesar A. Perez


    Full Text Available Thrombotic thrombocytopenic purpura (TTP is an uncommon life-threatening disease characterized by microangiopathic hemolytic anemia and thrombocytopenia, commonly associated with infections, malignancy, drugs, and autoimmune diseases. We report a case of 19-year-old previously healthy female that presents with anemia and thrombocytopenia diagnosed with thrombotic thrombocytopenic purpura that was treated successfully with plasmapheresis and corticosteroids. Laboratory findings also revealed antinuclear antibodies and antibodies to double-stranded DNA. Two weeks after presentation developed inflammatory arthritis, fulfilling diagnostic criteria for systemic lupus erythematosus (SLE. Prompt diagnosis and treatment with plasma exchange and corticosteroids should be instituted as soon as the diagnosis of TTP is suspected, even if other diagnoses, including lupus, are possible. When present, the coexistence of these two etiologies can have a higher mortality than either disease alone. An underlying diagnosis of SLE should be considered in all patients presenting TTP and the study of this association may provide a better understanding of their immune-mediated pathophysiology.

  18. Pseudo-hypoproteinemia in a hyperbilirubinemic dog with immune-mediated hemolytic anemia.

    Garner, Bridget C; Priest, Heather; Smith, Jo


    A 10-year-old spayed female Miniature Poodle was presented to the University of Georgia veterinary teaching hospital for evaluation of lethargy, vomiting and anorexia of 4 days' duration. Physical examination, history and a minimum database led to a diagnosis of immune-mediated hemolytic anemia accompanied by marked hyperbilirubinemia. Refractometric protein determination was within the reference interval, whereas the biuret method indicated hypoproteinemia. This discrepancy was attributed to interference of bilirubin and biliverdin with the spectrophotometric read-out of the biuret total protein assay. The albumin concentration, determined by bromcresol green, and refractometric total protein were less affected by this interference.

  19. 肾脏病患者血小板减少症的诊治策略%Strategies of diagnosis and treatment for thrombocytopenia in patients with renal diseases



    Apart from accelerating hemostasis,promoting clotting,and maintaining the integrity of capillaries,thrombocytes possess functions of regulating the immune system including gathering leukocytes, capturing and containing pathogens,and killing infected cellular targets directly,etc.Thrombocytopenia may occur in both acute kidney injury (AKI)and chronic kidney disease (CKD)patients,but with differences in etiology and pathophysiology.Thrombocytopenia in AKI is mainly caused by infections,medicine,hemolytic-uremic syndrome (HUS),thrombotic thrombocytopenie purpura (TTP),and syndrome of hemolysis,elevated liver enzymes,and low platelets (HELLP).However,thrombocytopenia in CKD is mostly caused by autoimmune diseases, liver diseases, thrombotic microangiopathy (TMA ), idiopathic thrombocytopenic purpura (ITP),hyper-coagulation consumption,heparin-induced thrombocytopenia (HIT),drug allergies, uremia toxin,blood diseases,and disseminated intravascular coagulation (DIC ),etc.Therapy strategies include etiological treatment,pathogenesis treatment,plasmapheresis,platelet transfusions,promoting platelet formation,and symptomatic treatment.Additional attention should be paid to thrombocytopenia in patients with renal diseases,as it could be an essential clue to the cause of the renal disease,reflecting endothelial dysfunction, immune-mediated damage, thromboembolism, and/or adverse drug reactions. Progressive decrease of platelets may be an important indicator of poor prognosis in patients with renal diseases.%血小板除了止血、促进凝血、维持毛细血管完整性外,还具有调节免疫、募集白细胞、捕获和封存致病原、直接杀死受感染的细胞等功能。急性肾损伤和慢性肾脏病患者均可出现血小板减少症,但两者在病因及病理生理方面存在差异。前者病因主要是感染、药物、溶血尿毒综合征(HUS)、血栓性血小板减少性紫癜(TTP)、溶血、肝酶升高、血小板减少

  20. Immune-mediated bone marrow failure in C57BL/6 mice.

    Chen, Jichun; Desierto, Marie J; Feng, Xingmin; Biancotto, Angélique; Young, Neal S


    We established a model of immune-mediated bone marrow (BM) failure in C57BL/6 (B6) mice with 6.5 G total-body irradiation followed by the infusion of 4-10 × 10(6) lymph node (LN) cells/recipient from Friend leukemia virus B/N (FVB) donors. Forty-three percent of animals succumbed, with surviving animals showing marked declines in blood neutrophils, red blood cells, platelets and total BM cells at 8 to 14 days following LN cell infusion. Lowering the total-body irradiation dose to 5 G or altering the LN source from FVB to BALB/cBy donors failed to produce BM destruction. Affected animals showed significant expansion and activation of CD8 T lymphocytes in both the blood and BM; cytotoxic T cells had elevated Fas ligand expression and were oligoclonal, mainly displaying Vβ7 and Vβ17 T cell receptors. There were significant increases in blood plasma interferon γ and tissue necrosis factor α in affected animals. Chemokine ligands CCL3, CCL4, CCL5, CCL20, CXCL2, and CXCL5 and hematopoietic growth factors G-CSF, M-CSF, GM-CSF, VEGF were also elevated. In B6 mice carrying a Fas gene mutation, BM failure was attenuated when they were infused with FVB LN cells. Our model establishes a useful platform to define the roles of individual genes and their products in immune-mediated BM failure.

  1. Comparison of cytokine responses between dogs with sepsis and dogs with immune-mediated hemolytic anemia.

    Johnson, Valerie; Burgess, Brandy; Morley, Paul; Bragg, Ryan; Avery, Anne; Dow, Steven


    Cytokine abnormalities have been described previously in dogs with varied immune mediated and inflammatory conditions such as IMHA and sepsis. The purpose of this study was to establish references ranges for cytokine levels in dogs and to compare cytokine levels in normal dogs and dogs with two common inflammatory diseases (sepsis and IMHA). We hypothesized that cytokine response profiles in dogs with sepsis would be significantly different from those in dogs with IMHA due to the very different etiologies of the two diseases. Concentrations of 14 different cytokines in serum were measured and values grouped according to cytokine function. Serum from clinically normal dogs was used to establish cytokine concentration reference ranges. Rank values for each of the 4 cytokine groups were then compared statistically between healthy control, septic and IMHA dogs. This analysis revealed differences in cytokine groups between dogs with sepsis and IMHA when compared to healthy control dogs but no difference between dogs with either of these conditions. In conclustion, dogs in the early stage of sepsis and IMHA have similar circulating cytokines despite different etiologies suggesting activation of common immunologic pathways. This may have implications for immunotherapy of immune mediated diseases in dogs of varying etiology.

  2. Golimumab as Rescue Therapy for Refractory Immune-Mediated Uveitis: A Three-Center Experience

    Miguel Cordero-Coma


    Full Text Available Objective. To evaluate, in three Spanish tertiary referral centres, the short-term safety and efficacy of golimumab (GLM for treatment of immune-mediated uveitis resistant to previous immunosuppressive therapy. Methods. Nonrandomized retrospective interventional case series. Thirteen patients with different types of uveitis that were resistant to treatment with at least 2 previous immunosuppressors were included in this study. All included patients were treated with GLM (50 mg every four weeks during at least 6 months. Clinical evaluation and treatment-related side effects were assessed at least four times in all included patients. Results. Eight men and 5 women (22 affected eyes with a median age of 30 years (range 20–38 and active immune-mediated uveitides were studied. GLM was used in combination with conventional immunosuppressors in 7 patients (53.8%. GLM therapy achieved complete control of inflammation in 12/13 patients (92.3% after six months of treatment. There was a statistically significant improvement in mean BCVA (0.60 versus 0.68, P=0.009 and mean 1 mm central retinal thickness (317 versus 261.2 μ, P=0.05 at the six-month endpoint when compared to basal values. No major systemic adverse effects associated with GLM therapy were observed. Conclusions. GLM is a new and promising therapeutic option for patients with severe and refractory uveitis.

  3. Potential role of NKT regulatory cell ligands for the treatment of immune mediated colitis


    Natural killer T lymphocytes (NKT) have been implicated in the regulation of autoimmune processes in both mice and humans. In response to stimuli, this subset of cells rapidly produces large amounts of cytokines thereby provoking immune responses, including protection against autoimmune diseases. NKT cells are present in all lymphoid compartments, but are most abundant in the liver and bone marrow. They are activated by interaction of their T-cell receptor with glycolipids presented by CD1d, a nonpolymorphic, major histocompatibility complex class Mike molecule expressed by antigen presenting cells. Several possible ligands for NKT cells have recently been suggested, p-glucosylceramide, a naturally occurring glycolipid, is a metabolic intermediate in the anabolic and catabolic pathways of complex glycosphingolipids. Like other p-glycolipids, p-glucosylceramide has an immunomodulatory effect in several immune mediated disorders, including immune mediated colitis. Due to the broad impact that NKT cells have on the immune system, there is intense interest in understanding how NKT cells are stimulated and the extent to which NKT cell responses can be controlled. These novel ligands are currently being evaluated in animal models of colitis. Here, we discuss strategies to alter NKT lymphocyte function in various settings and the potential clinical applications of natural glycolipids.

  4. Risk factors of thrombocytopenia in pregnancy

    Ayisha Begam


    Conclusions: Thrombocytopenia should be evaluated by making a practice of routinely checking the platelet count and peripheral smear in early pregnancy and also in third trimester to enable early diagnosis since most cases may be asymptomatic.

  5. Heparin-Induced Thrombocytopenia Antibody Test

    ... Global Sites Search Help? Heparin-induced Thrombocytopenia PF4 Antibody Share this page: Was this page helpful? Also known as: Heparin-PF4 Antibody; HIT Antibody; HIT PF4 Antibody; Heparin Induced Antibody; ...

  6. Drug-induced immune thrombocytopenia: incidence, clinical features, laboratory testing, and pathogenic mechanisms.

    Curtis, Brian R


    Drug-induced immune thrombocytopenia (DIIT) is a relatively uncommon adverse reaction caused by drug-dependent antibodies (DDAbs) that react with platelet membrane glycoproteins only when the implicated drug is present. Although more than 100 drugs have been associated with causing DIIT, recent reviews of available data show that carbamazepine, eptifibatide, ibuprofen, quinidine, quinine, oxaliplatin, rifampin, sulfamethoxazole, trimethoprim, and vancomycin are probably the most frequently implicated. Patients with DIIT typically present with petechiae, bruising, and epistaxis caused by an acute, severe drop in platelet count (often to transfusion refractoriness, and must be differentiated by temporal association of exposure to a candidate drug with an acute, severe drop in platelet count. Treatment consists of immediate withdrawal of the implicated drug. Criteria for strong evidence of DIIT include (1) exposure to candidate drug-preceded thrombocytopenia; (2) sustained normal platelet levels after discontinuing candidate drug; (3) candidate drug was only drug used before onset of thrombocytopenia or other drugs were continued or reintroduced after resolution of thrombocytopenia, and other causes for thrombocytopenia were excluded; and (4) reexposure to the candidate drug resulted in recurrent thrombocytopenia. Flow cytometry testing for DDAbs can be useful in confirmation of a clinical diagnosis, and monoclonal antibody enzyme-linked immunosorbent assay testing can be used to determine the platelet glycoprotein target(s), usually GPIIb/IIIa or GPIb/IX/V, but testing is not widely available. Several pathogenic mechanisms for DIIT have been proposed, including hapten, autoantibody, neoepitope, drug-specific, and quinine-type drug mechanisms. A recent proposal suggests weakly reactive platelet autoantibodies that develop greatly increased affinity for platelet glycoprotein epitopes through bridging interactions facilitated by the drug is a possible mechanism for the

  7. Clinical development of reovirus for cancer therapy: An oncolytic virus with immune-mediated antitumor activity

    Gong, Jun; Sachdev, Esha; Mita, Alain C; Mita, Monica M


    Reovirus is a double-stranded RNA virus with demonstrated oncolysis or preferential replication in cancer cells. The oncolytic properties of reovirus appear to be dependent, in part, on activated Ras signaling. In addition, Ras-transformation promotes reovirus oncolysis by affecting several steps of the viral life cycle. Reovirus-mediated immune responses can present barriers to tumor targeting, serve protective functions against reovirus systemic toxicity, and contribute to therapeutic efficacy through antitumor immune-mediated effects via innate and adaptive responses. Preclinical studies have demonstrated the broad anticancer activity of wild-type, unmodified type 3 Dearing strain reovirus (Reolysin®) across a spectrum of malignancies. The development of reovirus as an anticancer agent and available clinical data reported from 22 clinical trials will be reviewed. PMID:27019795

  8. Clinical development of reovirus for cancer therapy: An oncolytic virus with immune-mediated antitumor activity.

    Gong, Jun; Sachdev, Esha; Mita, Alain C; Mita, Monica M


    Reovirus is a double-stranded RNA virus with demonstrated oncolysis or preferential replication in cancer cells. The oncolytic properties of reovirus appear to be dependent, in part, on activated Ras signaling. In addition, Ras-transformation promotes reovirus oncolysis by affecting several steps of the viral life cycle. Reovirus-mediated immune responses can present barriers to tumor targeting, serve protective functions against reovirus systemic toxicity, and contribute to therapeutic efficacy through antitumor immune-mediated effects via innate and adaptive responses. Preclinical studies have demonstrated the broad anticancer activity of wild-type, unmodified type 3 Dearing strain reovirus (Reolysin(®)) across a spectrum of malignancies. The development of reovirus as an anticancer agent and available clinical data reported from 22 clinical trials will be reviewed.

  9. Neuromyelitis optica-IgG (aquaporin-4) autoantibodies in immune mediated optic neuritis.

    Petzold, A; Pittock, S; Lennon, V; Maggiore, C; Weinshenker, B G; Plant, G T


    The clinical course of immune mediated optic neuritis (ON) will depend on the specific underlying inflammatory disease. These disorders have traditionally been classified according to clinical and MRI findings. Aquaporin-4 (AQP4) autoantibodies (neuromyelitis optica-IgG (NMO-IgG)) may have diagnostic and prognostic value in patients who present with isolated ON. In this prospective study, NMO-IgG was evaluated in 114 patients with ON in the following contexts: neuromyelitis optica (NMO), multiple sclerosis (MSON), chronic relapsing inflammatory ON (CRION), relapsing isolated ON (RION) and single isolated ON (SION). The proportion seropositive was 56% for NMO (n = 9), 0% for MSON (n = 28) and 5% for the remaining diagnostic categories (CRION (n = 19), RION (n = 17) and SION (n = 41)). Testing for NMO-IgG in patients with recurrent or severe ON who lack convincing evidence of MS may identify patients who would benefit from immunosuppression rather than MS directed immunomodulatory therapies.

  10. 25-Hydroxyvitamin D and Peripheral Immune Mediators: Results from Two Nationwide Danish Pediatric Cohorts.

    Thorsen, Steffen U; Pipper, Christian B; Skogstrand, Kristin; Pociot, Flemming; Svensson, Jannet


    (1) Background: We aimed to examine if 25-hydroxyvitamin D (25(OH)D) was related to the peripheral immunological and inflammatory signature both at birth, and in newly diagnosed patients with childhood type 1 diabetes (T1D) and their healthy controls; (2) Methods: The birth cohort consisted of 470 patients and 500 healthy controls. Dried blood samples were collected from the neonates in the period 1981-1999. The newly diagnosed cohort consisted of 460 patients and 453 siblings. Serum samples were collected in the period 1997-2005. A variety of peripheral immune mediators were measured and compared to total 25(OH)D levels (25(OH)D₂ + 25(OH)D₃). For each immune mediator, the relative change (RC) in the mean level was modeled by robust log-normal regression and correction for multiple testing was performed; (3) Results: Two associations were identified; there was a negative association between 25(OH)D (10 nmol/L increase) and leptin (RC (95% confidence interval (CI)), 0.98 (0.96; 1.00)), and a positive association between 25(OH)D (10 nmol/L increase) and the chemokine, chemokine (c-x-c motif) ligand (CXCL) 8 (RC (95% CI), 1.07 (1.01; 1.13)); (4) Conclusion: CXCL8 and leptin have significant associations with levels of 25(OH)D in the newly diagnosed cohort. These results do not indicate a strong influence of 25(OH)D on the peripheral immunological or inflammatory signature.

  11. How Is Immune Thrombocytopenia Treated?

    ... counts. Adults who have ITP with very low platelet counts or bleeding problems often are treated. The acute (short-term) type of ITP that occurs in children often goes away within a few weeks or ...

  12. Pharmacologic treatment options in patients with thrombocytopenia.

    Demetri, G D


    Thrombocytopenia that results from chemotherapy has become an increasingly important issue in the treatment of cancer and remains a difficult clinical problem. The identification of a safe and effective platelet growth factor could significantly improve the management of severe chemotherapy-induced thrombocytopenia. Over the past decade, a number of hematopoietic growth factors with thrombopoietic activity have been identified, including stem-cell factor (c-kit ligand), interleukin (IL)-1, IL-3, IL-6, and IL-11, as well as thrombopoietin (TPO) and its derivatives. Only a few of these agents have shown acceptable tolerability and sufficient ability to stimulate thrombopoiesis to justify testing in randomized clinical trials. Currently, IL-11 is the only cytokine licensed in the United States for treatment of chemotherapy-induced thrombocytopenia. However, its thrombopoietic activity is modest and its use is often associated with unfavorable side effects. Identification of TPO, the c-Mpl ligand, as the primary physiologic regulator of megakaryocyte and platelet development offers important promise for treatment of thrombocytopenia. Preliminary clinical studies of recombinant human TPO (rhTPO), a full-length glycosylated molecule, indicate that it is safe and biologically active in reducing severe chemotherapy-induced thrombocytopenia. In addition to rhTPO, the future may see the development of novel genetically engineered, high-affinity cytokine receptor agonists and c-Mpl ligand mimetic peptides.

  13. Lack of evidence of a beneficial effect of azathioprine immune-mediated hemolytic anemia: a retrospective cohort study

    Piek, C.J.; Spil, Van W.E.; Junius, G.; Dekker, A.


    Background Azathioprine is used as an immunosuppressant in canine immune-mediated hemolytic anemia (IMHA), but this potentially toxic and carcinogenic drug has not been proven to be beneficial. The aim of this study was to determine the difference in outcome and survival of dogs with idiopathic IMHA

  14. The use of the rapid osmotic fragility test as an additional test to diagnose canine immune-mediated haemolytic anaemia

    Paes, Geert; Paepe, Dominique; Meyer, Evelyne;


    Background: Diagnosing canine immune-mediated haemolytic anaemia (IMHA) is often challenging because all currently available tests have their limitations. Dogs with IMHA often have an increased erythrocyte osmotic fragility (OF), a characteristic that is sometimes used in the diagnosis of IMHA...

  15. Good agreement of conventional and gel-based direct agglutination test in immune-mediated haemolytic anaemia

    Piek, C.J.; Teske, E.; van Leeuwen, M.W.; Day, M.J.


    Abstract Background The aim of this study was to compare a gel-based test with the traditional direct agglutination test (DAT) for the diagnosis of immune-mediated haemolytic anaemia (IMHA). Methods Canine (n = 247) and feline (n = 74) blood samples were submitted for DAT testing to two laboratories

  16. Reliability and responsiveness of a graduated tuning fork in immune mediated polyneuropathies. The Inflammatory Neuropathy Cause and Treatment (INCAT) Group

    I.S.J. Merkies (Ingemar); P.I.M. Schmitz (Paul); F.G.A. van der Meché (Frans); P.A. van Doorn (Pieter)


    textabstractThe interobserver and intraobserver reliability of the Rydel-Seiffer (RS) graduated tuning fork was evaluated in 113 patients with a clinically stable immune mediated polyneuropathy (83 patients who had had Guillain-Barre syndrome (GBS) in the past, 22 with

  17. Are newly discovered drivers of immune-mediated skin disorders expressed in normal skin regenerating from standardized surface injury?

    Hendriks, A.G.M.; Keijsers, R.R.M.C.; Seyger, M.M.B.; Erp, P.E.J. van; Kerkhof, P.C.M. van de


    Background: In healthy skin, tape stripping induces a transient wave of histological changes resembling immune-mediated skin diseases, such as psoriasis. The response to surface trauma may harbor mechanisms which are also relevant to the development of Koebner-positive skin disorders. However, studi

  18. Effect observation of recombinant human thrombopoietin in treatment of thrombocytopenia caused by chemotherapy of acute leukemia%重组人促血小板生成素治疗急性白血病化疗后血小板减少的效果观察

    章志学; 肖牛明; 肖小芳; 谢将; 肖文琼


    Objective To investigate the clinical effect of recombinant human thrombopoietin (rhTPO) in the treatment of thrombocytopenia caused by chemotherapy of acute leukemia. Methods Fifty-six patients who received chemothera-py and suffered from thrombocytopenia due to it in our hospital were selected and randomly divided into the observa-tion group (n=28) and the control group (n=28).The observation group received rhTPO treatment and the control group received recombinant human interleukin-11 (rhIL-11) treatment.The efficacy of the two groups was compared. Results After treatment,the platelet level in the observation group was significantly higher than that in the control group,and duration of platelets<50í109/L and time of platelet returning to 70í109/L and 100í109/L in the observation group were significantly shorter than those in the control group (P<0.05).The incidence rate in the the observation group was obvi-ously lower than that in the control group (3.6% vs 42.8%) (P<0.05). Conclusion In the treatment of thrombocytopenia caused by chemotherapy of acute leukemia,rhTPO shows remarkable effects and high safety,thereby it is worthy of clin-ical promotion and application.%目的:探讨重组人促血小板生成素(rhTPO)治疗急性白血病化疗后血小板减少的临床效果。方法选取2012年1月~2014年1月在本院接受化疗治疗且发生血小板减少症的急性白血病患者56例,将其随机分为观察组和对照组,每组各28例。观察组给予rhTPO治疗,对照组给予重组人白介素-11(rhIL-11)治疗,比较两组的疗效。结果观察组治疗后的血小板水平明显高于对照组,且血小板<50×109/L的持续时间、恢复至70×109/L和100×109/L所需时间明显短于对照组(P<0.05);观察组的不良反应发生率明显低于对照组(3.6% vs 42.8%)(P<0.05)。结论 rhTPO治疗急性白血病化疗后血小板减少的效果显著,安全性高,值得临床推广应用。

  19. Genetics Home Reference: thrombocytopenia-absent radius syndrome

    ... Genetics Home Health Conditions TAR syndrome thrombocytopenia-absent radius syndrome Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Thrombocytopenia-absent radius (TAR) syndrome is characterized by the absence of ...

  20. Octreotide-induced thrombocytopenia: a case report

    Rizvi Nahid


    Full Text Available Abstract Introduction Thrombocytopenia is an extremely rare complication of octreotide therapy and can be life threatening in the setting of esophageal variceal bleeding. We report a case of octreotide-induced reversible thrombocytopenia in a 54-year-old Caucasian man with alcohol-induced cirrhosis and upper gastrointestinal bleeding. Case presentation Our patient's platelet count dropped from 155,000/mm3 upon admission to 77,000/mm3 a few hours after initiation of octreotide therapy and stayed low until the drug's administration was discontinued. Significant recovery was achieved quickly after discontinuation of octreotide. Conclusions Thrombocytopenia is a rare but potentially serious side effect of octreotide therapy and may complicate esophageal variceal bleeding. Physicians should be vigilant in identifying this potentially serious condition.

  1. Thrombophilia in patients with chronic immune thrombocytopenia.

    Wong, Raymond S M; Bakshi, Kalpana; Brainsky, Andres


    An increased risk of thromboembolic events among patients with chronic immune thrombocytopenia has been reported but is still not fully understood. A thrombophilia panel (factors suspected/known to denote a thrombophilic state or indicate activation of the clotting cascade) was measured in previously treated patients with chronic immune thrombocytopenia enrolled in an eltrombopag trial to assess potential thrombophilia risk markers. Of 167 patients, 136 (81%) had abnormal levels of at least 1 known or suspected thrombosis risk marker or coagulation cascade activation marker. Six patients reported thromboembolic events, and all of these patients had at least two abnormal analytes in the thrombophilia panel. The presence of multiple baseline thrombophilia risk markers support the theory that chronic immune thrombocytopenia is a pro-thrombotic disease.

  2. Glycan elongation beyond the mucin associated Tn antigen protects tumor cells from immune-mediated killing.

    Caroline B Madsen

    Full Text Available Membrane bound mucins are up-regulated and aberrantly glycosylated during malignant transformation in many cancer cells. This results in a negatively charged glycoprotein coat which may protect cancer cells from immune surveillance. However, only limited data have so far demonstrated the critical steps in glycan elongation that make aberrantly glycosylated mucins affect the interaction between cancer cells and cytotoxic effector cells of the immune system. Tn (GalNAc-Ser/Thr, STn (NeuAcα2-6GalNAc-Ser/Thr, T (Galβ1-3GalNAc-Ser/Thr, and ST (NeuAcα2-6Galβ1-3GalNAc-Ser/Thr antigens are recognized as cancer associated truncated glycans, and are expressed in many adenocarcinomas, e.g. breast- and pancreatic cancer cells. To investigate the role of the cancer associated glycan truncations in immune-mediated killing we created glyco-engineered breast- and pancreatic cancer cells expressing only the shortest possible mucin-like glycans (Tn and STn. Glyco-engineering was performed by zinc finger nuclease (ZFN knockout (KO of the Core 1 enzyme chaperone COSMC, thereby preventing glycan elongation beyond the initial GalNAc residue in O-linked glycans. We find that COSMC KO in the breast and pancreatic cancer cell lines T47D and Capan-1 increases sensitivity to both NK cell mediated antibody-dependent cellular-cytotoxicity (ADCC and cytotoxic T lymphocyte (CTL-mediated killing. In addition, we investigated the association between total cell surface expression of MUC1/MUC16 and NK or CTL mediated killing, and observed an inverse correlation between MUC16/MUC1 expression and the sensitivity to ADCC and CTL-mediated killing. Together, these data suggest that up-regulation of membrane bound mucins protects cells from immune mediated killing, and that particular glycosylation steps, as demonstrated for glycan elongation beyond Tn and STn, can be important for fine tuning of the immune escape mechanisms in cancer cells.

  3. 重组人白介素11对儿童急性淋巴细胞白血病化疗后血小板减少的疗效观察%Effects of recombinant human interleukin 11 treatment on thrombocytopenia induced by chemotherapy in children with acute lymphoblastic leukemia

    梁卉; 刘华林; 宋亮


    Objective To investigate the effects of recombinant human interleukin-11 (rhIL-11 ) treatment on thrombocytopenia in childhood acute lymphoblastic leukemia (ALL) after chemotherapy. Methods Total of 36 patients of childhood ALL suffering thrombocytopenia were randomly divided into treatment group and control group. Twenty-four hours after chemotherapy, only patients of the treatment group were given daily subcutaneous injection of rhIL-11 for 5 days. Changes of the platelet count were observed, the amount of platelet transfusion and adverse reactions were recorded. Results Compared with the control group, recovery time of platelet count was shorter, platelet transfusion was less in the treatment group, and the differences were statistically significant, while adverse reaction was mild.Conclusions Application of rhIL-11 can improve platelet count obviously after chemotherapy of ALL children, reduce platelet transfusion, and it is clinically safe and affordable.%目的 观察重组人白介素11(rhIL-11)对急性淋巴细胞白血病(ALL)患儿化疗后血小板减少的疗效和安全性.方法 选取36例ALL化疗后血小板减少患儿,随机分为治疗组和对照组,治疗组患儿在化疗结束后24 h每日皮下注射rhIL-11,应用5 d;对照组不用rhIL-11.观察两组患儿血小板数值变化,记录血小板输注量及治疗组不良反应.结果 治疗组较对照组血小板恢复时间短,输注血小板少,差异有统计学意义.治疗组rhIL-11不良反应轻微.结论 rhIL-11能明显提高儿童ALL化疗后血小板数量,减少血小板输注,临床应用安全,综合临床费用降低.

  4. Evaluation of the diagnostic performance of platelet-derived indices for the differential diagnosis of thrombocytopenia in pediatrics

    Nelson Hernando Aponte-Barrios


    Full Text Available Background. Platelet-derived indices have a well-established correlation with the differential diagnosis of thrombocytopenia in adult-based research. These indices include mean platelet volume, platelet distribution width, and platelet-large cell ratio. Objective. To determine the values of platelet-derived indices in a pediatric population with diagnoses of thrombocytopenia and their etiologic correlation. Materials and methods. Analytic observational diagnostic-test study. The population for this analytical study was pediatric patients between 6 months and 18 years of age who had thrombocytopenia (<100x10(9/L. The study period was 18 months long. Results. Of 54 subjects, 18 (33.3% were diagnosed with idiopathic thrombocytopenic purpura, and 36 (66.7% were diagnosed with acute leukemia. Mean age was 7.4 years and 6.8 years for immune thrombocytopenic purpura and acute leukemia, respectively. Mean platelet distribution width values for immune thrombocytopenic purpura and acute leukemia were 15.08 fL and 10.73, respectively. Mean MPV for immune thrombocytopenic purpura and acute leukemia was 11.7 fL and 9.8 fL, respectively. Mean platelet-large cell ratio was 38.26% and 24.97% for idiopathic thrombocytopenic purpura and acute leukemia, respectively. Differences in these three distinct platelet indices between idiopathic thrombocytopenic purpura and acute leukemia were statistically significant (p=0.00. The area under the ROC curve for platelet-derived indices showed that they were adequate for defining the causes of thrombocytopenia. MPV and platelet-large cell ratio had an area under the curve of 0.89 and 0.88, respectively, while platelet size deviation width had an area under the curve of 0.903. Conclusions. Platelet-derived indices could be useful in the initial approach for the differential diagnosis of pediatric patients with thrombocytopenia.

  5. [Heparin induced thrombocytopenia and anticoagulation in renal replacemant therapy].

    Steinfeldt, Thorsten; Rolfes, Caroline


    The decision for an anticoagulant for renal replacement therapy (RRT) in patients with acute renal failure and heparin-induced thrombocytopenia (HIT) has to be made carefully. Based on results from the literature argatroban is favoured in patients without hepatic dysfunction, referring to its short halftime and easy feasable monitoring. In the case of coexsisting hepatic disorder, danaparoid provides a safe alternative therapy. However, long halftime and the difficult elimination of the substance are unfavourable. Lepirudin represents another possible anticoagulant therapy. Bleeding complications and monitoring of the ecarin clotting time imposes limitations. Experiences with bivalirudin, fondaparinux and prostaglandines are limited and future trials will have to determine the significance of their application in RRT in HIT patients. Furthermore it has to be proven whether the combination of alternative anticoagulants with citrate prolongates circuit halftime of CVVH.

  6. Use of thrombopoietin receptor agonists in childhood immune thrombocytopenia

    Angelica Maria Garzon


    Full Text Available Most children with immune thrombocytopenia (ITP will have spontaneous remission regardless of therapy, while about 20% will go on to have chronic ITP. In those children with chronic ITP who need treatment, standard therapies for acute ITP may have adverse effects that complicate their long term use. Thus, alternative treatment options are needed for children with chronic ITP. Thrombopoietin receptor agonists (TPO-RA have been shown to be safe and efficacious in adults with ITP, and represent a new treatment option for children with chronic ITP. One TPO-RA, eltrombopag, is now approved for children. Clinical trials in children are ongoing and data is emerging on safety and efficacy. This review will focus on the physiology of TPO-RA, their clinical use in children, as well as the long term safety issues that need to be considered when using these agents

  7. Thrombocytopenia and thrombosis in disseminated intravascular coagulation (DIC).

    Kitchens, Craig S


    Disseminated intravascular coagulation (DIC) is the physiologic result of pathologic overstimulation of the coagulation system. Despite multiple triggers, a myriad of laboratory abnormalities, and a clinical presentation ranging from gross hemostatic failure to life-threatening thrombosis, or even both simultaneously, a simplified clinical approach augmented by a few readily available tests allows prompt identification of the process and elucidation of treatment opportunities. Platelet counts in DIC may be low, especially in acute sepsis-associated DIC, yet increased in malignancy-associated chronic DIC. Thrombotic risk is not a function of the platelet count, and thrombocytopenia does not protect the patient from thrombosis. The stratification of both thrombotic risk and hemorrhagic risk will be addressed.

  8. Immune-mediated bile duct injury: The case of primary biliary cirrhosis

    Selmi, Carlo; Affronti, Andrea; Ferrari, Laura; Invernizzi, Pietro


    Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies and autoreactive T cells. Nevertheless, the condition is universally named primary biliary cirrhosis (PBC). The disease etiology and pathogenesis remain largely unknown despite the proposed lines of evidence. One twin study and numerous epidemiology reports suggest that both a susceptible genetic background and environmental factors determine disease onset while a recent genome-wide association study proposed highly significant associations with several common genetic polymorphisms in subgroups of patients. Specific infectious agents and chemicals may contribute to the disease onset and perpetuation in a genetically susceptible host, possibly through molecular mimicry. Importantly, several murine models have been proposed and include strains in which PBC is genetically determined or induced by immunization with chemicals and bacteria. From a pathogenetic standpoint, new exciting data have demonstrated the unique apoptotic features of bile duct cells that allow the mitochondrial autoantigens to be taken up in their intact form within apoptotic blebs. We are convinced that the application of the most recent molecular techniques will soon provide developments in PBC etiology and pathogenesis with likely implications in diagnostics and therapeutics. PMID:21607152

  9. Adalimumab for the treatment of immune-mediated diseases: an update on old and recent indications.

    Murdaca, G; Colombo, B M; Puppo, F


    Ongoing progress in understanding the pathogenic mechanisms regulating various immune-mediated and inflammatory diseases, as well as the availability of innovative biotechnological approaches, have lead to the development of new drugs that add to conventional treatments. Among these, tumor necrosis factor (TNF)-α inhibitors such as infliximab, adalimumab, etanercept, golimumab and certolizumab pegol, are now available for clinical use. Adalimumab is a fully recombinant human immunoglobulin G1 monoclonal antibody that specifically binds with high affinity to human TNF-α and inhibits its binding to TNF receptors. Adalimumab was approved by the U.S. FDA in 2002 and was granted approval from the European Medicines Agency in September 2003 for the treatment of moderate to severe rheumatoid arthritis and subsequently for the treatment of ankylosing spondylitis, chronic plaque psoriasis, psoriatic arthritis, juvenile idiopathic arthritis and Crohn's disease. In this paper, we will briefly review the structure and biological effects of TNF-α, the old and recent indications of adalimumab, the pretreatment considerations, the reported adverse events and finally, the recommendations for its use in pregnancy.

  10. Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes

    Christopher A. Aoki


    Full Text Available Primary sclerosing cholangitis (PSC is a chronic disease of the bile ducts characterized by an inflammatory infiltrate and obliterative fibrosis. The precise role of the immune system in the pathogenesis of PSC remains unknown. We used RNA microarray analysis to identify immune-related genes and pathways that are differentially expressed in PSC. Messenger RNA (mRNA from peripheral blood mononuclear cells (PBMC was isolated from both patients with PSC and age and sex matched healthy controls. Samples from 5 PSC patients and 5 controls were analyzed by microarray and based upon rigorous statistical analysis of the data, relevant genes were chosen for confirmation by RT-PCR in 10 PSC patients and 10 controls. Using unsupervised hierarchical clustering, gene expression in PSC was statistically different from our control population. Interestingly, genes within the IL-2 receptor beta, IL-6 and MAP Kinase pathways were found to be differently expressed in patients with PSC compared to controls. Further, individual genes, TNF-α induced protein 6 (TNFaip6 and membrane-spanning 4-domains, subfamily A (ms4a were found to be upregulated in PSC while similar to Mothers against decapentaplegic homolog 5 (SMAD 5 was downregulated. In conclusion, several immune-related pathways and genes were differentially expressed in PSC compared to control patients, giving further evidence that this disease is systemic and immune-mediated.

  11. Month of birth, vitamin D and risk of immune-mediated disease: a case control study

    Disanto Giulio


    Full Text Available Abstract Background A season of birth effect in immune-mediated diseases (ID such as multiple sclerosis and type 1 diabetes has been consistently reported. We aimed to investigate whether season of birth influences the risk of rheumatoid arthritis, Crohn's disease, ulcerative colitis and systemic lupus erythematosus in addition to multiple sclerosis, and to explore the correlation between the risk of ID and predicted ultraviolet B (UVB light exposure and vitamin D status during gestation. Methods The monthly distribution of births of patients with ID from the UK (n = 115,172 was compared to that of the general population using the Cosinor test. Predicted UVB radiation and vitamin D status in different time windows during pregnancy were calculated for each month of birth and correlated with risk of ID using the Spearman's correlation coefficient. Results The distributions of ID births significantly differed from that of the general population (P = 5e-12 with a peak in April (odds ratio = 1.045, 95% confidence interval = 1.024, 1.067, P P P = 0.00005 and third trimester vitamin D status (Spearman's rho = -0.44, P = 0.0003. Conclusions The risk of different ID in the UK is significantly influenced by the season of birth, suggesting the presence of a shared seasonal risk factor or factors predisposing to ID. Gestational UVB and vitamin D exposure may be implicated in the aetiology of ID.

  12. Steroid sparing regimens for management of oral immune-mediated diseases

    Arti Agrawal


    Full Text Available Immune-mediated mucocutaneous disease may present oral symptoms as a first sign of the disease. The primary etiology could be the cellular and/or humoral immune responses directed against epithelial or connective tissue, in a chronic and recurrent pattern. Lichen planus, pemphigus vulgaris and bullous pemphigoid are the most frequent immunologically mediated mucocutaneous diseases. More often than not, patients present with complaints of blisters, oral ulcers, pain, burning sensation, and bleeding from the various oral sites. Steroids, whether topical or systemic, are the treatment of choice as they have both anti-inflammatory and immune-suppressant properties; however, challenges in the treatment of autoimmune diseases are the complexity of symptoms, the need to manage long-term medications for preserving organ function, and the long-term adverse effects of steroids. In such situations steroid sparing agents, such as, tacrolimus, dapsone, azathioprine, cyclosporine, and so on, may be helpful. Here an attempt is made to review various treatment regimens that could be used as alternatives to steroids for management of such diseases.

  13. Severe thrombocytopenia before liver transplantation is associated with delayed recovery of thrombocytopenia regardless of donor type

    Jae Hyuck Chang; Dong Goo Kim; Jong Young Choi; Hyun Young Woo; Jung Hyun Kwon; Chan Ran You; Si Hyun Bae; Seung Kew Yoon; Myung-Gyu Choi; In Sik Chung


    AIM: To compare the recovery of thrombocytopenia and splenomegaly during long-term follow-up after liver transplantation in patients receiving a living donor transplant or a cadaveric donor transplant.METHODS: This was a retrospective cohort study of 216 consecutive liver transplant patients who survived for > 6 mo after transplantation; 169 received a liver transplant from a living donor and 47 from a cadaveric donor.The platelet counts or spleen volumes were examined before transplant,1,6,and 12 mo after transplant,and then annually until 5 years after transplant.RESULTS: The mean follow-up period was 49 mo (range,21-66).Platelet counts increased continuously for 5 years after orthotopic liver transplant.The restoration of platelet counts after transplant was significantly slower in patients with severe pretransplant thrombocytopenia (< 50000/μL) until 4 years after transplant (P = 0.005).Donor type did not significantly affect the recovery of platelet count and spleen volume in either patient group.In multivariate analysis,pretransplant severe thrombocytopenia (< 50000/μL)was an independent factor associated with sustained thrombocytopenia (P < 0.001,odds ratio 6.314; confidence interval,2.828-14.095).Thrombocytopenia reappeared after transplant in seven patients with portal flow disturbance near the anastomosis site.CONCLUSION: Our study suggests that severe thrombocytopenia before transplant is closely associated with delayed recovery of platelet count after transplant and donor type did not affect the recovery of thrombocytopenia.The reappearance of thrombocytopenia after transplant should be considered a possible indicator of flow disturbance in the portal vein.

  14. Thrombocytopenia in Dengue: Interrelationship between Virus and the Imbalance between Coagulation and Fibrinolysis and Inflammatory Mediators.

    de Azeredo, Elzinandes Leal; Monteiro, Robson Q; de-Oliveira Pinto, Luzia Maria


    Dengue is an infectious disease caused by dengue virus (DENV). In general, dengue is a self-limiting acute febrile illness followed by a phase of critical defervescence, in which patients may improve or progress to a severe form. Severe illness is characterized by hemodynamic disturbances, increased vascular permeability, hypovolemia, hypotension, and shock. Thrombocytopenia and platelet dysfunction are common in both cases and are related to the clinical outcome. Different mechanisms have been hypothesized to explain DENV-associated thrombocytopenia, including the suppression of bone marrow and the peripheral destruction of platelets. Studies have shown DENV-infected hematopoietic progenitors or bone marrow stromal cells. Moreover, anti-platelet antibodies would be involved in peripheral platelet destruction as platelets interact with endothelial cells, immune cells, and/or DENV. It is not yet clear whether platelets play a role in the viral spread. Here, we focus on the mechanisms of thrombocytopenia and platelet dysfunction in DENV infection. Because platelets participate in the inflammatory and immune response by promoting cytokine, chemokine, and inflammatory mediator secretion, their relevance as "immune-like effector cells" will be discussed. Finally, an implication for platelets in plasma leakage will be also regarded, as thrombocytopenia is associated with clinical outcome and higher mortality.

  15. Thrombocytopenia in Dengue: Interrelationship between Virus and the Imbalance between Coagulation and Fibrinolysis and Inflammatory Mediators

    Elzinandes Leal de Azeredo


    Full Text Available Dengue is an infectious disease caused by dengue virus (DENV. In general, dengue is a self-limiting acute febrile illness followed by a phase of critical defervescence, in which patients may improve or progress to a severe form. Severe illness is characterized by hemodynamic disturbances, increased vascular permeability, hypovolemia, hypotension, and shock. Thrombocytopenia and platelet dysfunction are common in both cases and are related to the clinical outcome. Different mechanisms have been hypothesized to explain DENV-associated thrombocytopenia, including the suppression of bone marrow and the peripheral destruction of platelets. Studies have shown DENV-infected hematopoietic progenitors or bone marrow stromal cells. Moreover, anti-platelet antibodies would be involved in peripheral platelet destruction as platelets interact with endothelial cells, immune cells, and/or DENV. It is not yet clear whether platelets play a role in the viral spread. Here, we focus on the mechanisms of thrombocytopenia and platelet dysfunction in DENV infection. Because platelets participate in the inflammatory and immune response by promoting cytokine, chemokine, and inflammatory mediator secretion, their relevance as “immune-like effector cells” will be discussed. Finally, an implication for platelets in plasma leakage will be also regarded, as thrombocytopenia is associated with clinical outcome and higher mortality.

  16. Molecular mechanisms of drug-induced thrombocytopenia

    Burgess, Janette K.


    A wide range of drugs can induce thrombocytopenia. Molecular mechanisms for the formation of specific epitopes for all the drug-dependent antibodies appear to be very similar. A restricted set of glycoproteins on the platelet surface interacts with the drugs to form neoepitopes, to which the drug-de


    Emmanuel Gyan


    Full Text Available Background. The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT, and refractory neutropenia (RN, characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors.  Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medications, viral infections, or hypersplenism. Diagnosis of RN should also be made after ruling out differential diagnoses such as ethnic or familial neutropenia, as well as acquired, drug-induced, infection-related or malignancy-related neutropenia. An accurate quantification of dysplasia should be performed in order to distinguish RT or RN from the provisional entity named idiopathic cytopenia of unknown significance (ICUS. Cytogenetic analysis, and possibly in the future somatic mutation analysis (of genes most frequently mutated in MDS, and flow cytometry analysis aberrant antigen expression on myeloid cells may help in this differential diagnosis. Importantly, we and others found that, while isolated neutropenia and thrombocytopenia are not rare in MDS, those patients can generally be classified (according to WHO 2008 classification as refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts, while RT and RN (according to WHO 2008 are quite rare.These results suggest in particular that identification of RT and RN as distinct entities could be reconsidered in future WHO classification updates.

  18. [Diagnosis and treatment of heparin-induced thrombocytopenia (HIT) based on its atypical immunological features].

    Miyata, Shigeki; Maeda, Takuma


    Heparin-induced thrombocytopenia (HIT) is a prothrombotic side effect of heparin therapy caused by HIT antibodies, i.e., anti-platelet factor 4 (PF4)/heparin IgG with platelet-activating properties. For serological diagnosis, antigen immunoassays are commonly used worldwide. However, such assays do not indicate their platelet-activating properties, leading to low specificity for the HIT diagnosis. Therefore, over-diagnosis is currently the most serious problem associated with HIT. The detection of platelet-activating antibodies using a washed platelet activation assay is crucial for appropriate HIT diagnosis. Recent advances in our understanding of the pathogenesis of HIT include it having several clinical features atypical for an immune-mediated disease. Heparin-naïve patients can develop IgG antibodies as early as day 4, as in a secondary immune response. Evidence for an anamnestic response on heparin re-exposure is lacking. In addition, HIT antibodies are relatively short-lived, unlike those in a secondary immune response. These lines of evidence suggest that the mechanisms underlying HIT antibody formation may be compatible with a non-T cell-dependent immune reaction. These atypical clinical and serological features should be carefully considered while endeavoring to accurately diagnose HIT, which leads to appropriate therapies such as immediate administration of an alternative anticoagulant to prevent thromboembolic events and re-administration of heparin during surgery involving cardiopulmonary bypass when HIT antibodies are no longer detectable.

  19. Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology

    Rossin, Elizabeth J.; Hansen, Kasper Lage; Raychaudhuri, Soumya


    Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed by these r......Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed......-immune traits to assess its applicability to complex traits in general. We find that genes in loci associated to height and lipid levels assemble into significantly connected networks but did not detect excess connectivity among Type 2 Diabetes (T2D) loci beyond chance. Taken together, our results constitute...

  20. Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study

    Handel Adam E


    Full Text Available Abstract Background Venous thromboembolism (VTE is a common complication during and after a hospital admission. Although it is mainly considered a complication of surgery, it often occurs in people who have not undergone surgery, with recent evidence suggesting that immune-mediated diseases may play a role in VTE risk. We, therefore, decided to study the risk of deep vein thrombosis (DVT and pulmonary embolism (PE in people admitted to hospital with a range of immune-mediated diseases. Methods We analysed databases of linked statistical records of hospital admissions and death certificates for the Oxford Record Linkage Study area (ORLS1:1968 to 1998 and ORLS2:1999 to 2008 and the whole of England (1999 to 2008. Rate ratios for VTE were determined, comparing immune-mediated disease cohorts with comparison cohorts. Results Significantly elevated risks of VTE were found, in all three populations studied, in people with a hospital record of admission for autoimmune haemolytic anaemia, chronic active hepatitis, dermatomyositis/polymyositis, type 1 diabetes mellitus, multiple sclerosis, myasthenia gravis, myxoedema, pemphigus/pemphigoid, polyarteritis nodosa, psoriasis, rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus. Rate ratios were considerably higher for some of these diseases than others: for example, for systemic lupus erythematosus the rate ratios were 3.61 (2.36 to 5.31 in the ORLS1 population, 4.60 (3.19 to 6.43 in ORLS2 and 3.71 (3.43 to 4.02 in the England dataset. Conclusions People admitted to hospital with immune-mediated diseases may be at an increased risk of subsequent VTE. Our findings need independent confirmation or refutation; but, if confirmed, there may be a role for thromboprophylaxis in some patients with these diseases.

  1. Treatment of chronic immune-mediated neuropathies: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and the Lewis-Sumner syndrome.

    Sederholm, Benson H


    Current treatment approaches for the management of chronic immune-mediated peripheral neuropathies are reviewed, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and the Lewis-Sumner syndrome (LSS). A summary of existing evidence for commonly used treatment modalities, such as corticosteroids, intravenous immune globulin (IVIG), and plasma exchange is provided. Evidence for the use of additional immunosuppressant and immunomodulatory agents is also reviewed.

  2. The Association of Specific Constituents of the Fecal Microbiota with Immune-Mediated Brain Disease in Dogs

    Jeffery, Nick D.; Barker, Andrew K.; Alcott, Cody J.; Levine, Jon M.; Meren, Ilyssa; Wengert, Jane; Jergens, Albert E.; Suchodolski, Jan S.


    Meningoencephalomyelitis of unknown origin (MUO) is a common, naturally-occurring, clinical disease of pet dogs. It is an immune-mediated condition that has many similarities with experimental autoimmune encephalitis (EAE) in rodents and so investigation of its pathogenesis may aid in understanding factors that contribute to development of multiple sclerosis in people. Gut microbiota are known to modulate immune responses that influence susceptibility to immune-mediated brain disease. In this study we aimed to compare abundance of specific constituents of the fecal microbiota, namely Faecalibacterium prausnitzii and Prevotellaceae, between dogs diagnosed with MUO and matched controls. Fecal samples were obtained from 20 dogs diagnosed with MUO and 20 control dogs matched for breed, age and gender. Bacterial abundance was measured using qPCR and 16S rRNA sequencing. We found that Prevotellaceae were significantly less abundant in cases compared with controls (p = 0.003) but there was no difference in abundance of F.prausnitzii. There was no evidence of other differences in gut microbiota between groups. These data, derived from this naturally-occurring canine clinical model, provide strong corroborative evidence that high abundance of Prevotellaceae in the gut is associated with reduced risk for developing immune-mediated brain disease. PMID:28125651

  3. Tumor-induced CD11b(+) Gr-1(+) myeloid-derived suppressor cells exacerbate immune-mediated hepatitis in mice in a CD40-dependent manner.

    Kapanadze, Tamar; Medina-Echeverz, José; Gamrekelashvili, Jaba; Weiss, Jonathan M; Wiltrout, Robert H; Kapoor, Veena; Hawk, Nga; Terabe, Masaki; Berzofsky, Jay A; Manns, Michael P; Wang, Ena; Marincola, Francesco M; Korangy, Firouzeh; Greten, Tim F


    Immunosuppressive CD11b(+) Gr-1(+) myeloid-derived suppressor cells (MDSCs) accumulate in the livers of tumor-bearing (TB) mice. We studied hepatic MDSCs in two murine models of immune-mediated hepatitis. Unexpectedly, treatment of TB mice with Concanavalin A (Con A) or α-galactosylceramide resulted in increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels in comparison to tumor-free mice. Adoptive transfer of hepatic MDSCs into naïve mice exacerbated Con A induced liver damage. Hepatic CD11b(+) Gr-1(+) cells revealed a polarized proinflammatory gene signature after Con A treatment. An IFN-γ-dependent upregulation of CD40 on hepatic CD11b(+) Gr-1(+) cells along with an upregulation of CD80, CD86, and CD1d after Con A treatment was observed. Con A treatment resulted in a loss of suppressor function by tumor-induced CD11b(+) Gr-1(+) MDSCs as well as enhanced reactive oxygen species (ROS)-mediated hepatotoxicity. CD40 knockdown in hepatic MDSCs led to increased arginase activity upon Con A treatment and lower ALT/AST serum levels. Finally, blockade of arginase activity in Cd40(-/-) tumor-induced myeloid cells resulted in exacerbation of hepatitis and increased ROS production in vivo. Our findings indicate that in a setting of acute hepatitis, tumor-induced hepatic MDSCs act as proinflammatory immune effector cells capable of killing hepatocytes in a CD40-dependent manner.

  4. Syndromic mental retardation with thrombocytopenia due to 21q22.11q22.12 deletion: Report of three patients.

    Katzaki, Eleni; Morin, Gilles; Pollazzon, Marzia; Papa, Filomena Tiziana; Buoni, Sabrina; Hayek, Joussef; Andrieux, Joris; Lecerf, Laure; Popovici, Cornel; Receveur, Aline; Mathieu-Dramard, Michèle; Renieri, Alessandra; Mari, Francesca; Philip, Nicole


    During the last few years, an increasing number of microdeletion/microduplication syndromes have been delineated. This rapid evolution is mainly due to the availability of microarray technology as a routine diagnostic tool. Microdeletions of the 21q22.11q22.12 region encompassing the RUNX1 gene have been reported in nine patients presenting with syndromic thrombocytopenia and mental retardation. RUNX1 gene is responsible for an autosomal dominant platelet disorder with predisposition to acute myelogenous leukemia. We report on three novel patients with an overlapping "de novo" interstitial deletion involving the band 21q22 characterized by array-CGH. All our patients presented with severe developmental delay, dysmorphic features, behavioral problems, and thrombocytopenia. Comparing the clinical features of our patients with the overlapping ones already reported two potential phenotypes related to 21q22 microdeletion including RUNX1 were highlighted: thrombocytopenia with +/- mild dysmorphic features and syndromic thrombocytopenia with growth and developmental delay.

  5. Acute lymphoblastic leukemia presenting with gross hematuria

    Kalbani, Naifain Al; Weitzman, Sheila; Abdelhaleem, Mohamed; Carcao, Manuel; Abla, Oussama


    A case of a six-year-old boy presenting with gross hematuria is reported. Investigations revealed the etiology of the hematuria to be thrombocytopenia in the setting of newly diagnosed acute lymphoblastic leukemia. The diagnosis of leukemia was confirmed by bone marrow examination. The patient’s hematuria completely resolved with platelet transfusions. Although thrombocytopenia is a very common presenting feature of acute lymphoblastic leukemia, gross hematuria is exceedingly rare. Thus, thro...

  6. Immunological HCV-Associated Thrombocytopenia: Short Review

    Dimitrios Dimitroulis


    Full Text Available Infection with Hepatitis C virus (HCV is affecting about 3% of the world's population, leading to liver damage, end-stage liver disease, and development of hepatocellular carcinoma, being thus the first indication for liver transplantation in the USA. Apart from the cirrhotic-liver-derived clinical signs and symptoms several conditions with immunological origin can also arise, such as, glomerulonephritis, pulmonary fibrosis, and thrombocytopenia. HCV-related autoimmune thrombocytopenia shows specific pathogenetic characteristics as well as symptoms and signs that differ in severity and frequency from symptoms in patients that are not HCV infected. Aim of this short paper is to estimate the epidemiological characteristics of the disease, to investigate the pathogenesis and clinical manifestation, and to propose treatment strategies according to the pertinent literature.

  7. Current management of heparin-induced thrombocytopenia.

    Cosmi, Benilde


    Heparin-induced thrombocytopenia (HIT) is an immune adverse reaction to heparin (both unfractionated and low-molecular-weight), which is mediated by the formation of IgG antibodies against platelet factor 4-heparin complexes. The IgG/platelet factor 4 immunocomplexes activate platelets with resulting thrombocytopenia, which is not associated with bleeding, but with paradoxical life-threatening thrombotic complications, for coagulation activation. HIT diagnosis requires the assessment of pre-test clinical probability in combination with the measurement of platelet activating antibodies against platelet factor 4-heparin complexes with immunological and functional assays. When HIT is diagnosed, any form of heparin should be stopped and a non-heparin alternative anticoagulant should be started. Argatroban and danaparoid are currently the only drugs licensed for HIT, with different country availability. Bivalirudin is an option in cardiac surgery and procedures in HIT patients.

  8. Thrombocytopenia during pregnancy: an institutional based study

    Rajshree Dayanand Katke


    Methods: The study was conducted in this tertiary institute over a period of two years and three months. 103 pregnant patients with a platelet count of or less than 100000/mL were included. The course of pregnancy was studied and the investigation profile was monitored. Results: Out of 103 cases of thrombocytopenia, 73 (70.9% patients had moderate, 30 (29.1% patients had severe thrombocytopenia. In this study 35% cases were primigravidas, 32% cases were gravida 2, 33% cases were gravida 3 to 5. Gestational thrombocytopenia was the most common etiological factor with 30.1% cases, 27.2% cases due to hypertensive disorders, 18.4% cases due to malaria followed by 12.6% cases due to dengue. In the study group the mean gestational age was 33 +/- 5.139, maximum cases belonged to gestational age 30 to and #8805;40. 14 patients (14.1% had still births. 9 patients (8.7% had Neonatal deaths (NNDs. Conclusions: The challenge to the clinician is to weigh the risks of maternal and fetal bleeding complications against the benefits of diagnostic tests and interventions. [Int J Reprod Contracept Obstet Gynecol 2014; 3(4.000: 947-951

  9. A rare case of infantile cerebellar pilocytic astrocytoma and thrombocytopenia presenting with intratumoral hemorrhage

    Shashank R Ramdurg


    Full Text Available Incidence of gliomas presenting with hemorrhage is around 3.7–7.2%. Low-grade gliomas account for <1% tumor with hemorrhage. Infants presenting with cerebellar pilocytic astrocytomas (PAs and hemorrhage with thrombocytopenia have not been reported. We report an interesting case of a 9-month-old infant who presented to the emergency department in a drowsy state with recurrent vomiting. Laboratory investigations showed anemia, thrombocytopenia, and coagulopathy. Radiological evaluation showed a large PA with bleed. The patient was treated with retromastoid suboccipital craniotomy and tumor excision and improved postoperatively. Cerebellar PA with bleed and coagulopathy in infants has not been reported in literature till date. Their presentation seems to be acute in nature, and high index of suspicion is required for the diagnosis of these posterior fossa tumors, which can deteriorate rapidly in infants.

  10. Bone marrow pathology in dogs and cats with non-regenerative immune-mediated haemolytic anaemia and pure red cell aplasia.

    Weiss, D J


    Many dogs and cats with immune-mediated haemolytic anaemia (IMHA) lack a bone marrow erythroid regenerative response. To better understand the failure of the bone marrow to respond to the anaemia, bone marrow pathology associated with non-regenerative IMHA and pure red cell aplasia (PRCA) was reviewed. Eighty-two affected dogs and 57 affected cats were identified from a population presenting to a referral hospital over a 10-year period. Fifty-five dogs had non-regenerative IMHA (38 had bone marrow erythroid hyperplasia and 17 had erythroid maturation arrest) and 27 had pure red cell aplasia (PRCA). Twenty-eight cats had non-regenerative IMHA (24 had erythroid hyperplasia and 4 had erythroid maturation arrest) and 29 had PRCA. A variety of pathological changes were observed in bone marrow aspirates and core biopsy specimens taken from these animals. These changes included dysmyelopoiesis, myelonecrosis, myelofibrosis, interstitial oedema, haemorrhage, acute inflammation, haemophagocytic syndrome, lymphocyte aggregation, and lymphocyte or plasma cell hyperplasia. In both dogs and cats, dysmyelopoiesis, myelonecrosis, myelofibrosis, interstitial oedema, haemorrhage, acute inflammation and haemophagocytic syndrome were primarily noted in bone marrow specimens where there was evidence of erythroid hyperplasia. These animals were also more often neutropenic and thrombocytopenic, and had decreased 60 day survival when compared with dogs or cats with non-regenerative anaemia associated with erythroid maturation arrest or PRCA. Therefore, the pathogenesis of the non-regenerative anaemia in non-regenerative IMHA may involve both antibody-mediated destruction of bone marrow precursor cells and pathological events within the bone marrow that result in ineffective erythropoiesis.

  11. Ustekinumab in chronic immune-mediated diseases: a review of long term safety and patient improvement

    Toussirot E


    Full Text Available Éric Toussirot,1–4 Fabrice Michel,5 Matthieu Béreau,6 Delphine Binda1,7 1Clinical Investigation Center – Biotherapy CBT-506, University Hospital of Besançon, Besançon, France; 2Department of Rheumatology, University Hospital of Besançon, Besançon, France; 3Department of Therapeutics, University of Franche-Comté, Besançon, France; 4Equipe d'Acceuil 4266 Pathogens and Inflammation, Structure Fédérative de Recherche–Fédération de Recherche 4234, University of Franche-Comté, Besançon, France; 5Department of Physical Medicine and Rehabilitation, University Hospital of Besançon, Besançon, France; 6Department of Neurology, University Hospital of Besançon, Besançon, France; 7Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1098, Blood Transfusion Center, Besançon, France Abstract: Ustekinumab is a fully human monoclonal antibody targeting the common p40 subunit shared by interleukin (IL-12 and IL-23. Ustekinumab prevents the interaction of IL-12 and IL-23 with their cell surface receptors, and thus blocks T helper (Th-1 IL-12 and Th-17 IL-23 inflammatory pathways. Ustekinumab has been evaluated in the treatment of various chronic immune-mediated diseases including, psoriasis, psoriatic arthritis, Crohn's disease, and multiple sclerosis. It led to a rapid and durable improvement in psoriasis area and severity index in patients with moderate to severe psoriasis. Ustekinumab also improved joint symptoms of psoriatic arthritis. Results in Crohn's disease were more mitigated, albeit with a symptomatic improvement in patients refractory to tumor necrosis factor-α inhibitors. Ustekinumab did not reduce the number of magnetic resonance imaging brain lesions in multiple sclerosis. The most common adverse events to have been observed during clinical trials are mild in intensity, and include respiratory tract infections, nasopharyngitis, headaches, and injection site reactions. A pooled analysis of

  12. 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury.

    Fullerton, Aaron M; Roth, Robert A; Ganey, Patricia E


    Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30 μg/kg TCDD or vehicle control on day zero and then given either Con A or saline intravenously on day four. Mice treated with TCDD did not develop liver injury; however, TCDD pretreatment increased liver injury resulting from moderate doses of Con A (4-10 mg/kg). TCDD-pretreated mice had altered plasma concentrations of inflammatory cytokines, including interferon gamma (IFNγ), and TCDD/Con A-induced hepatotoxicity was attenuated in IFNγ knockout mice. At various times after treatment, intrahepatic immune cells were isolated, and expression of cell activation markers as well as cytolytic proteins was determined. TCDD pretreatment increased the proportion of activated natural killer T (NKT) cells and the percent of cells expressing Fas ligand (FasL) after Con A administration. In addition FasL knockout mice and mice treated with CD18 antiserum were both protected from TCDD/Con A-induced hepatotoxicity, suggesting a requirement for direct cell-cell interaction between effector immune cells and parenchymal cell targets in the development of liver injury from TCDD/Con A treatment. In summary, exposure to TCDD increased NKT cell activation and exacerbated immune-mediated liver injury induced by Con A through a mechanism involving IFNγ and FasL expression.

  13. Immune-Mediated Nephropathy and Systemic Autoimmunity in Mice Does Not Require Receptor Interacting Protein Kinase 3 (RIPK3)

    Corradetti, Chelsea; Jog, Neelakshi R.; Gallucci, Stefania; Madaio, Michael; Balachandran, Siddharth


    Immune mediated nephropathy is one of the most serious manifestations of lupus and is characterized by severe inflammation and necrosis that, if untreated, eventually leads to renal failure. Although lupus has a higher incidence in women, both sexes can develop lupus glomerulonephritis; nephritis in men develops earlier and is more severe than in women. It is therefore important to understand the cellular and molecular mechanisms mediating nephritis in each sex. Previous work by our lab found that the absence or pharmacological inhibition of Poly [ADP-ribose] polymerase 1 (PARP-1), an enzyme involved in DNA repair and necrotic cell death, affects only male mice and results in milder nephritis, with less in situ inflammation, and diminished incidence of necrotic lesions, allowing for higher survival rates. A second pathway mediating necrosis involves Receptor-Interacting Serine-Threonine Kinase 3 (RIPK3); in this study we sought to investigate the impact of RIPK3 on the development of lupus and nephritis in both sexes. To this end, we used two inducible murine models of lupus: chronic graft versus host disease (cGvHD) and pristane-induced lupus; and nephrotoxic serum (NTS)-induced nephritis as a model of immune mediated nephropathy. We found that the absence of RIPK3 has neither positive nor negative impact on the disease development or progression of lupus and nephritis in all three models, and in both male and female mice. We conclude that RIPK3 is dispensable for the pathogenesis of lupus and immune mediated nephropathy as to accelerate, worsen or ameliorate the disease. PMID:27669412

  14. Linezolid-associated thrombocytopenia: prevention and treatment%利奈唑胺致血小板减少及其防治

    王博雅; 闫素英


    Linezolid is an oxazolidinone antibacterial used for the treatment of Gram-positive infection of the respiratory tract and skin, including those due to vancomycin resistant enterocooci. The common adverse reactions are diarrhea, nausea, vomiting, headache, and rash. Linezolid may cause thrombocytopenia, and the risk factors for thrombocytopenia are prolonged use of linezolid, advanced age, and renal insufficiency. The mechanism of thrombocytopenia induced by linezolid might be linked to bone marrow suppression or immune-mediated platelet decrease. The measures for prevention and treatment of thrombocytopenia are as follows: high-dose and prolonged use of linezolid should be avoided; platelet count should be closely monitored during linezolid therapy; linezolid combined with drugs that produce bone marrow suppression should be avoided; linezolid therapy should be discontinued in patients who developed thrombocytopenia, and transfusion of platelets should be considered in patients having severe thrombocytopenia.%利奈唑胺为恶唑烷酮类抗生素,主要用于革兰阳性细菌引起的呼吸道和皮肤感染以及耐万古霉素肠球菌引起的感染.利奈唑胺的常见不良反应为腹泻、恶心、呕吐、头痛、皮疹等.利奈唑胺可致血小板减少,其危险因素为长时间治疗、高龄以及肾功能不全.利奈唑胺所致血小板减少的机制可能与骨髓抑制或免疫介导致血小板减少有关.防治血小板减少的措施:避免大剂量和长时间应用利奈唑胺;用药期间严密监测血小板水平;避免将利奈唑胺与抑制骨髓的药物联用;患者出现血小板减少应立即停药,严重患者可考虑输注血小板.

  15. 脂联素与免疫性皮肤病%Adiponectin and immune-mediated skin diseases

    罗丽敏; 何春涤


    脂联素是一种主要由脂肪细胞分泌的内源性生物活性蛋白质,以三聚体、六聚体和高分子量多聚体3种不同的形式存在于外周血中.脂联素与其受体结合后,通过激活下游的信号通路,发挥调控新陈代谢、调节免疫平衡、抑制细胞增殖和炎症反应、维持血管稳态等重要作用,而其免疫调节作用日益成为研究的焦点.近年来研究表明,脂联素积极参与免疫性皮肤病的进程,随着对脂联素免疫调节作用研究的不断深入,其与免疫性皮肤病的关系亦取得了较大进展.拟为今后免疫性皮肤病的临床治疗及用药提供新的方法和思路.概述脂联素与银屑病、系统性红斑狼疮、硬皮病及干燥综合征等免疫性皮肤病的关系.%Adiponectin is an endogenous bioactive protein secreted mainly by adipocytes, and exists in peripheral blood in three forms, including trimers, hexamers and high-molecular weight multimers.By binding to its receptor and activating downstream signaling pathways, it plays an important role in regulating metabolism and immune balance, inhibiting cell proliferation and inflammatory reaction, and maintaining vascular homeostasis.The immunoregulatory effect of adiponectin has been gradually becoming a focus of researches.Recent studies have indicated that adiponectin is actively involved in the development of immune-mediated skin diseases.With further insights into the immunoregulatory effect of adiponectin, great progress has been made in elucidating the relationship between adiponectin and immune-mediated skin diseases, which will provide new methods and ideas for clinical treatment of immune-mediated skin diseases.This review summarizes the relationship between adiponectin and immune-mediated skin diseases, such as psoriasis, systemic lupus erythematosus, scleroderma and Sj(o)gren's syndrome.

  16. Thrombocytopenia in leptospirosis and role of platelet transfusion

    Sharma Jayashree


    Full Text Available Aim : The study was designed to find out the incidence of thrombocytopenia in leptospirosis and to correlate thrombocytopenia with other parameters like renal failure, hepatic failure and bleeding manifestation like adult respiratory distress syndrome and to assess the role of platelet transfusion. Materials and Methods : 50 cases of leptospirosis during the month of July and August 2005 were retrospectively analyzed. Criteria for selection were Lepto Tek Dri - dot test positive cases of the clinically suspected cases of Leptospirosis. Degree of thrombocytopenia was categorized as severe, moderate and mild. Presence of thrombocytopenia was clinically correlated with parameters like renal dysfunction, hepatic dysfunction and hemorrhagic manifestations (mainly ARDS. Role of platelet transfusion was assessed with reference to presence and degree of thrombcytopenia and hemorrhagic manifestations. Results : Out of total 50 patients 26 were male and 24 were females. Major bleeding manifestation in the form of ARDS was seen in 15 (30% of patients. 28 (56% patients had thrombocytopenia and 22 (44% patients had normal platelet counts. Total number of patients with renal dysfunction was 24 (48%. Only four (18.18% patients with normal platelet counts had renal dysfunction while 20 (71.42% patients with thrombocytopenia had renal dysfunction. Only two (9.09% patients with normal platelet counts and 48 (46.42% patients with thrombocytopenia had hepatorenal dysfunction. Total number of patients with ARDS was 15 (30%. Of these two (13.33% had normal platelet count while 13 (86.6% patients were thrombocytopenic. Total 47 units of platelets were transfused to 12 patients in our study. Of these seven patients with severe thrombocytopenia required total 28 units, two patients with moderate thrombocytopenia required total seven units and patients with mild thrombocytopenia were transfused total 12 units of platelets. Conclusion : It is important to anticipate and

  17. Incidence and risk factors of neonatal thrombocytopenia: a pr

    Nila Kusumasari


    Conclusions The incidence of neonatal thrombocytopenia was 12.2%. Significant risk factor of mother that caused thrombocytopenia was pre-eclampsia, while risk factors of neonates were asphyxia, sepsis and necrotizing enterocolitis.[Paediatr Indones. 2010;50:31-7].

  18. Interplay among cytokines and T cell subsets in the progression and control of immune-mediated diseases.

    Moudgil, Kamal D


    Cytokines serve as key mediators of inflammation and tissue damage in a variety of immune-mediated disorders. The induction, progression, and resolution of inflammation in such disorders are characterized by a dynamic balance between both the pro-inflammatory and anti-inflammatory cytokines as well as the pathogenic and protective T cell subsets. Over the past two decades, the roles of the interleukin-17 (IL-17) /IL-23 axis and the T helper 17 (Th17)/ T regulatory (Treg) cell balance in the pathogenesis of autoimmunity and other inflammatory diseases have extensively been analyzed, and their significance validated. However, these studies, coupled with others devoted to well-established Th1/Th2 cytokines, have unraveled some challenging issues including the dual action of cytokines and the plasticity of T cell subsets. Nevertheless, major positive advances have also been made regarding cytokines and T cell subsets as therapeutic targets/agents. In this special issue, "Cytokines in Immune Pathology and Therapy," leading experts have shared their research work and perspectives on the roles of cytokines in the development and control of immune-mediated diseases. An outline of 14 articles in the first volume is presented here. The second volume will follow soon.

  19. Management of thrombocytopenia in the ICU (pregnancy excluded).

    Van der Linden, Thierry; Souweine, Bertrand; Dupic, Laurent; Soufir, Lilia; Meyer, Pascal


    Thrombocytopenia is a very frequent disorder in the intensive care unit. Many etiologies should be searched, and therapeutic approaches differ according to these different causes. However, no guideline exists regarding optimum practices for these situations in critically ill patients. We present recommendations for the management of thrombocytopenia in intensive care unit, excluding pregnancy, developed by an expert group of the French-Language Society of Intensive Care (Société de Réanimation de Langue Française (SRLF), the French Language Group of Paediatric Intensive Care and Emergencies (GFRUP) and of the Haemostasis and Thrombosis Study Group (GEHT) of the French Society of Haematology (SFH). The recommendations cover six fields of application: definition, epidemiology, and prognosis; diagnostic approach; therapeutic aspects; thrombocytopenia and sepsis; iatrogenic thrombocytopenia, with a special focus on heparin-induced thrombocytopenia; and thrombotic microangiopathy.

  20. Study of thrombopoietin for gene therapy of thrombocytopenia

    崇松; 卢大儒; 李昌本; 邱信芳; 薛京伦


    Thrombopoietin (TPO) is likely to be a potent, specific and reliable medication in the treatment of thrombocytopenia. A TPO-highly-expressed plasmid pcDNA3-TPO was constructed and a primary study was made on the expression of TPO cDNA in vitro and gene transfer study for thrombocytopenia in vivo. rhTPO showed complete and stable bioactivity by a series of indicators. High expression of TPO was detected in plasma from healthy mice or thrombocytopenia mice model receiving direct intramuscular injection of pcDNA3-TPO. And the platelet level of healthy mice peaked to 1.9-fold of baseline. Mice with CTX-induced thrombocytopenia achieved profound nadirs, acceleration of recovery, even 1.8—2.0-fold supranormal levels of peripheral platelet counts. The results offered experimental support for clinical application of gene therapy for thrombocytopenia via direct intramuscular injection of TPO cDNA.

  1. Evaluation of the immature platelet fraction in the diagnosis and prognosis of childhood immune thrombocytopenia.

    Adly, Amira Abdel Moneam; Ragab, Iman Ahmed; Ismail, Eman Abdel Rahman; Farahat, Mona Mohammed


    Rapid assessment of platelet production would distinguish between thrombocytopenia due to decreased platelet production or increased peripheral platelet destruction. We evaluated the value of immature platelet fraction (IPF) in differentiating immune thrombocytopenia (ITP) from thrombocytopenia secondary to bone marrow failure and its potential use as a prognostic marker. Forty-one young patients with ITP were compared with 14 patients with hematological malignancies under chemotherapy, representing a control group with thrombocytopenia due to bone marrow suppression and 30 age- and sex-matched healthy controls. Patients were studied stressing on bleeding manifestations, organomegaly/lymphadenopathy and therapy. Complete blood count including IPF was performed using Sysmex XE-2100. ITP patients were classified into two subgroups: acute ITP with spontaneous resolution within 3 months from diagnosis and chronic ITP that lasted ≥ 1 year from diagnosis. Median IPF was 11.8% in patients with ITP, 7% in those with hematological malignancy and 3% in the control group (p < 0.001). ITP patients had significantly higher mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR) and IPF compared with patients with malignancy or healthy controls, while plateletcrit (PCT) was significantly lower in ITP patients than other groups (p < 0.001). IPF was increased in patients with chronic ITP compared with acute ITP group (p < 0.001). Patients with active ITP had the highest IPF followed by those in partial remission, while ITP patients in remission had the lowest IPF. IPF was positively correlated to the number of lines of treatment used, MPV, PDW and P-LCR, while negatively correlated to platelet count and PCT among ITP patients (p < 0.001). Multiple regression analysis showed that platelet count and P-LCR were independently related to IPF. ROC curve analysis revealed that the cut-off value of IPF at 9.4% could be diagnostic for ITP patients




    Full Text Available Ovarian corpus luteal cyst occurs during reproductive years, at end of menstrual cycle, or during pregnancy. The presentation of ruptured luteal cyst may vary from no symptoms to symptoms and signs of acute abdomen . 1 Ruptured corpus luteal cyst in some instances causes massive intraperitoneal hemorrhage leading to death in patient , 2 particularly those with bleeding diathesis. Fitzgerald & Berrigan (1959 called it an “ovarian accident”& it is rarely accurately diagnosed before operation . 3 In this case report, we will depict a case of ruptured corpus luteal cyst which became catastrophic for the patient with thrombocytopenia.

  3. Hashimoto's Encephalopathy Presenting with Acute Cognitive Dysfunction and Convulsion.

    Kang, Woo-Hyuk; Na, Ju-Young; Kim, Meyung-Kug; Yoo, Bong-Goo


    Hashimoto's encephalopathy is an immune-mediated disorder characterized by acute or subacute encephalopathy related to increased anti-thyroid antibodies. Clinical manifestations of Hashimoto's encephalopathy may include stroke-like episodes, altered consciousness, psychosis, myoclonus, abnormal movements, seizures, and cognitive dysfunction. Acute cognitive dysfunction with convulsion as initial clinical manifestations of Hashimoto's encephalopathy is very rare. We report a 65-year-old man who developed acute onset of cognitive decline and convulsion due to Hashimoto's encephalopathy.

  4. 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury

    Fullerton, Aaron M., E-mail: [Department of Pharmacology and Toxicology, Center for Integrative Toxicology, Michigan State University, 1129 Farm Lane, Room 215, East Lansing, MI 48824 (United States); Roth, Robert A., E-mail: [Department of Pharmacology and Toxicology, Center for Integrative Toxicology, Michigan State University, Food Safety and Toxicology Building, 1129 Farm Lane, Room 221, East Lansing, MI 48824 (United States); Ganey, Patricia E., E-mail: [Department of Pharmacology and Toxicology, Center for Integrative Toxicology, Michigan State University, Food Safety and Toxicology Building, 1129 Farm Lane, Room 214, East Lansing, MI 48824 (United States)


    Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30 μg/kg TCDD or vehicle control on day zero and then given either Con A or saline intravenously on day four. Mice treated with TCDD did not develop liver injury; however, TCDD pretreatment increased liver injury resulting from moderate doses of Con A (4–10 mg/kg). TCDD-pretreated mice had altered plasma concentrations of inflammatory cytokines, including interferon gamma (IFNγ), and TCDD/Con A-induced hepatotoxicity was attenuated in IFNγ knockout mice. At various times after treatment, intrahepatic immune cells were isolated, and expression of cell activation markers as well as cytolytic proteins was determined. TCDD pretreatment increased the proportion of activated natural killer T (NKT) cells and the percent of cells expressing Fas ligand (FasL) after Con A administration. In addition FasL knockout mice and mice treated with CD18 antiserum were both protected from TCDD/Con A-induced hepatotoxicity, suggesting a requirement for direct cell–cell interaction between effector immune cells and parenchymal cell targets in the development of liver injury from TCDD/Con A treatment. In summary, exposure to TCDD increased NKT cell activation and exacerbated immune-mediated liver injury induced by Con A through a mechanism involving IFNγ and FasL expression. -- Highlights: ► TCDD pretreatment sensitizes mice to Con A-induced hepatotoxicity. ► TCDD pretreatment increased concentration of IFNγ in plasma after Con A. ► Con A-induced activation of NKT cells was increased by TCDD pretreatment. ► Fas

  5. Thrombocytopenia in Preterm Infants with Intrauterine Growth Restriction



    Full Text Available Sick preterm infants often have thrombocytopenia at birth, and this is often associated with intrauterine growth restriction (IUGR, or birth weights less than the 10th percentile. The pathogenesis of the thrombocytopenia and its importance in IUGR are still unclear. We studied the characteristics of preterm IUGR infants with thrombocytopenia. Twenty-seven singleton Japanese preterm IUGR infants were born between January 2002 and June 2007 at Okayama University Hospital. Infants with malformation, chromosomal abnormalities, alloimmune thrombocytopenia, sepsis, and maternal aspirin ingestion were excluded. The infants were divided into group A (n=8, which had thrombocytopenia within 72h after birth, and group B (n=19, which did not. There were significant differences in birth weight, head circumference, umbilical artery (UA-pulsatility index (PI, middle cerebral artery-PI, UA-pH, UA-pO2, and UA-pCO2. The infants in group A were smaller, had abnormal blood flow patterns, and were hypoxic at birth. We speculate that the infants with thrombocytopenia were more severely growth-restricted by chronic hypoxia. Thrombocytopenia is an important parameter for chronic hypoxia in the uterine.

  6. Co-stimulation with LPS or Poly I:C markedly enhances the anti-platelet immune response and severity of fetal and neonatal alloimmune thrombocytopenia.

    Li, Conglei; Chen, Pingguo; Vadasz, Brian; Ma, Li; Zhou, Hui; Lang, Sean; Freedman, John; Ni, Heyu


    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal antibodies against fetal/neonatal platelets. FNAIT is also linked with miscarriages, although the incidence and mechanisms of fetal death have not been well studied. IntegrinαIIbβ3 (GPIIbIIIa) and the GPIbα complex are major glycoproteins expressed on platelets and are also major antigens targeted in autoimmune thrombocytopenia (ITP), but reported cases of anti-GPIb-mediated FNAIT are rare. Bacterial and viral infections have been causally linked with the pathogenesis of immune-mediated thrombocytopenia (ITP); however, it is unknown whether these infections contribute to the severity of FNAIT. Here, immune responses against platelet antigens were examined by transfusing wild-type (WT) mouse platelets into β3-/- or GPIbα-/- mice. To mimic bacterial or viral infections, lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (Poly I:C) were injected intraperitoneally following platelet transfusions. The FNAIT model was established by breeding the immunised female mice with WT male mice. We demonstrated for the first time that the platelet GPIbα has lower immunogenicity compared to β3 integrin. Interestingly, co-stimulation with LPS or Poly I:C markedly enhanced the immune response against platelet GPIbα and caused severe pathology of FNAIT (i.e. miscarriages). LPS or Poly I:C also enhanced the immune response against platelet β3 integrin. Our data suggest that bacterial and viral infections facilitate the anti-platelet GPIbα response, which may lead to a severe non-classical FNAIT (i.e. miscarriage but not neonatal bleeding) that has not been adequately reported in humans.

  7. Immune Thrombocytopenia and Obesity: Predictive Relationship

    Hanafy, Ehab; Pakra, Mohammed Al


    Background: Chronic refractory immune thrombocytopenia (ITP) is defined as the failure of any modality to maintain the platelet count above 20 × 103/μL for an appreciable time without unacceptable toxicity. To date, certain predictive factors have been associated with refractory ITP. However, none of the published studies has declared the possible association between obesity and refractory ITP. Case Reports: We present the cases of 3 children with ITP who failed to achieve remission on different therapeutic approaches including rituximab, vincristine, and romiplostim. The 3 children had obesity as a common feature. Conclusion: We present these cases to propose a possible association between obesity and refractoriness of ITP to different therapeutic approaches and to emphasize the need for further study to establish whether a causal relationship exists.

  8. Good agreement of conventional and gel-based direct agglutination test in immune-mediated haemolytic anaemia

    Piek Christine J


    Full Text Available Abstract Background The aim of this study was to compare a gel-based test with the traditional direct agglutination test (DAT for the diagnosis of immune-mediated haemolytic anaemia (IMHA. Methods Canine (n = 247 and feline (n = 74 blood samples were submitted for DAT testing to two laboratories. A subset of canine samples was categorized as having idiopathic IMHA, secondary IMHA, or no IMHA. Results The kappa values for agreement between the tests were in one laboratory 0.86 for canine and 0.58 for feline samples, and in the other 0.48 for canine samples. The lower agreement in the second laboratory was caused by a high number of positive canine DATs for which the gel test was negative. This group included significantly more dogs with secondary IMHA. Conclusions The gel test might be used as a screening test for idiopathic IMHA and is less often positive in secondary IMHA than the DAT.

  9. Leptin inhibitors from fungal endophytes (LIFEs): Will be novel therapeutic drugs for obesity and its associated immune mediated diseases.

    Chandra Mouli, K; Pragathi, D; Naga Jyothi, U; Shanmuga Kumar, V; Himalaya Naik, M; Balananda, P; Suman, B; Seshadri Reddy, V; Vijaya, T


    Treatment of obesity and its associated immune mediated diseases is challenging due to impaired function of leptin system. Thus leptin is providing an interesting target for therapeutic intervention. Leptin, an adipose tissue-derived adipokine, displays a variety of immune functions, and regulate both innate and adaptive immune responses. The increased secretion of leptin (hyperleptinemia) and production of proinflammatory cytokines has been implicated in the pathogenesis of obesity-related immune diseases such as diabetes mellitus, hypertension, atherosclerosis, cancer, systemic lupus erythematosus, rheumatoid arthritis, crohn's disease and multiple sclerosis. These disorders are managed through antibiotics and by cytokines replacement. However, the effectiveness of cytokines coupled to the complexity of the cytokine network leads to severe side-effects, which can still occur after careful preclinical evaluation. In addition, synthetic immunotherapeutics carries a degree of risk, is time-consuming and expensive. Hence, the complexity of existing therapy and adverse effects emphasizes the need of an alternative approach for the management of immune dysfunction associated with obesity and its related diseases. For the aforementioned diseases that are related to leptin overabundance, new drugs blocking leptin signaling need to be generated. The research on the discovery of clinically important novel compounds from natural source is expanding due to their safety and no side effect. The fungal endophytes are the microbes that colonize internal tissue of plants without causing negative effects to the host. They produce plethora of substances of potential use to modern medicinal and pharmaceutical industry. The increasing body of evidence associated with application of bioactive metabolites derived from fungal endophytes in diverse disease states merits its use as therapeutic drugs. In particular, the saponins have been extensively proved to modulate the immune system

  10. Retrospective study on clinical features and interventional therapy of acute deep venous thrombosis of lower extremity combined with type Ⅱ heparin-induced thrombocytopenia%急性下肢深静脉血栓形成合并Ⅱ型肝素诱导血小板减少症的临床特征及介入综合治疗效果

    苏浩波; 赵伯翔; 黄昊; 楼文胜; 顾建平; 何旭; 陈亮; 陈国平; 宋进华; 施万印; 汪涛


    此类患者深静脉血栓介入治疗效果。%Objective To explore the clinical features, diagnosis and interventional management of acute deep venous thrombosis of lower extremity (LEDVT)combined with type Ⅱ heparin-induced thrombocytopenia (HITⅡ) and to improve the knowledge of this disease. Methods A retrospective review and analysis of the clinical data of the patients with acute LEDVT combined with HIT Ⅱ enrolled from January 2010 to June 2014. All of them underwent anticoagulation with low molecular weight heparin (LMWH) and the comprehensive interventional therapy at the beginning of treatment.When HIT Ⅱ was identified, all forms of heparin and LMWH were avoided . Alternative anticoagulation was commenced with argatrobam. Adjustments in interventional therapy were taken while the short-term low-dose glucocorticoid treatment were used.The clinical manifestations, changes of PLT, 4Ts score (Warkentin 4T scoring system, 4Ts) , HIT antibody assay (ELISA) and response to therapy of the patients were analyzed and the treatment effect was observed . The efficacy of interventional therapy was evaluated according to the improvement clinical symptoms and venography. Results The incidence of acute LEDVT combined with HIT Ⅱ was 1.9%(8/416). There were 4 males and 4 females with a median age of 24 years in this study. The median time between their initiation exposure to heparin and onset of thrombocytopenia was 5 days (range,3 to 8 days). The median platelet counts prior to HIT Ⅱ was 218 × 109/L( range,122 × 109/L to 254 × 109/L ). Platelet counts decreased to the lowest level range from 20 × 109/L to 51 × 109/L(median 32 × 109/L). After alternative anticoagulation, the interval period which PLT recovered to the basic level was range from 3 to 7 days (median 3.5 days) . According to the score of 4Ts , there were 2 cases score 6 and 6 cases score 8. HIT antibody assay (ELISA) was detected in 6 patients which the results were positive. During heparin

  11. Short-course oral prednisone treatment in children with acute immune thrombocytopenia%大剂量短疗程泼尼松治疗儿童急性免疫性血小板减少症的疗效观察

    王娴静; 邹湘; 赵晓武


    目的 观察大剂量短疗程泼尼松(Pred)疗法对儿童急性免疫性血小板减少症(ITP)的疗效.方法 162例ITP患儿根据治疗方法不同随机分为大剂量静脉丙种球蛋白+甲基泼尼松龙组(IVIG+MP)、静脉丙种球蛋白组(IVIG)、甲基泼尼松龙组(MP)与Predl组.IVIG+MP组41例,采用IVIG(1g/kg,共1次)+MP[10 mg/(kg·d),每3天减半量,共9 d]冲击治疗,继之口服Pred[1.5~2.0 mg/(kg·d)],并逐渐减量维持治疗;IVIG组39例,采用丙种球蛋白(1 g/kg,共1次)冲击治疗,继之口服Pred[1.5~2.0 mg/(kg·d)]并逐渐减量维持治疗;MP组40例,采用MP[10 mg/(kg·d),每3天减半量,共9 d]冲击治疗,继之口服Pred[1.5~2.0 mg/(kg·d)]并逐渐减量维持治疗;Pred组42例,采用口服Pred[4 mg/(kg·d),共4 d]治疗后停药,无减量维持治疗.比较各组治疗前后血小板数、治疗有效率、不良反应发生率及药费支出.结果 各治疗组治疗前后血小板数及治疗有效率差异无显著性,IVIG+MP组、IVIG组、MP组治疗不良反应发生率及药费支出均高于Pred组.结论 大剂量短疗程Pred疗法治疗儿童急性ITP能有效提升血小板计数,有效率与IVIG及MP冲击治疗相比差异无显著性,不良反应少,花费低.%Objective To analyze the effects of large dose of short-course oral prednisone on the childhood acute immune thrombocytopenia ( ITP) . Methods We conducted 162 children with primary acute ITP and randomized divided them into 4 groups; IVIG + MP group, IVIG group, MP group and prednisone group. For IVIG + MP group, 41 children with ITP were treated with intravenous immunoglobulin G ( IVIG) 1 g/kg once and methylprednisolone ( MP) 10 mg/( kg · d) for 3 days, and with tapering and discontinuation of prednisone by 4 ~6 months. For IVIG group, 39 children with ITP were treated with IVIG 1g/kg once, and with tapering and discontinuation of prednisone by 4 ~ 6 months. For the MP group, 40 children with ITP were treated with MP 10 mg/( kg · d

  12. Beyond the platelet count: immature platelet fraction and thromboelastometry correlate with bleeding in patients with immune thrombocytopenia.

    Greene, Lindsey A; Chen, Siqi; Seery, Caroline; Imahiyerobo, Allison M; Bussel, James B


    Platelet counts (PC) estimate bleeding risk in Immune Thrombocytopenia (ITP). We investigated whether measures of thromboelastometry and absolute immature platelet fraction (A-IPF) would correlate better with acute bleeding score (ABS) than PC or mean platelet volume (MPV). Simultaneous determination of ABS, complete blood count and thromboelastometry was performed in 141 ITP patients; 112 underwent A-IPF testing. Subgroup analyses were performed for paediatric subjects, PC children with PC children and children with PC platelet function, contribute to ITP bleeding pathophysiology. Thromboelastometry, A-IPF and ABS can be incorporated into routine or acute visits.

  13. Efalizumab-induced severe thrombocytopenia can be resolved

    Francesca Prignano


    Full Text Available Francesca Prignano, F Zanieri, S Mokhtarzadeh, T LottiUniversity Unit of Dermatology and Physiotherapy, School of Medicine, University of Florence, Florence, ItalyAbstract: Efalizumab is a monoclonal a humanized recombinant IgG1 monoclonal antibody which targets the CD11a, the alpha-subunit of LFA-1 (lymphocyte function-associated antigen-1. It acts by blocking the T-lymphocyte pathogenetic mechanisms of psoriasis. Thrombocytopenia is an adverse event that occurs during therapy. Thrombocytopenia can be mild and can occur quite early during treatment, together with leukocytosis. Both adverse events tend to normalize with ongoing therapy, or, in cases worsening, with therapy suspension. There have been multiple reports of thrombocytopenia associated with efalizumab therapy for the treatment of psoriasis. The general recommendation is to check platelet counts monthly for the first 3 months of efalizumab therapy, then every 3 months for the duration of therapy. According to our experience on a wide range of patients, it is useful to check platelets every month for the first 6 months of therapy. We report a case of efalizumab-associated thrombocytopenia that occurred after 16 weeks of therapy together with clinical worsening of skin lesions. The peculiarity of our case is the absence of signs and symptoms linked to thrombocytopenia and the quick return to normal platelet count without corticosteroid therapy.Keywords: efalizumab, thrombocytopenia, psoriasis

  14. Thrombocytopenia after therapeutic hypothermia in severe traumatic brain injury

    QIU Wu-si; WANG Wei-min; DU Hong-ying; LIU Wei-guo; SHEN Hong; SHEN Lei-fen; ZHU Ming-lan


    Objective: To investigate the clinical characteristics and significance of thrombocytopenia after therapeutic hypothermia in severe traumatic brain injury (TBI).Methods: Ninety-six inpatients with severe brain injury were randomized into three groups: SBC (selective brain cooling ) group (n =24), MSH ( mild systemic hypothermia ) group ( n = 30), and control (normothermia) group ( n = 42). The platelet counts and prognosis were retrospectively analyzed.Results: Thrombocytopenia was present in 18 (75 % ), 23 (77 % ) and 15 (36 % ) patients in SBC group,MSH group and control group, respectively (P <0.01 ).Thrombocytopenia, in which the minimum platelet count was seen 3 days after hypothermia, showed no significant difference between SBC and MSH group (P > 0.05). Most platelet counts (37 cases, 90% ) in hypothermia group were returned to normal level after 1 to 2 days of natural rewarming. The platelet count in SBC group reduced by 16%, 27% and 29% at day 1, 3 and 5 respectively compared with the baseline value. Good recovery (GOS score 4-5) rate of thrombocytopenia 1 year after injury for hypothermia group ( 17 cases, 37 % ) was significantly lower than that of control group (P <0.01).Conclusions: Therapeutic hypothermia increases the incidence of thrombocytopenia in severe TBI, and patients with thrombocytopenia after therapeutic hypothermia are associated with unfavorable neurological prognosis.




    Full Text Available ABSTRACT: BACKGROUND: Malaria is commonly associated with various degrees of haematological complications most frequently with anaemia and thrombocytopenia. However there are contrasting reports about frequency of thrombocytopenia in P. vivax infection. MATERIAL AND METHODS: A total of 140 patients were included in the study. The details of the patients history along with their clinical f eatures, laboratory reports were recorded in a standard proforma. Sample of venous blood were collected for haematological examination like Haemoglobin, total and differential count and platelet count, which was done under automated cell counter. RESULTS: Out of 140, there were 119(85% patients who had thrombocytopenia, of them 75(54% patients had mild, 38(27% patients had moderate and 6(4% patients had severe thrombocytopenia., 30(21% out of 140 patients had leucopenia. Significant inverse association was seen between degree of parasitemia and platelet count. CONCLUSION: Various theories have been postulated for the cause of thrombocytopenia in P. Vivax infection but none of them is conclusive. Frequency or severity of thrombocytopenia doesn’t appear t o be any particular strain of plasmodium infection.

  16. Pattern and prevalence of neonatal thrombocytopenia in Port Harcourt, Nigeria

    Zaccheaus A Jeremiah


    Full Text Available Zaccheaus A Jeremiah1, Justina E Oburu21Hematology and Blood Transfusion Science Unit, Department of Medical Laboratory Sciences, College of Health Sciences, Niger Delta University, Wilberforce Island, Bayelsa State, Nigeria; 2Department of Hematology and Blood Transfusion University of Port Harcourt Teaching Hospital, Port Harcourt, NigeriaBackground: In Port Harcourt, evidence-based guidelines for platelet transfusion therapy in neonatal patients are yet to be defined and the prevalence and pattern of neonatal thrombocytopenia has not yet been reported.Methods: Platelet counts of 132 neonatal patients admitted into the special care baby unit (SCBU at the University of Port Harcourt Teaching Hospital in Nigeria were assessed using the International Committee on Standards in Hematology (ICSH approved manual procedures for hemocytometry.6Study design: This is a cross sectional study carried out on neonates to determine the prevalence and pattern of neonatal thrombocytopenia.Results: The median platelet count of the neonates was 97.0 × 109/L (interquartile range [IQR] 50–152 while the mean age was 61.7 hours (range 1–336 hours. The overall prevalence of neonatal thrombocytopenia was 53.0%. Mild thrombocytopenia (platelet count 51–100 × 109/L was found in 39.4% of the neonates, 12.1% had moderate thrombocytopenia (platelet count 30–50 × 109/L, while severe thrombocytopenia (platelet count <30 × 109/L was detected in 1.5% of the neonates. Of these, 84.84% of the cases occurred within 72 hours (early onset. The most common clinical diagnosis among the neonates was severe birth asphyxia (33.3%, followed by neonatal jaundice (19.7%, neonatal sepsis (16.7%, low birth weight (13.6%, anemia and bleeding (6.1%, and other clinical conditions (10.6%. There was no association between clinical diagnosis and thrombocytopenia (Fisher’s exact test = 10.643; P = 0.923.Conclusion: There is a high prevalence of early onset neonatal thrombocytopenia

  17. Effect of Moringa oleifera Lam. seed extract on toluene diisocyanate-induced immune-mediated inflammatory responses in rats.

    Mahajan, Shailaja G; Mali, Ravindra G; Mehta, Anita A


    Moringa oleifera Lam. is a small tree cultivated throughout India. We have investigated the effect of ethanolic extract of seeds of Moringa oleifera (MOEE, an herbal remedy) on the potential prevention of immune-mediated inflammatory responses in toluene diisocyanate (TDI as antigen)-induced asthma in Wistar rats. Rats were divided into five different groups (n = 8/group): Group-I = unsensitized control; Group-II = TDI control/vehicle; Group-III = dexamethasone (DXM) 2.5 mg/kg; and, Groups IV and V = 100 mg/kg and 200 mg/kg body weight [BW] of MOEE, respectively. All rats (except unsensitized controls) were sensitized by intranasal application of 10% TDI to induce airway hypersensitivity. Animals in Groups II-V were given their respective drug treatment per os from 1 wk prior to initiation of sensitization until the day of final provocation with 5% TDI. After this last challenge, all rats were examined for hyperreactivity symptoms and then sacrificed to determine their total and differential leucocytes in blood and bronchoalveolar (BAL) fluid and levels of TNF proportional, variant, IL-4, and IL-6 in their BAL and serum. Homogenates of one lung lobe from each animal were utilized to assess oxidative stress; a separate lobe underwent histologic examination to assess airway inflammatory status. The results suggest that asthmatic symptoms were found in TDI control rats only, while both MOEE- and DXM-treated rats did not manifest any airway abnormality. In MOEE- and DXM-treated rats, neutrophil and eosinophil levels in the blood were decreased significantly; levels of total cells and each different cell in their BAL fluid were markedly decreased as compared to those in TDI controls. TNF alpha, IL-4, and IL-6 were predominant in serum as well as in BAL fluids in TDI controls, but these levels were reduced significantly by MOEE treatment. The antioxidant activity in relation to antiinflammatory activity of the extract and histopathological observations also reflected a

  18. A study of thrombocytopenia in hospitalized vivax malaria patients

    Hassan Abu Zaid


    Full Text Available Objective: To assess the occurrence and severity of thrombocytopenia in hospitalized vivax malaria patients.Design and setting:Retrospective and descriptive hospital based case series from March 2005 to March 2007, conducted in the medical unit of Al Khor Hospital.Patients and methods: 78 patients with peripheral smear positive were enrolled in the study. Peripheral smear examination for malaria parasites was used as the method of choice for the diagnosis of malaria. Hematological parameters were determined by using an automated analyzer. Low platelet counts were re-evaluated by manual methods.Results:Study sample was 78 patients, of which 65 patients (83.3% were thrombocytopenic. Of these, 41 patients (52.6% had mild thrombocytopenia, 23 patients (29.5% had moderate thrombocytopenia and 1 patient (1.3% had severe thrombocytopenia. All patients (100% were male.Conclusion:High prevalence of thrombocytopenia was seen in vivax malaria patients, making it a common hematological feature in vivax malaria.

  19. Simultaneous occurrence of fetal and neonatal alloimmune thrombocytopenia and neonatal neutropenia due to maternal neutrophilic autoantibodies

    Taaning, Ellen; Jensen, Lise; Varming, Kim


    Foetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal neutropenia caused by maternal autoantibodies against neutrophils are rare disorders. We describe a newborn with severe thrombocytopenia and intracerebral bleeding caused by maternal anti-HPA-3a alloantibodies and mild neutropenia...

  20. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study

    Cheng, Gregory; Saleh, Mansoor N; Marcher, Claus


    Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia. We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period....

  1. Cerebrospinal fluid neopterin analysis in neuropediatric patients: establishment of a new cut off-value for the identification of inflammatory-immune mediated processes.

    Marta Molero-Luis

    Full Text Available OBJECTIVE: A high level of cerebrospinal fluid (CSF neopterin is a marker of central nervous system inflammatory-immune mediated processes. We aimed to assess data from 606 neuropediatric patients, describing the clinical and biochemical features of those neurological disorders presenting CSF neopterin values above a new cut-off value that was defined in our laboratory. METHODS: To establish the new CSF neopterin cut-off value, we studied two groups of patients: Group 1 comprised 68 patients with meningoencephalitis, and Group 2 comprised 52 children with a confirmed peripheral infection and no central nervous system involvement. We studied 606 CSF samples from neuropediatric patients who were classified into 3 groups: genetic diagnosis (A, acquired/unknown etiologic neurologic diseases (B and inflammatory-immune mediated processes (C. RESULTS: The CSF neopterin cut-off value was 61 nmol/L. Out of 606 cases, 56 presented a CSF neopterin level above this value. Group C had significantly higher CSF neopterin, protein and leukocyte values than the other groups. Sixteen of twenty-three patients in this group had a CSF neopterin level above the cut-off, whereas three and seven patients presented increased leukocyte and protein values, respectively. A significant association was found among CSF neopterin, proteins and leukocytes in the 606 patients. White matter disturbances were associated with high CSF neopterin concentrations. CONCLUSIONS: Although children with inflammatory-immune mediated processes presented higher CSF neopterin values, patients with other neurological disorders also showed increased CSF neopterin concentrations. These results stress the importance of CSF neopterin analysis for the identification of inflammatory-immune mediated processes.

  2. Altered distribution of regulatory lymphocytes by oral administration of soy-extracts exerts a hepatoprotective effect alleviating immune mediated liver injury, non-alcoholic steatohepatitis and insulin resistance

    Khoury, Tawfik; Ben Ya'acov, Ami; Shabat, Yehudit; Zolotarovya, Lidya; Snir, Ram; Ilan, Yaron


    AIM: To determine the immune-modulatory and the hepatoprotective effects of oral administration of two soy extracts in immune mediated liver injury and non-alcoholic steatohepatitis (NASH). METHODS: Two soy extracts, M1 and OS, were orally administered to mice with concanavalin A (ConA) immune-mediated hepatitis, to high-fat diet (HFD) mice and to methionine and choline reduced diet combined with HFD mice. Animals were followed for disease and immune biomarkers. RESULTS: Oral administration of OS and M1 had an additive effect in alleviating ConA hepatitis manifested by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels. Oral administration of the OS and M1 soy derived fractions, ameliorated liver injury in the high fat diet model of NASH, manifested by a decrease in hepatic triglyceride levels, improvement in liver histology, decreased serum cholesterol and triglycerides and improved insulin resistance. In the methionine and choline reduced diet combined with the high fat diet model, we noted a decrease in hepatic triglycerides and improvement in blood glucose levels and liver histology. The effects were associated with reduced serum tumor necrosis factor alpha and alteration of regulatory T cell distribution. CONCLUSION: Oral administration of the combination of OS and M1 soy derived extracts exerted an adjuvant effect in the gut-immune system, altering the distribution of regulatory T cells, and alleviating immune mediated liver injury, hyperlipidemia and insulin resistance. PMID:26139990

  3. Heparin-Induced Thrombocytopenia: A Comprehensive Clinical Review.

    Salter, Benjamin S; Weiner, Menachem M; Trinh, Muoi A; Heller, Joshua; Evans, Adam S; Adams, David H; Fischer, Gregory W


    Heparin-induced thrombocytopenia is a profoundly dangerous, potentially lethal, immunologically mediated adverse drug reaction to unfractionated heparin or, less commonly, to low-molecular weight heparin. In this comprehensive review, the authors highlight heparin-induced thrombocytopenia's risk factors, clinical presentation, pathophysiology, diagnostic principles, and treatment. The authors place special emphasis on the management of patients requiring procedures using cardiopulmonary bypass or interventions in the catheterization laboratory. Clinical vigilance of this disease process is important to ensure its recognition, diagnosis, and treatment. Misdiagnosis of the syndrome, as well as misunderstanding of the disease process, continues to contribute to its morbidity and mortality.

  4. Tuberculous splenic abscess in a neonate with thrombocytopenia

    Amodio, John; Biskup, Darius; Rivera, Rafael; Fefferman, Nancy [New York University Medical Center, Department of Radiology, NY (United States); Shah, Shetal [New York University Medical Center, Division of Neonatology, Department of Pediatrics, Avenue, NY (United States)


    We present a case of a premature neonate who presented with anemia and persistent thrombocytopenia. The patient was ultimately diagnosed with disseminated tuberculosis. Initial sonographic evaluation of the abdomen revealed a heterogeneous but predominately hypoechoic spleen; there was subsequent evolution of a splenic abscess. The patient was treated medically with anti-tubercular drugs. Follow-up post-treatment sonograms of the spleen showed diminution of the abscess and the evolution of multiple calcifications compatible with calcified granulomas. This case is an unusual presentation of tuberculosis in an infant with splenic abscess associated with thrombocytopenia and anemia. (orig.)

  5. Targeting B cells in immune-mediated inflammatory disease: a comprehensive review of mechanisms of action and identification of biomarkers.

    Dörner, Thomas; Kinnman, Nils; Tak, Paul P


    B cell-depletion therapy, particularly using anti-CD20 treatment, has provided proof of concept that targeting B cells and the humoral response may result in clinical improvements in immune-mediated inflammatory disease. In this review, the mechanisms of action of B cell-targeting drugs are investigated, and potential biomarkers associated with response to treatment in patients with autoimmune diseases are identified. Most available data relate to B cell depletion using anti-CD20 therapy (rituximab) in patients with rheumatoid arthritis (RA). Treatment leads to significant clinical benefit, but apparently fails to deplete long-lived plasma cells, and discontinuation is associated with relapse. Biomarkers commonly used in studies of B cell-targeted therapies include rheumatoid factor, anti-citrullinated peptide antibodies, and immunoglobulin (Ig) levels. More recently, there has been interest in markers such as B cell phenotype analysis, and B lymphocyte stimulator (BLyS)/a proliferation-inducing ligand (APRIL), the latter particularly in studies of the IgG Fc-transmembrane activator and CAML interactor (TACI) fusion protein (atacicept) and anti-BLyS therapy (belimumab). Data from clinical trials of B cell-depleting agents in RA suggest that specific autoantibodies, BLyS, APRIL, and circulating and synovial B lineage cell levels may have potential as biomarkers predictive of response to treatment. Further trials validating these markers against clinical outcomes in RA are required. In patients with systemic lupus erythematosus, Fc receptors and levels of circulating immune cells (including B cells and natural killer cells) may be relevant markers.

  6. IFN-γ-mediated hematopoietic cell destruction in murine models of immune-mediated bone marrow failure.

    Chen, Jichun; Feng, Xingmin; Desierto, Marie J; Keyvanfar, Keyvan; Young, Neal S


    Interferon gamma (IFN-γ) has been reported to have both negative and positive activity on hematopoietic cells, adding complexity to the interpretation of its pleiotropic functions. We examined the effects of IFN-γ on murine hematopoietic stem cells (HSCs) and progenitors in vitro and in vivo by using mouse models. IFN-γ treatment expanded bone marrow (BM) c-Kit(+)Sca1(+)Lin(-) (KSL) cell number but reduced BM KLCD150(+) and KLCD150(+)CD48(-) cells. IFN-γ-expanded KSL cells engrafted poorly when tested by competitive repopulation in vivo. KSL, KLCD150(+), and KLCD150(+)CD48(-) cells from IFN-γ-treated animals all showed significant upregulation in Fas expression. When cocultured with activated T cells in vitro, KSL and KLCD150(+) cells from IFN-γ-treated donors showed increased apoptosis relative to those from untreated animals, and infusion of activated CD8 T cells into IFN-γ-injected animals in vivo led to partial elimination of KSL cells. Exposure of BM cells or KSL cells to IFN-γ increased expression of Fas, caspases, and related proapoptotic genes and decreased expression of Ets-1 and other hematopoietic genes. In mouse models of BM failure, mice genetically deficient in IFN-γ receptor expression showed attenuation of immune-mediated marrow destruction, whereas effector lymphocytes from IFN-γ-deficient donors were much less potent in initiating BM damage. We conclude that the activity of IFN-γ on murine hematopoiesis is context dependent. IFN-γ-augmented apoptotic gene expression facilitates destruction of HSCs and progenitors in the presence of activated cytotoxic T cells, as occurs in human BM failure.

  7. Significant correlation between spleen volume and thrombocytopenia in liver transplant patients: a concept for predicting persistent thrombocytopenia.

    Ohira, Masahiro; Ishifuro, Minoru; Ide, Kentaro; Irei, Toshimitsu; Tashiro, Hirotaka; Itamoto, Toshiyuki; Ito, Katsuhide; Chayama, Kazuaki; Asahara, Toshimasa; Ohdan, Hideki


    Interferon (IFN) therapy with or without ribavirin treatment is well established as a standard antiviral treatment for hepatitis C virus (HCV)-infected patients. However, susceptibility to thrombocytopenia is a major obstacle for initiating or continuing this therapy, particularly in liver transplant (LTx) recipients with HCV. Studies have reported that splenectomy performed concurrently with LTx is a feasible strategy for conditioning patients for anti-HCV IFN therapy. However, the relationship between the severity of splenomegaly and alterations in the blood cytopenia in LTx recipients remains to be clarified. Here, we analyzed the relationship between spleen volume (SV) and thrombocytopenia in 45 patients who underwent LTx at Hiroshima University Hospital. The extent of pre-LTx splenomegaly [the SV to body surface area (BSA) ratio in an individual] was inversely correlated with both the post-LTx white blood cell count and platelet (PLT) count (P or= 400), persistent thrombocytopenia is predictable after LTx.

  8. Petechial Hemorrhage: A clinical diagnosis of neonatal Thrombocytopenia and sepsis

    Deepak Kumar sharma


    Full Text Available A preterm female baby with birth weight of 1.5kg was referred to our hospital on day 6 for difficulty in breathing. Baby was admitted at birth for respiratory distress and feed intolerance to other hospital and in view of clinical deterioration baby was referred. Baby had thrombocytopenia with platelets counts of 11000/ mm3 and high CRP titer. Baby had petechial haemorrhagic spots all over the body with hepatosplenomegaly and sclerema (figure 1,2,3. Baby further platelets counts were 3000, 43000, 67000 and then normal. Baby was managed with antibiotics and platelets transfusion. Gradually baby counts improved and petechial spots disappeared. Discussion Neonatal Sepsis is a common complication in the neonatal intensive care unit. It is most common in the smallest and most premature infants in whom the clinical presentation can be subtle and nonspecific. Thrombocytopenia is the common manifestation of neonatal sepsis in sick babies(1. The manifestation can be seen in newborn as petechial spots over the body with predominance over chest and abdomen(2.Thrombocytopenia is seen in 18% to 35% of NICU patients, and in 73% of extremely low birth weight (ELBW infants(3. Bacterial,fungal and viral infection causes thrombocytopenia. Infection causes damage to vascular endothelium which increases the destruction of platelets and there removal by reticuloendothelial system(4

  9. A study on association of thrombocytopenia with pregnancy induced hypertension

    Kasturi V. Donimath


    Conclusions: Thrombocytopenia is the most common complications of PIH and at times is life threatening. Therefore, platelet count can be used as an early, simple, and rapid test to assess the severity of pre eclampsia and prevent progression to HELLP syndrome and DIC. [Int J Reprod Contracept Obstet Gynecol 2016; 5(3.000: 808-812

  10. Petechial Hemorrhage: A clinical diagnosis of neonatal Thrombocytopenia and sepsis

    Deepak sharma


    Full Text Available A preterm female baby with birth weight of 1.5kg was referred to our hospital on day 6 for difficulty in breathing. Baby was admitted at birth for respiratory distress and feed intolerance to other hospital and in view of clinical deterioration baby was referred. Baby had thrombocytopenia with platelets counts of 11000/ mm3 and high CRP titer. Baby had petechial haemorrhagic spots all over the body with hepatosplenomegaly and sclerema (figure 1,2,3. Baby further platelets counts were 3000, 43000, 67000 and then normal. Baby was managed with antibiotics and platelets transfusion. Gradually baby counts improved and petechial spots disappeared. DiscussionNeonatal Sepsis is a common complication in the neonatal intensive care unit. It is most common in the smallest and most premature infants in whom the clinical presentation can be subtle and nonspecific. Thrombocytopenia is the common manifestation of neonatal sepsis in sick babies(1. The manifestation can be seen in newborn as petechial spots over the body with predominance over chest and abdomen(2.Thrombocytopenia is seen in 18% to 35% of NICU patients, and in 73% of extremely low birth weight (ELBW infants(3. Bacterial,fungal and viral infection causes thrombocytopenia. Infection causes damage to vascular endothelium which increases the destruction of platelets and there removal by reticuloendothelial system(4

  11. Intracerebral hemorrhage caused by varicella-induced thrombocytopenia.

    Lizarazo, Jairo; Castellanos, María Fernanda; Omaña, Claudia Rosa; Chaín, Miguel; Villamizar, Sergio


    We present the case of a previously healthy 44-years-old man with chickenpox, severe thrombocytopenia, mucosal hemorrhage, and intracerebral hemorrhage in the right hemisphere. The patient was treated with platelets and high doses of steroids. He recovered although with persistent left homonymous hemianopsia and epilepsy, which were controlled with medication.

  12. A patient with Graves' disease, thrombocytopenia and chronic hepatitis B.

    Szeto, C C; Chow, C C; Ko, G. T.; K. Y. LI; Yeung, V. T.; Cockram, C S


    A 22-year-old Chinese man, a HBsAg carrier, presented with relapse of thyrotoxic Graves' disease complicated by thrombocytopenia and hepatitis. Platelet count and liver enzymes gradually improved following successful treatment of the thyrotoxicosis with radioactive iodine. Possible pathogenetic links and therapeutic implications are discussed.

  13. Salmonella enteritidis from a case of fever with thrombocytopenia

    Shamma Arora; Naveen Gupta; Ashwani Kumar; IR Kaur


    Non typhoidalSalmonella species are thought to be potentially infectious to humans. We isolated Salmonella enteritidis from a 10-year-old boy with fever and thrombocytopenia. We reviewed the literature concerning infections caused bySalmonella but we could not find any such case report from India.

  14. Comprehensive analysis of inflammatory immune mediators of the intraocular fluid aspirated from the foldable capsular vitreous body filled-eyes.

    Peijuan Wang

    Full Text Available PURPOSE: To analyze the level of human inflammatory immune mediators in the intraocular fluid aspirated from foldable capsular vitreous body (FCVB filled-eyes during FCVB removal surgery, 3 months after implantation. METHODS: 8 samples of intra-FCVB fluids (n = 8 were collected from 8 FCVB filled patients in our previous FCVB exploratory clinical trial. The intra-FCVB fluids were aspirated from the FCVB filled-eyes during the FCVB removal surgeries at the third month. For the control groups, the vitreous fluids were collected from patients with idiopathic macular hole (n = 9 or rhegmatogenous retinal detachment (n = 6 during pars plana vitrectomy. A multiplex immunoassay was used to determine levels of 9 cytokines (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-17, TNF-α, IFN-γ and VEGF in these samples. The VEGF level of some intra-FCVB fluids (n = 6 were re-tested using enzyme-linked immunosorbent assay (ELISA. RESULTS: In the intra-FCVB fluids, 9 cytokines concentrations of most samples (n = 5 measured by Multiplex immunoassay showed low values, except for Patient 02, 06, and 09. The VEGF concentrations of some intra-FCVB fluids (n = 6 tested by ELISA were in accordance with Multiplex immunoassay results. For all eight patients (n = 8, the concentrations of IL-1β, IL-2, IL-6, TNF-α, IFN-γ and VEGF were slightly higher as compared to the idiopathic macular hole control group. While, the concentrations of IL-8, IL-10, and IL-17 were not statistically significant different compared with the idiopathic macular hole control samples. Most cytokines concentrations (IL-2, IL-6, IL-8, IL-10, IL-17, TNF-α, IFN-γ, VEGF were not statistically significant different compared to the rhegmatogenous retinal detachment control group except IL-1β. CONCLUSIONS: The FCVB had sufficient porosity to allow cytokines to pass through. This study first discovered that the FCVB possesses favorable permeability of proteins in the human eye.

  15. Building an immune-mediated coagulopathy consensus: early recognition and evaluation to enhance post-surgical patient safety

    Voils Stacy A


    Full Text Available Abstract Topical hemostats, fibrin sealants, and surgical adhesives are regularly used in a variety of surgical procedures involving multiple disciplines. Generally, these adjuncts to surgical hemostasis are valuable means for improving wound visualization, reducing blood loss or adding tissue adherence; however, some of these agents are responsible for under-recognized adverse reactions and outcomes. Bovine thrombin, for example, is a topical hemostat with a long history of clinical application that is widely used alone or in combination with other hemostatic agents. Hematologists and coagulation experts are aware that these agents can lead to development of an immune-mediated coagulopathy (IMC. A paucity of data on the incidence of IMC contributes to under-recognition and leaves many surgeons unaware that this clinical entity, originating from normal immune responses to foreign antigen exposure, requires enhanced post-operative vigilance and judicious clinical judgment to achieve best outcomes. Postoperative bleeding may result from issues such as loosened ties or clips or the occurrence of a coagulopathy due to hemodilution, vitamin K deficiency, disseminated intravascular coagulation (DIC or post-transfusion, post-shock coagulopathic states. Other causes, such as liver disease, may be ruled out by a careful patient history and common pre-operative liver function tests. Less common are coagulopathies secondary to pathologic immune responses. Such coagulopathies include those that may result from inherent patient problems such as patients with an immune dysfunction related to systemic lupus erythrematosus (SLE or lymphoma that can invoke antibodies against native coagulation factors. Medical interventions may also provoke antibody formation in the form of self-directed anti-coagulation factor antibodies, that result in problematic bleeding; it is these iatrogenic post-operative coagulopathies, including those associated with bovine thrombin

  16. High syndecan-1 levels in acute myeloid leukemia are associated with bleeding, thrombocytopathy, endothelial cell damage, and leukocytosis

    Larsen, Anne Mette Vestskov; Leinøe, Eva Birgitte; Johansson, Pär I;


    The risk of hemorrhage is influenced by multiple factors in acute myeloid leukemia (AML). We investigated whether hemorrhage in AML patients was associated with endothelial perturbation, potentially caused by thrombocytopenia, platelet dysfunction and leukocytosis. Biomarkers of endothelial...

  17. Tyrosine kinase inhibitors induced immune thrombocytopenia in chronic myeloid leukemia?

    Avital F. Barak


    Full Text Available The outcome and quality of life of chronic myeloid leukemia (CML patients has remarkably changed with the treatment of tyrosine kinase inhibitors (TKIs. Currently, hematopoietic stem cell transplantation (HSCT is considered mainly as a third line salvage therapy in cases of TKIs resistance or intolerance. Here we describe a patient with chronic phase CML who developed both resistance and late occurrence of s severe thrombocytopenia on first and second generation TKIs and eventually underwent HSCT. Although the mechanism of the myelosuppression is not fully understood, we showed for the first time the development of dose dependent platelet antibodies in the presence of TKIs, suggesting the possibility of TKIs induced thrombocytopenia. Our case emphasizes that late development of severe myelosuppression during imatinib treatment is probably an important indication for consideration of early HSCT.

  18. Immune Thrombocytopenia in a Child with T Cell Lymphoblastic Lymphoma

    Kayo Tokeji


    Full Text Available We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children. Diagnosis of ITP with lymphoma is challenging due to the many factors affecting platelet counts, and ITP often complicates the diagnosis or treatment course of lymphoma. The underlying mechanism of ITP with NHL is still unclear. Drug-induced immunomodulation with a reduction of regulatory T cells might have contributed to the development of ITP in our case.




    Full Text Available Anemia is a group of disorders characterized by decrease in number of circulating red blood cells, decrease in amount of hemoglobin in each cell or both. We report an interesting case of young female who presented to us with clinical presentation of anemic retinopathy with thrombocytopenia. History of bleeding gums with menorrhagia was present. She had short history of diminish vision in both eyes. Fundus changes were very typical of anemic retinopathy with presence of Roth spots as characteristic finding. Disc pallor and venous tortousity was also present in both eyes. Fundus picture showed marked improvement with blood transfusion. Our case confirms the association of anemic retinopathy in patients suffering with severe anemia with coexisting thrombocytopenia

  20. Acute Hepatitis Induced by Alpha-Interferon in a Patient with Chronic Hepatitis C

    Ivan Kraus; Dinko Vitezic


    Hepatic adverse effects occur very rarely with alpha-interferon therapy. A case of acute hepatitis induced by alpha-interferon in a 33-year-old man with chronic hepatitis C is described. The patient developed acute hepatitis with very high aminotransferase activity and jaundice. After discontinuing alpha-interferon therapy, hepatitis resolved rapidly. The immune-mediated mechanism is the most probable cause of this hepatitis.

  1. Hashimoto’s Encephalopathy Presenting with Acute Cognitive Dysfunction and Convulsion

    Kang, Woo-Hyuk; Na, Ju-Young; Kim, Meyung-Kug; Yoo, Bong-Goo


    Hashimoto’s encephalopathy is an immune-mediated disorder characterized by acute or subacute encephalopathy related to increased anti-thyroid antibodies. Clinical manifestations of Hashimoto’s encephalopathy may include stroke-like episodes, altered consciousness, psychosis, myoclonus, abnormal movements, seizures, and cognitive dysfunction. Acute cognitive dysfunction with convulsion as initial clinical manifestations of Hashimoto’s encephalopathy is very rare. We report a 65-year-old man wh...

  2. Acute Hepatitis Induced by Alpha-Interferon in a Patient with Chronic Hepatitis C

    Ivan Kraus


    Full Text Available Hepatic adverse effects occur very rarely with alpha-interferon therapy. A case of acute hepatitis induced by alpha-interferon in a 33-year-old man with chronic hepatitis C is described. The patient developed acute hepatitis with very high aminotransferase activity and jaundice. After discontinuing alpha-interferon therapy, hepatitis resolved rapidly. The immune-mediated mechanism is the most probable cause of this hepatitis.

  3. Sports Participation in Children and Adolescents with Immune Thrombocytopenia (ITP).

    Kumar, Manjusha; Lambert, Michele P; Breakey, Vicky; Buchanan, George R; Neier, Michelle; Neufeld, Ellis J; Kempert, Pamela; Neunert, Cindy E; Nottage, Kerri; Klaassen, Robert J


    We surveyed 278 pediatric hematologists/oncologists regarding how children with immune thrombocytopenia (ITP) are counseled for participation in sports. Results show substantial variation in physician perception of contact risk for different sports, and the advice offered about restriction of sport activities of affected children. Many physicians recommend restriction of sports when platelet counts are under 50 × 10(9) /L. Such restriction may affect the child's quality of life despite their having an overall benign disease.

  4. Acquired amegakaryocytic thrombocytopenia: Three case reports and a literature review

    Antonijević Nebojša


    Full Text Available Introduction Acquired amegakaryocytic thrombocytopenia (AAT is a rare disease characterized by thrombocytopenia due to selective reduction/absence of bone marrow (BM megakaryocytes. In the BM culture isolated reduction of colony-forming units-megakaryocyte (CFU-Mk may occur. Material and methods BM aspirates and trephine biopsies were obtained from all patients and processed by routine methods. In vitro BM culture and cytogenetic analysis was performed in one patient. Results This article presents three patients with manifested signs of hemorrhagic syndrome due to severe thrombocytopenia caused by an absence/significant reduction of BM megakaryocytes. Eexistence of systemic or any other disease was excluded in all patients. BM culture of the second patient showed reduction of all hematopoietic progenitors. In the subsequent course of the disease in this patient, signs of dysplastic erythrocytic series and megakaryocytes were also noted, although there were no positive proofs of evolution into myelodysplastic syndrome. Discussion AAT is a disease of hematopoietic stem cells manifesting in a certain period as amegakaryocytic thrombocytopenia which subsequently may progress into aplastic anemia or myelodysplastic syndrome. Patients were treated with corticosteroids, lithium carbonate, androgens, vincristine, immunoglobulins, folic acid, platelet and erythrocyte transfusions along with plasma substitution. The first patient reacted positively to the therapy. In two other patients a minimal, short-term therapeutic effect was achieved, followed by improvement of hemorrhagic syndrome and an insignificant increase in platelet count. In one patient the treatment was stopped after 4 months and the other died of bleeding after 4 months. Conclusion AAT is a rare disease with unpredictable course. This is a case report of three patients with AAT and different therapeutic effects.

  5. Trombocitopenia induzida por heparina Heparin-induced thrombocytopenia

    Fernanda Longhi


    Full Text Available O objetivo deste relato é fazer uma revisão a fim de obter informações atualizadas sobre trombocitopenia induzida por heparina, suas manifestações clínicas, seu diagnóstico e seu manejo terapêutico. Após, concluímos que a trombocitopenia induzida por heparina é uma complicação comum em pacientes submetidos a tratamento com heparina, indiferentemente da doença de base. Complicações trombóticas potencialmente fatais têm sido descritas. Por essa razão, se houver suspeita de trombocitopenia induzida por heparina, uma abordagem adequada incluindo suspensão precoce da heparina é mandatória. Produtos que substituem a heparina incluem hirudina e danaparóide sódico. Heparina de baixo peso molecular é contra-indicada.The aim of this paper is to review current information about the clinical manifestations, diagnosis and management of heparin-induced thrombocytopenia. This was achieved by a bibliographic review using Public Medline and consulting Hematology textbooks. From this study we concluded that heparin-induced thrombocytopenia is a common complication of patients exposed to heparin therapy regardless of underlying conditions. Potentially fatal thrombotic complications have been reported. Therefore, if heparin-induced thrombocytopenia is suspected, an adequate approach including early heparin discontinuation is mandatory. Alternative products for heparin include hirudin and danaparoid sodium. Low-molecular-weight heparin is contraindicated.

  6. Effect of recombinant human thrombopoietin on exsanguine thrombocytopenia mice


    AIM:To investigate effect of recombinant human thrombopoietin on exsanguine thrombocytopenia mice. METHODS:Normal peripheral platelet counts were performed on sample obtained from the tail vein of purebred Babl/c mice including experimental and control groups before experimentation. rhTPO was injected into the mice by intraperitoneal injection once a day for 7 days. On the seventh and the fourteenth day, the mice were phlebotomized from the supra-obitalis vein in order to make exsanguine thrombocytopenia animal model. At the same time, we observed the biological activity of recombinant human thrombopoietin in vivo and the mice's death rate. RESULTS: On the seventh day and the fourteenth day, platelet counts of mice treated by rhTPO were higher than those by PBS (P<0.05). Moreover the platelet counts of mice in experimental group of rhTPO showed increasing tendency following experimental days. In addition, death happened in two groups after those mice were phlebotomized from the supra-obitalis vein, but the death rate in negative control group was evidently higher than that in experimental group (P<0.05). CONCLUSION:rhTPO had obvious biological activity in increasing platelet production, which resulted in the drop in thrombocytopenia mice's death rate.

  7. Platelet activation determines the severity of thrombocytopenia in dengue infection

    Ojha, Amrita; Nandi, Dipika; Batra, Harish; Singhal, Rashi; Annarapu, Gowtham K.; Bhattacharyya, Sankar; Seth, Tulika; Dar, Lalit; Medigeshi, Guruprasad R.; Vrati, Sudhanshu; Vikram, Naval K.; Guchhait, Prasenjit


    Thrombocytopenia is common in patients with dengue virus (DENV) infections. With a focus on understanding the possible mechanism of thrombocytopenia in DENV infections we described a direct correlation between activation and depletion of platelets in patients. Our data showed a sharp decrease in platelet counts at day 4 of fever in patients. The high DENV genome copies in platelets correlated directly with the elevated platelet activation along with increased binding of complement factor C3 and IgG on their surface at day 4. Recovery in platelet count was observed on day 10 through day 6 and 8 with simultaneous decrease in platelet activation markers. Further, our in vitro data supported the above observations describing a concentration-dependent increase in platelet activation by DENV serotype-2. The high copy number of DENV2 genome in the platelet pellet correlated directly with platelet activation, microparticle generation and clot formation. Furthermore the DENV2-activated platelets were phagocytosed in large numbers by the monocytes. The DENV2-mediated lysis and clearance of platelets were abrogated in presence of platelet activation inhibitor, prostacyclin. These observations collectively suggest that platelet activation status is an important determinant of thrombocytopenia in dengue infections. A careful strategy of inactivation of platelets may rescue them from rapid destruction during DENV infections. PMID:28139770

  8. Discovery of Innovative Therapies for Rare Immune-Mediated Inflammatory Diseases via Off-Label Prescription of Biologics: The Case of IL-6 Receptor Blockade in Castleman's Disease.

    Musters, Anne; Assaf, Amira; Gerlag, Danielle M; Tak, Paul P; Tas, Sander W


    Biologics have revolutionized the field of clinical immunology and proven to be both effective and safe in common immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, inflammatory bowel diseases, and various hematological disorders. However, in patients with rare, severe IMIDs failing on standard therapies, it is virtually impossible to conduct randomized controlled trials. Therefore, biologics are usually prescribed off-label in these often severely ill patients. Unfortunately, off-label prescription is sometimes hampered in these diseases due to a lack of reimbursement that is often based on a presumed lack of evidence for effectiveness. In the present article, we will discuss that off-label prescription of biologics can be a good way to discover new treatments for rare diseases. This will be illustrated using a case of multicentric Castleman's disease, an immune-mediated lymphoproliferative disorder, in which off-label tocilizumab (humanized anti-IL-6 receptor blocking antibody) treatment resulted in remarkable clinical improvement. Furthermore, we will give recommendations for monitoring efficacy and safety of biologic treatment in rare IMIDs, including the use of registries. In conclusion, we put forward that innovative treatments for rare IMIDs can be discovered via off-label prescription of biologicals, provided that this is based on rational arguments including knowledge of the pathophysiology of the disease.

  9. Report: Heparin-induced thrombocytopenia associated with cardiopulmonary bypass: Preliminary attempt with recombinant human thrombopoietin therapy.

    Yuan, Shi-Min


    Recombinant human thrombopoietin (rhTPO) is popularly used for the treatment of chemotherapy-induced thrombocytopenia. However, rhTPO therapy for heparin-induced thrombocytopenia relating to cardiopulmonary bypass has not been previously described. A young patient developed heparin-induced thrombocytopenia during open-heart surgery. Postoperative rhTPO therapy (15000 units injection hypodermatica once daily for consecutive 3 days) made a quick platelet recovery without any side effects. Heparin-induced thrombocytopenia associated with cardiopulmonary bypass is more likely to be benign, and is curable to rhTPO therapy. The preliminary rhTPO administration of heparin-induced thrombocytopenia in association with cardiopulmonary bypass shows satisfactory pharmaceutical effects with lower dose, shorter duration treatment and shorter platelet increase time and recovery time in comparison with those for the treatment of chemotherapy-induced thrombocytopenia. rhTPO therapy does not produce any side effects and it could avoid or minimize necessary blood product infusions.

  10. Cutaneous angiosarcoma of the buttock complicated by severe thrombocytopenia: A case report

    Nagao, Kaoru; Suzuki, Kayo; Yasuda, Taketoshi; HORI, TAKESHI; HACHINODA, JUN; Kanamori, Masahiko; Kimura, Tomoatsu


    Angiosarcoma (AS) is an aggressive, malignant endothelial cell tumor of vascular or lymphatic origin, the presentation and clinical behavior of which may vary according to its location. This is the case report of a 56-year-old woman with cutaneous angiosarcoma (CAS) of the buttock complicated by severe thrombocytopenia. A review of the literature revealed that only nine cases of CAS with thrombocytopenia have been previously reported. The prognosis of CAS complicated by thrombocytopenia is po...

  11. Heparin-Induced Thrombocytopenia in a Patient with Essential Thrombocythemia: A Case Based Update

    Edva Noel


    Full Text Available Vascular thrombosis is a common clinical feature of both essential thrombocythemia (ET and heparin-induced thrombocytopenia (HIT. The development of HIT in a patient with ET is rare and underrecognized. We report the case of a 77-year-old woman with preexisting ET, who was admitted with acute coronary syndrome, and IV heparin was started. She was exposed to unfractionated heparin (UFH 5 days prior to this admission. Decrease in platelet count was noted, and HIT panel was sent. Heparin was discontinued. Patient developed atrial fibrillation, and Dabigatran was started. On day three, patient also developed multiple tiny cerebral infarctions and acute right popliteal DVT. On day ten of admission, HIT panel was positive, and Dabigatran was changed to Lepirudin. Two days later, Lepirudin was also discontinued because patient developed pseudoaneurysm on the right common femoral artery at the site of cardiac catheterization access. A progressive increase in the platelet count was noted after discontinuing heparin. Physicians should be aware of the coexistence of HIT and ET, accompanied challenges of the prompt diagnosis, and initiation of appropriate treatment.

  12. Lower segment cesarean section in a patient with severe thrombocytopenia and pregnancy induced hypertension

    Minal Harde


    Full Text Available Thrombocytopenia in pregnancy carries a major risk of feto-maternal morbidity and mortality. We present a case of hypocellular bone marrow with severe thrombocytopenia with pregnancy induced hypertension (PIH for emergency lower segment cesarean section (LSCS. This disease is characterized by pancytopenia and hypocellular bone marrow with impaired morphology and maturation. Causes of death due to this disease include hemorrhage and infection secondary to thrombocytopenia and neutropenia especially following surgery. We report successful management of emergency LSCS with severe thrombocytopenia with severe PIH.

  13. Cost-effectiveness of antenatal screening for neonatal alloimmune thrombocytopenia

    Killie, M K; Kjeldsen-Kragh, J; Husebekk, A


    OBJECTIVES: To estimate the costs and health consequences of three different screening strategies for neonatal alloimmune thrombocytopenia (NAIT). DESIGN: Cost-utility analysis on the basis of a decision tree that incorporates the relevant strategies and outcomes. SETTING: Three health regions...... in Norway encompassing a 2.78 million population. POPULATION: Pregnant women (n = 100,448) screened for human platelet antigen (HPA) 1a and anti-HPA 1a antibodies, and their babies. METHOD: Decision tree analysis. In three branches of the decision tree, pregnant women entered a programme while in one...

  14. Resolution of chronic severe refractory thrombocytopenia after treatment of hypothyroidism

    Bowles, K M; Turner, G E; Wimperis, J Z


    The case of a 52 year old woman with chronic severe refractory thrombocytopenia is presented. Over a three year period, her platelet count was persistently less than 20 × 109/litre (normal range, 150–400). She required repeated hospital admission for management of bleeding and received multiple blood transfusions. She was given repeated courses of steroids, immunosuppression, immunoglobulin, and splenectomy, without success, in an attempt to stop the chronic blood loss. Eventually, she was found to be profoundly hypothyroid. On correction of her thyroid deficiency the platelet count returned to the normal range and all bleeding stopped. The platelet count remains in the normal range three years later. PMID:15333667

  15. View Point on Severe Fever with Thrombocytopenia Syndrome


    Severe fever with thrombocytopenia syndrome (SFTS), a new disease of zoonotic natural foci has been increasing in recent years. In this review, the disease of human granulocytic anaplasmosis infection due to tick-borne and new Bunia virus infection, have similar clinical symptoms. Total of 11 articles were retrieved. The emergence, etiology, nomenclature and pathogenic mechanisms, clinical diagnosis and genotyping of SFTS were summarized, and the current situation of treatment was also evaluated. In conclusion, early detection, identiifcation and treatment are the key points to SFTS, but how to reduce the mortality of critically ill patients is still the focus in the future.

  16. Shared Genetic Basis for Type 1 Diabetes, Islet Autoantibodies, and Autoantibodies Associated With Other Immune-Mediated Diseases in Families With Type 1 Diabetes

    Brorsson, Caroline Anna; Pociot, Flemming


    Diabetes Genetics Consortium (T1DGC). These were tested for association with three islet autoantibodies—against autoantibodies to GAD (GADA), IA-2 (IA-2A), and zinc transporter 8 (ZnT8A)—and autoantibodies against thyroid peroxidase (TPOA) in autoimmune thyroid disease, gastric parietal cells (PCA......Type 1 diabetes (T1D) is a polygenic autoimmune disease that is often present with autoantibodies directed against pancreatic islet proteins. Many genetic susceptibility loci are shared with other autoimmune or immune-mediated diseases that also cosegregate in families with T1D. The aim...... of this study was to investigate whether susceptibility loci identified in genome-wide association studies (GWAS) of T1D were also associated with autoantibody positivity in individuals with diabetes. Fifty single nucleotide polymorphisms (SNPs) were genotyped in 6,556 multiethnic cases collected by the Type 1...

  17. The role of the Th1 transcription factor T-bet in a mouse model of immune-mediated bone-marrow failure.

    Tang, Yong; Desierto, Marie J; Chen, Jichun; Young, Neal S


    The transcription factor T-bet is a key regulator of type 1 immune responses. We examined the role of T-bet in an animal model of immune-mediated bone marrow (BM) failure using mice carrying a germline T-bet gene deletion (T-bet(-/-)). In comparison with normal C57BL6 (B6) control mice, T-bet(-/-) mice had normal cellular composition in lymphohematopoietic tissues, but T-bet(-/-) lymphocytes were functionally defective. Infusion of 5 x 10(6) T-bet(-/-) lymph node (LN) cells into sublethally irradiated, major histocompatibility complex-mismatched CByB6F1 (F1) recipients failed to induce the severe marrow hypoplasia and fatal pancytopenia that is produced by injection of similar numbers of B6 LN cells. Increasing T-bet(-/-) LN-cell dose to 10 to 23 x 10(6) per recipient led to only mild hematopoietic deficiency. Recipients of T-bet(-/-) LN cells had no expansion in T cells or interferon-gamma-producing T cells but showed a significant increase in Lin(-)Sca1(+)CD117(+)CD34(-) BM cells. Plasma transforming growth factor-beta and interleukin-17 concentrations were increased in T-bet(-/-) LN-cell recipients, possibly a compensatory up-regulation of the Th17 immune response. Continuous infusion of interferon-gamma resulted in hematopoietic suppression but did not cause T-bet(-/-) LN-cell expansion or BM destruction. Our data provided fresh evidence demonstrating a critical role of T-bet in immune-mediated BM failure.

  18. Bilateral lower extremity gangrene requiring amputation associated with heparin-induced thrombocytopenia: a case report.

    Dickinson, Brian P; Lawrence, Peter F


    Heparin is a common cause of thrombocytopenia in hospitalized patients. Between 10% and 15% of patients receiving therapeutic doses of heparin develop thrombocytopenia. Heparin-induced thrombocytopenia (HIT) can cause severe bleeding and thrombosis owing to intravascular platelet aggregation. HIT must be distinguished from other causes of thrombocytopenia. Importantly, heparin use is often associated with an early fall in the platelet count that usually occurs within the first 4 days of initiation and recovers without cessation of heparin treatment. This nonimmune heparin-associated thrombocytopenia has not been found to be associated with thrombosis and does not necessitate discontinuation of heparin. The authors present a case report of a 70-year-old man who received heparin therapy following aortic tissue valve replacement and aortic root repair with graft and developed bilateral lower extremity arterial clots 6 days postoperatively in the setting of positive heparin antibody titers. Ultimately the patient required bilateral above-knee amputations.

  19. Fatal thrombocytopenia: A rare case with possible explanation

    Barik, Ramachandra; Patnaik, A. N.; Gulati, A. S.


    A 22 year old male presented with breathlessness on exertion, ecchymosis, jaundice and features of worsening right heart failure for the last fifteen days. On physical examination, he had a mid diastolic murmur in the tricuspid area and an ejection systolic murmur in the pulmonary area. Bone marrow histopathology report showed an increased in megakaryocytes count. Routine investigations reports were normal. Echocardiography and computerized tomography (CT) revealed a single mobile large intra cardiac mass originating from the right atrium and causing dynamic obstruction of the right ventricular inflow and outflow tract. Associated fatal thrombocytopenia did not respond to intravenous steroids or platelet transfusion. Patient could not be operated because of very low platelet count, and died during hospital stay before excision biopsy could be done. Pathological autopsy was not done. This is a rare case, as the fatal thrombocytopenia observed here was the result of mechanical effects like frictional and shear force, which can be attributed to the physical presence of a large intra cardiac mass resulting in obstruction to flow. PMID:22629036

  20. Elevated Plasma P-Selectin Autoantibodies in Primary Sjögren Syndrome Patients with Thrombocytopenia.

    Hu, Ya-Hui; Zhou, Peng-Fei; Long, Guang-Feng; Tian, Xin; Guo, Yu-Fan; Pang, Ai-Ming; Di, Ran; Shen, Yan-Na; Liu, Yun-De; Cui, Yu-Jie


    BACKGROUND Primary Sjögren's syndrome (pSS) is one of the most common chronic systemic autoimmune diseases, and thrombocytopenia is one of the hematological manifestations of pSS. When platelet and endothelial cells are activated, P-selectin is expressed on the cell surface. This study aimed to investigate the role of P-selectin autoantibodies in the pathogenesis of thrombocytopenia in pSS. MATERIAL AND METHODS P-selectin autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA) in 38 pSS patients without thrombocytopenia and 32 pSS patients with thrombocytopenia, 32 idiopathic thrombocytopenic purpura (ITP) patients, and 35 healthy controls. RESULTS The plasma P-selectin autoantibodies (A490) in ITP patients and pSS patients with/without thrombocytopenia were significantly higher than those in healthy controls, but there were no significant differences between ITP patients and pSS patients with thrombocytopenia. The positive rate of P-selectin autoantibodies in pSS patients with thrombocytopenia was significantly higher than that in ITP patients. The platelet count was lower in P-selectin autoantibodies-positive patients, while among pSS patients with thrombocytopenia, the platelet count was lower in P-selectin autoantibodies-positive patients than in P-selectin autoantibodies-negative patients. In ITP patients and pSS patients with thrombocytopenia, the platelet count was lower in P-selectin autoantibodies-positive patients. CONCLUSIONS Elevated plasma P-selectin autoantibodies may play a role in the pathogenesis of thrombocytopenia in pSS patients.

  1. CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis.

    Patrick J Mott

    Full Text Available Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7, also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics.

  2. Emergence of infectious malignant thrombocytopenia in Japanese macaques (Macaca fuscata) by SRV-4 after transmission to a novel host

    Okamoto, Munehiro; Miyazawa, Takayuki; Morikawa, Shigeru; Ono, Fumiko; Nakamura, Shota; Sato, Eiji; Yoshida, Tomoyuki; Yoshikawa, Rokusuke; Sakai, Kouji; Mizutani, Tetsuya; Nagata, Noriyo; Takano, Jun-ichiro; Okabayashi, Sachi; Hamano, Masataka; Fujimoto, Koji; Nakaya, Takaaki; Iida, Tetsuya; Horii, Toshihiro; Miyabe-Nishiwaki, Takako; Watanabe, Akino; Kaneko, Akihisa; Saito, Akatsuki; Matsui, Atsushi; Hayakawa, Toshiyuki; Suzuki, Juri; Akari, Hirofumi; Matsuzawa, Tetsuro; Hirai, Hirohisa


    We discovered a lethal hemorrhagic syndrome arising from severe thrombocytopenia in Japanese macaques kept at the Primate Research Institute, Kyoto University. Extensive investigation identified that simian retrovirus type 4 (SRV-4) was the causative agent of the disease. SRV-4 had previously been isolated only from cynomolgus macaques in which it is usually asymptomatic. We consider that the SRV-4 crossed the so-called species barrier between cynomolgus and Japanese macaques, leading to extremely severe acute symptoms in the latter. Infectious agents that cross the species barrier occasionally amplify in virulence, which is not observed in the original hosts. In such cases, the new hosts are usually distantly related to the original hosts. However, Japanese macaques are closely related to cynomolgus macaques, and can even hybridize when given the opportunity. This lethal outbreak of a novel pathogen in Japanese macaques highlights the need to modify our expectations about virulence with regards crossing species barriers. PMID:25743183

  3. Consensus Paper-ICIS Expert Meeting Basel 2009 treatment milestones in immune thrombocytopenia.

    Tamary, Hannah; Roganovic, Jelena; Chitlur, Meera; Nugent, Diane J


    The rarity of severe complications of this disease in children makes randomized clinical trials in immune thrombocytopenia (ITP) unfeasible. Therefore, the current management recommendations for ITP are largely dependent on clinical expertise and observations. As part of its discussions during the Intercontinental Cooperative ITP Study Group Expert Meeting in Basel, the Management working group recommended that the decision to treat an ITP patient be individualized and based mainly on bleeding symptoms and not on the actual platelet count number and should be supported by bleeding scores using a validated assessment tool. The group stressed the need to develop a uniform validated bleeding score system and to explore new measures to evaluate bleeding risk in thrombocytopenic patients-the role of rituximab as a splenectomy-sparing agent in resistant disease was also discussed. Given the apparently high recurrence rate to rituximab therapy in children and the drug's possible toxicity, the group felt that until more data are available, a conservative approach may be considered, reserving rituximab for patients who failed splenectomy. More studies of the effectiveness and side effects of drugs to treat refractory patients, such as TPO mimetics, cyclosporine, mycophenolate mofetil, and cytotoxic agents are required, as are long-term data on post-splenectomy complications. In the patient with either acute or chronic ITP, using a more personalized approach to treatment based on bleeding symptoms rather than platelet count should result in less toxicity and empower both physicians and families to focus on quality-of-life.

  4. Cytokine and chemokine levels in patients with severe fever with thrombocytopenia syndrome virus.

    Baocheng Deng

    Full Text Available BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV, which can cause hemorrhagic fever-like illness, is a newly discovered bunyavirus in China. The pathogenesis of SFTSV infection is poorly understood. However, it has been suggested that immune mechanisms, including cytokines and chemokines, play an important role in disease pathogenesis. In the present study, we investigated host cytokine and chemokine profiles in serum samples of patients with SFTSV infection from Northeast China and explored a possible correlation between cytokine levels and disease severity. METHODS AND PRINCIPAL FINDINGS: Acute phase serum samples from 40 patients, diagnosed with SFTSV infection were included. Patients were divided into two groups--severe or non-severe--based on disease severity. Levels of tumor necrosis factor (TNF-α, transforming growth factor (TGF-β, interleukin-6, interferon (IFN-γ, IFN- γ-induced protein (IP-10 and RANTES were measured in the serum samples with commercial ELISAs. Statistical analysis showed that increases in TNF-α, IP-10 and IFN-γ were associated with disease severity. CONCLUSIONS: We suggest that a cytokine-mediated inflammatory response, characterized by cytokine and chemokine production imbalance, might be in part responsible for the disease progression of patients with SFTSV infection.

  5. RhIG for the treatment of immune thrombocytopenia: consensus and controversy (CME).

    Despotovic, Jenny M; Lambert, Michele P; Herman, Jay H; Gernsheimer, Terry B; McCrae, Keith R; Tarantino, Michael D; Bussel, James B


    Anti-D immune globulin (RhIG) is a front-line option in North America for the treatment of immune thrombocytopenia (ITP) in children and adults. Recently, addition of a Food and Drug Administration-mandated black box warning highlighted the risks of intravascular hemolysis, renal failure, and disseminated intravascular coagulation after anti-D infusion, prompting concern within the medical community regarding its use. A working group convened in response to this warning to prepare a consensus document regarding the safety of RhIG because there has been no increased incidence of adverse events since the initial discovery of these reactions many years ago. The efficacy of anti-D is well documented and only briefly reviewed. The estimated incidence and proposed mechanisms for the rare, major treatment-related complications are discussed, and signal detection data associated with heightened risk of acute hemolytic reactions are presented. The importance of considering host factors, given the rarity of severe reactions, is emphasized. Safety profiles of parallel treatment options are reviewed. The working group consensus is that RhIG has comparable safety and efficacy to other front-line agents for the treatment of children and adults with ITP. Safety may be further improved by careful patient selection.

  6. An inducible transgenic mouse model for immune mediated hepatitis showing clearance of antigen expressing hepatocytes by CD8+ T cells.

    Marcin Cebula

    Full Text Available The liver has the ability to prime immune responses against neo antigens provided upon infections. However, T cell immunity in liver is uniquely modulated by the complex tolerogenic property of this organ that has to also cope with foreign agents such as endotoxins or food antigens. In this respect, the nature of intrahepatic T cell responses remains to be fully characterized. To gain deeper insight into the mechanisms that regulate the CD8+ T cell responses in the liver, we established a novel OVA_X_CreER(T2 mouse model. Upon tamoxifen administration OVA antigen expression is observed in a fraction of hepatocytes, resulting in a mosaic expression pattern. To elucidate the cross-talk of CD8+ T cells with antigen-expressing hepatocytes, we adoptively transferred K(b/OVA257-264-specific OT-I T cells to OVA_X_CreER(T2 mice or generated triple transgenic OVA_X CreER(T2_X_OT-I mice. OT-I T cells become activated in OVA_X_CreER(T2 mice and induce an acute and transient hepatitis accompanied by liver damage. In OVA_X_CreER(T2_X_OT-I mice, OVA induction triggers an OT-I T cell mediated, fulminant hepatitis resulting in 50% mortality. Surviving mice manifest a long lasting hepatitis, and recover after 9 weeks. In these experimental settings, recovery from hepatitis correlates with a complete loss of OVA expression indicating efficient clearance of the antigen-expressing hepatocytes. Moreover, a relapse of hepatitis can be induced upon re-induction of cured OVA_X_CreER(T2_X_OT-I mice indicating absence of tolerogenic mechanisms. This pathogen-free, conditional mouse model has the advantage of tamoxifen inducible tissue specific antigen expression that reflects the heterogeneity of viral antigen expression and enables the study of intrahepatic immune responses to both de novo and persistent antigen. It allows following the course of intrahepatic immune responses: initiation, the acute phase and antigen clearance.

  7. Thrombocytopenia in Plasmodium vivax malaria is related to platelets phagocytosis.

    Helena Cristina C Coelho

    Full Text Available BACKGROUND: Although thrombocytopenia is a hematological disorder commonly reported in malarial patients, its mechanisms are still poorly understood, with only a few studies focusing on the role of platelets phagocytosis. METHODS AND FINDINGS: Thirty-five malaria vivax patients and eight healthy volunteers (HV were enrolled in the study. Among vivax malaria patients, thrombocytopenia (<150,000 platelets/µL was found in 62.9% (22/35. Mean platelet volume (MPV was higher in thrombocytopenic patients as compared to non-thrombocytopenic patients (p = 0.017 and a negative correlation was found between platelet count and MPV (r = -0.483; p = 0.003. Platelets from HV or patients were labeled with 5-chloromethyl fluorescein diacetate (CMFDA, incubated with human monocytic cell line (THP-1 and platelet phagocytosis index was analyzed by flow cytometry. The phagocytosis index was higher in thrombocytopenic patients compared to non-thrombocytopenic patients (p = 0.042 and HV (p = 0.048. A negative correlation was observed between platelet count and phagocytosis index (r = -0.402; p = 0.016. Platelet activation was assessed measuring the expression of P-selectin (CD62-P in platelets' surface by flow cytometry. No significant difference was found in the expression of P-selectin between thrombocytopenic patients and HV (p = 0.092. After evaluating the cytokine profile (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17 in the patients' sera, levels of IL-6, IL-10 and IFN-γ were elevated in malaria patients compared to HV. Moreover, IL-6 and IL-10 values were higher in thrombocytopenic patients than non-thrombocytopenic ones (p = 0.044 and p = 0.017, respectively. In contrast, TNF-α levels were not different between the three groups, but a positive correlation was found between TNF-α and phagocytosis index (r = -0.305; p = 0.037. CONCLUSION/SIGNIFICANCE: Collectively, our findings indicate that platelet

  8. The Incidence, Clinical Outcomes, and Risk Factors of Thrombocytopenia in Intra-Abdominal Infection Patients: A Retrospective Cohort Study.

    Qin Wu

    Full Text Available Studies on the incidence and risk factors of thrombocytopenia among intra-abdominal infection patients remain absent, hindering efficacy assessments regarding thrombocytopenia prevention strategies.We retrospectively studied 267 consecutively enrolled patients with intra-abdominal infections. Occurrence of thrombocytopenia was scanned for all patients. All-cause 28-day mortality was recorded. Variables from univariate analyses that were associated with occurrence of hospital-acquired thrombocytopenia were included in a multivariable logistic regression analysis to determine thrombocytopenia predictors.Median APACHE II score and SOFA score of the whole cohort was 12 and 3 respectively. The overall ICU mortality was 7.87% and the 28-day mortality was 8.98%. The incidence of thrombocytopenia among intra-abdominal infection patients was 21.73%. Regardless of preexisting or hospital-acquired one, thrombocytopenia is associated with an increased ICU mortality and 28-day mortality as well as length of ICU or hospital stay. A higher SOFA and ISTH score at admission were significant hospital-acquired thrombocytopenia risk factors.This is the first study to identify a high incidence of thrombocytopenia in patients with intra-abdominal infections. Our findings suggest that the inflammatory milieu of intra-abdominal infections may uniquely predispose those patients to thrombocytopenia. More effective thrombocytopenia prevention strategies are necessary in intra-abdominal infection patients.

  9. Sex bias in experimental immune-mediated, drug-induced liver injury in BALB/c mice: suggested roles for Tregs, estrogen, and IL-6.

    Joonhee Cho

    Full Text Available BACKGROUND AND AIMS: Immune-mediated, drug-induced liver injury (DILI triggered by drug haptens is more prevalent in women than in men. However, mechanisms responsible for this sex bias are not clear. Immune regulation by CD4+CD25+FoxP3+ regulatory T-cells (Tregs and 17β-estradiol is crucial in the pathogenesis of sex bias in cancer and autoimmunity. Therefore, we investigated their role in a mouse model of immune-mediated DILI. METHODS: To model DILI, we immunized BALB/c, BALB/cBy, IL-6-deficient, and castrated BALB/c mice with trifluoroacetyl chloride-haptenated liver proteins. We then measured degree of hepatitis, cytokines, antibodies, and Treg and splenocyte function. RESULTS: BALB/c females developed more severe hepatitis (p<0.01 and produced more pro-inflammatory hepatic cytokines and antibodies (p<0.05 than did males. Castrated males developed more severe hepatitis than did intact males (p<0.001 and females (p<0.05. Splenocytes cultured from female mice exhibited fewer Tregs (p<0.01 and higher IL-1β (p<0.01 and IL-6 (p<0.05 than did those from males. However, Treg function did not differ by sex, as evidenced by absence of sex bias in programmed death receptor-1 and responses to IL-6, anti-IL-10, anti-CD3, and anti-CD28. Diminished hepatitis in IL-6-deficient, anti-IL-6 receptor α-treated, ovariectomized, or male mice; undetectable IL-6 levels in splenocyte supernatants from ovariectomized and male mice; elevated splenic IL-6 and serum estrogen levels in castrated male mice, and IL-6 induction by 17β-estradiol in splenocytes from naïve female mice (p<0.05 suggested that 17β-estradiol may enhance sex bias through IL-6 induction, which subsequently discourages Treg survival. Treg transfer from naïve female mice to those with DILI reduced hepatitis severity and hepatic IL-6. CONCLUSIONS: 17β-estradiol and IL-6 may act synergistically to promote sex bias in experimental DILI by reducing Tregs. Modulating Treg numbers may provide a

  10. Recurrent febrile neutropenia and thrombocytopenia in a chronic cocaine user: a case of levamisole induced complications.

    Martinez, Eduardo; Alvi, Raza; Venkatram, Sindhaghatta; Diaz-Fuentes, Gilda


    Cocaine is used by approximately 1.5 million Americans each month and up to 69% of the cocaine seized contains levamisole. The real incidence of cocaine-levamisole induced neutropenia is unclear but probably underestimated. Associated complications include fever, thrombocytopenia, skin-vasculitis disorders, and rarely kidney injury. We present a young male, with chronic active cocaine use presenting with recurrent episodes of febrile neutropenia and thrombocytopenia. He underwent extensive work-up and was treated with many antibiotics and we suspect that his neutropenia and thrombocytopenia were caused by recurrent cocaine-levamisole use.

  11. Recurrent Febrile Neutropenia and Thrombocytopenia in a Chronic Cocaine User: A Case of Levamisole Induced Complications

    Eduardo Martinez


    Full Text Available Cocaine is used by approximately 1.5 million Americans each month and up to 69% of the cocaine seized contains levamisole. The real incidence of cocaine-levamisole induced neutropenia is unclear but probably underestimated. Associated complications include fever, thrombocytopenia, skin-vasculitis disorders, and rarely kidney injury. We present a young male, with chronic active cocaine use presenting with recurrent episodes of febrile neutropenia and thrombocytopenia. He underwent extensive work-up and was treated with many antibiotics and we suspect that his neutropenia and thrombocytopenia were caused by recurrent cocaine-levamisole use.

  12. Acute pancreatitis : a newly recognised potential complication of canine babesiosis

    A.J. Möhr


    Full Text Available This retrospective study describes 4 cases of canine babesiosis with histologically confirmed acute pancreatitis. In addition, 16 dogs with babesiosis are reported with serum amylase (>3500 U/l and/or lipase (>650 U/l activity elevations of a magnitude that would support a diagnosis of probable acute pancreatitis, although extra-pancreatic sources of the enzymes could not be excluded in these cases. Median time of pancreatitis diagnosis was 2.5 days post-admission, with primarily young (median age 3 years, sexually intact dogs affected. The development of pancreatitis was unrelated to the degree of anaemia at time of admission. In addition to pancreatitis, 80 % of cases suffered from other babesial complications, namely icterus (13, acute respiratory distress syndrome (6, immune-mediated haemolytic anaemia (6, renal failure (3, haemoconcentration (2 and cerebral syndrome (2. Acute respiratory distress syndrome, renal failure and cerebral syndrome were associated with a poor prognosis, with 4 of the 5 dogs included in the overall 26 % mortality rate having at least 1 of these complications. Haemolytic anaemia with ischaemia-reperfusion injury to the pancreas is proposed as a possible primary pathophysiological mechanism in babesial pancreatitis. Hypotensive shock, immune-mediated haemolytic anaemia, haemoconcentration and possibly altered lipid metabolism in babesiosis may also be involved. The previously postulated pro-inflammatory cytokine milieu of complicated babesiosis may underlie the progression, if not the primary initiation, of pancreatic pathology. Acute pancreatitis may represent the previously reported 'gut' form of babesiosis.

  13. Spontaneous acute subdural hematoma in a patient with multiple myeloma

    Abrar Ahad Wani


    Full Text Available Acute spontaneous subdural hematoma in a patient of multiple myeloma receiving chemotherapy is an unknown event, needing an urgent neurosurgical management. We report this patient who presented with progressive neurological deterioration and a low platelet count. She was successfully managed by craniotomy and evacuation of subdural hematoma with intraoperative transfusion of platelets. The acute spontaneous subdural hematoma in her was probably related to the bleeding diathesis due to thrombocytopenia associated with chemotherapy.

  14. Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease.

    James E Peters


    Full Text Available Genome-wide association studies (GWAS have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91, anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46 and healthy controls (n = 43, revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases.

  15. Lack of evidence of a beneficial effect of azathioprine in dogs treated with prednisolone for idiopathic immune-mediated hemolytic anemia: a retrospective cohort study

    Junius Greet


    Full Text Available Abstract Background Azathioprine is used as an immunosuppressant in canine immune-mediated hemolytic anemia (IMHA, but this potentially toxic and carcinogenic drug has not been proven to be beneficial. The aim of this study was to determine the difference in outcome and survival of dogs with idiopathic IMHA treated with a protocol that included azathioprine and prednisolone versus a protocol that included prednisolone alone. Results The study included 222 dogs with a hematocrit lower than 0.30 L/L and either a positive Coombs' test or spherocytosis and no evidence of diseases that could trigger IMHA. The clinical and laboratory data at the time of diagnosis and the response to therapy and survival were compared in dogs treated according to the prednisolone and azathioprine protocol (AP protocol; n = 149 and dogs treated according to the prednisolone protocol (P protocol; n = 73. At study entry, the two groups were comparable, except that thrombocyte counts were significantly lower and clinical signs had been present significantly longer in the AP protocol group. No significant difference in survival was found between the two groups: the 1-year survival was 64% (95% CI 54 - 77% in the P protocol group and 69% (95% CI 59-80% in the AP protocol group, respectively. Conclusions Azathioprine would appear not to be beneficial as standard treatment for all cases of IMHA; however, a blinded, randomized clinical trial is needed to establish whether outcome is different with the two treatment protocols.

  16. Women's health and fertility, family planning and pregnancy in immune-mediated rheumatic diseases: a report from a south-eastern European Expert Meeting.

    Ntali, Stella; Damjanov, Nemanja; Drakakis, Peter; Ionescu, Ruxandra; Kalinova, Desislava; Rashkov, Rasho; Malamitsi-Puchner, Ariadne; Mantzaris, Gerassimos; Michala, Lina; Pamfil, Cristina; Rednic, Simona; Tektonidou, Maria G; Tsiodras, Sotirios; Vassilopoulos, Dimitrios; Vojinovic, Jelena; Bertsias, George K; Boumpas, Dimitrios T


    With current advances in medical treatment, reproductive issues have become more important for women with chronic immune-mediated diseases. Most, if not all, patients report that their disease affects their personal relationships, their decision to have children, and the size of their family. These decisions are multi-factorial, influenced mainly by concerns over the effect of pregnancy on the rheumatic disease, the impact of disease activity during pregnancy on foetal health, the patient's ability to care for the child, and the possible harmful effects medication could have on the child, both pre- and post-natally during breastfeeding. Apart from that, women's health issues tend to be overlooked in favour of the management of the underlying rheumatic disease. To this end, we convened an expert panel to review the published literature on women's health and reproductive issues and provide evidence- and eminence-based points to consider for the treating physicians. We conclude that there is a need for a change in mind-set from one which 'cautions against pregnancy' to one which 'embraces pregnancy' through the practice of individualised, pre- and post-conceptual, multi-disciplinary care.

  17. The IL23R R381Q gene variant protects against immune-mediated diseases by impairing IL-23-induced Th17 effector response in humans.

    Paola Di Meglio

    Full Text Available IL-23 and Th17 cells are key players in tissue immunosurveillance and are implicated in human immune-mediated diseases. Genome-wide association studies have shown that the IL23R R381Q gene variant protects against psoriasis, Crohn's disease and ankylosing spondylitis. We investigated the immunological consequences of the protective IL23R R381Q gene variant in healthy donors. The IL23R R381Q gene variant had no major effect on Th17 cell differentiation as the frequency of circulating Th17 cells was similar in carriers of the IL23R protective (A and common (G allele. Accordingly, Th17 cells generated from A and G donors produced similar amounts of Th17 cytokines. However, IL-23-mediated Th17 cell effector function was impaired, as Th17 cells from A allele carriers had significantly reduced IL-23-induced IL-17A production and STAT3 phosphorylation compared to G allele carriers. Our functional analysis of a human disease-associated gene variant demonstrates that IL23R R381Q exerts its protective effects through selective attenuation of IL-23-induced Th17 cell effector function without interfering with Th17 differentiation, and highlights its importance in the protection against IL-23-induced tissue pathologies.

  18. Wiskott-Aldrich syndrome mutation in two Turkish siblings with X-linked thrombocytopenia

    Göksel Leblebisatan


    Full Text Available Wiskott-Aldrich syndrome (WAS is a clinical condition characterized by thrombocytopenia, eczema, and life-threatening infections. In some cases autoimmunity-related problems and even malignancy might be seen; however, some patients have milder clinical manifestations due to mutations in the same gene family, such as in X-linked thrombocytopenia (XLT, which is generally not associated with serious symptoms of disease, except for thrombocytopenia. Herein we report 2 siblings with chronic thrombocytopenia that were diagnosed with XLT based on a missense mutation in the WASP gene (223G>A, Val75Met. To the best of our knowledge this mutation has not been previously reported in a Turkish patient with XLT.

  19. Fetal/neonatal allo-immune thrombocytopenia (FNAIT): past, present, and future.

    Serrarens-Janssen, V.M.; Semmekrot, B.A.; Novotny, V.M.J.; Porcelijn, L.; Lotgering, F.K.; Delemarre, F.M.C.; Steegers, E.A.P.


    We reviewed the English, American, and German literature for articles describing the prevalence, clinical presentation, outcome, therapeutic options, and screening possibilities for fetal/neonatal allo-immune thrombocytopenia (FNAIT), published between January 1950 and March 2007. The reported preva

  20. Bilateral lower extremity gangrene requiring amputation associated with heparin-induced thrombocytopenia--a case report.

    Dickinson, Brian P; De Ugarte, Daniel A; Reil, Todd D; Beseth, Bryce D; Lawrence, Peter F


    Heparin use, both prophylactically and therapeutically, is prevalent among hospitalized patients. Patients on heparin may develop a thrombocytopenia that is self-limited. Fewer patients develop a heparin-induced thrombocytopenia that can cause severe bleeding and thrombosis owing to intravascular platelet aggregation. The authors present a case report of heparin-induced thrombocytopenia in a patient who underwent aortic arch and aortic valve replacement that resulted in bilateral above-knee amputations. The patient developed limb ischemia related to heparin-associated thrombosis, but had a delay in antibody seroconversion. Early and accurate diagnosis of heparin-induced thrombocytopenia requires a high clinical suspicion and may be present despite the absence of serum antibodies.

  1. The clinical characteristics of 169 cases of severe fever with thrombocytopenia syndrome



    Objective To analyze the clinical characteristics of severe fever with thrombocytopenia syndrome(SFTS) so as to improve the recognition of the emerging infectious disease. Methods A retrospective analysis was performed upon clinical manifestations,laboratory test results and

  2. Prevalence of Thrombocytopenia among Chinese Adult Antiretroviral-naïve HIV-positive Patients

    Hong-Wei Fan


    Full Text Available Background: The prevalence of thrombocytopenia among Chinese antiretroviral therapy (ART-naïve HIV-infected adults has not been well-described. The aim of this study was to investigate the prevalence and associated risk factors of thrombocytopenia among Chinese ART-naïve HIV-infected adults. Methods: We performed a cross-sectional study of Chinese adult ART-naïve HIV-infected patients from September 2005 through August 2014. Socio-demographic variables and laboratory results including platelets, CD4+ cell count, and viral load were obtained from medical records. Factors and outcomes associated with thrombocytopenia were assessed using logistic regression. Results: A total of 1730 adult ART-naïve HIV-infected patients was included. The mean age was 38 years. The prevalence of thrombocytopenia was 4.5%. There were significant differences in the prevalence of thrombocytopenia between patients 350 cells/mm 3 (2.8% compared with patients with CD4+ counts of 50-199 cells/mm 3 (7.1% (P = 0.002 and P = 0.005, respectively. The prevalence of thrombocytopenia was significantly different by hepatitis C virus antibody (HCV-Ab seropositivity (10.2% for HCV-Ab positive vs. 3.9% for HCV-Ab negative, P = 0.001. We observed differences in prevalence of thrombocytopenia by mode of transmission of HIV infection: Blood transmission (10.7% versus men who have sex with men (3.9% (P = 0.002 and versus heterosexual transmission (3.9% (P = 0.001. In binary logistic regression analyses, age ≥50 years, HCV-Ab positivity and having a CD4+ cell count of 50-199 cells/mm 3 were significantly associated with thrombocytopenia with adjusted odds ratio of 2.482 (95% confidence interval [CI]: 1.167, 5.281, P = 0.018, 2.091 (95% CI: 1.078, 4.055, P = 0.029 and 2.259 (95% CI: 1.028, 4.962, P = 0.042, respectively. Conclusions: Thrombocytopenia is not common among adult ART-naïve HIV-infected patients in China. Older age (age over 50 years, HCV-Ab positivity and lower CD4

  3. Prevalence of cirrhosis in patients with thrombocytopenia who receive bone marrow biopsy

    Muhammad Y Sheikh


    Full Text Available Background/Aim: Thrombocytopenia is a common finding in patients with cirrhosis and may lead to unnecessary referral for bone marrow (BM biopsy. To date, the prevalence of cirrhosis in patients with thrombocytopenia who receive BM biopsy is largely unknown. Materials and Methods: Between fiscal years 2006-2010, 744 patients (≥18 years who underwent BM biopsies for thrombocytopenia at our hospital were identified retrospectively. 541 patients were excluded who had hematologic malignancies and received chemotherapy. Remaining 203 patients with predominant isolated thrombocytopenia were included in the study. Results: Of 203 patients, 136 (67% had a normal and 67 (33% had an abnormal BM examination. Prevalence of cirrhosis in the study population was 35% (95% CI: 28.4-41.9. 51% patients with normal BM were found to have cirrhosis compared to 3% of patients with abnormal BM exam (P < 0.0001. Common causes of cirrhosis were nonalcoholic steatohepatitis (NASH (47%, followed by alcohol and Hepatitis C virus infection. Idiopathic thrombocytopenia and myelodysplastic syndrome were most frequent causes of thrombocytopenia in patients without cirrhosis. Patients with NASH had higher body mass index (BMI (33.4 vs. 25.8, P < 0.001 and lower MELD scores (11.1 vs. 16, P = 0.028 when compared to non-NASH patients with cirrhosis. Conclusion: Approximately, one third (35% of patients with cirrhosis induced thrombocytopenia may undergo unwarranted BM biopsies. Clinical diagnosis of cirrhosis is still a challenge for many physicians, particularly with underlying NASH. We propose cirrhosis to be the prime cause of isolated thrombocytopenia.

  4. Thrombocytopenia in Paediatric ICU: Incidence, Transfusion Requirement and Role as Prognostic Indicator

    Sethi, Gurmeet Kaur; Goyal, Ram Kumar; Kaur, Avneet; Kaur, Rupinderjeet; Dhir, Shashi Kant; Gupta, Harshvardhan


    Introduction Thrombocytopenia is defined as platelet count less than 150×109/L, it has a greater incidence in Intensive Care Units (ICUs) compared to wards and its most common cause is increased platelet consumption. Aims To investigate incidence of thrombocytopenia, platelet transfusions requirement, associated diseases and relationship between thrombocytopenia and mortality. Materials and Methods Eleven months hospital records between October 2013 and August 2014 of the PICU in a tertiary care teaching hospital was investigated retrospectively and 275 critically ill children formed the sample. Statistical analysis Odds ratio with 95% confidence interval was used. Probability value (p-value) of less than 0.05 was considered statistically significant. Results were confirmed using χ2 test. Results Out of 275 patients {168 males (61.09%) and 107 females (38.91%)}, 89 patients had thrombocytopenia. Out of these 89 patients, 43 patients (48.31%) had severe, 24 patients (27.91%) had moderate and 22 patients (24.72%) had mild thrombocytopenia. The 43 patients having severe thrombocytopenia received platelet transfusion and out of these 43 patients 24 (55.81%) received more than one transfusion and 18 (41.86%) of the transfused patients expired. Among thrombocytopaenic patients, Sepsis (25.84%) was the most common diagnosis followed by Pneumonia (19.10%), Meningitis (13.48%), Diabetic Ketoacidosis (5.62%), Enteric fever (7.86%), Tubercular Meningitis (3.37%), Infantile Tremor Syndrome (2.25%), Congenital heart disease (5.62%), Burns(3.37%), Brain Haemorrhage (2.25%%), Hepatic abscess (1.12%), Chronic Renal Failure (3.37%), Malaria (2.25%) and Hepatitis (4.49%). There is a statistically significant association between thrombocytopenia and mortality. A significant association was established between mortality in thrombocytopenic patients of sepsis. Conclusion Thrombocytopenia is commonly associated with sepsis. Mortality rate is higher in thrombocytopenic patients. PMID

  5. Thrombocytopenia absent radius syndrome with Tetralogy of Fallot: a rare association

    Kumar C


    Full Text Available Chetan Kumar,1 Deepak Sharma,2 Aakash Pandita,2 Sanjay Bhalerao1 1Department of Pediatrics, Madras Institute of Orthopedic and Trauma, Manapakkam, Chennai, India; 2Department of Neonatology, Fernandez Hospital, Hyderabad, India Abstract: Thrombocytopenia absent radius (TAR syndrome is a very rare and infrequently seen congenital disorder with an approximate frequency of 0.42/100,000 live births. It is associated with bilateral absence of radii, hypo-megakaryocytic thrombocytopenia, and presence of both thumbs. The other systems which are affected by TAR syndrome include skeletal, hematologic, and cardiac systems. Intracranial hemorrhages due to thrombocytopenia and cardiac disorders are a common association usually seen with this syndrome and are usual cause of death. We describe a 3-month-old infant who was diagnosed with TAR syndrome on the basis of clinical features (thrombocytopenia and bilateral absent radius bone and confirmed by genetic analysis. The patient was diagnosed to have Tetralogy of Fallot, for which the infant was managed with definitive repair and thrombocytopenia was managed with platelet transfusion. Infants with TAR syndrome should be assessed for other associated malformations of various systems and followed up regularly and parents should be counseled for associated expected complications in these patients. We report an infant with TAR syndrome with Tetralogy of Fallot, which has not been reported in medical literature until now and this is the first case of its type. Keywords: thrombocytopenia absent radius syndrome, Tetralogy of Fallot, microdeletion 1q21.1, RBM8A

  6. ST-Elevation Myocardial Infarction and Myelodysplastic Syndrome with Acute Myeloid Leukemia Transformation


    Acute myocardial infarction and acute myeloid leukemia are rarely reported as concomitant conditions. The management of ST-elevation myocardial infarction (STEMI) in patients who have acute myeloid leukemia is challenging: the leukemia-related thrombocytopenia, platelet dysfunction, and systemic coagulopathy increase the risk of bleeding, and the administration of thrombolytic agents can be fatal. We report the case of a 76-year-old man who presented emergently with STEMI, myelodysplastic syn...


    Usha Suresh


    Full Text Available BACKGROUND Thrombocytopenia is the second most common haematological finding in pregnancy after anaemia. The aim of the study is to study the various aetiological factors associated with thrombocytopenia and its management in pregnancy. MATERIALS AND METHODS It is a prospective study carried out in 160 cases, which were identified to have moderate-to-severe thrombocytopenia during over a period of 2 years. History taken regarding preeclampsia, ITP, drug usage, viral infection, thrombocytopenia in previous pregnancy. General, systemic and obstetric examination were done. RESULTS The highest incidence of thrombocytopenia was found in the age group of 21-25 years, i.e. 83 cases (51.8%. Out of total 160 cases, 90 (56.25% cases are multigravida while 61 (38.1% are primigravida. Out of total 160 cases, 128 i.e. 80% are unbooked while 32 i.e. 20% are booked. Of 68 cases delivered by LSCS, spinal anaesthesia was given in 45 cases, i.e. 66.1% general anaesthesia in 22 cases (32.3%, epidural was given in 1 case (1.47%. Gestational thrombocytopenia has highest aetiology of 21.25%, i.e. 34 cases. Severe preeclampsia were 30 cases (18.75%. Dengue, SLE and chronic liver disease are least with incidence of 1.25%, i.e. 2 cases each. Partial HELLP are 25 cases (15.6% and HELLP are 24 cases (15%. Severe preeclampsia with abruption 21 cases (13.1%. DIC are 9 (5.6%. Pancytopenia are 4 (2.5%. Platelet transfusions were required in 69 patients out of 160, i.e. in 43.1% of cases. All the cases of IUGR belonged to preeclampsia and associated disorders group. 26 out of 109 cases of preeclampsia were associated with IUGR. In preeclampsia and associated disorders group, 49 out of 109 cases were IUD, stillborn, nonviable. Chi-square test, p value is 0.0001, which is highly statistically significant, implying there is an association between IUD, stillborn and thrombocytopenia due to severe preeclampsia group when compared to other group including ITP, gestational

  8. Decreased IL-35 levels in patients with immune thrombocytopenia.

    Yang, Yanhui; Xuan, Min; Zhang, Xian; Zhang, Donglei; Fu, Rongfeng; Zhou, Fangfang; Ma, Li; Li, Huiyuan; Xue, Feng; Zhang, Lei; Yang, Renchi


    IL-35 is a novel heterodimeric anti-inflammatory cytokine consisting of Epstein-Barr virus-induced gene 3 (EBI3) and the p35 subunit of IL-12. IL-35 has been shown to possess the potency of inhibiting the CD4+ effector T cells and alleviating autoimmune diseases. In the study we investigated the levels of IL-35 as well as its prospective role in immune thrombocytopenia (ITP).ELISA was adopted to measure plasma IL-35, TGF-β and IL-10 levels. The mRNA expression levels of P35 and EBI3 in peripheral blood mononuclear cells (PBMCs) were studied based on real-time quantitative PCR. The correlation between plasma cytokine levels and clinical parameters was analyzed. Significantly lower plasma IL-35 levels were found in active ITP patients compared with those in remission (p = 0.017) and the healthy controls (p IL-35 levels displayed a significantly positive correlation with platelet counts (r = 0.5335, p IL-35 levels in ITP patients, suggesting that IL-35 may be involved in the pathogenesis of ITP.

  9. Patient-reported treatment burden of chronic immune thrombocytopenia therapies

    Brown T


    Full Text Available Abstract Background Chronic immune thrombocytopenia (ITP is a debilitating autoimmune disorder that causes a reduction in blood platelets and increased risk of bleeding. ITP is currently managed with various pharmacologic therapies and splenectomy. This study was conducted to assess patient perceived and reported treatment side effects, as well as the perceived burden or bother, and need to reduce or stop treatment, associated with these side effects among adult patients with chronic ITP. Methods A Web-enabled survey was administered to members of a US-based ITP patient support group. Patients reported demographic and clinical characteristics, ITP treatments' side effects for treatments received since diagnosed, level of bother (or distress, and need to reduce or stop treatment, associated with side effects. Current and past exposure was assessed for five specific treatment types: corticosteroids (CS, intravenous immunoglobulin (IVIg, anti-D immunoglobulin (anti-D, rituximab (RT, and splenectomy (SPL, as well as for other patient-referenced therapies (captured as "other". Results The survey was completed by 589 patients; 78% female, 89% white, mean age 48 years (SD = 14.71, and 68% reported a typical low platelet count of P P P P Conclusions Current ITP treatments, particularly corticosteroids, are associated with multiple bothersome side effects that may lead to patients stopping or reducing therapy. Open, informed and complete communication between clinician and patient regarding both the benefits and the side effects of ITP treatment may better prepare patients for their prescribed regimens.

  10. Immune-mediated hemolytic anemia - report of three cases / Anemia hemolítica imunomediada em cães - relato de três casos

    Luciana Curotto Nolasco de Carvalho

    Full Text Available Immune-mediated hemolytic anemia (IMHA is a common type of anemia in dogs and cats. The disease é most common in middle-aged female dogs, especially American Cocker Spaniel. The clinical signs are associated with severe anemia. There is no pathognomonic test for IMHA, but the presence of hemolytic anemia in a young adult or middle age, autoagglutination and spherocytosis or positive results of Coombs test, elimination of any other underlying cause of anemia and an appropriate response to immunosuppressive therapy are suggestive of it. The aim of the present paper is to report of three cases of serious IMHA, and highlighting the therapeutic modalities and prognosis associated with them.A anemia hemolítica imunomediada (AHIM é um tipo comum de anemia em cães e gatos. A doença é mais comum em fêmeas caninas de meia-idade, especialmente Cocker Spaniel Americano. Os sinais clínicos estão associados com a anemia severa. Não há achados patognomônicos, mas a presença de anemia hemolítica em um cão jovem ou de meia idade, auto-aglutinação e esferócitos ou teste de Coombs positivo, eliminação de outros diagnósticos diferenciais e a resposta apropriada a terapia imunossupressora indicam AHIM. Apesar de inúmeras opções terapêuticas, os índices de mortalidade permanecem elevados. O objetivo do presente trabalho é relatar três casos graves de AHIM, ressaltando as modalidades terapêuticas e o prognóstico associado a elas.

  11. Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study.

    Musset, Lucile; Allenbach, Yves; Benveniste, Olivier; Boyer, Olivier; Bossuyt, Xavier; Bentow, Chelsea; Phillips, Joe; Mammen, Andrew; Van Damme, Philip; Westhovens, René; Ghirardello, Anna; Doria, Andrea; Choi, May Y; Fritzler, Marvin J; Schmeling, Heinrike; Muro, Yoshinao; García-De La Torre, Ignacio; Ortiz-Villalvazo, Miguel A; Bizzaro, Nicola; Infantino, Maria; Imbastaro, Tiziana; Peng, Qinglin; Wang, Guochun; Vencovský, Jiří; Klein, Martin; Krystufkova, Olga; Franceschini, Franco; Fredi, Micaela; Hue, Sophie; Belmondo, Thibaut; Danko, Katalin; Mahler, Michael


    In an effort to find naturally occurring substances that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), statins were first discovered by Endo in 1972. With the widespread prescription and use of statins to decrease morbidity from myocardial infarction and stroke, it was noted that approximately 5% of all statin users experienced muscle pain and weakness during treatment. In a smaller proportion of patients, the myopathy progressed to severe morbidity marked by proximal weakness and severe muscle wasting. Remarkably, Mammen and colleagues were the first to discover that the molecular target of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is an autoantibody target in patients that develop an immune-mediated necrotizing myopathy (IMNM). These observations have been confirmed in a number of studies but, until today, a multi-center, international study of IMNM, related idiopathic inflammatory myopathies (IIM), other auto-inflammatory conditions and controls has not been published. Accordingly, an international, multi-center study investigated the utility of anti-HMGCR antibodies in the diagnosis of statin-associated IMNM in comparison to different forms of IIM and controls. This study included samples from patients with different forms of IIM (n=1250) and patients with other diseases (n=656) that were collected from twelve sites and tested for anti-HMGCR antibodies by ELISA. This study confirmed that anti-HMGCR autoantibodies, when found in conjunction with statin use, characterize a subset of IIM who are older and have necrosis on muscle biopsy. Taken together, the data to date indicates that testing for anti-HMGCR antibodies is important in the differential diagnosis of IIM and might be considered for future classification criteria.

  12. Indispensable roles of OX40L-derived signal and epistatic genetic effect in immune-mediated pathogenesis of spontaneous pulmonary hypertension

    Rabieyousefi Moloud


    Full Text Available Abstract Background Pulmonary hypertension (PH refers to a spectrum of diseases with elevated pulmonary artery pressure. Pulmonary arterial hypertension (PAH is a disease category that clinically presents with severe PH and that is histopathologically characterized by the occlusion of pulmonary arterioles, medial muscular hypertrophy, and/or intimal fibrosis. PAH occurs with a secondary as well as a primary onset. Secondary PAH is known to be complicated with immunological disorders. The aim of the present study is to histopathologically and genetically characterize a new animal model of PAH and clarify the role of OX40 ligand in the pathogenesis of PAH. Results Spontaneous onset of PAH was stably identified in mice with immune abnormality because of overexpression of the tumor necrosis factor (TNF family molecule OX40 ligand (OX40L. Histopathological and physical examinations revealed the onset of PAH-like disorders in the C57BL/6 (B6 strain of OX40L transgenic mice (B6.TgL. Comparative analysis performed using different strains of transgenic mice showed that this onset depends on the presence of OX40L in the B6 genetic background. Genetic analyses demonstrated a susceptibility locus of a B6 allele to this onset on chromosome 5. Immunological analyses revealed that the excessive OX40 signals in TgL mice attenuates expansion of regulatory T cells the B6 genetic background, suggesting an impact of the B6 genetic background on the differentiation of regulatory T cells. Conclusion Present findings suggest a role for the OX40L-derived immune response and epistatic genetic effect in immune-mediated pathogenesis of PAH.

  13. An Evaluation of Twenty Years of EU Framework Programme-funded Immune-mediated Inflammatory Translational Research in Non-human Primates

    Krista Geraldine Haanstra


    Full Text Available Ageing western societies are facing an increasing prevalence of chronic inflammatory and degenerative diseases for which often no effective treatments exist, resulting in increasing health care expenditure. Despite high investments in drug development, the number of promising new drug candidates decreases. We propose that preclinical research in non-human primate can help to bridge the gap between drug discovery and drug prescription.Translational research covers various stages of drug development of which pre-clinical efficacy tests in valid animal models is usually the last stage. Pre-clinical research in non-human primates may be essential in the evaluation of new drugs or therapies when a relevant rodent model is not available. Non-human primate models for life-threatening or severely debilitating diseases in humans are available at the Biomedical Primate Research Centre (BPRC. These have been instrumental in translational research for several decades.In order to stimulate European health research and innovation from bench to bedside, the European Commission (EC has invested heavily in access to non-human primate research for more than 20 years. BPRC has hosted European users in a series of transnational access programs covering a wide range of research areas with the common theme being immune-mediated inflammatory disorders. We present an overview of the results and give an account of the studies performed as part of European Union Framework Programme (EU FP-funded translational non-human primate research performed at the BPRC. The data illustrate value of translational non-human primate research for the development of new therapies and emphasize the importance of EU FP funding

  14. Role of the mitochondria in immune-mediated apoptotic death of the human pancreatic β cell line βLox5.

    Yaíma L Lightfoot

    Full Text Available Mitochondria are indispensable in the life and death of many types of eukaryotic cells. In pancreatic beta cells, mitochondria play an essential role in the secretion of insulin, a hormone that regulates blood glucose levels. Unregulated blood glucose is a hallmark symptom of diabetes. The onset of Type 1 diabetes is preceded by autoimmune-mediated destruction of beta cells. However, the exact role of mitochondria has not been assessed in beta cell death. In this study, we examine the role of mitochondria in both Fas- and proinflammatory cytokine-mediated destruction of the human beta cell line, βLox5. IFNγ primed βLox5 cells for apoptosis by elevating cell surface Fas. Consequently, βLox5 cells were killed by caspase-dependent apoptosis by agonistic activation of Fas, but only after priming with IFNγ. This beta cell line undergoes both apoptotic and necrotic cell death after incubation with the combination of the proinflammatory cytokines IFNγ and TNFα. Additionally, both caspase-dependent and -independent mechanisms that require proper mitochondrial function are involved. Mitochondrial contributions to βLox5 cell death were analyzed using mitochondrial DNA (mtDNA depleted βLox5 cells, or βLox5 ρ(0 cells. βLox5 ρ(0 cells are not sensitive to IFNγ and TNFα killing, indicating a direct role for the mitochondria in cytokine-induced cell death of the parental cell line. However, βLox5 ρ(0 cells are susceptible to Fas killing, implicating caspase-dependent extrinsic apoptotic death is the mechanism by which these human beta cells die after Fas ligation. These data support the hypothesis that immune mediators kill βLox5 cells by both mitochondrial-dependent intrinsic and caspase-dependent extrinsic pathways.

  15. MHC class II up-regulation and co-localization with Fas in experimental models of immune-mediated bone marrow failure

    Erie, Andrew J.; Samsel, Leigh; Takaku, Tomoiku; Desierto, Marie J.; Keyvanfar, Keyvan; McCoy, J. Philip; Young, Neal S.; Chen, Jichun


    Objective To test the hypothesis that gamma interferon (IFN-γ) promotes MHC class II expression on bone marrow (BM) cell targets that facilitates T cell-mediated BM destruction in immune-mediated BM failure. Materials and Methods Allogeneic lymph node (LN) cells were infused into MHC or minor histocompatibility antigen (minor-H) mismatched hosts to induce BM failure. MHC class II and Fas expression and cell apoptosis were analyzed by flow cytometry. MHC class II-Fas co-localization was detected by ImageStream Imaging Flow Cytometry and other cell-cell associations were visualized by confocal microscopy. T cell-mediated BM cell apoptosis and effects of IFN-γ on MHC class II-Fas co-localization on normal BM cells were studied using cell culture in vitro followed by conventional and imaging flow cytometry. Results BM failure animals had significantly up-regulated MHC class II expression on CD4−CD8−CD11b−CD45R− residual BM cells and significantly increased MHC class II-Fas co-localization on BM CD150+ and CD34+ hematopoietic cells. MHC class II+Fas+ BM cells were closely associated with CD4+ T cells in the BM of affected animals, and they were significantly more responsive to T-cell mediated cell apoptosis relative to MHC class II−Fas− BM cells. Infusion of IFN-γ-deficient LN cells into minor-H mismatched recipients resulted in no MHC class II-Fas up-regulation and no clinically overt BM failure. Treatment with recombinant IFN-γ significantly increased both MHC class II-Fas co-expression and co-localization on normal BM cells. Conclusion Elevation of the inflammatory cytokine IFN-γ stimulated MHC class II expression and MHC class II-Fas co-localization, which may facilitate T-cell mediated cell destruction. PMID:21635935

  16. Homing in on Acute Graft vs. Host Disease: Tissue-Specific T Regulatory and Th17 Cells

    Engelhardt, Brian G.; Crowe, James E.


    Acute graft vs. host disease (aGVHD) is a major limitation of hematopoietic stem cell transplantation (HSCT), and it causes significant morbidity and mortality for this patient population. This immune-mediated injury occurs unpredictably and is caused by donor-derived T cells reacting to recipient alloantigens. Although donor Th1 cells play a critical role in aGVHD generation, numerous arms of both the innate and the adaptive immune systems along with determinants of lymphocyte trafficking ar...

  17. Successful treatment of post-transplant thrombocytopenia with romiplostim in a pediatric patient with X-linked chronic granulomatous disease.

    Buchbinder, David; Hsieh, Loan; Krance, Robert; Nugent, Diane J


    Thrombocytopenia is a frequent complication following HSCT in pediatric patients. Romiplostim is a TPO receptor agonist that has been utilized successfully in the treatment of pediatric patients with immune thrombocytopenia. We describe a three-yr-old male with X-linked CGD treated with an unrelated donor bone marrow transplant. His course was complicated by the development of symptomatic thrombocytopenia. He was started on romiplostim with prompt improvement in his thrombocytopenia. We found the use of romiplostim to be an effective and safe alternative to the potential complications as well as morbidity and mortality associated with the use of immunosuppressive agents such as corticosteroids.


    I. Salehi.


    Full Text Available In systemic lupus erythematosus- (SLE various antibodies are produced against cells including platelets and result in thrombocytopenia. In the literature, the incidence of thrombocytopenia varied from 7% to 52%, in seven series of SLE patients with a mean cumulative percentage of 14.5% (1-5. SLE patients referred to the Lupus Unit of the Rheumatology Research Center, Tehran University for Medical Sciences (Shariati Hospital during the period of 1975 to 1977 were included in this study. T/irombocytopenic patients were selected and 72 items were studied. Tiie incidence of thrombocytopenia in Iranian SLE patients was 16.6%, which is similar to the mean cumulative percentage mentioned above. There was no difference in sex ratio between thrombocytopenic ami nonthrombocytopenic patients: Tiie same was true for the mean age at the onset of the disease. In 70% of patients there was mild to moderate thrombocytopenia (platelet from 50000 to lS0000/mm3. the remaining (30% had severe to very severe thrombocytopenia. In 1.9% of patients had a previous diagnosis of idiopathic thrombocytopenic purpura (ITP. the following symptoms were seen more oflen in thrombocy¬topenic patients than in others: Hemolytic anemia (p<0.001, leukopenia (p<0.001, lymphopenia (p<0.001, splenomegaly (p<0.00007, and abortion (p<0.0006. For the fallowings the p value was less than 0.05: ESR> 700, positive FANA, positive Anti-dsDNA antibodies, positive VDRL, and positive anticardiolipin antibodies. All thrombocytopenic patients' except one (previously sptenectomized were controlled by the medical treatment. Severe and very severe thrombocytopenia were controlled in 86% of cases by moderate to high dose steroids, with or without cytotoxic drugs: In 10% of cases, thrombocytopenia was controlled by a combination of chloroquine and low dose steroid (< 15 mg prednisolone daily. In 4%, other medical treatments (Danazol, etc. were needed.

  19. Are patients with erythema migrans who have leukopenia and/or thrombocytopenia coinfected with Anaplasma phagocytophilum or tick-borne encephalitis virus?

    Franc Strle

    Full Text Available Lyme borreliosis (LB, tick-borne encephalitis (TBE and human granulocytic anaplasmosis (HGA are endemic in central part of Slovenia. We tested the hypothesis that patients with erythema migrans (EM from this region, who have leukopenia and/or thrombocytopenia (typical findings in HGA and in the initial phase of TBE but not in patients with LB are coinfected with Anaplasma phagocytophilum and/or with TBE virus, i.e. that cytopenia is a result of concomitant HGA or the initial phase of TBE. Comparison of clinical and laboratory findings for 67 patients with EM who disclosed leukopenia/thrombocytopenia with the corresponding results in sex- and age-matched patients with EM and normal blood cell counts revealed no differences. In addition, patients with typical EM and leukopenia and/or thrombocytopenia tested negative for the presence of IgM and IgG antibodies to TBE virus by ELISA as well as for the presence of specific IgG antibodies to A. phagocytophilum antigens by IFA in acute and convalescent serum samples. Thus, none of 67 patients (95% CI: 0 to 5.3% with typical EM (the presence of this skin lesion attests for early Lyme borreliosis and is the evidence for a recent tick bite was found to be coinfected with A. phagocytophilum or had a recent primary infection with TBE virus. The findings in the present study indicate that in Slovenia, and probably in other European countries endemic for LB, TBE and HGA, patients with early LB are rarely coinfected with the other tick-transmitted agents.

  20. Immune-mediated hemolytic anemia.

    Rosse, Wendell F; Hillmen, Peter; Schreiber, Alan D


    Hemolytic anemia due to immune function is one of the major causes of acquired hemolytic anemia. In recent years, as more is known about the immune system, these entities have become better understood and their treatment improved. In this section, we will discuss three areas in which this progress has been apparent. In Section I, Dr. Peter Hillmen outlines the recent findings in the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH), relating the biochemical defect (the lack of glycosylphosphatidylinositol [GPI]-linked proteins on the cell surface) to the clinical manifestations, particularly hemolysis (and its effects) and thrombosis. He discusses the pathogenesis of the disorder in the face of marrow dysfunction insofar as it is known. His major emphasis is on innovative therapies that are designed to decrease the effectiveness of complement activation, since the lack of cellular modulation of this system is the primary cause of the pathology of the disease. He recounts his considerable experience with a humanized monoclonal antibody against C5, which has a remarkable effect in controlling the manifestations of the disease. Other means of controlling the action of complement include replacing the missing modulatory proteins on the cell surface; these studies are not as developed as the former agent. In Section II, Dr. Alan Schreiber describes the biochemistry, genetics, and function of the Fc gamma receptors and their role in the pathobiology of autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura due to IgG antibodies. He outlines the complex varieties of these molecules, showing how they vary in genetic origin and in function. These variations can be related to three-dimensional topography, which is known in some detail. Liganding IgG results in the transduction of a signal through the tyrosine-based activation motif and Syk signaling. The role of these receptors in the pathogenesis of hematological diseases due to IgG antibodies is outlined and the potential of therapy of these diseases by regulation of these receptors is discussed. In Section III, Dr. Wendell Rosse discusses the forms of autoimmune hemolytic anemia characterized by antibodies that react preferentially in the cold-cold agglutinin disease and paroxysmal cold hemoglobinuria (PCH). The former is due to IgM antibodies with a common but particular structure that reacts primarily with carbohydrate or carbohydrate-containing antigens, an interaction that is diminished at body temperature. PCH is a less common but probably underdiagnosed illness due to an IgG antibody reacting with a carbohydrate antigen; improved techniques for the diagnosis of PCH are described. Therapy for the two disorders differs somewhat because of the differences in isotype of the antibody. Since the hemolysis in both is primarily due to complement activation, the potential role of its control, as by the monoclonal antibody described by Dr. Hillmen, is discussed.

  1. [Significance of regulatory B cells in nosogenesis of immune thrombocytopenia].

    Li, Xin; Wang, Fang; Ding, Kai Yang; Dai, Lan


    This study was aimed to investigate the role of regulatory B cells (Breg) in pathogenesis of immune thrombocytopenia (ITP) and its clinical significance. A total of 35 ITP patients and 20 normal controls were enrolled in this study. The expression of CD19(+)CD24(hi)CD38(hi) B cells was detected by flow cytometry and the expression of IL-10 mRNA and TGF-β1 mRNA was assayed by RT-PCR. The results indicated that the expression level of CD19(+)CD24(hi)CD38(hi) B cells in peripheral blood of newly diagnosed ITP patients was obviously lower than that in normal controls (P < 0.05); the expression level of CD19(+)CD24(hi)CD38(hi) B cells in ITP patients with increased platelet count after treatment was higher than that before treatment (P < 0.05); the expression level of IL-10 mRNA in newly diagnosed ITP patients was significantly lower than that the in normal controls (P < 0.05), the expression level of TGF-β1 mRNA in newly diagnosed ITP patients increases as compared with normal controls (P < 0.05), after treatment with DXM the expression of IL-10 mRNA was enhanced, the expression of TGF-β1 mRNA was reduced as compared with expression level before treatment (P < 0.05). It is concluded that the Breg cells may play an important role in the pathogenesis of ITP via humoral immunity and its regulation of T lymphocytes.

  2. An improbable and unusual case of thrombotic thrombocytopenia purpura

    Jaymon Patel


    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a life-threatening medical emergency which may be difficult to recognize given the wide spectrum in which it presents. A delay in treatment may be catastrophic as untreated cases of TTP have a mortality rate exceeding 90%. Given the high fatality rate of untreated TTP and its range of presenting symptoms, we present our unusual case of TTP in a post-splenectomy patient with early treatment and positive outcome. This case describes a 54-year-old female who presented with hematuria and gingival bleeding, followed by the development of a bilateral lower extremity petechial rash. Her past medical history was significant for multiple episodes of TTP, the last of which resulted in a splenectomy and a 20-year history of remission thereafter. On exam, she was alert, well appearing, and neurologically intact. Her only significant finding was a bilateral lower extremity petechial rash. Laboratory studies revealed mild anemia and thrombocytopenia, an elevated lactate dehydrogenase, and a decreased haptoglobin. Peripheral smear showed poikilocytosis, helmet cells, and schistocytes. Corticosteroid therapy was promptly initiated, her platelets were monitored closely, and she underwent urgent therapeutic plasma exchange. Due to the risk of significant morbidity and mortality that may result from delayed treatment of TTP as well as the significant variations of presentation, TTP requires a consistently high index of suspicion. Our patient suffered multiple relapses of TTP within a 30-year span, underwent splenectomy in early adulthood, and presented with atypical symptoms during her most recent relapse illustrating how persistent TTP can be as well as how unusually it may present. Providers should be aware of the vast spectrum of presentation and remember that TTP may recur following splenectomy despite prolonged remission.

  3. Rituximab for children with immune thrombocytopenia: a systematic review.

    Yi Liang

    Full Text Available BACKGROUND: Rituximab has been widely used off-label as a second line treatment for children with immune thrombocytopenia (ITP. However, its role in the management of pediatric ITP requires clarification. To understand and interpret the available evidence, we conducted a systematic review to assess the efficacy and safety of rituximab for children with ITP. METHODOLOGY/PRINCIPAL FINDINGS: We searched MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, abstract databases of American Society of Hematology, American Society of Clinical Oncology and Pediatric Academic Society. Clinical studies published in full text or abstract only in any language that met predefined inclusion criteria were eligible. Efficacy analysis was restricted to studies enrolling 5 or more patients. Safety was evaluated from all studies that reported data of toxicity. 14 studies (323 patients were included for efficacy assessment in children with primary ITP. The pooled complete response (platelet count ≥ 100 × 10(9/L and response (platelet count ≥ 30 × 10(9/L rate after rituximab treatment were 39% (95% CI, 30% to 49% and 68% (95%CI, 58% to 77%, respectively, with median response duration of 12.8 month. 4 studies (29 patients were included for efficacy assessment in children with secondary ITP. 11 (64.7% of 17 patients associated with Evans syndrome achieved response. All 6 patients with systemic lupus erythematosus associated ITP and all 6 patients with autoimmune lymphoproliferative syndrome associated ITP achieved response. 91 patients experienced 108 adverse events associated with rituximab, among that, 91 (84.3% were mild to moderate, and no death was reported. CONCLUSIONS/SIGNIFICANCE: Randomized controlled studies on effect of rituximab for children with ITP are urgently needed, although a series of uncontrolled studies found that rituximab resulted in a good platelet count response both in children with primary and children secondary ITP. Most adverse events

  4. Platelet reactive alloantibodies responsible for immune thrombocytopenia in Malay population

    Mohd I. Armawai


    Full Text Available Background: Alloantibodies against human platelet alloantigens (HPAs are responsible for the development of platelet transfusion refractoriness (PTR in patients receiving random platelets and bleeding disorder in babies with fetal neonatal alloimmune thrombocytopenia (FNAIT. Recently, our results based on the analysis of the allelic distribution of HPAs indicated that immunization may occur among Malay. In this study, we sought to analyze the frequencies of platelet reactive alloantibodies responsible for FNAIT and PTR in Malaysia.Methods: Sera from suspected FNAIT (n = 295 and PTR (n = 74 were collected in five years period (2008-2013 and tested for the presence of platelet reactive antibodies by the use of antigen capture assay.Results: In 5/74 (5.41% platelet specific antibodies against HPA-2b (n = 1, HPA-5a (n = 1, HPA-5b (n = 1, HPA-15b (n = 2 could be identified in our PTR cohort. In FNAIT cohort, platelet specific alloantibodies could be detected in 18 sera (6.10% consisting anti-HPA-1a (n = 1, anti-HPA-3a (n = 3, anti-HPA-5a (n = 6, anti-HPA-5b (n = 6, anti-HPA-15a (n = 1, and anti-HPA-15b (n = 1.Conclusion: Our study indicates that anti-HPA-3, -HPA-5 and -HPA-15 antibodies seems to be the most platelet specific antibodies involved in FNAIT and PTR cases in Malaysian population. Since similar HPA allelic distribution among Malaysian and Indonesian populations have been observed, immunization against these three HPA systems are expected to be the most potential risk of alloimmune mediated platelet disorders in Indonesia.

  5. Hepatitis C virus-associated thrombocytopenia in pregnancy: impact upon multidisciplinary care provision.

    Monteith, Cathy


    Abstract Objective: Recent studies have implicated hepatitis C virus (HCV) in the pathogenesis of immune thrombocytopenia. In pregnancy-associated immune thrombocytopenia, multidisciplinary management is required due to a potential for bleeding complications. We performed a retrospective review of HCV-infected pregnant women and age-matched controls who were not infected with HCV. Methods: One hundred and six women with a HCV viral load were identified from 2009 to 2011. Results: Thrombocytopenia was identified in 10.3% of HCV-infected pregnant women and 1.6% of age-matched controls (P<0.001). Mean platelet count during pregnancy was 120±23×109\\/L in HCV-infected women and at delivery was significantly lower in HCV-infected women than in controls (P=0.01). Despite the significant difference in platelet counts, there was no significant difference in estimated blood loss (EBL) at delivery. Regional anaesthesia was performed in 73% of thrombocytopenic HCV-infected women and no complications were recorded. There were no fetal bleeding complications. Conclusion: In the first study to date to investigate the impact of HCV on maternal platelet count we demonstrated a significantly higher frequency of thrombocytopenia and a significantly lower platelet count in HCV-infected pregnant women compared with controls. Interestingly, thrombocytopenia had no detectable impact on EBL at delivery.

  6. Antiphospholipid syndrome in a pregnant female presenting with severe thrombocytopenia and bleeding.

    Mahajan, Kunal; Katyal, Virender; Arya, Suvrat; Shrama, Meha


    The antiphospholipid antibody syndrome (APS) is defined by the persistent presence of antiphospholipid antibodies in patients with recurrent venous or arterial thromboembolism or pregnancy morbidity. Antithrombotic therapy is the mainstay of treatment given the high risk of recurrent thromboembolism that characterizes this condition. Despite the prothrombotic nature of APS, thrombocytopenia is present in a proportion of patients, which can complicate management and limit the use of antithrombotic therapy. The mechanism of APS-associated thrombocytopenia is multifactorial and its relation to thrombotic risk is poorly characterized. The presence of thrombocytopenia does not appear to reduce thrombotic risk in patients with APS, who can develop thromboembolic complications necessitating antithrombotic treatment. In these cases, treatment of the thrombocytopenia may be necessary to facilitate administration of antithrombotic agents. We present such a pregnant lady with history of recurrent pregnancy losses who presented with severe thrombocytopenia and bleeding manifestations, who was subsequently diagnosed to have antiphospholipid antibody syndrome. She was initially managed with steroids and when her platelet counts improved, antithrombotic therapy was started. She delivered an uneventful and successful pregnancy outcome without any complications during follow-up.

  7. Antiphospholipid Syndrome in a Pregnant Female Presenting with Severe Thrombocytopenia and Bleeding

    Kunal Mahajan


    Full Text Available The antiphospholipid antibody syndrome (APS is defined by the persistent presence of antiphospholipid antibodies in patients with recurrent venous or arterial thromboembolism or pregnancy morbidity. Antithrombotic therapy is the mainstay of treatment given the high risk of recurrent thromboembolism that characterizes this condition. Despite the prothrombotic nature of APS, thrombocytopenia is present in a proportion of patients, which can complicate management and limit the use of antithrombotic therapy. The mechanism of APS-associated thrombocytopenia is multifactorial and its relation to thrombotic risk is poorly characterized. The presence of thrombocytopenia does not appear to reduce thrombotic risk in patients with APS, who can develop thromboembolic complications necessitating antithrombotic treatment. In these cases, treatment of the thrombocytopenia may be necessary to facilitate administration of antithrombotic agents. We present such a pregnant lady with history of recurrent pregnancy losses who presented with severe thrombocytopenia and bleeding manifestations, who was subsequently diagnosed to have antiphospholipid antibody syndrome. She was initially managed with steroids and when her platelet counts improved, antithrombotic therapy was started. She delivered an uneventful and successful pregnancy outcome without any complications during follow-up.

  8. The role of eltrombopag in the management of hepatitis C virus-related thrombocytopenia

    Danish FA


    Full Text Available Fazal-i-Akbar Danish,1 Saeeda Yasmin21James Paget University Hospital, Great Yarmouth, Norfolk, United Kingdom; 2Shifa International Hospital, Islamabad, PakistanAbstract: Eltrombopag is a 2nd generation thrombopoietin-receptor agonist. It binds with the thrombopoietin-receptors found on the surfaces of the megakaryocytes & increases platelet production. Many recent studies have suggested a potential role for this novel agent in the treatment of thrombocytopenia associated with hepatitis-C infection. Studies have shown that adjunct treatment with Eltrombopag can help avoid dose reductions/withdrawals of pegylated interferon secondary to thrombocytopenia. It may also have a role in priming up platelet levels to help initiate antiviral therapy. Similarly, chronic liver disease patients with thrombocytopenia who need to undergo an invasive procedure may be potential candidates for short two-week courses of eltrombopag in the periprocedural period to help reduce the risk of bleeding. Besides the price (deemed very expensive and probably not cost-effective, there are some legitimate concerns about the safety profile of this novel agent (most importantly, portal vein thrombosis, bone marrow fibrosis and hepatotoxicity. In this article, the potential role of eltrombopag in the context of hepatitis C virus (HCV-related thrombocytopenia is reviewed. To write this article, a MEDLINE search was conducted (1990 to November 2012 using the search terms “eltrombopag,” “HCV,” and “thrombocytopenia.”Keywords: liver disease, chronic immune thrombocytopenic purpura, thrombopoietin-receptor agonist, romiplostim

  9. Delayed-onset heparin-induced thrombocytopenia presenting with multiple arteriovenous thromboses: case report

    Omran Abbas


    Full Text Available Abstract Background Delayed-onset heparin-induced thrombocytopenia with thrombosis, albeit rare, is a severe side effect of heparin exposure. It can occur within one month after coronary artery bypass grafting (CABG with manifestation of different thrombotic events. Case presentation A 59-year-old man presented with weakness, malaise, bilateral lower limb pitting edema and a suspected diagnosis of deep vein thrombosis 18 days after CABG. Heparin infusion was administered as an anticoagulant. Clinical and paraclinical work-up revealed multiple thrombotic events (stroke, renal failure, deep vein thrombosis, large clots in heart chambers and 48 ×103/μl platelet count, whereupon heparin-induced thrombocytopenia was suspected. Heparin was discontinued immediately and an alternative anticoagulant agent was administered, as a result of which platelet count recovered. Heparin-induced thrombocytopenia, which causes thrombosis, is a serious side effect of heparin therapy. It is worthy of note that no case of delayed-onset heparin-induced thrombocytopenia with thrombosis associated with cardiopulmonary bypass surgery has thus far been reported in Iran. Conclusion Delayed-onset heparin-induced thrombocytopenia should be suspected in any patient presenting with arterial or venous thromboembolic disorders after recent heparin therapy, even though the heparin exposure dates back to more than a week prior to presentation; and it should be ruled-out before the initiation of heparin therapy.

  10. Congenital thrombocytopenia with nephritis: The first case of MYH9 related disorder in Serbia

    Kuzmanović Miloš


    Full Text Available Introduction. The group of autosomal dominant disorders - Epstein syndrome, Sebastian syndrome, Fechthner syndrome and May-Hegglin anomaly - are characterised by thrombocytopenia with giant platelets, inclusion bodies in granulocytes and variable levels of deafness, disturbances of vision and renal function impairment. A common genetic background of these disorders are mutations in MYH9 gene, coding for the nonmuscle myosin heavy chain IIA. Differential diagnosis is important for the adequate treatment strategy. The aim of this case report was to present a patient with MYH9 disorder in Serbia. Case report. A 16-year-old boy was referred to our hospital with the diagnosis of resistant immune thrombocytopenia for splenectomy. Thrombocytopenia was incidentally discovered at the age of five. The treatment with corticosteroids on several occasions was unsuccessful. Although the platelet count was below 10 × 109/L, there were no bleeding symptoms. Besides thrombocytopenia with giant platelets, on admission the patient also suffered sensorineuronal hearing loss and proteinuria. The diagnosis was confirmed with immunofluorescence and genetic analyses. Conclusion. Early recognition of MYH9-related diseases is essential to avoid unnecessary and potentially harmful treatments for misdiagnosed immune thrombocytopenia, and also for timely and proper therapy in attempt to delay end-stage renal failure and improve quality of life. [Projekat Ministartsva nauke Republike Srbije, br. 175056 i br. 15079

  11. Management of Thrombocytopenia in Chronic Liver Disease: Focus on Pharmacotherapeutic Strategies.

    Maan, Raoel; de Knegt, Robert J; Veldt, Bart J


    Thrombocytopenia (platelet count management of these patients. The prevalence of this manifestation ranges from 6% among non-cirrhotic patients with chronic liver disease to 70% among patients with liver cirrhosis. It has also been shown that the severity of liver disease is associated with both prevalence and level of thrombocytopenia. Its development is often multifactorial, although thrombopoietin is thought to be a major factor. The discovery of and ability to clone thrombopoietin led to new treatment opportunities for this clinical manifestation. This review discusses data on the three most important thrombopoietin receptor agonists: eltrombopag, avatrombopag, and romiplostim. Currently, only eltrombopag is approved for usage among patients with thrombocytopenia and chronic hepatitis C virus infection in order to initiate and maintain interferon-based antiviral treatment. Nevertheless, the optimal management of hematologic abnormalities among patients with chronic liver disease, and its risk for bleeding complications, is still a matter of discussion. Thrombocytopenia definitely contributes to hemostatic defects but is often counterbalanced by the enhanced presence of procoagulant factors. Therefore, a thorough assessment of the patient's risk for thrombotic events is essential when the use of thrombopoietin receptor agonists is considered among patients with chronic liver disease and thrombocytopenia.

  12. Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

    Johnson, Ben; Lowe, Gillian C.; Futterer, Jane; Lordkipanidzé, Marie; MacDonald, David; Simpson, Michael A.; Sanchez-Guiú, Isabel; Drake, Sian; Bem, Danai; Leo, Vincenzo; Fletcher, Sarah J.; Dawood, Ban; Rivera, José; Allsup, David; Biss, Tina; Bolton-Maggs, Paula HB; Collins, Peter; Curry, Nicola; Grimley, Charlotte; James, Beki; Makris, Mike; Motwani, Jayashree; Pavord, Sue; Talks, Katherine; Thachil, Jecko; Wilde, Jonathan; Williams, Mike; Harrison, Paul; Gissen, Paul; Mundell, Stuart; Mumford, Andrew; Daly, Martina E.; Watson, Steve P.; Morgan, Neil V.


    Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×109/L to 186×109/L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified “pathogenic” or “likely pathogenic” variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia. PMID:27479822

  13. Gender and the treatment of immune-mediated chronic inflammatory diseases: rheumatoid arthritis, inflammatory bowel disease and psoriasis: an observational study

    Lesuis Nienke


    Full Text Available Abstract Background Rheumatoid arthritis (RA, inflammatory bowel disease (IBD, and psoriasis are immune-mediated inflammatory diseases with similarities in pathophysiology, and all can be treated with similar biological agents. Previous studies have shown that there are gender differences with regard to disease characteristics in RA and IBD, with women generally having worse scores on pain and quality of life measurements. The relationship is less clear for psoriasis. Because treatment differences between men and women could explain the dissimilarities, we investigated gender differences in the disease characteristics before treatment initiation and in the biologic treatment prescribed. Methods Data on patients with RA or IBD were collected from two registries in which patients treated with biologic medication were enrolled. Basic demographic data and disease activity parameters were collected from a time point just before the initiation of the biologic treatment. For patients with psoriasis, the data were taken from the 2010 annual report of the Swedish Psoriasis Register for systemic treatment, which included also non-biologic treatment. For all three diseases, the prescribed treatment and disease characteristics were compared between men and women. Results In total, 4493 adult patients were included in the study (1912 with RA, 131 with IBD, and 2450 with psoriasis. Most of the treated patients with RA were women, whereas most of the patients with IBD or psoriasis were men. There were no significant differences between men and women in the choice of biologics. At treatment start, significant gender differences were seen in the subjective disease measurements for both RA and psoriasis, with women having higher (that is, worse scores than men. No differences in objective measurements were found for RA, but for psoriasis men had higher (that is, worse scores for objective disease activity measures. A similar trend to RA was seen in IBD

  14. Advances in fetal immune mediated atrioventricular block%胎儿免疫性房室传导阻滞研究进展

    严华林; 李一飞(综述); 周开宇; 华益民(审校)


    Fetal atrioventricular block (AVB) is a type of fetal bradyarrhythmias. The reported incidence of fetal complete atrioventricular block (CAVB) and mortality of perinatal fetuses and neonates are signiifcantly higher in pregnancies of anti-SSA/Ro-positive mothers than that of anti-SSA/Ro-negative mothers. The auto-antibodies in maternal serum that can be transported into fetal circulation through placenta may damage fetal cardiac conductive system and eventually result in fetal AVB. There are evidences that early diagnosis and proper treatment can improve the prognosis and survival rate of affected fetuses. In this article, the pathogenesis, risk factors, prenatal diagnosis, treatment and prognosis of fetal immune mediated AVB is reviewed.%胎儿房室传导阻滞属于胎儿缓慢性心律失常。当母体血清抗-SSA/Ro、抗-SSB/La抗体阳性时,胎儿完全性房室传导阻滞发病率和相关围生期胎儿/新生儿死亡率显著升高。母体血清自身抗体可经胎盘转运进入胎儿体内,可能导致胎儿心脏传导系统免疫损伤,从而引起房室传导阻滞发生。如果能进行胎儿免疫性房室传导阻滞的早期诊断和及时干预,可能阻止病情进展,改善免疫性房室传导阻滞胎儿的预后并提高其生存率。文章综述胎儿免疫性房室传导阻滞的发病机制、危险因素、产前诊断、胎儿期干预及预后等。

  15. Risk of subsequent coronary heart disease in patients hospitalized for immune-mediated diseases: a nationwide follow-up study from Sweden.

    Bengt Zöller

    Full Text Available BACKGROUND: Certain immune-mediated diseases (IMDs, such as rheumatoid arthritis and systemic lupus erythematosus, have been linked to cardiovascular disorders. We examined whether there is an association between 32 different IMDs and risk of subsequent hospitalization for coronary heart disease (CHD related to coronary atherosclerosis in a nationwide follow up study in Sweden. METHODS AND FINDINGS: All individuals in Sweden hospitalized with a main diagnosis of an IMD (n = 336,479 without previous or coexisting CHD, between January 1, 1964 and December 31 2008, were followed for first hospitalization for CHD. The reference population was the total population of Sweden. Standardized incidence ratios (SIRs for CHD were calculated. Overall risk of CHD during the first year after hospitalization for an IMD was 2.92 (95% CI 2.84-2.99. Twenty-seven of the 32 IMDs studied were associated with an increased risk of CHD during the first year after hospitalization. The overall risk of CHD decreased over time, from 1.75 after 1-5 years (95% CI 1.73-1.78, to 1.43 after 5-10 years (95% CI 1.41-1.46 and 1.28 after 10+ years (95% CI 1.26-1.30. Females generally had higher SIRs than males. The IMDs for which the SIRs of CDH were highest during the first year after hospitalization included chorea minor 6.98 (95% CI 1.32-20.65, systemic lupus erythematosus 4.94 (95% CI 4.15-5.83, rheumatic fever 4.65 (95% CI 3.53-6.01, Hashimoto's thyroiditis 4.30 (95% CI 3.87-4.75, polymyositis/dermatomyositis 3.81 (95% CI 2.62-5.35, polyarteritis nodosa 3.81 (95% CI 2.72-5.19, rheumatoid arthritis 3.72 (95% CI 3.56-3.88, systemic sclerosis 3.44 (95% CI 2.86-4.09, primary biliary cirrhosis 3.32 (95% CI 2.34-4.58, and autoimmune hemolytic anemia 3.17 (95% CI 2.16-4.47. CONCLUSIONS: Most IMDs are associated with increased risk of CHD in the first year after hospital admission. Our findings suggest that many hospitalized IMDs are tightly linked to coronary atherosclerosis.

  16. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1–risk myelodysplastic syndrome and thrombocytopenia

    Giagounidis, Aristoteles; Mufti, Ghulam J; Fenaux, Pierre; Sekeres, Mikkael A; Szer, Jeffrey; Platzbecker, Uwe; Kuendgen, Andrea; Gaidano, Gianluca; Wiktor-Jedrzejczak, Wieslaw; Hu, Kuolung; Woodard, Paul; Yang, Allen S; Kantarjian, Hagop M


    BACKGROUND Thrombocytopenia in patients with myelodysplastic syndrome (MDS) is associated with shortened survival and an increased risk of evolution to acute myeloid leukemia (AML). In this study, the authors evaluated the efficacy of romiplostim in patients who had thrombocytopenia with low-risk/intermediate-1–risk MDS. METHODS Patients who had thrombocytopenia with low-risk/intermediate-1–risk MDS (N = 250) were randomized 2:1 to receive romiplostim or placebo weekly for 58 weeks. RESULTS The primary endpoint— the number of clinically significant bleeding events (CSBEs) per patient—had a hazard ratio for romiplostim:placebo of 0.83 (95% confidence interval, 0.66-1.05; P = .13). CSBEs were reduced significantly in the romiplostim group for patients who had baseline platelet counts ≥20 × 109/L (P < .0001). For patients who had baseline platelet counts <20 × 109/L, there was no difference in the number of CSBEs, but the platelet transfusion rates were higher in the placebo group (P < .0001), which may have affected the overall CSBE results in this group with severe thrombocytopenia. The incidence of bleeding events was reduced significantly in the romiplostim group (relative risk, 0.92), as were protocol-defined platelet transfusions (relative risk, 0.77). Platelet response rates according to 2006 International Working Group criteria were higher for the group that received romiplostim (odds ratio, 15.6). On the basis of interim data, an independent data monitoring committee advised halting study drug because of concerns regarding excess blasts and AML rates with romiplostim (interim hazard ratio, 2.51). At 58 weeks, the AML rates were 6% in the romiplostim group and 4.9% in the placebo group (hazard ratio, 1.20; 95% confidence interval, 0.38-3.84), and the overall survival rates were similar. CONCLUSIONS Romiplostim treatment in patients with low-risk/intermediate-1–risk MDS increased platelet counts and decreased the number of

  17. Detection of antiplatelet antibody in serum and on megakaryocytes of dogs with autoimmune thrombocytopenia.

    Joshi, B C; Jain, N C


    Blood and bone marrow samples from 13 thrombocytopenic dogs were examined to determine whether immunologic thrombocytopenia existed. Antiplatelet antibody was detected in serum of 8 of the dogs by platelet factor 3 test or its modification. Moderate to strong immunofluorescence of megakaryocytes was noticed in bone marrow smears stained with rabbit anticanine globulin conjugated with fluorescin isothiocyanate. Negative results were obtained with serum and bone marrow samples collected from 6 of the dogs during therapy for autoimmune thrombocytopenia. Clinical and laboratory findings varied in individual patients with circulating antiplatelet antibodies. Thrombocytopenia was present in all the dogs, with platelet counts ranging from less than 3,000 to 20,000/mu1 of blood. Signs of bleeding in tissues and body cavities were present in all dogs, but anemia was evidenced in only 3 dogs. Differential leukocyte counts were variable. Morphologic abnormalities such as vacuolation and reduced or absence of granulation of the cytoplasm and nuclear fragmentation were seen in some megakaryocytes.

  18. Hepatitis C virus-associated thrombocytopenia is not related to serum thrombopoietin levels

    Afifi Ola


    Full Text Available Objective: Hepatitis C virus (HCV infection is one of the most important health problems in Egypt. Thrombocytopenia is a common finding in subjects with chronic hepatitis. The precise etiology of this thrombocytopenia is still obscure. There is increasing interest in the potential role of thrombopoietin (TPO as a cause of this thrombocytopenia. The aim of this work was to determine serum TPO levels in HCV-positive patients and to test the assumption that HCV-associated thrombocytopenia could be due to low TPO levels. Materials and Methods: Forty patients with HCV infection were included in this study and classified into three groups according to the degree of thrombocytopenia (IA-mild, IB-moderate, II-none. Twenty five healthy volunteers served as control (Group III. All patients and controls had undergone full clinical assessment and the following laboratory investigations: complete blood count, liver function tests, prothrombin time and concentration and serum TPO level. Results: TPO levels were significantly elevated in Group IA as compared to the control group ( P < 0.05. No significant difference was found between groups IA and II. TPO in Group IB was slightly, but insignificantly reduced compared to Group IA but did not differ statistically from the control or Group II. Significant negative correlation was found between serum TPO levels and platelet counts in Groups IA, IB and II (r=-0.421, P < 0.05. No correlations were found between serum TPO levels and liver function tests or hematological parameters. Conclusion: An impaired TPO production did not explain the development of thrombocytopenia in HCV and other mechanisms must be involved.

  19. Flavonoid-induced acute nephropathy by Cupressus funebris Endl (Mourning Cypress).

    Lee, Jia-Jung; Chen, Hung-Chun


    Worldwide use of herbal therapy has increased dramatically in recent years. Most herbal therapies were not regulated as medicines, and their adverse effects often were underreported. We report a patient who developed acute renal failure, acute hepatic failure, autoimmune hemolytic anemia, and thrombocytopenia after oral intake of hot-water extract of Cupressus funebris Endl (Mourning Cypress), which is rich in flavonoids. Her renal biopsy showed acute tubular necrosis, interstitial nephritis, and hemoglobin casts. The clinical course and pathological findings were consistent with flavonoid-induced acute nephropathy. We emphasize that flavonoids are not harmless and may induce acute life-threatening renal damage.

  20. Vancomycin-induced thrombocytopenia in a 60-year-old man: a case report

    Shah Ravish A


    Full Text Available Abstract Introduction Vancomycin, a glycopeptide antibiotic, is used to treat resistant gram-positive infections. There has been a 10- to 20-fold increase in its use over the past 25 years. Although ototoxicity and nephrotoxicity are well known side effects of vancomycin, it can also induce platelet reactive antibodies leading to life-threatening thrombocytopenia. Vancomycin is often clinically overlooked as a cause of thrombocytopenia, especially in a scenario of sepsis or when there is use of heparin. We report a proven case of vancomycin-induced thrombocytopenia and its reversal after discontinuation of vancomycin. Case presentation A 60-year-old man with a history of hypertension, congestive heart failure and dyslipidemia was admitted for a right shoulder rotator cuff tear. He underwent right-shoulder arthroscopy and rotator cuff repair. About three weeks later, he developed pain, swelling and purulent drainage from his right shoulder. Arthroscopic irrigation and drainage was then performed. Intraoperative fluid revealed the presence of Methicillin susceptible Staphylococcus aureus, vancomycin-sensitive Enterococcus spp. and Serratia marcescens. The patient had no known allergies. After reviewing his antimicrobial susceptibility, he was started on vancomycin 1500 mgs intravenously every 12 hours (to treat both Staphylococcus aureus and Enterococcus spp and ciprofloxacin 750 mgs by oral induction every 12 hours. The patient's condition improved following antibiotic treatment. He was discharged and allowed to go home on IV vancomycin and oral ciprofloxacin. The patient's platelet count on the day of starting vancomycin therapy was 253 × 103/mm3. At weeks one, two and three, the counts were 231 × 103/mm3, 272 × 103/mm and 6 × 103/mm3, respectively. The patient was admitted for further work-up of the thrombocytopenia. He was later shown to have vancomycin-induced platelet-reactive antibodies, causing significant thrombocytopenia, and then

  1. ST-elevation myocardial infarction and myelodysplastic syndrome with acute myeloid leukemia transformation.

    Jao, Geoffrey T; Knovich, Mary Ann; Savage, Rodney W; Sane, David C


    Acute myocardial infarction and acute myeloid leukemia are rarely reported as concomitant conditions. The management of ST-elevation myocardial infarction (STEMI) in patients who have acute myeloid leukemia is challenging: the leukemia-related thrombocytopenia, platelet dysfunction, and systemic coagulopathy increase the risk of bleeding, and the administration of thrombolytic agents can be fatal. We report the case of a 76-year-old man who presented emergently with STEMI, myelodysplastic syndrome, and newly recognized acute myeloid leukemia transformation. Standard antiplatelet and anticoagulation therapy were contraindicated by the patient's thrombocytopenia and by his reported ecchymosis and gingival bleeding upon admission. He declined cardiac catheterization, was provided palliative care, and died 2 hours after hospital admission. We searched the English-language medical literature, found 8 relevant reports, and determined that the prognosis for patients with concomitant STEMI and acute myeloid leukemia is clearly worse than that for either individual condition. No guidelines exist to direct the management of STEMI and concomitant acute myeloid leukemia. In 2 reports, dual antiplatelet therapy, anticoagulation, and drug-eluting stent implantation were used without an increased risk of bleeding in the short term, even in the presence of thrombocytopenia. However, we think that a more conservative approach--balloon angioplasty with the provisional use of bare-metal stents--might be safer. Simultaneous chemotherapy for the acute myeloid leukemia is crucial. Older age seems to be a major risk factor: patients too frail for emergent treatment can die within hours or days.

  2. Prevalence of Thrombocytopenia among Chinese Adult Antiretroviral-na(i)ve HIV-positive Patients

    Hong-Wei Fan; Fu-Ping Guo; Yi-Jia Li; Ning Li; Tai-Sheng Li


    Background:The prevalence ofthrombocytopenia among Chinese antiretroviral therapy (ART)-na(i)ve HIV-infected adults has not been well-described.The aim of this study was to investigate the prevalence and associated risk factors of thrombocytopenia among Chinese ART-na(i)ve HIV-infected adults.Methods:We performed a cross-sectional study of Chinese adult ART-na(i)ve HIV-infected patients from September 2005 through August 2014.Socio-demographic variables and laboratory results including platelets,CD4+ cell count,and viral load were obtained from medical records.Factors and outcomes associated with thrombocytopenia were assessed using logistic regression.Results:A total of 1730 adult ART-na(i)ve HIV-infected patients was included.The mean age was 38 years.The prevalence of thrombocytopenia was 4.5%.There were significant differences in the prevalence of thrombocytopenia between patients <30 years of age (2.8%) and 30-39 years (4.0%) compared with patients greater than 50 years (7.0%) (P =0.006 and P =0.044,respectively).The prevalence of thrombocytopenia was also significantly different between patients with CD4+ counts of 200-349 cells/mm3 (3.3%) and >350 cells/mm3 (2.8%) compared with patients with CD4+ counts of50-199 cells/mm3 (7.1%) (P =0.002 and P =0.005,respectively).The prevalence of thrombocytopenia was significantly different by hepatitis C virus antibody (HCV-Ab) seropositivity (10.2% for HCV-Ab positive vs.3.9% for HCV-Ab negative,P =0.001).We observed differences in prevalence of thrombocytopenia by mode of transmission of HIV infection:Blood transmission (10.7%) versus men who have sex with men (3.9%) (P =0.002) and versus heterosexual transmission (3.9%) (P =0.001).In binary logistic regression analyses,age ≥>50 years,HCV-Ab positivity and having a CD4+ cell count of 50-199 cells/mm3 were significantly associated with thrombocytopenia with adjusted odds ratio of 2.482 (95% confidence interval [CI]:1.167,5.281,P=0

  3. Haemolytic Uraemic Syndrome Following Acute Pancreatitis

    Sinha A


    Full Text Available CONTEXT: Haemolytic uraemic syndrome is a common cause of renal failure in children but it is a rare condition in adults. Acute pancreatitis in adult as a cause of haemolytic uraemic syndrome is very rare. CASE REPORT: A 19-year-old male presented with symptom and signs suggestive of acute pancreatitis which was confirmed as his serum amylase was significantly raised. Within three days of admission he developed acute renal failure with evidence of haemolytic anaemia and thrombocytopenia. A clinical diagnosis of haemolytic uraemic syndrome was made and he was treated with plasma exchange. He made a complete recovery. CONCLUSION: Renal failure in a patient with acute pancreatitis is rarely due to haemolytic uraemic syndrome. But it is important to consider this differential diagnosis so that early treatment can be instituted to prevent mortality.

  4. Successful liver transplantation in a patient with splanchnic vein thrombosis and pulmonary embolism due to polycythemia vera with Jak2v617f mutation and heparin-induced thrombocytopenia.

    Biagioni, Emanuela; Pedrazzi, Paola; Marietta, Marco; Di Benedetto, Fabrizio; Villa, Erica; Luppi, Mario; Girardis, Massimo


    Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin treatment resulting in a severe acquired thrombophilic condition with an associated mortality of about 10 %. We report the first case of successful urgent liver transplantation (LT) in a patient with end-stage liver disease due to a Budd-Chiari syndrome, portal vein thrombosis and pulmonary embolism due to acquired thrombophilia associated to polycythemia vera carrying JAK2V617F gene mutation and HIT in the acute phase. Lepirudin was used to provide anticoagulation in the LT perioperative period that was performed without haemorrhagic and thrombotic complications despite the donor received heparin during liver explantation.

  5. Study Progress on Pathogenesis of Primary immune thrombocytopenia%原发免疫性血小板减少症发病机制的研究进展

    薛晗; 贾瑞萍


    Primary immune thrombocytopenia (ITP), is the most common clinical autoimmune disorder and the pathogenesis is not completely clear, which clinical features are mucocutaneous bleeding and visceral hemorrhage.The main Pathogenesis of ITP includes humoral and cellular immunity-mediated platelet destruction,abnormal magakaryoyte quantity and quality, suppressed platelet production.In recenct years, The opinions of complement system and T fol icular helper cells has caused more attention, This review wil be made to sum up the study progress on the pathogenesisof ITP.%原发免疫性血小板减少症(Primary immune thrombocytopenic purpura ITP)是一种常见的以皮肤黏膜、内脏出血为主要临床表现的自身免疫性疾病,其发病机制尚未完全明确。目前认为体液和细胞免疫介导的血小板过度破坏、巨核细胞数量和质量异常、血小板生成不足是该病的主要发病机制。近年来,随着对ITP发病机制的不断深入研究,补体作用、滤泡辅助性T细胞的异常等许多观点引起了越来越多的关注,本文将对ITP的发病机制的研究进展做一综述。

  6. Risk of subsequent ischemic and hemorrhagic stroke in patients hospitalized for immune-mediated diseases: a nationwide follow-up study from Sweden

    Zöller Bengt


    Full Text Available Abstract Background Certain immune-mediated diseases (IMDs have been associated with increased risk for cardiovascular disorders. The aim of the present study was to examine whether there is an association between 32 different IMDs and first hospitalization for ischemic or hemorrhagic stroke. Methods All individuals in Sweden hospitalized with a main diagnosis of IMD (without previous or coexisting stroke, between January 1, 1987 and December 31, 2008 (n = 216,291, were followed for first hospitalization for ischemic or hemorrhagic stroke. The reference population was the total population of Sweden. Adjusted standardized incidence ratios (SIRs for ischemic and hemorrhagic stroke were calculated. Results Totally 20 and 15 of the 32 IMDs studied, respectively, were associated with an increased risk of ischemic and hemorrhagic stroke during the follow-up. The overall risks of ischemic and hemorrhagic stroke during the first year after hospitalization for IMD were 2.02 (95% CI 1.90–2.14 and 2.65 (95% CI 2.27–3.08, respectively. The overall risk of ischemic or hemorrhagic stroke decreased over time, to 1.50 (95% CI 1.46–1.55 and 1.83 (95% CI 1.69–1.98, respectively, after 1–5 years, and 1.29 (95% CI 1.23–1.35 and 1.47 (95% CI 1.31–1.65, respectively, after 10+ years. The risk of hemorrhagic stroke was ≥2 during the first year after hospitalization for seven IMDs: ankylosing spondylitis (SIR = 8.11, immune thrombocytopenic purpura (SIR = 8.60, polymyalgia rheumatica (SIR = 2.06, psoriasis (SIR = 2.88, rheumatoid arthritis (SIR = 3.27, systemic lupus erythematosus (SIR = 8.65, and Wegener´s granulomatosis (SIR = 5.83. The risk of ischemic stroke was ≥2 during the first year after hospitalization for twelve IMDs: Addison’s disease (SIR = 2.71, Crohn´s disease (SIR = 2.15, Grave´s disease (SIR = 2.15, Hashimoto´s thyroiditis (SIR = 2.99, immune thrombocytopenic purpura (SIR = 2

  7. Severe fever with thrombocytopenia syndrome virus in ticks collected from humans, South Korea, 2013.

    Yun, Seok-Min; Lee, Wook-Gyo; Ryou, Jungsang; Yang, Sung-Chan; Park, Sun-Whan; Roh, Jong Yeol; Lee, Ye-Ji; Park, Chan; Han, Myung Guk


    We investigated the infection rate for severe fever with thrombocytopenia syndrome virus (SFTSV) among ticks collected from humans during May-October 2013 in South Korea. Haemaphysalis longicornis ticks have been considered the SFTSV vector. However, we detected the virus in H. longicornis, Amblyomma testudinarium, and Ixodes nipponensis ticks, indicating additional potential SFTSV vectors.

  8. Isolated anti-Ro/SSA thrombocytopenia: a rare feature of neonatal lupus.

    Ayadi, Imene Dahmane; Ben Hamida, Emira; Boukhris, Mohamed Riadh; Bezzine, Ahlem; Chaouachi, Sihem; Marrakchi, Zahra


    We report a rare case of isolated thrombocytopenia related to anti-Ro/SSA antibodies. The mother was followed for unlabeled familial thrombocytopenia. The mother had positive anti-Ro/SSA antibodies. She was asymptomatic without skin lesions or other criteria neither of systemic lupus erythematosus nor other connective tissue disease. Pregnancy was uneventful. The postnatal examination was normal. On the first day of life, blood cells count showed thrombocytopenia at 40 x 10(9)/L. Within the second day of life, platelet level dropped to 20 x 10(9)/L. The management of thrombocytopenia included platelet transfusion and human immunoglobulin infusion. On the fifth day of life, there has been a drop in platelet count to 10 x 10(9)/L requiring renewed platelet transfusion and human immunoglobulin infusion. On the 10(th) of life platelets rate was stable around 60 x 10(9)/L. The infant had no evidence of cardiac, dermatologic or hepatobilary involvement initially or throughout follow up.

  9. Reduced corticosteroid use in adult patients with primary immune thrombocytopenia receiving romiplostim

    M. Michel (Marc); P.A.W. te Boekhorst (Peter); A. Janssens (Andre); I. Pabinger-Fasching (Ingrid); M.A. Sanz (Miguel Angel); K. Nie (Kun); G. Kreuzbauer (Georg)


    textabstractAdult patients with primary immune thrombocytopenia requiring first-line treatment typically receive corticosteroids, which are associated with low response rates and many potential side effects. In a retrospective analysis of two 6-month, placebo-controlled, phase III trials, corticoste

  10. The clinical usefulness of the platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia

    Chong, B H; Burgess, J; Ismail, F


    The platelet aggregation test is widely used for the diagnosis of heparin-induced thrombocytopenia (HIT), a potentially serious complication of heparin therapy. We have evaluated its sensitivity and specificity in comparison with those of the 14C-serotonin release test. The sensitivity of the platel

  11. Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia

    Noris, Patrizia; Schlegel, Nicole; Klersy, Catherine; Heller, Paula G.; Civaschi, Elisa; Pujol-Moix, Nuria; Fabris, Fabrizio; Favier, Remi; Gresele, Paolo; Latger-Cannard, Véronique; Cuker, Adam; Nurden, Paquita; Greinacher, Andreas; Cattaneo, Marco; De Candia, Erica; Pecci, Alessandro; Hurtaud-Roux, Marie-Françoise; Glembotsky, Ana C.; Muñiz-Diaz, Eduardo; Randi, Maria Luigia; Trillot, Nathalie; Bury, Loredana; Lecompte, Thomas; Marconi, Caterina; Savoia, Anna; Balduini, Carlo L.; Bayart, Sophie; Bauters, Anne; Benabdallah-Guedira, Schéhérazade; Boehlen, Françoise; Borg, Jeanne-Yvonne; Bottega, Roberta; Bussel, James; De Rocco, Daniela; de Maistre, Emmanuel; Faleschini, Michela; Falcinelli, Emanuela; Ferrari, Silvia; Ferster, Alina; Fierro, Tiziana; Fleury, Dominique; Fontana, Pierre; James, Chloé; Lanza, Francois; Le Cam Duchez, Véronique; Loffredo, Giuseppe; Magini, Pamela; Martin-Coignard, Dominique; Menard, Fanny; Mercier, Sandra; Mezzasoma, Annamaria; Minuz, Pietro; Nichele, Ilaria; Notarangelo, Lucia D.; Pippucci, Tommaso; Podda, Gian Marco; Pouymayou, Catherine; Rigouzzo, Agnes; Royer, Bruno; Sie, Pierre; Siguret, Virginie; Trichet, Catherine; Tucci, Alessandra; Saposnik, Béatrice; Veneri, Dino


    Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 × 109/L. PMID:24763399

  12. Thrombocytopenia in pregnancy in a tertiary care hospital: a retrospective study

    Shiny Varghese


    Conclusions: Commonest cause of thrombocytopenia in pregnancy is GT, followed by preeclampsia, eclampsia and HELLP syndrome. ITP is a rare cause of this disorder in pregnancy. Early detection and treatment of expected complications is the key focus in management of such cases. [Int J Reprod Contracept Obstet Gynecol 2016; 5(5.000: 1532-1535

  13. Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients

    Claushuis, Theodora A M; van Vught, Lonneke A; Scicluna, Brendon P; Wiewel, Maryse A; Klein Klouwenberg, Peter M C; Hoogendijk, Arie J; Ong, David S Y; Cremer, Olaf L; Horn, Janneke; Franitza, Marek; Toliat, Mohammad R; Nürnberg, Peter; Zwinderman, Aeilko H; Bonten, Marc J M; Schultz, Marcus J; van der Poll, Tom


    Preclinical studies have suggested that platelets influence the host response during sepsis. We sought to assess the association of admission thrombocytopenia with the presentation, outcome, and host response in patients with sepsis. Nine hundred thirty-one consecutive sepsis patients were stratifie

  14. Pharmacokinetic-pharmacodynamic analysis of sunitinib-induced thrombocytopenia in Japanese patients with renal cell carcinoma.

    Nagata, Masashi; Ishiwata, Yasuyoshi; Takahashi, Yutaka; Takahashi, Hiromitsu; Saito, Kazutaka; Fujii, Yasuhisa; Kihara, Kazunori; Yasuhara, Masato


    The aim of the present study was to clarify the therapeutic range and adequate dose of sunitinib in Japanese renal cell carcinoma patients by means of a pharmacokinetic-pharmacodynamic analysis of sunitinib-induced thrombocytopenia. Six patients with renal cell carcinoma were enrolled in this study. After starting the sunitinib treatment, between three and seven blood samples were obtained from each patient just before the administration of sunitinib. Serum concentrations of sunitinib and its active metabolite N-desethyl-sunitinib were fit to the 1-compartment model with first-order absorption. Changes in platelet counts were fit to the pharmacokinetic-pharmacodynamic model, in which the proliferation of platelet progenitor cells was assumed to be linearly inhibited by sunitinib and its metabolite. All patients using 50 mg as an initial dose of sunitinib developed grade 2 or 3 thrombocytopenia. The pharmacokinetic-pharmacodynamic model created successfully described the time course of sunitinib-induced thrombocytopenia and could predict changes in platelet counts after alterations to the dosage of sunitinib administered. The simulation results indicated that the total trough level of sunitinib to avoid severe thrombocytopenia should be Japanese patients. In addition to the pharmacokinetic-guided dosage adjustment, the careful monitoring of platelet counts is required for the safe use of sunitinib.

  15. Effect of recombinant human thrombopoietin in nonhuman primates with chemotherapy-induced thrombocytopenia.

    Akahori, H; Shibuya, K; Obuchi, M; Nishizawa, Y; Tsuji, A; Kabaya, K; Kusaka, M; Ohashi, H; Tsumura, H; Kato, T; Miyazaki, H


    We examined the effects of recombinant human thrombopoietin (rhTPO) on myelosuppressive chemotherapy-induced thrombocytopenia in cynomolgus monkeys. After treatment with nimustine (ACNU) on day 0, the monkeys intravenously received rhTPO at a dose of 0.04, 0.2 or 1 microgram/kg/d or monkey's serum once each day from day 1 to day 28. Administration of rhTPO reduced the severity of thrombocytopenia and accelerated the rate of platelet recovery in a dose-dependent fashion. Treatment with the highest rhTPO dose completely prevented thrombocytopenia and stimulated a marked increase in platelet counts over the normal values. Animals treated with ACNU also became neutropenic and slightly anaemic. Administration of rhTPO following ACNU treatment significantly improved neutropenia with increasing doses of rhTPO, but had no effect on anaemia. Compared to the control animals, rhTPO-treated animals exhibited no significant changes in several serum parameters. C-reactive protein concentration and some blood coagulation profiles within the study period. These results suggest a therapeutic efficacy of rhTPO in improving chemotherapy-induced thrombocytopenia.

  16. Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia

    Marković-Sovtić Gordana


    Full Text Available Background/Aim. Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. Methods. We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. Results. There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. Conclusion. The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

  17. Chronic Subdural Hematoma Associated with Thrombocytopenia in a Patient with Human Immunodeficiency Virus Infection in Cameroon

    Clovis Nkoke


    Full Text Available Hematological abnormalities including thrombocytopenia are common in patients living with HIV infection. Patients with HIV infection related thrombocytopenia present generally with only minor bleeding problems. But cases of subdural hematoma are very rare. A 61-year-old female with a history of HIV infection of 9 years’ duration presented with a 3-month history of generalized headache associated with visual blurring and anterograde amnesia. There was no history of trauma or fever. She was treated empirically for cerebral toxoplasmosis for 6 weeks without any improvement of the symptoms. One week prior to admission, she developed weakness of the left side of the body. Clinical examination revealed left-sided hemiparesis. Computed tomography scan of the brain showed a 25 mm chronic right frontoparietotemporal subdural hematoma compressing the lateral ventricle with midline shift. There was no appreciable cerebral atrophy. A complete blood count showed leucopenia and thrombocytopenia at 92,000 cells/mm3. Her CD4-positive cell count was 48 cells/mm3 despite receiving combination antiretroviral therapy for 9 years. A complete blood count analysis suggestive of thrombocytopenia should raise suspicion of possibilities of noninfectious focal brain lesions like subdural hematoma amongst HIV infected patients presenting with nonspecific neurological symptoms. This will enable prompt diagnosis and allow early appropriate intervention.

  18. Fibroproliferative activity in patients with immune thrombocytopenia (ITP) treated with thrombopoietic agents

    Ghanima, W.; Bussel, J.B.; Junker, P.


    This study assessed the grade of bone marrow (BM) fibrosis and its association with a seromarker for collagen-III formation and fibrosis-related cytokines in 25 immune thrombocytopenia (ITP) patients treated with thrombopoietin receptor agonists (Tpo-RA) who had at least one BM biopsy. Assessment...

  19. Discovery of innovative therapies for rare immune-mediated inflammatory diseases via off-label prescription of biologics: the case of IL-6 receptor blockade in Castleman’s disease

    Anne eMusters


    Full Text Available Biologics have revolutionized the field of clinical immunology and proven to be both effective and safe in common immune-mediated inflammatory diseases (IMIDs such as rheumatoid arthritis, inflammatory bowel diseases, and various haematological disorders. However, in patients with rare, severe IMIDs failing on standard therapies it is virtually impossible to conduct randomized controlled trials. Therefore, biologics are usually prescribed off-label in these often severely ill patients. Unfortunately, off-label prescription is sometimes hampered in these diseases due to a lack of reimbursement that is often based on a presumed lack of evidence for effectiveness. In the present article will discuss that off-label prescription of biologics can be a good way to discover new treatments for rare diseases. This will be ilustrated using a case of multicentric Castleman’s disease, an immune-mediated lymphoproliferative disorder, in which off-label tocilizumab (humanized anti-IL-6 receptor blocking antibody treatment resulted in remarkable clinical improvement. Furthermore, we will give recommendations for monitoring efficacy and safety of biologic treatment in rare IMIDs, including the use of registries. In conclusion, we put forward that innovative treatments for rare IMIDs can be discovered via off-label prescription of biologicals, provided that this is based on rational arguments including knowledge of the pathophysiology of the disease.

  20. Association of severe thrombocytopenia and poor prognosis in pregnancies with aplastic anemia.

    Jae Eun Shin

    Full Text Available PURPOSE: We sought to estimate the risks of adverse obstetric outcomes and disease outcomes associated with severe thrombocytopenia in pregnant women with aplastic anemia (AA. METHODS: In a retrospective study, we compared demographics, clinical characteristics, laboratory results, and outcomes between severe thrombocytopenia (ST and non-severe thrombocytopenia (non-ST groups comprising pregnant women with AA. RESULTS: Of 61 AA patients, 43 (70% were diagnosed as AA before pregnancy and 18 (30% were AA during pregnancy. The ST group exhibited lower gestational age at nadir of platelet count (26.0 versus 37.0 weeks, p<0.001 and at delivery (37.3 versus 39.1 weeks, p = 0.008, and a higher rate of bleeding gums (33.8 versus 7.7%, p = 0.015 than the non-ST group. In addition, the ST group exhibited more transfusions during pregnancy (72.7 versus 15.4%, p<0.001 and postpartum period (45.0 versus 2.7%, p<0.001, and more bone marrow transplant after delivery (25.0 versus 0.0%, p<0.001 than the non-ST group. The ST group had a higher odds ratio of composite disease complications (OR, 9.63; 95% CI, 2.82-32.9; p<0.001 and composite obstetric complications (OR, 6.78; 95% CI, 2.11-21.8; p = 0.001 than the non-ST group. CONCLUSIONS: Severe thrombocytopenia is more associated with obstetric and disease complications than is non-severe thrombocytopenia in pregnant women with AA.

  1. Actively induced platelet-bound IgG associated with thrombocytopenia in the marmoset

    Gengozian, N.; McLaughlin, C.L.


    Interspecies platelet immunizations among marmosets lead to antibody formation to the donor platelets and a profound thrombocytopenia, which when associated with anemia may result in death of the animal. This actively induced immonologic thrombocytopenia closely resembles two clinical disease entities manifesting autoimmune thrombocytopenia, posttransfusion purpura and idiopathic thrombocytopenic purpura. Although antibody to donor-type platelets could be demonstrated readily, antihost activity was most often nondetectable or, when present, was in very low titer. A consistent finding was the appearance of IgG on the host's platelets shortly after immunization and concomitant with the appearance of antidonor platelet antibody. In 3 of 13 immunized animals thromoocytopenia did not occur even though antibody was formed and the host's platelets became IgG positive. In those animals that recovered from the induced thrombocytopenia IgG-positive platelets were found for periods ranging from 30 to greater than 100 days. Splenectomy before or after immunization did not alter the sequential development of antibody formation, appearance of IgG-positive platelets, and thrombocytopenia. Eluates prepared from IgG-positive platelets contained IgG and platelet antigens; the eluted IgG could attach nonspecifically to platelets of host or donor (immunizing) type, in contrast to the species specificity demonstrated for IgG eluted from platelets that had been reacted in vitro with specific antibody. Platelets in a few normal, nonimmunized marmosets were found to have signficant amounts of IgG on their surface, comparable to that observed in the immunized animal; interestingly, such IgG-positive platelets were found among imported but not laboratory-bred marmosets.

  2. Frank hematuria as the presentation feature of acute leukemia

    Suriya Owais


    Full Text Available Muco-cutaneous bleeding is a common presenting feature of acute leukemias. Mucosal bleeding usually manifests as gum bleeding and/or epistaxis but may occur in any mucosal surface of the body. Hematuria as an isolated or main presenting feature of acute leukemia is rare. We describe two cases of acute leukemia, a 19 year old male with acute lymphoblastic leukemia and a 52 year old male with acute myeloid leukemia, both presenting with gross hematuria. There was no demonstrable leukemic infiltration of the urinary tract on imaging studies. Hematuria in these patients was likely to be due to occult leukemic infiltration of the urinary system, aggravated by thrombocytopenia, as it subsided after starting chemotherapy. Our cases highlight that hematuria should be remembered as a rare presenting feature of acute leukemia.

  3. Clinical Analysis of 38 Pregnancies with Thrombocytopenia%妊娠合并血小板减少症38例临床分析

    刘桂玲; 邹青


    目的 探讨妊娠合并血小板减少症的病因、临床特征和诊治.方法 选取蚌埠第三人民医院2004年1月-2011年6月间就诊的38例妊娠合并血小板减少症患者进行回顾性分析.结果 妊娠合并血小板减少症的病因为妊娠相关性血小板减少(PAT)24例,免疫性血小板减少症(ITP)7例,再生障碍性贫血2例,营养性巨幼细胞性贫血2例,急性白血病1例,系统性红斑狼疮2例.治疗方法是给予糖皮质激素或丙种球蛋白或输注血小板等,其中23例行剖宫产,有1例出现产后出血,所有患者均未出现新生儿颅内出血及新生儿死亡.结论 妊娠期血小板减少原因较多并且多发生于妊娠中晚期,应积极治疗合并症和并发症,预防出血倾向及加强胎儿监护.对于血小板<50×109/L或有严重出血倾向的患者可予以糖皮质激素和(或)人血丙种球蛋白治疗,产前适当提高血小板水平,可以减少并发症的出现.%Objective To study the pathogeny,clinical characteristic,diagnosis and treatment of thrombocytopenia in pregnancy. Methods The clinical data of 38 pregnancies with thrombocytopenia from Jan. 2004 to Jun. 2011 in our hospital was analyzed retrospectively. Results In all 38 cases,24 were with pregnancy-associated thrombocytopenia (PAT) ,7 with immune thrombocytopenia,2 with aplastic anemia( AA) ,2 with nutritional megaloblastic anemia, 1 with acute leukemia(AL) ,2 with systemic lupus erythematosus( SLE). Glucocorticoid, immunoglobulin or platelet transfusion was selectively administered. The cesarean section was performed in 23 cases, and 1 case was with posrpartum hemorrhage. There was no intracranial hemorrhage of the newborn and perinatal mortality. Conclusion A number of causes may result in thrombocytopenia in pregnancy that mostly occurred in the middle-late pregnancy. More attentions should be paid on the treatment of complication to prevent the haemorrhage and carefully neonatal intensive care. For the

  4. Nonstructural Protein 2 (nsP2) of Chikungunya Virus (CHIKV) Enhances Protective Immunity Mediated by a CHIKV Envelope Protein Expressing DNA Vaccine

    Bao, Huihui; Ramanathan, Aarti A.; Kawalakar, Omkar; Sundaram, Senthil G.; Tingey, Colleen; Bian, Charoran B.; Muruganandam, Nagarajan; Vijayachari, Paluru; Sardesai, Niranjan Y.; Weiner, David B.; Ugen, Kenneth E; Muthumani, Karuppiah


    Chikungunya virus (CHIKV) is an important emerging mosquito-borne alphavirus, indigenous to tropical Africa and Asia. It can cause epidemic fever and acute illness characterized by fever and arthralgias. The epidemic cycle of this infection is similar to dengue and urban yellow fever viral infections. The generation of an efficient vaccine against CHIKV is necessary to prevent and/or control the disease manifestations of the infection. In this report, we studied immune response against a CHIK...

  5. Functional promoter haplotypes of the human FAS gene are associated with the phenotype of SLE characterized by thrombocytopenia

    Nolsøe, R L; Kelly, J A; Pociot, F;


    to SLE or subphenotypes in 126 multiplex American SLE pedigrees and found association of the FAS codon214 AC(C/T) as well as the FAS-670G>A'-codon214 AC(C/T)' haplotype to thrombocytopenia in SLE. Furthermore we have functionally characterized the FAS/FASL promoter polymorphisms associated with SLE...... variant, determines the promoter activity. We conclude that the FAS/FASL promoter haplotypes are functional and that polymorphisms in FAS may contribute to thrombocytopenia in SLE....

  6. 免疫介导性坏死性肌肉病四例临床病理分析及随访%The clinical pathological characteristics and follow-up of 4 cases of immune-mediated necrotizing myopathy

    张英爽; 孙阿萍; 陈璐; 董荣芳; 钟延丰; 樊东升


    Objective To characterize the clinical,electrophysiology and neuropathological features of 4 cases with immune-mediated necrotizing myopathy (IMNM).Methods We retrospectively analyzed the clinical,electrophysiology,neuropathological characteristics of 4 IMNM patients with muscular and skin biopsy in our department during 4 years (from January 2011 to January 2014).Results Among these 4 patients,2 were men and 2 were women (aged 37 to 58 years) with disease duration ranging from 1 month to 60 months.Two patients were with acute onset and 2 with chronic onset.All 4 patients had proximal muscle weakness with three patients with cervical flexor muscle weakness and one with respiratory muscles weakness and noninvasive ventilator assisted respiration.One patient had interstitial lung disease.The anti-signal recognition particle antibodies were strong positive in all 4 patients.Muscle biopsy showed group necrotizing and regenerating fibers in one patient and few scattered necrotizing and regenerating fibers in the other 3 patients.Both muscle fiber hypertrophy and muscle fiber atrophy together with proliferation of connective tissue on endomysium could be viewed in all 4 patients.However,very few inflammatory cells were detectable in patients.One patient was treated with corticosteroids and the other three were treated with combination of corticosteroids and immunosuppressant drugs.Conclusions IMNM is characterized by heterogeneity at disease onset,severity and ilnvolvement of muscles with,however,similary pathological changes including the presence of numerous necrotic and regenerating fibers with little or none inflammation.Corticosteroid and/or immunosuppressant is effective for patients.%目的 总结免疫介导性坏死性肌肉病(IMNM)患者的临床、电生理和骨骼肌病理改变特点.方法 回顾性分析北京大学第三医院2011年1月—2014年1月的4例IMNM患者的临床、电生理特点及肌肉、皮肤活检的病理特点和

  7. Anaemia and thrombocytopenia in patients with prostate cancer and bone metastases

    Pawinski Adam


    Full Text Available Abstract Background The purpose of this study was to determine the incidence, risk factors and prognostic impact of anaemia and thrombocytopenia in patients with bone metastases (BM from prostate cancer. Methods Retrospective cohort study including 51 consecutive patients treated at a community hospital. Twenty-nine patients (57% received taxotere after diagnosis of BM. Results Haemoglobin (Hb ≤ 12.0 g/dL at BM detection was associated with shorter overall survival. During follow-up, 25 patients (49% experienced episodes with Hb 9/L. All of these had previously received blood transfusion. Median interval from Hb 9/L was 2.5 months. Survival after thrombocytopenia was short (3 weeks to 4 months. Haematuria and subdural haematoma were among the causes of death. Conclusions We found high rates of significant bone marrow failure in treatment-refractory patients. Both Hb 9/L predict for unfavourable survival.

  8. Platelet cold agglutinins and thrombocytopenia: A diagnostic dilemma in the intensive care unit

    TV Bharath Kumar


    Full Text Available We report a case of pseudo-thrombocytopenia due to cold agglutinins against platelets. These cold agglutinins were the cause for diagnostic confusion and resulted in extensive workup and unnecessary therapeutic precautions. A thirty two year old female with Guillain-Barre syndrome was admitted in the ICU and serial work-up showed markedly low levels of platelets. The patient had no symptoms of bleeding and patient was investigated extensively for deciphering the etiology of low platelet count. In-vitro clumping of platelets was suspected and in-vitro studies showed marked clumping of platelets with ethylene-diamine-tetra-acetic acid, citrate and heparinized samples. The manual platelet count was found to be within normal limits. Thrombocytopenia as a result of platelet cold agglutinins is a rare cause of in-vitro low platelet counts. No clinical problems have been reported due to the same.

  9. Mild Clinical Course of Severe Fever with Thrombocytopenia Syndrome Virus Infection in an Elderly Japanese Patient

    Yuko Ohagi


    Full Text Available Severe fever with thrombocytopenia syndrome (SFTS is an emerging infectious and hemorrhagic disease recently described in China and western Japan. A 71-year-old healthy Japanese woman noticed a tick biting her after harvesting in an orchard and removed it herself. She developed diarrhea, anorexia, and chills eight days later. Because these symptoms continued, she visited a primary care physician 6 days after the onset. Laboratory data revealed thrombocytopenia, leukocytopenia, and elevated liver enzymes. She was then referred to our hospital. Although not completely fulfilling the diagnostic criteria used in a retrospective study in Japan, SFTS was suspected, and we detected SFTS virus in the patient’s blood using RT-PCR. However, she recovered without intensive treatment and severe complications 13 days after the onset. In this report, we present a mild clinical course of SFTS virus infection in Japan in detail.

  10. Acute Limb Ischemia and Coronary Artery Disease in a Case of Kimura’s Disease

    Heo, Woon; Jun, Hee Jae; Kang, Do Kyun; Min, Ho-Ki; Hwang, Youn-Ho; Kim, Ji Yong; Nam, Kyung Han


    Kimura disease (KD) is an immune-mediated chronic inflammatory disease of unknown etiology. KD has many complications associated with hypereosinophilia, including various forms of allergic reactions and eosinophilic lung disease. Additionally, hypereosinophilia is associated with hypercoagulability, which may lead to thromboembolic events. A 36-year-old man with KD presented with acute limb ischemia and coronary artery occlusion. He underwent thrombectomy, partial endarterectomy of both popliteal arteries, and coronary artery stent insertion. KD is a systemic disease that affects many organs and presents with thromboembolism and vasculitis. In a patient with KD, physicians should evaluate the vascular system, including the coronary arteries. PMID:28382271

  11. Haemaphysalis longicornis Ticks as Reservoir and Vector of Severe Fever with Thrombocytopenia Syndrome Virus in China

    Luo, Li-mei; Zhao, Li; Wen, Hong-Ling; Zhang, Zhen-Tang; Liu, Jian-Wei; Fang, Li-Zhu; Xue, Zai-Feng; Ma, Dong-Qiang; Zhang, Xiao-Shuang; Ding, Shu-Jun; Lei, Xiao-Ying; Yu, Xue-jie


    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia caused by SFTS virus (SFTSV), a newly discovered phlebovirus. The Haemaphysalis longicornis tick has been suspected to be the vector of SFTSV. To determine whether SFTSV can be transmitted among ticks, from ticks to animals, and from animals to ticks, we conducted transmission studies between developmental stages of H. longicornis ticks and between ticks and mice. Using reverse transcription PCR, ...

  12. ANA Negative Systemic Lupus Erythematosus Leading to CTEPH, TTP-Like Thrombocytopenia, and Skin Ulcers

    Sofi, Fayaz; Altaf, Sheikh Shoaib; Raina, Adnan; Raina, Ab. Hameed


    SLE affects almost every organ system, with differing degrees of severity. During its clinical course periods of flares may alternate with periods of remission culminating in disease and therapy related damage. We describe a case of ANA negative SLE with severe thrombocytopenia, cutaneous vasculitis, antiphospholipid antibody syndrome, and pulmonary artery hypertension. As there is no definitive cure for SLE the treatment lies in caring for the individual organ systems involved and simultaneously taking care of the patient as a whole. PMID:27006850

  13. ANA Negative Systemic Lupus Erythematosus Leading to CTEPH, TTP-Like Thrombocytopenia, and Skin Ulcers

    Khalid Hamid Changal


    Full Text Available SLE affects almost every organ system, with differing degrees of severity. During its clinical course periods of flares may alternate with periods of remission culminating in disease and therapy related damage. We describe a case of ANA negative SLE with severe thrombocytopenia, cutaneous vasculitis, antiphospholipid antibody syndrome, and pulmonary artery hypertension. As there is no definitive cure for SLE the treatment lies in caring for the individual organ systems involved and simultaneously taking care of the patient as a whole.


    Ashok S; Ankit; Aundhakar; Lekha; Umardand


    It is a rare genetic disorder characterized by the absence of the radius bone in the forearm and a dramatically reduced platelet count. This syndrome may occur as a part of the 1q21.1 deletion syndrome. Symptoms of thrombocytopenia or a lowered platelet count leads to bruising and potentially life-threatening haemorrhage. Affected children who survive this period and do not have damaging haemorrhages in the brain usually have a normal life expectancy and normal intellectual develo...

  15. Steroid-resistant autoimmune thrombocytopenia in systemic lupus erythematosus treated with rituximab

    Vasudha V Sardesai


    Full Text Available Systemic Lupus Erythematosus (SLE is a multisystem disorder characterized by production of numerous autoantibodies, some of which have pathogenic consequences and result in considerable morbidity. Herein, we present a case of 48-year-old female with SLE having autoimmune hemolytic anemia, autoimmune thrombocytopenia, renal involvement, and recurrent flares of skin manifestations. She did not respond to the conventional therapy and was controlled and treated with Rituximab, a chimeric, monoclonal antiCD20 antibody, which specifically depletes B lymphocytes.

  16. Immune-mediated severe hemolytic crisis with a hemoglobin level of 1.6 g/dl caused by anti-piperacillin antibodies in a patient with cystic fibrosis.

    Kunzmann, S; Thomas, W; Mayer, B; Kuhn, S; Hebestreit, H


    We report a 23-year-old female patient with cystic fibrosis developing severe intravascular hemolysis with a minimal hemoglobin level of 1.6 g/dl after 7 days of treatment with piperacillin, consistent with an immune-mediated hemolytic crisis. Twenty days later, the patient could leave the hospital in good condition without any neurological deficit. To our knowledge, this is the lowest reported hemoglobin value caused by hemolytic anemia with intact survival. As piperacillin is commonly used in patients with cystic fibrosis, it is important to monitor the full-blood counts of patients during treatment with piperacillin and to be aware of the potential for hemolytic anemia to develop. Anti-piperacillin antibodies should be considered whenever these patients develop hemolytic anemia or a positive direct antiglobulin test (DAT). Furthermore, drug-fever under piperacillin application could be a warning sign for the development of hemolytic anemia.

  17. Small Cell Lung Cancer Presenting as Severe Thrombocytopenia and Refractory Hypokalemia

    Rohan Mandaliya


    Full Text Available A 70-year-old female with a history of mild cirrhosis was referred by her primary care provider for a platelet count of 36,000/μL which had dropped from 47,000/μL in a week along with mild pain in extremities. Serum potassium was low (2.9 mEq/L in spite of the patient being recently started on potassium supplement on outpatient for hypokalemia. Initially thrombocytopenia was attributed to cirrhosis. However, platelet counts continued to drop to a nadir of 9000/μL in spite of several platelet transfusions. Hypokalemia was refractory to potassium supplements. Subsequent bone marrow biopsy revealed extensive marrow necrosis with a focus of small cell tumor cells of pulmonary origin. CT scan of the chest showed a spiculated left lung mass. The ACTH level was high, with normal rennin and aldosterone levels. The patient likely had ectopic ACTH syndrome from small cell lung cancer. She died within few days of diagnosis. Severe thrombocytopenia and refractory hypokalemia can rarely be initial presentations of small cell lung cancer. Thrombocytopenia should prompt an evaluation for bone marrow metastases and a search for undiagnosed systemic malignancy. In severe cases of metastases, bone marrow necrosis can be present. Refractory hypokalemia can be the sole presentation of ectopic ACTH production.

  18. Level of RUNX1 activity is critical for leukemic predisposition but not for thrombocytopenia.

    Antony-Debré, Iléana; Manchev, Vladimir T; Balayn, Nathalie; Bluteau, Dominique; Tomowiak, Cécile; Legrand, Céline; Langlois, Thierry; Bawa, Olivia; Tosca, Lucie; Tachdjian, Gérard; Leheup, Bruno; Debili, Najet; Plo, Isabelle; Mills, Jason A; French, Deborah L; Weiss, Mitchell J; Solary, Eric; Favier, Remi; Vainchenker, William; Raslova, Hana


    To explore how RUNX1 mutations predispose to leukemia, we generated induced pluripotent stem cells (iPSCs) from 2 pedigrees with germline RUNX1 mutations. The first, carrying a missense R174Q mutation, which acts as a dominant-negative mutant, is associated with thrombocytopenia and leukemia, and the second, carrying a monoallelic gene deletion inducing a haploinsufficiency, presents only as thrombocytopenia. Hematopoietic differentiation of these iPSC clones demonstrated profound defects in erythropoiesis and megakaryopoiesis and deregulated expression of RUNX1 targets. iPSC clones from patients with the R174Q mutation specifically generated an increased amount of granulomonocytes, a phenotype reproduced by an 80% RUNX1 knockdown in the H9 human embryonic stem cell line, and a genomic instability. This phenotype, found only with a lower dosage of RUNX1, may account for development of leukemia in patients. Altogether, RUNX1 dosage could explain the differential phenotype according to RUNX1 mutations, with a haploinsufficiency leading to thrombocytopenia alone in a majority of cases whereas a more complete gene deletion predisposes to leukemia.

  19. Tpl2 kinase regulates FcγR signaling and immune thrombocytopenia in mice.

    Kyrmizi, Irene; Ioannou, Marianna; Hatziapostolou, Maria; Tsichlis, Philip N; Boumpas, Dimitrios T; Tassiulas, Ioannis


    The MAPK3 Tpl2 controls innate and adaptive immunity by regulating TLR, TNF-α, and GPCR signaling in a variety of cell types. Its ablation gives rise to an anti-inflammatory phenotype characterized by resistance to LPS-induced endotoxin shock, DSS-induced colitis, and TNF-α-induced IBD. Here, we address the role of Tpl2 in autoimmunity. Our data show that the ablation and the pharmacological inhibition of Tpl2 protect mice from antiplatelet antibody-induced thrombocytopenia, a model of ITP. Thrombocytopenia in this model and in ITP is caused by phagocytosis of platelets opsonized with antiplatelet antibodies and depends on FcγR activation in splenic and hepatic myeloid cells. Further studies explained how Tpl2 inhibition protects from antibody-induced thrombocytopenia, by showing that Tpl2 is activated by FcγR signals in macrophages and that its activation by these signals is required for ERK activation, cytoplasmic Ca(2+) influx, the induction of cytokine and coreceptor gene expression, and phagocytosis.

  20. Hyperferritinemia as a Diagnostic Marker for Severe Fever with Thrombocytopenia Syndrome

    Kim, Uh Jin; Oh, Tae hoon; Kim, Bansuk; Kim, Seong Eun; Kang, Seung-Ji; Park, Kyung-Hwa; Jung, Sook-In


    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease in East Asia with high mortality. Few studies have examined markers that suggest SFTS in febrile patients. To determine useful biochemical markers for SFTS, patients aged 18 years or older with SFTS or microbiologically confirmed community-onset bacteremia with thrombocytopenia (BT) at presentation between June 2013 and December 2015 were included from two tertiary university hospitals in Republic of Korea retrospectively. Eleven patients with SFTS and 62 patients with bacteremia and thrombocytopenia were identified in the study period. Age and sex did not show significant difference among two groups. Fever was more commonly observed but comorbidities were less common in SFTS than in BT (P < 0.05, each). The areas under the curves of serum ferritin, C-reactive protein, white blood cell count, serum procalcitonin, and fibrinogen were above 0.9, indicating the discriminative power of these biomarkers (1.000, 0.991, 0.963, 0.931, and 0.934, resp., all P < 0.05). The optimal cutoff value of serum ferritin was 3,822 ng/mL in this study. These results suggest that hyperferritinemia is a typical laboratory feature of SFTS, and the serum ferritin level can be used as a marker for clinicians suspecting SFTS.

  1. Emergency Splenectomy in a patient with primary immune thrombocytopenia and hemoperitoneum

    Liermis Michael Dita Salabert


    Full Text Available Primary immune thrombocytopenia is an acquired autoimmune disease, with a very variable clinical course, which causes an accelerated destruction by antibodies and an impaired platelet production. A case of a 40 year-old female patient of rural origin with a history of mitral stenosis and atrial fibrillation, diagnosed two months prior to her admission to the Dr. Gustavo Aldereguía Lima University General Hospital in Cienfuegos, is presented. She attended the hospital with ecchymosis and petechiae on the lower and upper limbs. After confirming a severe thrombocytopenia (5x109/ l, she was admitted to the Hematology Department. Possible primary immune thrombocytopenia was found. During her stay in the hospital, her clinical condition was complicated by hemoperitoneum. The patient underwent surgery which confirmed the presence of four liters of blood in the abdominal cavity with few clots, bleeding and fissure in the left ovary and adherent clots. An early clamping of the splenic artery, evacuation of the hemoperitoneum, left adnexectomy, splenectomy and resection of accessory spleen were performed. The patient progressed satisfactorily.

  2. Thrombocytopenia in the experimental leptospirosis of guinea pig is not related to disseminated intravascular coagulation

    HU Bao-Yu


    Full Text Available Abstract Background Thrombocytopenia is commonly observed in severe leptospirosis. However, previous studies on coagulation alterations during leptospirosis resulted in inconsistent conclusions. Some findings showed that the prominent levels of thrombocytopenia observed in severe leptospirosis did not reflect the occurrence of disseminated intravascular coagulation (DIC syndrome, while the others reached the conclusion that the hemorrhages observed in leptospirosis were due to DIC. The aim of this study is to elucidate whether DIC is an important feature of leptospirosis. Methods The leptospirosis model of guinea pig was established by intraperitoneal inoculation of Leptospira interrogans strain Lai. Hematoxylin and eosin (HE staining, electron microscopy and immunohistochemistry staining were used to detect the pathologic changes. Platelet thrombus or fibrin thrombus was detected by HE, Martius Scarlet Blue (MSB staining and electron microscopy. Hemostatic molecular markers such as 11-dehydrogenate thromboxane B2 (11-DH-TXB2, thrombomodulin (TM, thrombin-antithrombin III complex (TAT, D-Dimer and fibrin (ogen degradation products (FDPs in the plasma were examined by quantitative enzyme-linked immunosorbent assay (ELISA to evaluate the hematological coagulative alterations in leptospirosis models. Results Pulmonary hemorrhage appeared in the model guinea pig 24 hours after leptospires intraperitoneal inoculation, progressing to a peak at 96 hours after the infection. Leptospires were detected 24 hours post-inoculation in the liver, 48 hours in the lung and 72 hours in the kidney by immunohistochemistry staining. Spiral form of the bacteria was initially observed in the liver, lung and kidney suggestive of intact leptospires, granular form of leptospires was seen as the severity increased. Platelet aggregation in hepatic sinusoid as well as phagocytosis of erythrocytes and platelets by Kupffer cells were both observed. Neither platelet thrombus

  3. Heparin-induced thrombocytopenia type II: Innovations in diagnostics and treatment

    Antonijević Nebojša


    Full Text Available Heparin-induced thrombocytopenia (HIT Management of heparin-induced thrombocytopenia (HIT and treatment options have significantly changed recently. Heparin may induce two types of thrombocytopenia. Type I, occurring earlier with a much higher rate of incidence (5-30%, is characterized by mild thrombocytopenia without significant clinical manifestations. Type II is less frequent (0.5-2%, life threatening immune type, develops following a period of minimum 5-7 days upon introduction of heparin therapy (patients earlier treated with heparin are excluded. Type II heparin-induced thrombocytopenia with severely reduced platelet count may be clinically manifested by thrombosis in 20-50% cases within the period of 30 days. HIT is suspected in persons resistant to heparin with relatively reduced platelet count, though HIT is described in person with normal platelet counts, as well. None of available assays used for HIT detection is completely reliable Sensitivity of a highly specific platelet aggregation assay is only 36% sensitivity and specificity of 14C-serotonin release assays amounts to 95% while ELISA using a heparin/platelet factor-4 target has a sensitivity of 85%. Thus, it is sometimes necessary to combine functional and antigen assays. Furthermore, new classes of antigen assays, like antibody detection tests of complexes between heparin and neutrophil-activating peptide-2 as well as those between heparin and interleukin-8, have been used. Current therapy options Current therapy options exclude formerly applied low-molecular-weight heparins due to the existing cross-reactivity of 80–100%. Danaparoid sodium exhibits in vitro cross-reactivity of 10–61%, clinically manifested in less than 5% of patients. Two drugs are drugs of choice in HIT type II treatment: lepirudin, especially in patients without renal failure and argatroban, particularly in patients with renal failure. The following procedures and agents are also efficient: asmapheresis

  4. PAIgG and PAIgM levels in secondary dengue virus infections lead to thrombocytopenia in patients from KP, Pakistan

    Ibrar Alam; Said Hassan; Iftikhar Alam; Rahmat Gul; Farhad Ali; Ijaz Ali; Sana Ullah; Imtiaz Ali Khan; Aasif Awan


    Objective:To understand the impact of platelet associated immunoglobulin G (PAIgG)/ platelet associated immunoglobulin M (PAIgM) on severity of dengue virus infection leading to thrombocytopenia. Methods: In this study we examined a total of 52 patients who were having secondary infection of dengue in acute phase by using competitive ELISA. Results: A decrease in the platelet count was observed at the acute phase of infection while all along the recovery stage the count of platelet was significantly increased. A significant decrease was observed inPAIgG andPAIgM in these subjects. Inverse correlation was found between platelets count andPAIgG/PAIgM among the subjects studied. In the platelets elution from ten subjects, anti-dengue virus immunoglobulin G and immunoglobulin M were observed.PAIgG andPAIgM with inclined levels were higher in dengue hemorrhagic fever than the classical dengue fever. In the development of dengue hemorrhagic feverPAIgM inclined level was independently associated with high specificity, showing a possible indication of dengue hemorrhagic fever. Conclusions: This study suggests that in secondary dengue virus infection, thePAIgGand PAIgM levels, and the activity of anti-dengue virus play key roles, both in the development and severity of the disease.

  5. PAIgG and PAIgM levels in secondary dengue virus infections lead to thrombocytopenia in patients from KP, Pakistan简

    Ibrar; Alam; Said; Hassan; Iftikhar; Alam; Rahmat; Gul; Farhad; Ali; Ijaz; Ali; Sana; Ullah; Imtiaz; Ali; Khan; Aasif; Awan


    Objective: To understand the impact of platelet associated immunoglobulin G(PAIg G)/platelet associated immunoglobulin M(PAIg M) on severity of dengue virus infection leading to thrombocytopenia.Methods: In this study we examined a total of 52 patients who were having secondary infection of dengue in acute phase by using competitive ELISA.Results: A decrease in the platelet count was observed at the acute phase of infection while all along the recovery stage the count of platelet was significantly increased. A significant decrease was observed in PAIg G and PAIg M in these subjects. Inverse correlation was found between platelets count and PAIg G/PAIg M among the subjects studied. In the platelets elution from ten subjects, anti-dengue virus immunoglobulin G and immunoglobulin M were observed. PAIg G and PAIg M with inclined levels were higher in dengue hemorrhagic fever than the classical dengue fever. In the development of dengue hemorrhagic fever PAIg M inclined level was independently associated with high specificity, showing a possible indication of dengue hemorrhagic fever.Conclusions: This study suggests that in secondary dengue virus infection, the PAIg G and PAIg M levels, and the activity of anti-dengue virus play key roles, both in the development and severity of the disease.

  6. Management of an acute outbreak of diarrhoea-associated haemolytic uraemic syndrome with early plasma exchange in adults from southern Denmark: an observational study

    Colic, Edin; Dieperink, Hans; Titlestad, Kjell


    Diarrhoea-associated haemolytic uraemic syndrome in adults is a life-threatening, but rare multisystem disorder that is characterised by acute haemolytic anaemia, thrombocytopenia, and renal insufficiency. We aimed to assess the success of management of this disorder with plasma exchange therapy....

  7. Nonstructural protein 2 (nsP2) of Chikungunya virus (CHIKV) enhances protective immunity mediated by a CHIKV envelope protein expressing DNA Vaccine.

    Bao, Huihui; Ramanathan, Aarti A; Kawalakar, Omkar; Sundaram, Senthil G; Tingey, Colleen; Bian, Charoran B; Muruganandam, Nagarajan; Vijayachari, Paluru; Sardesai, Niranjan Y; Weiner, David B; Ugen, Kenneth E; Muthumani, Karuppiah


    Chikungunya virus (CHIKV) is an important emerging mosquito-borne alphavirus, indigenous to tropical Africa and Asia. It can cause epidemic fever and acute illness characterized by fever and arthralgias. The epidemic cycle of this infection is similar to dengue and urban yellow fever viral infections. The generation of an efficient vaccine against CHIKV is necessary to prevent and/or control the disease manifestations of the infection. In this report, we studied immune response against a CHIKV-envelope DNA vaccine (pEnv) and the role of the CHIKV nonstructural gene 2 (nsP2) as an adjuvant for the induction of protective immune responses in a relevant mouse challenge model. When injected with the CHIKV pEnv alone, 70% of the immunized mice survived CHIKV challenge, whereas when co-injected with pEnv+pnsP2, 90% of the mice survived viral challenge. Mice also exhibited a delayed onset signs of illness, and a marked decrease in morbidity, suggesting a nsP2 mediated adjuvant effect. Co-injection of the pnsP2 adjuvant with pEnv also qualitatively and quantitatively increased antigen specific neutralizing antibody responses compared to vaccination with pEnv alone. In sum, these novel data imply that the addition of nsP2 to the pEnv vaccine enhances anti-CHIKV-Env immune responses and maybe useful to include in future CHIKV clinical vaccination strategies.

  8. Thrombocytopenia in Patients with Gastric Varices and the Effect of Balloon-occluded Retrograde Transvenous Obliteration on the Platelet Count

    W E Saad


    Full Text Available Objectives: Gastric varices primarily occur in cirrhotic patients with portal hypertension and splenomegaly and thus are probably associated with thrombocytopenia. However, the prevalence and severity of thrombocytopenia are unknown in this clinical setting. Moreover, one-third of patients after balloon-occluded retrograde transvenous obliteration (BRTO have aggravated splenomegaly, which potentially may cause worsening thrombocytopenia. The aim of the study is to determine the prevalence and degree of thrombocytopenia in patients with gastric varices associated with gastrorenal shunts undergoing BRTO, to determine the prognostic factors of survival after BRTO (platelet count included, and to assess the effect of BRTO on platelet count over a 1-year period. Materials and Methods: This is a retrospective review of 35 patients who underwent BRTO (March 2008-August 2011. Pre- and post-BRTO platelet counts were noted. Potential predictors of bleeding and survival (age, gender, liver disease etiology, platelet count, model for end stage liver disease [MELD]-score, presence of ascites or hepatocellular carcinoma were analyzed (multivariate analysis. A total of 91% (n = 32/35 of patients had thrombocytopenia (90% of patients in patients undergoing BRTO. However, BRTO (with occlusion of the gastrorenal shunt has little effect on the platelet count. Long-term outcomes of BRTO for bleeding gastric varices using sodium tetradecyl sulfate in the USA are impressive with a 4-year variceal rebleed rate and transplant-free survival rate of 9% and 76%, respectively. Platelet count is not a predictor of higher rebleeding or patient survival after BRTO.

  9. Estudo epidemiológico das doenças dermatológicas imunologicamente mediadas na cavidade oral An epidemiological study of immune-mediated skin diseases affecting the oral cavity

    Cyntia Helena Pereira de Carvalho


    Full Text Available FUNDAMENTO: As doenças dermatológicas imunologicamente mediadas compõem diversas patologias que apresentam formas variadas de manifestação no organismo. OBJETIVO: Foi proposição desta pesquisa, estabelecer a prevalência das principais doenças dermatológicas imunologicamente mediadas que apresentam manifestação oral. MÉTODOS: Foram avaliados laudos histopatológicos de 10.292 casos arquivados no Serviço de Anatomia Patológica da Disciplina de Patologia Oral da Universidade Federal do Rio Grande do Norte, no período de 1988 a 2009. Dos casos diagnosticados como algum tipo de doença em estudo, coletaram-se dados clínicos como sexo, idade, raça, sítio anatômico e sintomatologia das doenças. RESULTADOS: Do total de casos registrados, no serviço supracitado, 82 (0,8% corresponderam a doenças dermato lógicas imunologicamente mediadas com manifestação na cavidade oral. As doenças encontradas neste estudo foram: líquen plano oral, pênfigo vulgar e penfigoide benigno das membranas mucosas, sendo o líquen plano oral a lesão mais prevalente, representando 68,05% dos casos analisados, dos quais 64,3% apresentavam-se em mu lheres, sendo a mucosa jugal o sítio anatômico mais acometido (46,8%. CONCLUSÃO: A ocorrência de doenças dermatológicas imunologicamente mediadas que apresentam manifestação oral ainda é um fato incomum, semelhante ao observado na maioria das regiões mundiais. No entanto, a busca pelo diagnóstico precoce é um requisito essencial para a condução do tratamento dessas doenças, tendo em vista o possível comprometimento sistêmico do organismo nos pacientes.BACKGROUND: Immune-mediated skin diseases encompass a variety of pathologies that present in different forms in the body. OBJECTIVE: The objective of this study was to establish the prevalence of the principal immune-mediated skin diseases affecting the oral cavity. METHODS: A total of 10,292 histopathology reports stored in the archives of the

  10. Oxidative stress in severe dengue viral infection: association of thrombocytopenia with lipid peroxidation.

    Soundravally, R; Sankar, P; Bobby, Z; Hoti, S L


    Oxidative stress in viral infections has been suggested. The study was carried out to assess the oxidative stress in the different clinical spectrums of dengue infection and to evaluate if thrombocytopenia is associated with lipid and protein oxidative injury. Twenty-seven dengue fever (DF), 32 dengue hemorrhagic fever (DHF) and 21 dengue shock syndrome (DSS) cases were studied at 3, 5 and 7 days of illness. Sixty-three healthy subjects were selected as controls. Serum protein carbonyls (PCOs), malendialdehyde (MDA) and total antioxidant status (TAS) were estimated in blood. Dengue infected individuals had significantly high levels of PCOs and MDA on the three days tested in comparison to controls. In DF cases, no significant changes in the levels of MDA and PCOs were found in course of time. However, among DHF and DSS, significant increase in MDA levels was found in the fifth and seventh day samples in comparison to their respective third day sample (P platelet count and plasma lipid peroxidation levels among DHF and DSS on all three days tested [day 3 (DHF r = -0.392; p = 0.012 and DSS r = -0.453; p = 0.004), day 5 (DHF r = -0.592; p viral infection. The level of oxidative stress was maximal in DSS followed by DHF and its severity was minimal in DF. The thrombocytopenia of dengue infection was associated with the extent of lipid peroxidation. Future studies might be carried out to find the role of oxidative damage in the ethiopathogenesis of thrombocytopenia and vascular leakage in dengue infection.

  11. A whole blood model of thrombocytopenia that controls platelet count and hematocrit.

    Bercovitz, R S; Brenner, M K; Newman, D K


    In patients with thrombocytopenia, it can be difficult to predict a patient's bleeding risk based on platelet count alone. Platelet reactivity may provide additional information; however, current clinical assays cannot reliably assess platelet function in the setting of thrombocytopenia. New methods to study platelet reactivity in thrombocytopenic samples are needed. In this study, we sought to develop a laboratory model of thrombocytopenia using blood from healthy subjects that preserves the whole blood environment and reproducibly produces samples with a specific platelet count and hematocrit. We compared the activation state of unstimulated and agonist-stimulated platelets in thrombocytopenic samples derived from this method with normocytic controls. Whole blood was diluted with autologous red blood cell concentrate and platelet-poor plasma, which were obtained via centrifugation, in specific ratios to attain a final sample with a predetermined platelet count and hematocrit. P-selectin exposure and GPIIbIIIa activation in unstimulated platelets and platelets stimulated with collagen-related peptide (CRP) or adenosine diphosphate (ADP) in thrombocytopenic samples and the normocytic control from which they were derived were quantified by flow cytometry. Our methodology reliably produced thrombocytopenic samples with a platelet count ≤50,000/μL and an accurately and precisely controlled hematocrit. P-selectin exposure and GPIIbIIIa activation on unstimulated platelets or on ADP- or CRP-stimulated platelets did not differ in thrombocytopenic samples compared to normocytic controls. We describe a new method for creating thrombocytopenic blood that can be used to better understand the contributions of platelet number and function to hemostasis.

  12. Incidence of thrombocytopenia and changes in various platelet parameters, in blood culture positive neonatal sepsis

    Sartaj Bhat


    Full Text Available Abstract Objective: To assess the incidence of thrombocytopenia and changes in various platelet parameters, in culture positive neonatal sepsis. Methods: This was prospective study conducted over a period of one year from December 2009 to November 2010 in neonatal intensive care unit of DDUH Hospital, a tertiary care hospital in Delhi, North India. All babies who were admitted during this period were evaluated prospectively for evidence of sepsis. Results: sepsis was diagnosed in 560 neonates. Among 560 neonates, 80/560 (14.28% had Culture positive sepsis. Out of 80 blood culture positive neonates 73 were term neonates and 7 were near term. Gram positive sepsis occurred in 21/80 (26.25%, gram negative sepsis in 54/80 (67.5%, and fungal sepsis in 5/80 (6.25%. Incidence of thrombocytopenia in Gram negative sepsis was (35/54 64.81%, in gram positive sepsis (15/21 71.41% and in fungal sepsis was (3/5 60%. Mean platelet count at the onset of sepsis in all the patients was 123287.5±49428.68. The mean duration of thrombocytopenia in gram positive sepsis was 4.66 ±2.6 days, in gram negative sepsis 4.39 ± 2.22 days and in fungal sepsis 5.2±1.3 days. MPV at the time of onset of sepsis (MPV was high in gram positive sepsis than in gram negative sepsis (11.57±0.88 Vs 11.29 ± 0.76. The MPV of thrombocytopenic neonates was significantly higher than that of non-thrombocytopenic neonates (p < 0.01.

  13. Clinical experience with recombinant human thrombopoietin in chemotherapy-induced thrombocytopenia.

    Vadhan-Raj, S


    Since the identification and cloning of c-Mpl ligand, two forms of recombinant human thrombopoietin have undergone clinical development. Both the full-length molecule, known as rhTPO, and the truncated version of the molecule, known as pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), have been evaluated in phase I/II clinical trials in cancer patients receiving myelosuppressive chemotherapy. Early clinical trials with PEG-rHuMGDF in cancer patients demonstrated its clinical safety and platelet-stimulating activity. However, the development of neutralizing antibodies and clinically significant thrombocytopenia in some patients and normal donors who received PEG-rHuMGDF have led to discontinuation of clinical trials with this molecule in the United States. Clinical experience with rhTPO so far indicates that this full-length glycosylated molecule is remarkably well tolerated and has a favorable safety profile. In these studies, rhTPO exhibited dose-dependent increases in circulating platelet counts and bone marrow megakaryocytes before chemotherapy. In addition, there was an increase in the frequency and proliferation of bone marrow progenitor cells and mobilization of progenitors into the peripheral blood. Early results also showed that rhTPO can attenuate chemotherapy-induced severe thrombocytopenia and reduce the need for platelet transfusions. However, in this setting, the optimal schedule of rhTPO administration may depend on the length of the regimen and anticipated timing of the platelet nadir. These initial results indicate that rhTPO is a safe and potentially useful agent in the prevention and management of chemotherapy-induced thrombocytopenia. Results of larger randomized clinical trials will determine the therapeutic potential of this novel growth factor in various clinical settings.

  14. An unusual cause of mismanagement in an acute myocardial infarction case: pseudothrombocytopenia.

    Kocum, Tolga H; Katircibasi, Tuna M; Sezgin, Alpay T; Atalay, Hakan


    Thrombocytopenia determined by an automated counter may represent a benign, incidental finding in an asymptomatic patient or a potentially life-threatening disorder. Even if the low platelet count actually is a benign condition itself, in some conditions, any delay resulting from this condition consequently may be seriously hazardous. Low platelet count may alter the decision of heparin administration, which is an essential part of management during acute coronary syndromes. EDTA-dependent pseudothrombocytopenia (PTCP) is reported to have a prevalence of 0.1% in a general hospital; however, it is also reported that around 15% of the patients referred for a specialized center for isolated thrombocytopenia are actually cases of PTCP. In this report, we describe a patient with PTCP who could not receive reperfusion therapy during acute myocardial infarction because of the low platelet counts reported by an automated counter.

  15. Refractory thrombotic thrombocytopenic purpura following acute pancreatitis

    Ebisa Bekele; Bethel Shiferaw; Alexandra Sokolova; Arpan Shah; Phillip Saunders; Alida Podrumar; Javed Iqbal


    Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder with an estimated incidence of 4–5 cases per million people per year. It is characterized by small-vessel platelet-rich thrombi that cause thrombocytopenia, microangiopathic hemolytic anemia and organ damage. There are reports in literature that TTP and acute pancreatitis are associated, indicating each can be the cause of the other. However, acute pancreatitis triggering TTP is very rare. A 71 years old female presented with abdominal pain of 3 days, followed by dark urine. She had icteric sclera, petechial rash and mild epigastric tenderness. Lab findings were significant for hemolytic anemia, thrombocytopenia and elevated lipase. CT of abdomen showed evidence of pancreatitis and cholelithiasis. After admission, patient developed symptoms of stroke. Further investigation showed elevated lactate dehydrogenase and normal coagulation studied with peripheral blood smear showed 5–6 schistocytes/high power field. Disintegrin and metalloproteinase with thrombospondin motifs-13 (ADAMTS13) activity showed less than 3% with high ADAMTS13 inhibitor 2.2. Patient required 6–7 weeks of daily plasmapheresis until she showed complete response. Our patient presented with clinical features of pancreatitis prior to having dark urine and petechial rash. Therefore, we strongly believe that our patient had pancreatitis which was followed by TTP. Patient's ADMTS13 activity was 6%after 10 plasma exchanges, signifying refractory TTP and higher risk for morbidity and mortality. There are limited data and consensus on the management of refractory TTP. TTP and acute pancreatitis are associated. However, refractory TTP following acute pancreatitis is rarely mentioned in the literature. We would like to emphasize the importance of having higher clinical suspicion of the association of both disease entities.

  16. Thrombocytopenia and Postpartum Hemorrhage in a Woman with Chromosome 22q11.2 Deletion Syndrome

    Deng, Kathy; Nanda, Deepak


    Chromosome 22q11.2 deletion syndrome, also known as DiGeorge or velocardiofacial syndrome, is associated with a wide spectrum of phenotypic features. It is known to be associated with severe macrothrombocytopenia. Postpartum hemorrhage is a leading cause of maternal morbidity and mortality globally. Chromosome 22q11.2 deletion syndrome is rare cause of thrombocytopenia that can be a significant risk factor for life-threatening postpartum hemorrhage. We report a case of postpartum hemorrhage in a woman with 22q11.2 deletion syndrome causing severe macrothrombocytopenia. PMID:27366335

  17. Sterile water injection labour analgesia in a parturient with preeclampsia with thrombocytopenia

    Shivali Panwar


    Full Text Available Pregnancy induced hypertension is one of the most common causes of maternal morbidity and mortality. A G2L1A1 female with period of gestation 36 weeks presented in our hospital with early labour pains. She was a known case of pregnancy induced hypertension with thrombocytopenia and had been operated on the lumbar spine for Potts spine. She was administered intradermal sterile water injection labour analgesia every 3 hours. The labour was uneventful and patient had a normal vaginal delivery of a male baby. The postnatal course was uneventful and patient was satisfied with the labour analgesia.

  18. [Heparin immune thrombocytopenia in a hemodialysis patient. A case report. Literature review].

    Benítez, M; González Gómez, I; González Carmelo, I; Palma, A; Cruz, S; Rodríguez, E; Amián, A; Fernández M, F; Merino, M J; Fernández G, F; Suárez, C; Onaindía, J M; González, J


    Heparin-induced thrombocytopenia (HIT) is an important side effect of heparin therapy associated with significant morbidity and mortality if unrecognized. The platelet count typically falls below 150,000/ll 5-14 days after heparin is started. Thrombosis is the major clinical complication. We present the case gives a patient that develops a deep vein thrombosis ilio-femoral left, with trombocytopenia, one week after beginning treatment with haemodialysis in which Ac anti heparin is detected by test PaGIA (Particle Gel Inmuno Assay.

  19. Value of autoantibody detection for illness assessment in systemic lupus erythematosus patients with refractory thrombocytopenia

    Xiao-Liang Wu


    Objective:To analyze the value of autoantibody detection for illness assessment in systemic lupus erythematosus patients with refractory thrombocytopenia.Methods:A total of 60 cases of systemic lupus erythematosus (SLE) with refractory thrombocytopenia were the observation group A, 58 cases of patients with SLE alone were the observation group B, and 66 cases of healthy people who received physical examination were control group. Peripheral circulating blood was drawn from research subjects to detect the levels of autoantibody, illness-related factors, Th17, Th1 and Th2 cytokines, complements, and so on, and then the correlation between specific antibody positive rate and disease severity in SLE patients with refractory thrombocytopenia was further analyzed.Results:Anti-RNP antibody, anti-Sm antibody, anti-Scl-70 antibody, anti-AnuA antibody, anti-His antibody and anti-ds-DNA antibody positive rates of observation group A were higher than those of observation group B and control group (P<0.05); sICAM-1, PTM, sCD30L and MCP-1 values of observation group A were higher than those of observation group B and control group (P<0.05); serum IL-17, IL-23, IFN-γ, TNF-α, IL-4, IL-5 and IL-6 values of observation group A were higher than those of observation group B and control group (P<0.05); serum C1qAg, C3, C4 and CFH values of observation group A were lower than those of observation group B and control group while C1qAb value was higher than that of observation group B and control group (P<0.05); anti-Sm antibody and anti-ds-DNA antibody positive rates of SLE patients were positively correlated with serum sICAM-1, PTM, sCD30L, MCP-1, IL-17, IL-23, IFN-γ, TNF- , IL-4, IL-5, IL-6 and C1qAb values, and negatively correlated with C1qAg, C3, C4 and CFH values (P<0.05). Conclusions:Specific autoantibody positive rates are high in systemic lupus erythematosus patients with refractory thrombocytopenia, have direct correlation with the disease severity and can be used as the

  20. Acute pancreatitis-induced thrombotic thrombocytopenic purpura with recurrent acute pancreatitis.

    Fujino, Yasuhisa; Inoue, Yoshihiro; Onodera, Makoto; Kikuchi, Satoshi; Sato, Masayuki; Kojika, Masahiro; Sato, Hisaho; Suzuki, Keijiro; Matsumoto, Masanori


    Recent successive reports on acute pancreatitis-induced thrombotic thrombocytopenic purpura (TTP) have revealed that TTP-related microvascular damage is an aggravating factor of acute pancreatitis. Here, we report the case of a 26-year-old man diagnosed with acute pancreatitis due to high alcohol consumption. The patient was unconscious as he had taken an overdose of medication, and presented with fever and renal failure due to acute pancreatitis on admission. Although the pancreatitis subsequently improved, the symptoms were still observed; on the next day, he exhibited hemoglobinuria, anemia, and thrombocytopenia. Moreover, general blood examinations indicated the presence of schistocytes and reduced activity of ADAMTS13 (a disintegrin-like metalloproteinase with thrombospondin type 1 motif 13) to 47 %. Thus, the patient was diagnosed with TTP, and plasma exchange was performed. After the development of TTP, the acute pancreatitis recurred, but a severe pathogenesis was prevented by plasma exchange. Thus, ADAMTS13 activity may be useful for predicting a severe pathogenesis of acute pancreatitis. In ADAMTS13-deficient cases, plasma exchange may be an effective technique for preventing aggravation of acute pancreatitis.

  1. Successful Management of Heparin-Induced Thrombocytopenia Using Argatroban in a Very Old Woman: A Case Report

    A. Putot


    Full Text Available Thrombosis due to heparin-induced thrombocytopenia (HIT is rare but has a severe prognosis. Its management is not always easy, particularly in old patients with renal insufficiency. A 95-year-old woman was hospitalized for dyspnea. Curative treatment with unfractionated heparin was started because pulmonary embolism was suspected. Disseminated intravascular coagulation was then suspected because of thrombocytopenia, hypoprothrombinemia, hypofibrinogenemia, and a positive ethanol gelation test. The first immunoassay for HIT was negative. On the 12th day of hospitalization, bilateral cyanosis of the toes occurred associated with recent deep bilateral venous and arterial thrombosis at duplex ultrasound. New biological tests confirmed HIT and led us to stop heparin and to start argatroban with a positive clinical and biological evolution. Venous and arterial thrombosis associated with thrombocytopenia during heparin treatment must be considered HIT whatever the biological test results are. Argatroban is a good alternative treatment in the elderly.

  2. Acute pancreatitis

    ... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... pancreatitis; Pancreas - inflammation Images Digestive system Endocrine glands Pancreatitis, acute - CT scan Pancreatitis - series References Forsmark CE. Pancreatitis. ...

  3. Cystitis - acute

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  4. Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia

    Masayuki Miyazaki; Masatake Tanaka; Akihiro Ueda; Tsuyoshi Yoshimoto; Masaki Kato; Makoto Nakamuta; Kazuhiro Kotoh; Ryoichi Takayanagi


    Drug-induced hypersensitivity syndrome (DIHS) is a se-vere reaction usually characterized by fever, rash, and multiorgan failure, occurring 2-6 wk after drug introduction.It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release. A 54-year-old woman was diagnosed with rheumatic arthritis and initiated salazosulfapyridine by mouth. About 10 d later, she had a high fever, skin rash and liver dysfunction. She was admitted to hospital and diagnosed with a drug eruption. She was treated with oral prednisolone 30 mg/d; however, she developed high fever again and her blood tests showed acute liver failure and cytopenia associated with hyperferritinemia. She was diagnosed with acute liver failure and hemophagocytosis caused by DIHS. She was transferred to the Department of Medicine and Bioregulatory Science, Kyushu University, where she was treated with arterial steroid injection therapy. Following this treatment, her liver function improved and serum ferritin immediately decreased. We hypothesized that an immune-mediated reaction in DIHS may have generated over-activation of macrophages and T-lymphocytes, followed by a cytokine storm that affected various organs. The measurement of serum ferritin might be a useful marker of the severity of DIHS.

  5. Incidence and diagnosis of EDTA-dependent pseudothrombocytopenia in a consecutive outpatient population referred for isolated thrombocytopenia.

    Silvestri, F; Virgolini, L; Savignano, C; Zaja, F; Velisig, M; Baccarani, M


    Among 111 patients referred to our outpatient clinic for isolated thrombocytopenia during a 24-month period, 17 (15.3%) cases of EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) were identified. EDTA-PTCP represented the second most frequent cause of thrombocytopenia in this population. The diagnosis was confirmed by the following findings: (a) normal platelet numbers immediately after blood withdrawal; (b) progressive fall of platelet counts and evident platelet clumping over time, only in EDTA-anticoagulated blood. A simple, inexpensive and quick diagnostic method was devised, that consists in evaluating the platelet number in a blood sample anticoagulated with EDTA immediately after blood withdrawal and 4 h later.

  6. Treatment-associated severe thrombocytopenia affects survival rate in esophageal cancer patients undergoing concurrent chemoradiotherapy

    Y M Huang


    Full Text Available Background: Esophageal cancer is commonly treated with surgery, concurrent chemoradiotherapy (CCRT, or a combination of both. The correlation between the hematological parameters during CCRT and early survival of esophageal cancer has not been fully evaluated. Materials And Methods: We analyzed the records of 65 esophageal cancer patients treated by CCRT between 2007 and 2010 retrospectively. The association between CCRT-associated myelosuppression, demographic variables, and survival rates were analyzed by univariate and multivariate analysis. Results: The univariate analysis showed that tumor extent of T3-4, a higher stage of tumor, a lower albumin level, grade 3 or higher anemia and thrombocytopenia, and interruptions in treatment affected survival rates. Further, the multivariate analysis revealed that stage IV (P = 0.030 is an independently negative prognostic factor for a one-year survival rate. Stage IV (P = 0.035, tumor extent of T3-4 (P = 0.002, and grade 3-4 thrombocytopenia (P = 0.015 are independently negative prognostic factors for a two-year survival rate. Conclusions: Severe decrease in platelet count during CCRT independently affects survival of esophageal cancer patients in addition to stage of the tumor.

  7. Systematic review of severe fever with thrombocytopenia syndrome: virology, epidemiology, and clinical characteristics.

    Liu, Shelan; Chai, Chengliang; Wang, Chengmin; Amer, Said; Lv, Huakun; He, Hongxuan; Sun, Jimin; Lin, Junfen


    Severe fever with thrombocytopenia syndrome (SFTS) was firstly discovered in China in 2010, followed by several reports from many other countries worldwide. SFTS virus (SFTSV) has been identified as the causative agent of the disease and has been recognized as a public health threat. This novel Bunyavirus belongs to the Phlebovirus genus in the family Bunyaviridae. This review also describes the different aspects of virology, pathogenesis, epidemiology, and clinical symptoms on the basis of the published article surveillance data and phylogenetic analyses of viral sequences of large, medium, and small segments retrieved from database using mega 5.05, simplot 3.5.1, network 4.611, and epi information system 3.5.3 software. SFTS presents with fever, thrombocytopenia, leukocytopenia, and considerable changes in several serum biomarkers. The disease has 10~15% mortality rate, commonly because of multiorgan dysfunction. SFTSV is mainly reported in the rural areas of Central and North-Eastern China, with seasonal occurrence from May to September, mainly targeting those of ≥50 years of age. A wide range of domesticated animals, including sheep, goats, cattle, pigs, dogs, and chickens have been proven seropositive for SFTSV. Ticks, especially Haemaphysalis longicornis, are suspected to be the potential vector, which have a broad animal host range in the world. More studies are needed to elucidate the vector-animal-human ecological cycle, the pathogenic mechanisms in high level animal models and vaccine development.

  8. Significance of Periodontal Health in Primary Immune Thrombocytopenia- A Case Report and Review of Literature

    Rajinder K Sharma


    Full Text Available Primary immune thrombocytopenia is an acquired bleeding disorder with no clinically apparent cause of thrombocytopenia. Clinical indicators of ITP include easy bruising of the skin, prolonged bleeding on injury, mucocutaneous lesions such as petechiae and ecchymosis, epistaxis, gastrointestinal bleeding, hematuria and bleeding from the gums. It is important for a dentist to be aware of the clinical manifestations of ITP as it may not only lead to successful management of the patient, but in some cases it may even lead to formation of a provisional diagnosis of the condition in previously undetected cases. However, very few cases of ITP have been reported in dental practice making it difficult for a dentist to identify the disorder when a patient suffering from ITP reports for dental treatment. A case report of a female patient with ITP is thus described with emphasis on the importance of periodontal health in such patients to prevent consequent unwanted sequelae. It is followed by discussion of oral manifestations of the disorder and dental management of such patients.

  9. Successful laparoscopic splenectomy after living-donor liver transplantation for thrombocytopenia caused by antiviral therapy


    Although interferon (IFN) based therapy for recurrent hepatitis C virus (HCV) infection after liver transplantation has been widely accepted, it induces various adverse effects such as thrombocytopenia, resulting in its interruption. Recently, concomitant splenectomy at the time of living donor liver transplantation (LDLT) has been tried to overcome this problem, but this procedure leads to several complications such as excessive intraoperative bleeding and serious infection. A 60-year-old female received LDLT using a left lobe graft from her second son for liver failure caused by hepatitis C-related cirrhosis. Six months after LDLT, she was diagnosed as recurrent HCV infection by liver biopsy. IFN monotherapy was started from 7 mo after LDLT and her platelet count decreased to less than 50000/μL, which thus made it necessary to discontinue the treatment. We decided to attempt laparoscopic splenectomy (LS) under general anesthesia. Since intra-abdominal findings did not show any adhesion formations around the spleen, LS could be successfully performed. After LS, since her platelet count immediately increased to 225000/μL 14 d after operation, IFN therapy was restarted and we could convert the combination therapy of IFN and ribavirin, resulting in no detectable viral marker. In conclusion, LS can be performed safely even after LDLT, and LS after LDLT is a feasible and less invasive modality for thrombocytopenia caused by antiviral therapy.

  10. Prenatal testing for hemolytic disease of the newborn and fetal neonatal alloimmune thrombocytopenia - current status.

    Avent, Neil D


    Incompatibility of red cell and platelet antigens can lead to maternal alloimmunization causing hemolytic disease of the fetus & newborn and fetal neonatal alloimmune thrombocytopenia respectively. As the molecular background of these polymorphisms emerged, prenatal testing using initially fetal DNA obtained from invasively obtained amniotic fluid or chorionic villus was implemented. This evolved into testing using maternal plasma as source of fetal DNA, and this is in routine use as a safe non-invasive diagnostic that has no risk to the fetus of alloimmunization or spontaneous miscarriage. These tests were initially applied to high risk pregnancies, but has been applied on a mass scale, to screen fetuses in D-negative pregnant populations as national screening programs. Fetal neonatal alloimmune thrombocytopenia management has had comparatively small take up in non-invasive testing for causative fetal platelet alleles (e.g., HPA-1A), but mass scale genotyping of mothers to identify at risk HPA-1b1b pregnancies and their treatment with prophylactic anti-HPA-1A is being considered in at least one country (Norway).

  11. Heparin-induced thrombocytopenia: a review of concepts regarding a dangerous adverse drug reaction.

    Junqueira, Daniela Rezende Garcia; Carvalho, Maria das Graças; Perini, Edson


    Heparin is a natural agent with antithrombotic action, commercially available for therapeutic use as unfractionated heparin and low molecular weight heparin. Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin that promotes antibody-mediated platelet activation. HIT is defined as a relative reduction in platelet count of 50% (even when the platelet count at its lowest level is above>150 x 10(9)/L) occurring within five to 14 days after initiation of the therapy. Thrombocytopenia is the main feature that directs the clinical suspicion of the reaction and the increased risk of thromboembolic complications is the most important and paradoxical consequence. The diagnosis is a delicate issue, and requires a combination of clinical probability and laboratory tests for the detection of platelet activation induced by HIT antibodies. The absolute risk of HIT has been estimated between 1% and 5% under treatment with unfractionated heparin, and less than 1% with low molecular weight heparin. However, high-quality evidence about the risk of HIT from randomized clinical trials is scarce. In addition, information on the frequency of HIT in developing countries is not widely available. This review aims to provide a better understanding of the key features of this reaction and updated information on its frequency to health professionals and other interested parties. Knowledge, familiarity, and access to therapeutic options for the treatment of this adverse reaction are mandatory to minimize the associated risks, improving patient safety.

  12. Nye behandlingsmuligheder ved primær immun trombocytopeni

    Gudbrandsdottir, Sif; Frederiksen, Henrik; Birgens, Henrik Sverre


    Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved in the pathog...

  13. Acute Bronchitis

    ... Smoking also slows down the healing process. Acute bronchitis treatment Most cases of acute bronchitis can be treated at home.Drink fluids, but ... bronchial tree. Your doctor will decide if this treatment is right for you. Living with acute bronchitis Most cases of acute bronchitis go away on ...

  14. Experience of off-label use of Eltrombopag in the treatment of thrombocytopenia associated with solid tumors

    María Henar García Lagunar


    Full Text Available Purpose: To describe the results of the off-label use of eltrombopag in patients with solid tumors and thrombocytopenia that limits chemotherapy. Methods: Retrospective observational study including all patients with solid tumors who were treated with eltrombopag for thrombocytopenia during the chemotherapy treatment between January 2012 and December 2014. Results: Six patients, with solid tumors and thrombocytopenia that limits chemotherapy treatment, received eltrombopag during the study and it was observed a decrease in the delay of chemotherapy cycles (4.83 ± 4.79 delayed cycles before starting eltrombopag vs 2.50 ± 4.32 delayed cycles during the treatment with eltrombopag, p=0.492 and an increase in the percentage of administrated dosage (89.29 ± 13.36% vs 91.43 ± 10.69%, p=0.682. Also, there was an increase in platelet nadir (55.29 ± 16.45x109/L vs 76.14 ± 36.38x109/L, p=0.248 without platelet transfusion support in any patient during treatment with eltrombopag. Conclusions: eltrombopag has resulted to be an alternative in the treatment of patients with thrombocytopenia that limits chemotherapy, clinical trials with more number or patients are needed to confirm these results

  15. Efficacy and safety of low-dose rituximab combined with different dosage of glucocorticoids for immune thrombocytopenia



    Objective To compare the efficacy and safety of low-dose rituximab combined with different dosage of glucocorticoids for immune thrombocytopenia (ITP) .Methods Seventy-four patients (35 male,median age 34years,range 18—70 years) including 60 newly-diagnosed,6 persistent,5 chronic and 3 refractory patients

  16. The role of platelet and plasma markers of antioxidant status and oxidative stress in thrombocytopenia among patients with vivax malaria

    Claudio F Araujo


    Full Text Available Malaria remains an important health problem in tropical countries like Brazil. Thrombocytopenia is the most common hematological disturbance seen in malarial infection. Oxidative stress (OS has been implicated as a possible mediator of thrombocytopenia in patients with malaria. This study aimed to investigate the role of OS in the thrombocytopenia of Plasmodium vivax malaria through the measurement of oxidant and antioxidant biochemical markers in plasma and in isolated platelets. Eighty-six patients with P. vivax malaria were enrolled. Blood samples were analyzed for total antioxidant and oxidant status, albumin, total protein, uric acid, zinc, magnesium, bilirubin, total thiols, glutathione peroxidase (GPx, malondialdehyde (MDA, antibodies against mildly oxidized low-density lipoproteins (LDL-/nLDL ratio and nitrite/nitrate levels in blood plasma and GPx and MDA in isolated platelets. Plasma MDA levels were higher in thrombocytopenic (TCP (median 3.47; range 1.55-12.90 µmol/L compared with the non-thrombocytopenic (NTCP patients (median 2.57; range 1.95-8.60 µmol/L. Moreover, the LDL-/nLDL autoantibody ratio was lower in TCP (median 3.0; range 1.5-14.8 than in NTCP patients (median 4.0; range 1.9-35.5. Finally, GPx and MDA were higher in the platelets of TPC patients. These results suggest that oxidative damage of platelets might be important in the pathogenesis of thrombocytopenia found in P. vivax malaria as indicated by alterations of GPx and MDA.

  17. Drug-induced haemolysis, renal failure, thrombocytopenia and lactic acidosis in patients with HIV and cryptococcal meningitis: a diagnostic challenge.

    Camara-Lemarroy, Carlos R; Flores-Cantu, Hazael; Calderon-Hernandez, Hector J; Diaz-Torres, Marco A; Villareal-Velazquez, Hector J


    Patients with HIV are at risk of both primary and secondary haematological disorders. We report two cases of patients with HIV and cryptococcal meningitis who developed severe haemolytic anaemia, thrombocytopenia, renal failure and lactic acidosis while on treatment with amphotericin B and co-trimoxazole.

  18. Association of beta2-glycoprotein I IgG and IgM antibodies with thrombosis and thrombocytopenia

    Voss, Anne-Sofie Boertmann; Jacobsen, Søren; Heegaard, Niels Henrik Helweg


    Antiphospholipid antibodies (APA) have been known for decades. Their relation to clinical manifestations, primarily thromboses and thrombocytopenia, was recognised in the 1980s. In this clinical study two cohorts of patients, a population-based (84 patients with systemic lupus erythematosus (SLE)...

  19. Esophageal Candidiasis as the Initial Manifestation of Acute Myeloid Leukemia.

    Komeno, Yukiko; Uryu, Hideki; Iwata, Yuko; Hatada, Yasumasa; Sakamoto, Jumpei; Iihara, Kuniko; Ryu, Tomiko


    A 47-year-old woman presented with persistent dysphagia. A gastroendoscopy revealed massive esophageal candidiasis, and oral miconazole was prescribed. Three weeks later, she returned to our hospital without symptomatic improvement. She was febrile, and blood tests showed leukocytosis (137,150 /μL, blast 85%), anemia and thrombocytopenia. She was diagnosed with acute myeloid leukemia (AML). She received chemotherapy and antimicrobial agents. During the recovery from the nadir, bilateral ocular candidiasis was detected, suggesting the presence of preceding candidemia. Thus, esophageal candidiasis can be an initial manifestation of AML. Thorough examination to detect systemic candidiasis is strongly recommended when neutropenic patients exhibit local candidiasis prior to chemotherapy.

  20. Correlation between serum levels of interleukins 10 and 12 and thrombocytopenia in hepatitis C cirrhotic (class A patients

    N Abdallah


    Full Text Available Hepatitis C virus (HCV patients commonly have low platelet counts; however, the exact role of HCV infection in thrombocytopenia is unknown. This work aimed to study the serum levels of interleukins (IL 10 and 12 in patients with mild and moderate thrombocytopenia associated with chronic hepatitis C infection. Our study included 15 patients with chronic HCV infection and newly diagnosed isolated autoimmune thrombocytopenia (Group I and 15 patients with chronic HCV infection and normal platelet count as controls (Group II. All patients were examined for personal history and clinical aspects, complete blood count, bone marrow aspiration, liver function tests, HCV antibody assay by ELISA and polymerase chain reaction (PCR, abdominal ultrasound, Helicobacter pylori stool antigen test, evaluation of serum levels of IL-10, IL-12 and platelet specific antibodies. Our results revealed that eight patients from Group l had mild thrombocytopenia and seven patients had moderate thrombocytopenia. Serum IL-10 level was significantly elevated (t = 9.301, p < 0.001 while serum IL-12 showed a significant decrease (t = 6.502, p < 0.001 in Group I compared to the control group. No correlation was detected between platelet counts and the serum levels of either IL-10 [r = 0.454, p = 0.089 (Group I, r = 0.038, p = 0.89 (Group II] or IL-12 [r = 0.497, p = 0.06 (Group I, r = 0.499, p = 0.058 (Group II]. However, in Group I, a significant correlation was present only between moderate thrombocytopenia and serum levels of either IL-10 (r = 0.794, p = 0.033 or IL-12 (r = 0.967, p = 0.001, while no correlation was detected between these interleukin parameters and mild thrombocytopenia (r = 0.311 and p = 0.453 for IL-10 and r = -0.08 and p = 0.851 for IL-12. Based on our data, we may conclude that interleukins 10 and 12 are involved in low platelet levels.

  1. Clinical features and factors associated with severity and fatality among patients with severe fever with thrombocytopenia syndrome Bunyavirus infection in Northeast China.

    Baocheng Deng

    Full Text Available BACKGROUND: In 2009, severe fever with thrombocytopenia syndrome virus (SFTSV was identified as a novel member of the genus phlebovirus in the Bunyaviridae family in China. The detailed clinical features of cases with SFTSV infection have not been well described, and the risk factors for severity among patients and fatality among severe patients remain to be determined. METHODOLOGY/PRINCIPAL FINDINGS: Clinical and laboratory features of 115 hospitalized patients with SFTSV infection during the period from June 2010 to December 2011 in Northeast China were retrospectively reviewed. We assessed the risk factors associated with severity in confirmed cases and fatality in severe cases by multivariate analysis. One hundred and three (89.6% of 115 patients presented with multiple organ dysfunction, and 22 (19.1% of 115 proceeded to the stage of life threatening multiple organ failure. Of the 115 patients, 14 fatalities (12.2% were reported. Multivariate analysis demonstrated that the independent predictors of risk for severity were: albumin ≤ 30 g/l (OR, 8.09; 95% CI, 2.58-25.32, APTT ≥ 66 seconds (OR, 14.28; 95% CI, 3.28-62.24, sodium ≤ 130 mmol/l (OR, 5.44; 95% CI, 1.38-21.40, and presence of neurological manifestations (OR, 7.70; 95% CI, 1.91-31.12. Among patients with severe disease, presence of acute lung injury/acute respiratory distress syndrome (HR, 4.59; 95% CI, 1.48-14.19 and disseminated intravascular coagulation (HR, 4.24; 95% CI, 1.38-13.03 were independently associated with fatality. CONCLUSIONS/SIGNIFICANCE: SFTSV infection may present with more severe symptoms and laboratory abnormalities than hitherto reported. Due to infection with a novel bunyavirus, the patients may sufferer multiple organ dysfunction and die of multiple organ failure. In the clinical assessment of any case of SFTS, independent factors relating to prognosis need to be taken into account by clinicians.

  2. More on false thrombocytopenias: EDTA-dependent pseudothrombocytopenia associated with a congenital platelet release defect.

    Silvestri, F; Masotti, A; Pradella, P; Zaja, F; Barillari, G; De Marco, L


    We report herein the case of a 54-year-old woman with a moderate bleeding tendency, diagnosed as an EDTA-dependent pseudothrombocytopenia associated with a congenital platelet release defect. The patient, at the age of 12, had a misleading diagnosis of idiopathic thrombocytopenic purpura and all the recurrent bleeding problems she had during her life were referred to that disease. The recent correct diagnosis of a false thrombocytopenia stimulated further laboratory investigation on the cause of the patient's bleeding tendency with the consequent identification of a congenital platelet deficiency of the arachidonic acid pathway. This finding is of relevant importance for the management of the patient in case of elective surgery or hemorrhagic emergency.

  3. Hereditary Haemorrhagic Telangiectasia with Thrombocytopenia - A Rare Association with an Atypical Presentation

    Padmakumar R


    Full Text Available Hereditary Haemorrhagic Telangiectasia (Osler-Rendu-Weber disease is a rare autosomal dominant disorder commonly a ecting small vessels of skin and mucosa. It is usually misdiagnosed because of its atypical presentation. This disease frequently presents as epistaxis, GI bleed and visceral arterio venous malformations. Patient may present with stroke or migraine but presentation due to predominant respiratory symptoms may occur in the presence of pulmonary A-V stula. We present a 9 yr old male with dyspnoea on exertion and cyanosis and clubbing. He had a past history of intracerebral bleed with thrombocytopenia and he was being treated as ITP. Contrast echo revealed ndings suggestive of pulmonary arterio venous stula which led to subsequent investigations and retrospective evaluation and hence achieving the final diagnosis.

  4. Her-2 Positive Gastric Cancer Presented with Thrombocytopenia and Skin Involvement: A Case Report

    Deniz Arslan


    Full Text Available Gastric cancer is the 5th most frequent cancer around the world and the 3rd most frequent reason of deaths due to cancer. Every year, about 1 million new cases are taking place, with varying geographical distribution. Gastric cancer is often metastatic to liver, lungs, and bones in hematogenous way, to peripheral lymph nodes in lymphogenous way, and to peripheral tissues in adjacency way, yet bone marrow (BM and cutaneous metastasis are quite seldom. Pancytopenia is a more frequent finding identified in BM metastasis of solid organ cancers, and isolated thrombocytopenia is less often. The human epidermal growth factor 2 (HER-2 is positive in gastric cancer at a rate of 7–34%. Here, we have presented our HER-2 positive gastric cancer incident which presented with BM and cutaneous metastasis, and has no 18F-fluoro-2-deoxi-D-glucose (FDG involvement except bone metastases.

  5. Partial splenic embolization in a child with Gaucher disease, massive splenomegaly and severe thrombocytopenia

    Pena, Andres H.; Clevac, Egor; Marie Cahill, Anne [Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Kaplan, Paige; Ganesh, Jaya [Children' s Hospital of Philadelphia, Division of Metabolic Diseases, Philadelphia, PA (United States)


    A 13-month-old boy with Gaucher disease presented with severe thrombocytopenia, anemia and massive splenomegaly. In addition he had significant respiratory compromise caused by abdominal compartment syndrome, requiring mechanical ventilation. Because of the degree of respiratory compromise and his existing bone marrow suppression, splenic artery embolization was chosen as an alternative to splenectomy. Splenic artery embolization was performed using 355-500-{mu}m polyvinyl alcohol particles, with 70% ablation achieved. Within 24 h of the procedure the platelet count had risen to greater than 70,000/mm{sup 3} and to more than 170,000/mm{sup 3} on postoperative day 4. At the 8-month follow-up the splenic size had decreased from 18 cm to 8 cm, with a platelet count of 578,000/mm{sup 3}. Partial splenic embolization provides a minimally invasive alternative to splenectomy in patients with Gaucher disease with massive splenomegaly and bone marrow suppression. (orig.)

  6. Childhood immune thrombocytopenia: role of rituximab, recombinant thrombopoietin, and other new therapeutics.

    Journeycake, Janna M


    Childhood immune thrombocytopenia (ITP) is often considered a benign hematologic disorder. However, 30% of affected children will have a prolonged course and 5%-10% will develop chronic severe refractory disease. Until recently, the only proven therapeutic option for chronic severe ITP was splenectomy, but newer alternatives are now being studied. However, because immunosuppressive agents such as rituximab are not approved for use in ITP and the thrombopoietin receptor agonists are not yet approved in children, the decision to use alternatives to splenectomy needs to be considered carefully. This review describes the factors that should affect decisions to treat ITP at diagnosis and compares the options for the occasional child in whom ITP does not resolve within the first year.

  7. Her-2 Positive Gastric Cancer Presented with Thrombocytopenia and Skin Involvement: A Case Report

    Arslan, Deniz; Tatlı, Ali Murat; Goksu, Sema Sezgin; Başsorgun, Cumhur İbrahim; Coskun, Hasan Senol; Bozcuk, Hakan; Savaş, Burhan


    Gastric cancer is the 5th most frequent cancer around the world and the 3rd most frequent reason of deaths due to cancer. Every year, about 1 million new cases are taking place, with varying geographical distribution. Gastric cancer is often metastatic to liver, lungs, and bones in hematogenous way, to peripheral lymph nodes in lymphogenous way, and to peripheral tissues in adjacency way, yet bone marrow (BM) and cutaneous metastasis are quite seldom. Pancytopenia is a more frequent finding identified in BM metastasis of solid organ cancers, and isolated thrombocytopenia is less often. The human epidermal growth factor 2 (HER-2) is positive in gastric cancer at a rate of 7–34%. Here, we have presented our HER-2 positive gastric cancer incident which presented with BM and cutaneous metastasis, and has no 18F-fluoro-2-deoxi-D-glucose (FDG) involvement except bone metastases. PMID:25045559

  8. Recent progress in understanding the pathogenesis of fetal and neonatal alloimmune thrombocytopenia.

    Curtis, Brian R


    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) occurs in c. 1 in 1000 births and is caused by maternal antibodies against human platelet alloantigens that bind incompatible fetal platelets and promote their clearance from the circulation. Affected infants can experience bleeding, bruising and, in severe cases, intracranial haemorrhage and even death. As maternal screening is not routinely performed, and first pregnancies can be affected, most cases are diagnosed at delivery of a first affected pregnancy. Unlike its erythrocyte counterpart, Haemolytic Disease of the Fetus and Newborn, there is no prophylactic treatment for FNAIT. This report will review recent advances made in understanding the pathogenesis of FNAIT: the platelet alloantigens involved, maternal exposure and sensitization to fetal platelet antigens, properties of platelet Immunoglobulin G antibodies, maternal-fetal antibody transport mechanisms and efforts to develop an effective FNAIT prophylaxis.

  9. 利妥昔单抗在治疗免疫介导的肾小球肾炎中的应用%Rituximab for the treatment of immune-mediated glomerular diseases

    姜玲(综述); 李世军(审校)


    Rituximab ( RTX) is a monoclonal antibody to the CD 20 antigen on B-cells that was initially designed and approved for the treatment of non-Hodgkin′s B-cell lymphoma and has emerged as a potent immunosuppressant for many immune -mediated disea-ses.Given its efficacy , tolerability and safety profile in comparison to more conventional treatment regimens , RTX is rapidly emerging as a critical therapeutic modality for glomerular disease .The paper reviews the role of RTX in the treatment of ANCA-associated vascul-itis, lupus nephritis , mixed cryoglobulinemia , membranous nephropathy , minimal change disease , and focal segmental glomeruloscle-rosis.%利妥昔单抗( Rituximab, RTX)是用于治疗非霍奇金淋巴瘤的抗CD20人/鼠嵌合型单克隆抗体,也是一种有效治疗自身免疫性疾病的药物。其疗效确切,耐受性及安全性较好,已逐渐成为治疗肾小球肾炎的重要药物之一。文中主要对RTX在抗中性粒细胞胞浆抗体( antineutrophil cytoplasmic antibody , ANCA)相关小血管炎、狼疮性肾炎、混合性冷球蛋白血症、膜性肾病、微小病变肾病和局灶节段性肾小球硬化中的应用作一综述。

  10. Autoimmune thrombocytopenia in response to splenectomy in cirrhotic patients with accompanying hepatitis C

    Tetsuro Sekiguchi; Takeaki Nagamine; Hitoshi Takagi; Masatomo Mori


    AIM: To estimate the contribution of autoimmune thrombocytopenia to hepatitis C virus-related liver cirrhosis (type C cirrhosis), we evaluated the influence of splenectomy upon platelet-associated immunoglobulin G (PAIgG) levels and platelet numbers.METHODS: PAIgG titers and immune markers were determined in 24 type C cirrhotic patients with an intact spleen, 17 type C cirrhotic patients submitted to splenectomy, and 21 non-C cirrhosis with an intact spleen.RESULTS: Thrombocytopenia (PLT<15×104/μL) in type C cirrhosis was diagnosed in all patients with an intact spleen, 8 patients submitted to splenectomy, and in 19 non-C cirrhosis with intact spleen. Elevated titers of PAIgG at more than 25.0 ng/107 cells were detected in all cirrhotic patients except for one splenectomized patient.PAIgG titers (ng/107 cells) were significantly higher in the type C cirrhosis with an intact spleen (247.9 ± 197.0)compared with the splenectomized patients (125.6±87.8)or non-C cirrhosis (152.4± 127.4). PAIgG titers were negatively correlated with platelet counts in type C cirrhotic patients with an intact spleen. In comparison with the type C cirrhosis with an intact spleen, the splenectomized patients had a reduced CD4/CD8 ratio and serum neopterin levels. The spleen index (cm2) was negatively correlated with platelet counts in the non-C cirrhosis, but not in the type C cirrhosis.CONCLUSION: Our data indicate that the autoimmune mechanism plays an important role in thrombocytosis complicated by HCV-positive cirrhosis. In addition,splenectomy may impair T ceils function through, at least in part, a reduction of CD4/CD8 ratio, consequently suppressing PAIgG production.

  11. Characterization of severe fever with thrombocytopenia syndrome in rural regions of Zhejiang, China.

    Zhang, Lei; Ye, Ling; Ojcius, David M; Lou, Xiuyu; Wang, Chengwei; feng, Cen; Sun, Yi; Wang, Zhongfa; Li, Shibo; Zhang, Yanjun


    Severe fever with thrombocytopenia syndrome virus (SFTSV) infections have recently been found in rural regions of Zhejiang. A severe fever with thrombocytopenia syndrome (SFTS) surveillance and sero-epidemiological investigation was conducted in the districts with outbreaks. During the study period of 2011-2014, a total of 51 SFTSV infection cases were identified and the case fatality rate was 12% (6/51). Ninety two percent of the patients (47/51) were over 50 years of age, and 63% (32/51) of laboratory confirmed cases occurred from May to July. Nine percent (11/120) of the serum samples from local healthy people without symptoms were found to be positive for antibodies to the SFTS virus. SFTSV strains were isolated by culture using Vero, and the whole genomic sequences of two SFTSV strains (01 and Zhao) were sequenced and submitted to the GenBank. Homology analysis showed that the similarity of the target nucleocapsid gene from the SFTSV strains from different geographic areas was 94.2-100%. From the constructed phylogenetic tree, it was found that all the SFTSV strains diverged into two main clusters. Only the SFTSV strains from the Zhejiang (Daishan) region of China and the Yamaguchi, Miyazakj regions of Japan, were clustered into lineage II, consistent with both of these regions being isolated areas with similar geographic features. Two out of eight predicted linear B cell epitopes from the nucleocapsid protein showed mutations between the SFTSV strains of different clusters, but did not contribute to the binding ability of the specific SFTSV antibodies. This study confirmed that SFTSV has been circulating naturally and can cause a seasonal prevalence in Daishan, China. The results also suggest that the molecular characteristics of SFTSV are associated with the geographic region and all SFTSV strains can be divided into two genotypes.

  12. Weight loss, leukopenia and thrombocytopenia associated with sustained virologic response to Hepatitis C treatment

    Nuntra Suwantarat, Alan D. Tice, Thana Khawcharoenporn, Dominic C. Chow


    Full Text Available OBJECTIVE: To identify apparent adverse effects of treatment of chronic hepatitis C and their relationship to sustained virologic response (SVR. METHODS: A retrospective study was conducted of all Hepatitis C virus (HCV-infected patients treated with pegylated interferon and ribavirin in an academic ambulatory infectious disease practice. Clinical and laboratory characteristics were compared between patients with SVR and without SVR. RESULTS: Fifty-four patients completed therapy with the overall SVR rate of 76%. SVR was associated with genotype non-1 (P=0.01, weight loss more than 5 kilograms (P=0.04, end of treatment leukopenia (P=0.02 and thrombocytopenia (P=0.05. In multivariate analysis, SVR was significant associated with HCV genotype non-1 (Adjusted Odd Ratio [AOR] 15.22; CI 1.55 to 149.72; P=0.02, weight loss more than 5 kilograms, (AOR 5.74; CI 1.24 to 26.32; P=0.04, and end of treatment white blood cell count level less than 3 X 103 cells/µl (AOR 9.09; CI 1.59 to 52.63; P=0.02. Thrombocytopenia was not significant after adjustment. Other factors including age, gender, ethnicity, injection drug use, viral load, anemia, alanine transaminase level, and liver histology did not reach statistical significance. CONCLUSION: Besides non-1 genotype, SVR was found to be independently associated with weight loss during therapy, and leukopenia at the end of HCV treatment. These correlations suggest continuation of therapy despite adverse effects, may be of benefit.

  13. MOG抗体在不同类型免疫介导性视神经炎血清中的表达%Anti-MOG antibody in different types of immune-mediated optic neuritis

    孔秀云; 彭静婷; 刘丽娟; 颜榕; 张晓君


    目的 初步探索抗髓鞘少突胶质细胞糖蛋白抗体(MOG-Ab)在不同临床类型免疫介导性视神经炎(IM-ON)患者血清中的表达.方法 采用临床病例横断面研究.2010年5月至2011年2月至北京同仁医院神经内科就诊的免疫介导性视神经炎患者(IM-ON) 129例,根据其临床特点分为以下5组:多发性硬化相关视神经炎(MS-ON) 20例,视神经脊髓炎相关视神经炎(NMO-ON) 13例,自身免疫病相关视神经炎(AON) 33例,复发性孤立性视神经炎(RION) 43例及单发性孤立性视神经炎(SION)20例.用ELISA方法对其血清中MOG-Ab进行检测,应用SPSS17.0软件,采用x2检验及方差分析、t检验方法对数据进行统计学分析,比较其阳性率与抗体滴度在不同组间的区别.结果 所有129例IM-ON患者中12例(9.3%)患者的血清MOG-Ab阳性.其中MS-ON组血清MOG-Ab阳性者5例(5/20),NMO-ON组0例(0/13),AON组4例(4/33),RION组2例(2/43),SION组1例(1/20).5组间阳性率差异无统计学意义(Fisher确切概率法,x2=7.051,P=0.088).将除MS-ON组之外的其余4组合并为“视神经脊髓炎(NMO)谱系视神经炎”后与MS-ON组比较发现,MS-ON组的MOG-Ab阳性率和抗体滴度均明显高于“NMO谱系视神经炎”组.结论 MOG抗体见于除NMO-ON之外的各种类型的IM-ON,在MS-ON患者血清中的表达明显高于“NMO谱系视神经炎”.%Objective To investigate the expression of anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in different types of immune-mediated optic neuritis (IM-ON).Methods Case-control and cross section study.The serum of 129 consecutive cases of immune-mediated optic neuritis (IM-ON group) seen in Neuro-ophthalmology clinic in Department of Neurology,Beijing Tongren Hospital during May 2010 and February 2011 were collected.All IM-ON cases were further classified into five different types as:20 cases of multiple sclerosis related ON (MS-ON),13 cases of neuromyelitis optica related ON (NMO-ON),33 cases of

  14. Acute Viral Escape Selectively Impairs Nef-Mediated Major Histocompatibility Complex Class I Downmodulation and Increases Susceptibility to Antiviral T Cells.

    Weiler, Andrea M; Das, Arpita; Akinyosoye, Oluwasayo; Cui, Sherry; O'Connor, Shelby L; Scheef, Elizabeth A; Reed, Jason S; Panganiban, Antonito T; Sacha, Jonah B; Rakasz, Eva G; Friedrich, Thomas C; Maness, Nicholas J


    Nef-specific CD8(+) T lymphocytes (CD8TL) are associated with control of simian immunodeficiency virus (SIV) despite extensive nef variation between and within animals. Deep viral sequencing of the immunodominant Mamu-B*017:01-restricted Nef165-173IW9 epitope revealed highly restricted evolution. A common acute escape variant, T170I, unexpectedly and uniquely degraded Nef's major histocompatibility complex class I (MHC-I) downregulatory capacity, rendering the virus more vulnerable to CD8TL targeting other epitopes. These data aid in a mechanistic understanding of Nef functions and suggest means of immunity-mediated control of lentivirus replication.

  15. Immune thrombocytopenic purpura as sole manifestation in a case of acute hepatitis A.

    Tanir, Gönül; Aydemir, Cumhur; Tuygun, Nilden; Kaya, Ozge; Yarali, Neşe


    Acute hepatitis due to hepatitis A virus is usually a benign selflimiting disease during childhood. Although many viral infections such as hepatitis B virus, Parvovirus, and Epstein-Barr virus are associated with extrahepatic autoimmune phenomena, such manifestations are rare in patients with acute hepatitis A infection. Immune thrombocytopenia is a benign, self-limiting disease in children, responding well to treatment and generally associated with viral infections. Immune thrombocytopenic purpura is rarely reported as a manifestation of acute hepatitis A. We report a five-year-old boy with immune thrombocytopenic purpura as the sole manifestation of anicteric acute hepatitis A infection. Acute hepatitis A should be included in the differential diagnosis of immune thrombocytopenic purpura.

  16. Pathogenesis of immune-mediated neuropathies.

    Dalakas, Marinos C


    Autoimmune neuropathies occur when immunologic tolerance to myelin or axonal antigens is lost. Even though the triggering factors and the underling immunopathology have not been fully elucidated in all neuropathy subsets, immunological studies on the patients' nerves, transfer experiments with the patients' serum or intraneural injections, and molecular fingerprinting on circulating autoantibodies or autoreactive T cells, indicate that cellular and humoral factors, either independently or in concert with each other, play a fundamental role in their cause. The review is focused on the main subtypes of autoimmune neuropathies, mainly the Guillain-Barré syndrome(s), the Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), the Multifocal Motor Neuropathy (MMN), and the IgM anti-MAG-antibody mediated neuropathy. It addresses the factors associated with breaking tolerance, examines the T cell activation process including co-stimulatory molecules and key cytokines, and discusses the role of antibodies against peripheral nerve glycolipids or glycoproteins. Special attention is given to the newly identified proteins in the nodal, paranodal and juxtaparanodal regions as potential antigenic targets that could best explain conduction failure and rapid recovery. New biological agents against T cells, cytokines, B cells, transmigration and transduction molecules involved in their immunopathologic network, are discussed as future therapeutic options in difficult cases. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

  17. Cancer as an immune-mediated disease

    Shurin MR


    Full Text Available Michael R ShurinDepartments of Pathology and Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: The link between oncology and immunology has a long history and its development is forced by the necessity to develop innovative and highly efficient modalities for immunological destruction of malignant cells. The limited efficacy of surgery, chemotherapy and radiation also exemplify these issues, as these treatments do not eliminate all cancerous cells, do not address the immunosuppressive nature of the disease and can further impair the patient's immune response weakening patient's resistance to the cancer. Multidisciplinary analysis of the interaction between the immune system and cancer in preclinical and clinical settings suggests that the immune system is closely intertwined with both cancer pathogenesis and treatment. On the one hand, cancer is a manifestation of malfunctions in immunity, as malignant cells manage to escape recognition and elimination by the immune system. Chronic infections and inflammation associated with limited or polarized immune responses also contribute to carcinogenesis and tumor progression. The tumor immunoenvironment represents specific conditions and elements that support cancerous cell survival, proliferation and spreading. On the other hand, the specificity and strength of antitumor immunity is a powerful and efficient tool that can be used to recognize and destroy neoplastic cells or their supporting microenvironment. Understanding the role of the immune system in controlling and supporting tumor initiation, formation, growth and progression has crucial implications for cancer therapy and will therefore guide the future development of cancer immunotherapy and its combination with conventional therapies to achieve optimal antitumor effects in patients with different types of cancer.Keywords: tumor immunology and immunotherapy, tumor immunoenvironment, cancer, immunosuppression, regulatory immune cells

  18. Narcolepsy as an Immune-Mediated Disease

    Alberto K. De la Herrán-Arita


    Full Text Available Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns. This disease is secondary to the specific loss of hypothalamic hypocretin (orexin-producing neurons in the lateral hypothalamus. An autoimmune basis for the disease has long been suspected based on its strong association with the genetic marker DQB1*06:02, and current studies greatly support this hypothesis. Narcolepsy with hypocretin deficiency is associated with human leukocyte antigen (HLA and T cell receptor (TCR polymorphisms, suggesting that an autoimmune process targets a peptide unique to hypocretin-producing neurons via specific HLA-peptide-TCR interactions. This concept has gained a lot of notoriety after the increase of childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1 in China and vaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Scandinavia. The surge of narcolepsy cases subsequent to influenza A H1N1 infection and H1N1 vaccination suggests that processes such as molecular mimicry or bystander activation might be crucial for disease development.

  19. Rapid response of advanced squamous non-small cell lung cancer with thrombocytopenia after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells

    Zhenzhen eHui


    Full Text Available We present the first clinical evidence of advanced squamous non-small cell lung cancer with severe thrombocytopenia showing dramatic improvement after first-line treatment with pembrolizumab plus cytokine-induced killer cells.

  20. Acute disseminated encephalomyelitis: a comprehensive review

    LIU Zheng


    Full Text Available Acute disseminated encephalomyelitis (ADEM is a disease that is characterized by an immune-mediated inflammatory reaction and demyelination in the central nervous system, including optic nerve, brain and spinal cord, which is common in children, but also appears in adults. ADEM happens probably with a causative relationship to viral diseases or prior vaccinations. It can also occur without any cause. The clinical symptoms of ADEM can begin with fever, headache and meningeal signs, followed by abnormal mental status, seizures and focal neurological signs, such as limb pareses, visual decline and speech disturbances. And their clinical courses may be monophasic, recurrent or multiphasic, mild but also very aggressive. Neuroimaging may be characterized by large demyelinating lesions in the brain involving both the white and the grey matter, and spinal cord. Lesions in ADEM are typically large globular lesions, multiple, and asymmetric, partially with diffuse or ring-like gadolinium enhancement. The diagnosis of ADEM requires both multifocal involvement and encephalopathy by consensus criteria. The differential diagnoses of ADEM include a variety of disorders, such as viral encephalitis, multiple sclerosis, neuromyelitis optica spectrum disorders and primary central nervous system vasculitis, etc. Treatments of ADEM include corticosteroids, intravenous immunoglobulin, plasmapheresis and other immunosuppressive agents.

  1. Acute Renal Failure in Dengue Infection

    Subramanyam, Nambakam Tanuja


    Introduction Acute Renal Failure (RF) is a rare but well recognized complication of Dengue Infection (DI). There has been paucity of published data regarding renal involvement in DI. Aim The aim of the present study was to elucidate different clinical presentations, disease outcomes of DI. To study the frequency, severity and predictors of RF in DI. Materials and Methods Patients diagnosed either as Dengue Fever (DF) or Dengue Haemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS) respectively were enrolled for this study. The diagnostic criteria for DI were febrile illness associated with one of the following: 1) detection of dengue-specific IgM capture antibody or Non-Structural Protein1 (NS1) antigen; or 2) a four-fold or greater increase of dengue-specific IgG capture antibody by ELISA and haemoagglutination inhibition assay. Patients were diagnosed as having Acute RF, if serum creatinine was >1.2 mg/dl or who showed improvement by 50% in serum creatinine from the initial value. It is an observational study of medical charts, data of age, gender, and medical history of any underlying diseases in association with the severity of DI of each patient recorded. All of the laboratory results were collected. Parameters that influenced the clinical presentations and outcomes for development of classical DF or DHF/DSS in patients with or without RF were analysed and compared. Descriptive and inferential statistical analysis was carried. The Statistical software namely SAS 9.2, SPSS 15.0, Stata 10.1, Med Calc 9.0.1, Systat 12.0 and R environment ver.2.11.1 were used. Results Most common symptoms were fever followed by headache and pain in abdomen. Among the patients with RF, all patients had recovery. The patients with DHF/DSS were more susceptible to develop renal failure compared to DF group. There were statistically significant higher frequencies of renal failure, haemoconcentration, thrombocytopenia, low serum cholesterol. Patients in the RF group also had significantly

  2. Acute rheumatic fever and rheumatic heart disease among children--American Samoa, 2011-2012.

    Beaudoin, Amanda; Edison, Laura; Introcaso, Camille E; Goh, Lucy; Marrone, James; Mejia, Amelita; Van Beneden, Chris


    Acute rheumatic fever is a nonsuppurative, immune-mediated consequence of group A streptococcal pharyngitis (strep throat). Recurrent or severe acute rheumatic fever can cause permanent cardiac valve damage and rheumatic heart disease, which increases the risk for cardiac conditions (e.g., infective endocarditis, stroke, and congestive heart failure). Antibiotics can prevent acute rheumatic fever if administered no more than 9 days after symptom onset. Long-term benzathine penicillin G (BPG) injections are effective in preventing recurrent acute rheumatic fever attacks and are recommended to be administered every 3-4 weeks for 10 years or until age 21 years to children who receive a diagnosis of acute rheumatic fever. During August 2013, in response to anecdotal reports of increasing rates of acute rheumatic fever and rheumatic heart disease, CDC collaborated with the American Samoa Department of Health and the Lyndon B. Johnson Tropical Medical Center (the only hospital in American Samoa) to quantify the number of cases of pediatric acute rheumatic fever and rheumatic heart disease in American Samoa and to assess the potential roles of missed pharyngitis diagnosis, lack of timely prophylaxis prescription, and compliance with prescribed BPG prophylaxis. Using data from medical records, acute rheumatic fever incidence was calculated as 1.1 and 1.5 cases per 1,000 children aged ≤18 years in 2011 and 2012, respectively; 49% of those with acute rheumatic fever subsequently received a diagnosis of rheumatic heart disease. Noncompliance with recommended prophylaxis with BPG after physician-diagnosed acute rheumatic fever was noted for 22 (34%) of 65 patients. Rheumatic heart disease point prevalence was 3.2 cases per 1,000 children in August 2013. Establishment of a coordinated acute rheumatic fever and rheumatic heart disease control program in American Samoa, likely would improve diagnosis, treatment, and patient compliance with BPG prophylaxis.

  3. Acute pancreatitis

    Bo-Guang Fan


    Full Text Available Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions : Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  4. Acute pancreatitis

    Bo-Guang Fan


    Full Text Available Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions: Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  5. A Case of Thrombotic Thrombocytopenia Purpura Associated with Systemic Lupus Erythematosus: Diagnostic Utility of ADAMTS-13 Activity

    Risa Yamada


    Full Text Available Thrombotic thrombocytopenia purpura (TTP caused by a deficiency in ADAMTS-13 activity is considered to involve a subset of thrombotic microangiopathy (TMA. Although concept of TTP is included under the umbrella of TMA, discrimination of TTP from TMA is occasionally difficult in an autoimmune disorder. Herein, we report a case with TTP associated with systemic lupus erythematosus (SLE. In this case, it was difficult to discriminate TTP from TMA and the measurement of ADAMTS-13 activity was useful for obtaining an accurate diagnosis. SLE patients having thrombocytopenia in complication with anemia should be considered a monitoring of ADAMTS-13 activity even though the patients lacked symptoms of TTP related to the microvascular coagulation.

  6. Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

    Mirian S. Tamashiro


    Full Text Available OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years. In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70% vs. 1%, 54% vs. 32%, 30% vs. 8%, and 9% vs. 0%, respectively. Likewise, the frequencies of anemia, leukopenia, neutropenia, thrombocytopenia and high lactic dehydrogenase levels were statistically higher in leukemia patients than in patients with systemic-onset juvenile idiopathic arthritis (88% vs. 57%, 39% vs. 1%, 60% vs. 1%, 77% vs. 1%, and 56% vs. 14%, respectively. Remarkably, multivariate analysis revealed that limb pain (OR = 553; 95% CI =46.48-6580.42 and thrombocytopenia (OR = 754.13; 95% CI =64.57-8806.72 were significant independent variables that differentiated leukemia from systemic-onset juvenile idiopathic arthritis. The R2 of the Nagelkerke test was 0.91, and the Kaplan-Meier survival curves were similar for acute lymphoblastic leukemia patients with and without limb pain. CONCLUSION: Our study

  7. Cerebral venous thrombosis and heparin-induced thrombocytopenia in an 18-year old male with severe ulcerative colitis

    Gudrun Scheving Thorsteinsson; Maria Magnussson; Lena M Hallberg; Nils Gunnar Wahlgren; Fredrik Lindgren; Petter Malmborg; Thomas H Casswall


    The risk of thromboembolism is increased in inflammatory bowel disease and its symptoms may be overlooked. Furthermore, its treatment can be complex and is not without complications. We describe a case of an adolescent boy who developed a cerebral sinus venous thrombosis during a relapse of his ulcerative colitis and who, while on treatment with heparin,developed heparin-induced thrombocytopenia (HIT).The treatment was then switched to fondaparinux, a synthetic and selective inhibitor of activated factor x.

  8. Emphasis on the Role of PF4 in the Incidence, Pathophysiology and Treatment of Heparin Induced Thrombocytopenia

    Prechel, M Margaret; Walenga, Jeanine M.


    Heparin Induced Thrombocytopenia (HIT) is caused by antibodies that recognize platelet factor 4 (PF4) associated with polyanionic glycosaminoglycan drugs or displayed on vascular cell membranes. These antibodies are elicited by multimolecular complexes that can occur when heparin is administered in clinical settings associated with abundant PF4. Heparin binding alters native PF4 and elicits immune recognition and response. While the presence of heparin is integral to immunogenesis, the HIT an...

  9. Neurogenic chronic idiopathic intestinal pseudo-obstruction, patent ductus arteriosus, and thrombocytopenia segregating as an X linked recessive disorder.

    FitzPatrick, D R; Strain, L; Thomas, A E; Barr, D G; Todd, A; Smith, N M; Scobie, W G


    We present a family with three affected males in two generations with congenital neurogenic chronic idiopathic intestinal pseudo-obstruction (CIIP), patent ductus arteriosus, and large platelet thrombocytopenia apparently segregating as an X linked recessive disorder. The pattern of segregation of DNA markers within the family is consistent with linkage to the previously described neurogenic CIIP (CIIPX) locus at Xq28. This combination may represent a new contiguous gene disorder and appears to have a good prognosis with supportive therapy.

  10. Clinical manifestations and predictors of thrombocytopenia in hospitalized adults with dengue fever

    Akshatha Rao Aroor


    Full Text Available Background: India is one of the seven identified Southeast Asian countries reporting frequent outbreaks of dengue fever (DF. Aims: This study was to analyze clinical and laboratory profile and predictive markers of thrombocytopenia and length of hospital stay in DF. Materials and Methods: This record-based retrospective study conducted in a coastal district of Karnataka, South India, included all dengue cases in adults aged >18 years, admitted during period of January 2011 to December 2014. Multivariate logistic regression analysis was carried out to compute odds ratio (OR and 95% confidence interval (CI to assess independent associations of variables with low platelet count and longer duration of hospital stay. Results: Among 207 dengue immunoglobulin M (IgM antibody confirmed cases (mean age of 36.94 ± 14.61 years, 143 (69.1% were males and 64 were females. The mean duration of illness and hospital stay were 4.94 ± 3.58 days and 5.98 ± 2.58 days, respectively. Abdominal symptoms included nausea and vomiting (53.6%, abdominal pain (25.1%, and diarrhea (13.5%. Bleeding manifestations were seen in 24 (11.6% cases and fluid accumulation was revealed in 18 (8.7% cases. The mean platelet count was 110,159.42 ± 68,397.32 (cells/mm 3 . Low platelet count on admission was associated with the presence of rash (OR = 0.43, 95% CI 0.23-0.81, high aspartate aminotransferase (AST levels (OR = 3.14, 95% CI 1.58-6.23, high alanine aminotransferase (ALT levels (OR = 2.91, 95% CI 1.55-5.47, and low albumin levels (OR = 4.48, 95% CI 1.02-19.75. The duration of hospital stay was associated with diarrhea (OR = 0.4, 95% CI 0.18-0.9, abdominal pain (OR = 0.52, 95% CI 0.27-1.00, ascites (OR = 0.26, 95% CI 0.09-0.69, and low hemoglobin (OR = 0.46, 95% CI 0.25-0.86 level on admission. Conclusions: Though thrombocytopenia on admission was associated with the presence of rash, high AST and ALT levels, and low albumin levels, it was not predictive of length of

  11. Alleviation of viper venom induced platelet apoptosis by crocin (Crocus sativus): implications for thrombocytopenia in viper bites.

    Santhosh, M Sebastin; Thushara, R M; Hemshekhar, M; Sunitha, K; Devaraja, S; Kemparaju, K; Girish, K S


    Viper envenomations are characterized by prominent local and systemic manifestations including hematological alterations. Snake venom metalloproteinases (SVMPs) and phospholipase A2 (PLA2) plays crucial role in the pathophysiology of hemorrhage by targeting/altering the platelets function which may result in thrombocytopenia. Platelets undergo the classic events of mitochondria-mediated apoptotic pathway due to augmented endogenous reactive oxygen species (ROS) levels. The observed anticoagulant effects during viper envenomations could be due to exacerbated platelet apoptosis and thrombocytopenia. Moreover, antivenin treatments are ineffective against the venom-induced oxidative stress; therefore, it necessitates an auxiliary therapy involving antioxidants which can effectively scavenge the endothelium-generated/endogenous ROS and protect the platelets. The present study explored the effects of viper venom on platelet apoptosis and its amelioration by a phytochemical crocin. The study evaluated the Vipera russelli venom-induced apoptotic events including endogenous ROS generation, intracellular Ca(2+) mobilization, mitochondrial membrane depolarization, cyt-c translocation, caspase activation and phosphatidylserine externalization which were effectively mitigated when the venom was pre-treated with crocin. The study highlights one of the less studied features of venom-induced secondary complications i.e. platelet apoptosis and sheds light on the underlying basis for venom-induced thrombocytopenia, systemic hemorrhage and in vivo anticoagulant effect.

  12. Fatal alloimmune thrombocytopenia due to anti-HLA alloimmunization in a twin pregnancy: A very infrequent complication of assisted reproduction.

    Meler, Eva; Porta, Roser; Canals, Carme; Serra, Bernat; Lozano, Miguel


    The most frequently involved antigen in severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the human platelet antigen 1a. Platelets express the HLA-A and B antigens on their membrane and some studies report that maternal anti-HLA class I antibody can also cause FNAIT. We report here a very unusual case of a first twin pregnancy produced in vitro by oocyte and semen donation where the mother developed markedly elevated HLA antibodies, in the absence of anti-platelet or anti-neutrophil antibodies, that provoked in one of the twins a profound thrombocytopenia and intracranial hemorrhage and a mild thrombocytopenia and neutropenia in the second twin lasting until the fourth month of life. In addition, anti-D alloimmunization provoked hemolytic disease of the newborn with intrauterus anemia detected in the first twin and post-natal anemia in the second twin that required red blood cell transfusion and phototherapy. We hypothesize that the complete HLA-incompatible twin pregnancy due to the oocyte donation might have contributed to the severity of the clinical manifestations.

  13. Thrombocytopenia in pregnant women with Plasmodium falciparum malaria in an area of unstable malaria transmission in eastern Sudan

    Adam Mayyada B


    Full Text Available Abstract Background Blood platelet levels are being evaluated as predictive and prognostic indicators of the severity of malaria infections in humans. However, there are few studies on platelets and Plasmodium falciparum malaria during pregnancy. Methods A case–control study was conducted at Gadarif Hospital in Eastern Sudan, an area characterized by unstable malaria transmission. The aim of the study was to investigate thrombocytopenia in pregnant women with P. falciparum malaria (cases and healthy pregnant women (controls. Results The median (interquartile platelet counts were significantly lower in patients with malaria (N = 60 than in the controls (N = 60, 61, 000 (43,000–85,000 vs. 249,000 (204,000–300,000/μL, respectively, p P. falciparum malaria (N = 12 compared with those patients with uncomplicated P. falciparum malaria (N = 48, 68, 000 (33,000-88,000/μL vs. 61, 000 (45,000–85,000/μL, respectively, p = 0.8. While none of the control group had thrombocytopenia (platelet count p P. falciparum malaria, compared with the pregnant healthy control group, were at higher risk (OR = 10.1, 95% CI = 4.1–25.18; p  Conclusion P. falciparum malaria is associated with thrombocytopenia in pregnant women in this setting. More research is needed.

  14. Quadro seroproteico como auxílio diagnóstico na anemia hemolítica imunomediada em cães Serum proteic profile as diagnosis aids in immune-mediated hemolytic anemia in dogs

    Patrícia Mendes Pereira


    maior nestes. Tais achados analisados em conjunto agregam informações adicionais úteis à elucidação das AHIMs em cães.This assay aimed to determine the serum protein - via polyacrylamide gel electrophoresis, which contained duodecil sodium sulfate (SDS-PAGE - in 120 dogs, with different breeds and ages, seen by the Veterinary Hospital "Governor Laudo Natel." These animals were grouped into five experimental groups: Group 1 - group control with 20 dogs, group 2 - 28 dogs with regenerative anemia; group 3 - 27 dogs with arregenarative; anemia group 4 - 10 dogs with primary immune-mediated hemolytic anemia (AHIM 1.rd; group 5 - 35 dogs with secondary immune-mediated hemolytic anemia (AHIM 2.rd. The technique allowed the SDS-PAGE fractionation of 24 protein, whose molecular weights (PM ranged from 18,000 to 165,000 daltons (Da. The dogs with 1st and 2nd AHIM showed 24 protein fractions in their tracks electrophoretic, while other groups of dogs showed 23 fractions of protein, whose molecular protein weight of 68,000Da was not found. Thus, twenty-three proteins were common to proteinograms of the five experimental groups. From these, it was possible to identify eleven protein fractions nominally, and others were identified by their molecular weights. For control dogs, the anemic (groups 2, 3, 4 and 5 showed higher concentrations of serum transferrin and between them, the animals carrying the primary IMHA. All groups of dogs showed anemic levels of serum haptoglobin and phosphorylase significantly higher than the control dogs, while the serum ceruloplasmin was lower in anemic dogs. These findings provide additional information to the elucidation of the AHIMs in dogs.

  15. Acute Splenic Sequestration Crisis in a 70-Year-Old Patient With Hemoglobin SC Disease

    John J. Squiers BSE


    Full Text Available A 70-year-old African American female with a past medical history significant for chronic bilateral shoulder pain and reported sickle cell trait presented with acute-onset bilateral thoracolumbar pain radiating to her left arm. Two days after admission, Hematology was consulted for severely worsening microcytic anemia and thrombocytopenia. Examination of the patient’s peripheral blood smear from admission revealed no cell sickling, spherocytes, or schistocytes. Some targeting was noted. A Coombs test was negative. The patient was eventually transferred to the medical intensive care unit in respiratory distress. Hemoglobin electrophoresis confirmed a diagnosis of hemoglobin SC disease. A diagnosis of acute splenic sequestration crisis complicated by acute chest syndrome was crystallized, and red blood cell exchange transfusion was performed. Further research is necessary to fully elucidate the pathophysiology behind acute splenic sequestration crisis, and the role of splenectomy to treat hemoglobin SC disease patients should be better defined.

  16. C1galt1-deficient mice exhibit thrombocytopenia due to abnormal terminal differentiation of megakaryocytes.

    Kudo, Takashi; Sato, Takashi; Hagiwara, Kozue; Kozuma, Yukinori; Yamaguchi, Takashi; Ikehara, Yuzuru; Hamada, Michito; Matsumoto, Ken; Ema, Masatsugu; Murata, Soichiro; Ohkohchi, Nobuhiro; Narimatsu, Hisashi; Takahashi, Satoru


    C1galt1 is essential for synthesis of the core 1 structure of mucin-type O-glycans. To clarify the physiological role of O-glycans in adult hematopoiesis, we exploited the interferon-inducible Mx1-Cre transgene to conditionally ablate the C1galt(flox) allele (Mx1-C1). Mx1-C1 mice exhibit severe thrombocytopenia, giant platelets, and prolonged bleeding times. Both the number and DNA ploidy of megakaryocytes in Mx1-C1 bone marrow were similar to those in wild-type (WT) mice. However, there were few proplatelets in Mx1-C1 primary megakaryocytes. Conversely, bone marrow transplanted from Mx1-C1 to WT and splenectomized Mx1-C1 mice gave rise to observations similar to those described above. The expression of GPIbα messenger RNA was unchanged in Mx1-C1 bone marrow, whereas flow cytometric and western blot analyses using megakaryocytes and platelets revealed that the expression of GPIbα protein was significantly reduced in Mx1-C1 mice. Moreover, circulating Mx1-C1 platelets exhibited an increase in the number of microtubule coils, despite normal levels of α- and β-tubulin. Our observations suggest that O-glycan is required for terminal megakaryocyte differentiation and platelet production and that the decrease in GPIbα in cells lacking O-glycan might be caused by increased proteolysis.

  17. Detection and Clinical Signiifcance of Circulating Microvesicles in Severe Fever with Thrombocytopenia Syndrome


    Objective Microvesicles (MV) released from blood cells play an important role in the progress of diseases. The purpose of this study is to detect circulating MV level of patients suffering from severe fever with thrombocytopenia syndrome (SFTS) . Methods The plasma samples of SFTS patients and healthy controls were collected. And MV from samples were isolated and MV levels were detected quantitatively. Results The results showed that the level of the circulating MV in SFTS patients was obviously higher than that of the healthy control, with statistically signiifcant difference. Further analysis revealed that MV level was relevant to the severity of SFTS patients, namely the higher the concentration of MV, the more severity of the disease. Linear correlation analysis showed that the circulating MV level in SFTS was correlated positively with leukocyte count (r=0.243, P0.05). Conclusions We demonstrated that there existed high level of circulating MV in SFTS patients, and the level of circulating MV had a close relationship with the severity of the disease and leukocyte count. Therefore, monitoring the level of circulating MV may provide a new insight for predicting the prognosis of SFTS patients.

  18. Systemic Inflammatory Response and Severe Thrombocytopenia after Endovascular Thoracic Aortic Aneurysm Repair

    Valentina Silvestrin


    Full Text Available After Endovascular repair of thoracic aortic aneurysm, a systemic inflammatory response, named postimplantation syndrome, can develop. This syndrome is characterized by fever, leukocytosis, and elevated CRP plasma levels and its pathogenetic mechanisms are still unknown. Although this syndrome generally resolves within few days, some patients develop a persisting severe inflammatory reaction leading to mild or severe complications. Here we describe the case of a male patient who developed postimplantation inflammatory syndrome and severe thrombocytopenia after endovascular repair of thoracic aortic aneurysm. Treatment with prednisone (50 mg/bid for two weeks did not improve the clinical and laboratory findings. We utilized danazol, a weak androgen that has been shown to be effective in the treatment of immune and idiopathic thrombocytopenic purpura, and after 12 days of treatment with danazol (200 mg/bid, the patient improved progressively and platelet number increased up to 53,000/μL. Patients undergoing endovascular repair of thoracic aortic aneurysm should be carefully monitored for the development of postimplantation syndrome. This clinical condition is relatively common after the endovascular repair of aortic aneurysm but is rarely observed after endovascular repair of thoracic aortic aneurysms. The different known therapeutical approaches are still empiric, with reported beneficial effects with the use of NSAID, corticosteroids, and danazol.

  19. Systemic Inflammatory Response and Severe Thrombocytopenia after Endovascular Thoracic Aortic Aneurysm Repair

    Silvestrin, Valentina; Bonvini, Stefano; Antonello, Michele; Grego, Franco; Vettor, Roberto


    After Endovascular repair of thoracic aortic aneurysm, a systemic inflammatory response, named postimplantation syndrome, can develop. This syndrome is characterized by fever, leukocytosis, and elevated CRP plasma levels and its pathogenetic mechanisms are still unknown. Although this syndrome generally resolves within few days, some patients develop a persisting severe inflammatory reaction leading to mild or severe complications. Here we describe the case of a male patient who developed postimplantation inflammatory syndrome and severe thrombocytopenia after endovascular repair of thoracic aortic aneurysm. Treatment with prednisone (50 mg/bid) for two weeks did not improve the clinical and laboratory findings. We utilized danazol, a weak androgen that has been shown to be effective in the treatment of immune and idiopathic thrombocytopenic purpura, and after 12 days of treatment with danazol (200 mg/bid), the patient improved progressively and platelet number increased up to 53,000/μL. Patients undergoing endovascular repair of thoracic aortic aneurysm should be carefully monitored for the development of postimplantation syndrome. This clinical condition is relatively common after the endovascular repair of aortic aneurysm but is rarely observed after endovascular repair of thoracic aortic aneurysms. The different known therapeutical approaches are still empiric, with reported beneficial effects with the use of NSAID, corticosteroids, and danazol. PMID:28154580

  20. Feasibility of an Isometric Maximal Voluntary Contraction Test in Hematological Cancer Patients during Thrombocytopenia

    Philipp Zimmer


    Full Text Available Introduction. Resistance training is rarely offered to hemato-oncological patients in the daily clinical routine due to its potential harmful impact on the cardiovascular system and the long periods of thrombocytopenia experienced by these patients. Therefore, it is important to determine a valid assessment to define and control resistance training. In this study, the feasibility of a maximal voluntary contraction (MVC test was investigated in hemato-oncological patients. This inexpensive assessment may be a practicable alternative to the one repetition maximum test which is currently described as the gold standard. Methods. 29 hemato-oncological patients with platelet counts between 30000/μL and 70000/μL were recruited for this pilot study. Complications like petechial bleedings, muscle convulsion, and pain were assessed using the Brief Pain Inventory before and 48 hours after the MVC test, which was performed unidirectionally for the quadriceps muscle. Results. We did not detect any statistically significant test-related exacerbations or pain development. Discussion. MVC testing seems to be a feasible method to control a resistance training program in hemato-oncological patients. Further studies need to extend their methods and, for example, compare the MVC test with the one repetition maximum test.


    Ashok S


    Full Text Available It is a rare genetic disorder characterized by the absence of the radius bone in the forearm and a dramatically reduced platelet count. This syndrome may occur as a part of the 1q21.1 deletion syndrome. Symptoms of thrombocytopenia or a lowered platelet count leads to bruising and potentially life-threatening haemorrhage. Affected children who survive this period and do not have damaging haemorrhages in the brain usually have a normal life expectancy and normal intellectual development. Other common links between with TAR seem to include heart problems, kidney problems, knee joint problems, frequently lactose intolerance and often thumb hypoplasia. The incidence is 0.5-1 per 100,000 live births. Mutations in the RBM8A gene cause TAR syndrome. It is inherited in an autosomal recessive pattern. This disorder is to be differentiated from Holt-Oram syndrome, which has similar presentation. Prevention of bleeding with physiotherapy and occupational therapy are mainstay of management. With this case report we try to discuss the complexity of the condition and its management in the neonatal period.

  2. Haemaphysalis longicornis Ticks as Reservoir and Vector of Severe Fever with Thrombocytopenia Syndrome Virus in China.

    Luo, Li-Mei; Zhao, Li; Wen, Hong-Ling; Zhang, Zhen-Tang; Liu, Jian-Wei; Fang, Li-Zhu; Xue, Zai-Feng; Ma, Dong-Qiang; Zhang, Xiao-Shuang; Ding, Shu-Jun; Lei, Xiao-Ying; Yu, Xue-jie


    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia caused by SFTS virus (SFTSV), a newly discovered phlebovirus. The Haemaphysalis longicornis tick has been suspected to be the vector of SFTSV. To determine whether SFTSV can be transmitted among ticks, from ticks to animals, and from animals to ticks, we conducted transmission studies between developmental stages of H. longicornis ticks and between ticks and mice. Using reverse transcription PCR, we also analyzed the prevalence of SFTSV infection among H. longicornis ticks collected from vegetation in Shandong Province, China. Our results showed a low prevalence of SFTSV among collected ticks (0.2%, 8/3,300 ticks), and we showed that ticks fed on SFTSV-infected mice could acquire the virus and transstadially and transovarially transmit it to other developmental stages of ticks. Furthermore, SFTSV-infected ticks could transmit the virus to mice during feeding. Our findings indicate ticks could serve as a vector and reservoir of SFTSV.

  3. Corticosteroids compared with intravenous immunoglobulin for the treatment of immune thrombocytopenia in pregnancy.

    Sun, Dongmei; Shehata, Nadine; Ye, Xiang Y; Gregorovich, Sandra; De France, Bryon; Arnold, Donald M; Shah, Prakesh S; Malinowski, Ann Kinga


    Treatment options for immune thrombocytopenia (ITP) in pregnancy are limited, and evidence to guide management decisions is lacking. This retrospective study of singleton pregnancies from 2 tertiary centers compared the effectiveness of intravenous immunoglobulin (IVIg) and corticosteroids in treatment of ITP. Data from 195 women who had 235 pregnancies were reviewed. Treatment was not required in 137 pregnancies (58%). Of the remaining 98 pregnancies in 91 women, 47 (48%) were treated with IVIg and 51 were treated with corticosteroids as the initial intervention. Mean maternal platelet count at birth did not differ between groups (IVIg 69 × 10(9)/L vs corticosteroids 77 × 10(9)/L; P = .71) nor did the proportion of mothers who achieved a platelet count response (IVIg 38% vs corticosteroids 39%; P = .85). There were no fatal or severe maternal, fetal, or neonatal hemorrhages. Of 203 neonates in whom platelet counts were available, 56 (28%) had a birth platelet count <150 × 10(9)/L and 18 (9%) had platelet counts <50 × 10(9)/L. Nadir platelet counts for most affected neonates occurred at birth, although for some neonates, nadir platelet counts occurred up to 6 days postnatally. Intracranial hemorrhage was noted in 2 neonates (nadir platelet counts were 135 and 18 × 10(9)/L). There were no neonatal deaths. The majority of pregnant women with a history of ITP did not require treatment, and neonatal outcomes were comparable for mothers who received IVIg or corticosteroids for treatment of maternal ITP.

  4. Atomic features of an autoantigen in heparin-induced thrombocytopenia (HIT).

    Cai, Zheng; Zhu, Zhiqiang; Greene, Mark I; Cines, Douglas B


    Autoantigen development is poorly understood at the atomic level. Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by antibodies to an antigen composed of platelet factor 4 (PF4) and heparin or cellular glycosaminoglycans (GAGs). In solution, PF4 exists as an equilibrium among monomers, dimers and tetramers. Structural studies of these interacting components helped delineate a multi-step process involved in the pathogenesis of HIT. First, heparin binds to the 'closed' end of the PF4 tetramer and stabilizes its conformation; exposing the 'open' end. Second, PF4 arrays along heparin/GAG chains, which approximate tetramers, form large antigenic complexes that enhance antibody avidity. Third, pathogenic HIT antibodies bind to the 'open' end of stabilized PF4 tetramers to form an IgG/PF4/heparin ternary immune complex and also to propagate the formation of 'ultralarge immune complexes' (ULCs) that contain multiple IgG antibodies. Fourth, ULCs signal through FcγRIIA receptors, activating platelets and monocytes directly and generating thrombin, which transactivates hematopoietic and endothelial cells. A non-pathogenic anti-PF4 antibody prevents tetramer formation, binding of pathogenic antibody, platelet activation and thrombosis, providing a new approach to manage HIT. An improved understanding of the pathogenesis of HIT may lead to novel diagnostics and therapeutics for this autoimmune disease.

  5. Reducing the hospital burden of heparin-induced thrombocytopenia: impact of an avoid-heparin program.

    McGowan, Kelly E; Makari, Joy; Diamantouros, Artemis; Bucci, Claudia; Rempel, Peter; Selby, Rita; Geerts, William


    Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction occurring in up to 5% of patients exposed to unfractionated heparin (UFH). We examined the impact of a hospital-wide strategy for avoiding heparin on the incidence of HIT, HIT with thrombosis (HITT), and HIT-related costs. The Avoid-Heparin Initiative, implemented at a tertiary care hospital in Toronto, Ontario, Canada, since 2006, involved replacing UFH with low-molecular-weight heparin (LMWH) for prophylactic and therapeutic indications. Consecutive cases with suspected HIT from 2003 through 2012 were reviewed. Rates of suspected HIT, adjudicated HIT, and HITT, along with HIT-related expenditures were compared in the pre-intervention (2003-2005) and the avoid-heparin (2007-2012) phases. The annual rate of suspected HIT decreased 42%, from 85.5 per 10 000 admissions in the pre-intervention phase to 49.0 per 10 000 admissions in the avoid-heparin phase ( ITALIC! Pheparin phase. To the best of our knowledge, this is the first study demonstrating the success and feasibility of a hospital-wide HIT prevention strategy.

  6. Effects of Rapamycin Combined with Low Dose Prednisone in Patients with Chronic Immune Thrombocytopenia

    Jiaming Li


    Full Text Available We conducted this randomized trial to investigate the efficacy and safety of rapamycin treatment in adults with chronic immune thrombocytopenia (ITP. Eighty-eight patients were separated into the control (cyclosporine A plus prednisone and experimental (rapamycin plus prednisone groups. The CD4+CD25+CD127low regulatory T (Treg cells level, Foxp3 mRNA expression, and the relevant cytokines levels were measured before and after treatment. The overall response (OR was similar in both groups (experimental group versus control group: 58% versus 62%, P=0.70. However, sustained response (SR was more pronounced in the experimental group than in the control group (68% versus 39%, P<0.05. Both groups showed similar incidence of adverse events (7% versus 11%, P=0.51. As expected, the low pretreatment baseline level of Treg cells was seen in all patients (P<0.001; however, the experimental group experienced a significant rise in Treg cell level, and there was a strong correlation between the levels of Treg cells and TGF-beta after the treatment. In addition, the upregulation maintained a stable level during the follow-up phase. Thus, rapamycin plus low dose prednisone could provide a new promising option for therapy of ITP.

  7. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy

    D. J. Kuter


    Full Text Available Romiplostim was effective, safe, and well-tolerated over 6–12 months of continuous treatment in Phase 3 trials in patients with immune thrombocytopenia (ITP. This report describes up to 5 years of weekly treatment with romiplostim in 292 adult ITP patients in a long-term, single-arm, open-label study. Outcome measures included adverse events (including bleeding, thrombosis, malignancy, and reticulin / fibrosis, platelet response (platelet count >50 × 109 per litre, and the proportion of patients requiring rescue treatments. Treatment – related serious adverse events were infrequent and did not increase with longer treatment. No new classes of adverse events emerged. Thrombotic events occurred in 6.5 % of patients and were not associated with platelet count. Median platelet counts of 50–200 × 109 per litre were maintainedwith stable doses of romiplostim (mean 5–8 μg / kg; generally self-administered at home throughout the study. A platelet response was achieved at least once by 95 % of patients, with a platelet response maintained by all patients on a median 92 % of study visits. There was a low rate of bleeding and infrequent need for rescue treatments. In conclusion, this study demonstrated that romiplostim was safe and welltolerated over 614 patient-years of exposure in ITP patients, and that efficacy was maintained with stable dosing for up to 5 years of continuous treatment.

  8. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy

    D. J. Kuter


    Full Text Available Romiplostim was effective, safe, and well-tolerated over 6–12 months of continuous treatment in Phase 3 trials in patients with immune thrombocytopenia (ITP. This report describes up to 5 years of weekly treatment with romiplostim in 292 adult ITP patients in a long-term, single-arm, open-label study. Outcome measures included adverse events (including bleeding, thrombosis, malignancy, and reticulin / fibrosis, platelet response (platelet count >50 × 109 per litre, and the proportion of patients requiring rescue treatments. Treatment – related serious adverse events were infrequent and did not increase with longer treatment. No new classes of adverse events emerged. Thrombotic events occurred in 6.5 % of patients and were not associated with platelet count. Median platelet counts of 50–200 × 109 per litre were maintainedwith stable doses of romiplostim (mean 5–8 μg / kg; generally self-administered at home throughout the study. A platelet response was achieved at least once by 95 % of patients, with a platelet response maintained by all patients on a median 92 % of study visits. There was a low rate of bleeding and infrequent need for rescue treatments. In conclusion, this study demonstrated that romiplostim was safe and welltolerated over 614 patient-years of exposure in ITP patients, and that efficacy was maintained with stable dosing for up to 5 years of continuous treatment.

  9. CD8+ T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia

    Qiu, Jihua; Liu, Xuena; Li, Xiaoqing; Zhang, Xu; Han, Panpan; Zhou, Hai; Shao, Linlin; Hou, Yu; Min, Yanan; Kong, Zhangyuan; Wang, Yawen; Wei, Yu; Liu, Xinguang; Ni, Heyu; Peng, Jun; Hou, Ming


    In addition to antiplatelet autoantibodies, CD8+ cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8+ T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8+ T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8+ T cells than those without cytotoxicity and controls. In vitro, CD8+ T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8+ splenocytes were used. Platelets co-cultured with these CD8+ splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8+ splenocytes. These findings suggest that CD8+ T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP. PMID:27321376

  10. Identification of novel biomarkers in chronic immune thrombocytopenia (ITP) by microarray-based serum protein profiling.

    Bal, Gürkan; Futschik, Matthias E; Hartl, Daniela; Ringel, Frauke; Kamhieh-Milz, Julian; Sterzer, Viktor; Hoheisel, Jörg D; Alhamdani, Mohamed S S; Salama, Abdulgabar


    The pathological mechanisms underlying the development of immune thrombocytopenia (ITP) are unclear and its diagnosis remains a process of exclusion. Currently, there are no known specific biomarkers for ITP to support differential diagnosis and treatment decisions. Profiling of serum proteins may be valuable for identifying such biomarkers. Sera from 46 patients with primary chronic ITP and 34 healthy blood donors were analysed using a microarray of 755 antibodies. We identified 161 differentially expressed proteins. In addition to oncoproteins and tumour-suppressor proteins, including apoptosis regulator BCL2, breast cancer type 1 susceptibility protein (BRCA1), Fanconi anaemia complementation group C (FANCC) and vascular endothelial growth factor A (VEGFA), we detected six anti-nuclear autoantibodies in a subset of ITP patients: anti-PCNA, anti-SmD, anti-Ro/SSA60, anti-Ro/SSA52, anti-La/SSB and anti-RNPC antibodies. This finding may provide a rational explanation for the association of ITP with malignancies and other autoimmune diseases. While RUNX1mRNA expression in the peripheral blood mononuclear cells (PBMC) of patients was significantly downregulated, an accumulation of RUNX1 protein was observed in the platelets of ITP patients. This may indicate dysregulation of RUNX1 expression in PBMC and megakaryocytes and may lead to an imbalanced immune response and impaired thrombopoiesis. In conclusion, we provide novel insights into the pathogenic mechanisms of ITP that warrant further exploration.

  11. Natural language processor as a tool to assess heparin induced thrombocytopenia awareness.

    Tafur, Alfonso J; McBane, Robert D; Wysokinski, Waldemar E; Gregg, Melissa S; Daniels, Paul R; Mohr, David N


    The life-threatening consequences of heparin induced thrombocytopenia (HIT) may be prevented with early recognition, prompt heparin withdrawal and direct thrombin inhibitor use. To determine the level of HIT awareness, electronic term recognition software can be used to query the electronic medical record (EMR) to assess the thought process and test ordering behavior of health care providers confronted with falling platelet counts. We sought to assess the awareness of HIT in a large teaching institution using these tools. Mayo Clinic databases were queried to identify a cohort of hospitalized adults receiving heparin (06/1/08-06/1/09). Serial platelet counts for each patient were scrutinized for a 50% decrement from baseline. "Clinician awareness" was defined by mention of HIT (determined by electronic term recognition software) within the hospital record by any member of the healthcare team or requisition of platelet factor 4/heparin antibody testing. During this time period, 34,694 adults were hospitalized and 24,956 received heparin. Only 3,239 (13%) patients had more than 1 platelet count during the hospital stay. Of 199 patients (6.1%) with ≥50% platelet count drop, clinician awareness was 36%. The absolute platelet count was the only independent variable associated with HIT awareness (P awareness are low at this large teaching institution. Software tools for monitoring awareness and providing realtime alerts of significant platelet count decrements may be useful.

  12. Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis.

    Liu, Quan; He, Biao; Huang, Si-Yang; Wei, Feng; Zhu, Xing-Quan


    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging haemorrhagic fever that was first described in rural areas of China. The causative agent, SFTS virus (SFTSV), is a novel phlebovirus in the Bunyaviridae family. Since the first report in 2010, SFTS has been found in 11 provinces of China, with about 2500 reported cases, and an average case-fatality rate of 7·3%. The disease was also reported in Japan and Korea in 2012; Heartland virus, another phlebovirus genetically closely related to SFTSV, was isolated from two patients in the USA. The disease has become a substantial risk to public health, not only in China, but also in other parts of the world. The virus could undergo rapid evolution by gene mutation, reassortment, and homologous recombination in tick vectors and vertebrate reservoir hosts. No specific treatment of SFTS is available, and avoiding tick bites is an important measure to prevent the infection and transmission of SFTSV. This Review provides information on the molecular characteristics and ecology of this emerging tick-borne virus and describes the epidemiology, clinical signs, pathogenesis, diagnosis, treatment, and prevention of human infection with SFTSV.

  13. Abnormal lipid rafts related ganglioside expression and signaling in T lymphocytes in immune thrombocytopenia patients.

    Zhang, Xian; Zhang, Donglei; Liu, Wenjie; Li, Huiyuan; Fu, Rongfeng; Liu, Xiaofan; Xue, Feng; Yang, Renchi


    Aberrant T lymphocytes signaling is considered to play a crucial role in the abnormal immune state of primary immune thrombocytopenia (ITP). Lipid raft has been verified to engage in the T cell receptor (TCR)-mediated T lymphocytes signal transduction. Whether lipid raft-associated T cells signal transduction has impact on the pathogenesis of ITP is still unconfirmed. In this study, we aimed to reveal the abnormality in structure and function of lipid rafts (LRs) in CD4(+) and CD8(+) T lymphocytes of patients with ITP. Our results showed that there was an increased lipid raft aggregation in ITP patients, while this kind of increase would not be influenced by platelet counts or therapeutic regimes. Stimulation by anti-CD3/CD28 monoclonal antibodies promoted enhanced lipid raft clustering in T lymphocytes of ITP patients compared with negative controls. Methyl-β-cyclodextrin (MβCD) could block the abnormal lipid raft aggregation and disrupt the TCR-mediated T cells proliferation and cytokines secretion, including both proinflammatory cytokines and anti-inflammatory cytokines. The spontaneous activation of T lymphocytes from ITP patients might be due to the elevated co-localization of protein tyrosine phosphatase (PTP) CD45 and lipid rafts in patients' CD4(+) and CD8(+) T lymphocytes. These findings suggest that the autoactivation of T lymphocytes from ITP patients may lead to the abnormality in lipid raft structure and raft-anchored proteins, and the changes conversely promote the TCR-mediated T cells activation of ITP patients.

  14. A Non-Invasive Strategy for Neonatal Alloimmune Thrombocytopenia Diagnosis: Newborn Platelet Genotyping with Buccal Swabs

    Gérald Bertrand


    Full Text Available Neonatal alloimmune thrombocytopenia results from the maternal immune response against fetal-specific antigens inherited from the father. The diagnosis is ascertained only when the maternal alloantibody and the offending antigen present in the newborn are identified. Up until now most laboratories perform DNA extraction for neonatal genotyping from newborn blood samplings. In order to avoid such an invasive procedure, two protocols of DNA extraction from buccal swabs were developed: a manual protocol using the QIAamp mini blood kit (Qiagen, and an automated procedure with the MagNA Pure Compact instrument (Roche. Both EDTA-blood and buccal swabs from thrombocytopenic newborns were genotyped manually (14 samples, automatically (15 samples or both manually and automatically (two samples. Human Platelet Antigen (HPA genotyping was performed using the BeadChip assay (BioArray, Immucor. Concordant genotypings were obtained for all samples except for one swab with the manual method. The automated DNA extraction from newborn buccal swabs with the MagNA Pure Compact instrument was chosen as the first-line strategy, with a significant gain of time in processing buccal swabs.

  15. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia

    Gudbrandsdottir, Sif; Birgens, Henrik Sverre; Frederiksen, Henrik


    In this study, we report the results from the largest cohort to date of newly diagnosed adult immune thrombocytopenia patients randomized to treatment with dexamethasone alone or in combination with rituximab. Eligible were patients with platelet counts ≤25×10(9)/L or ≤50×10(9)/L with bleeding...... symptoms. A total of 133 patients were randomly assigned to either dexamethasone 40 mg/day for 4 days (n = 71) or in combination with rituximab 375 mg/m(2) weekly for 4 weeks (n = 62). Patients were allowed supplemental dexamethasone every 1 to 4 weeks for up to 6 cycles. Our primary end point, sustained...... response (ie, platelets ≥50×10(9)/L) at 6 months follow-up, was reached in 58% of patients in the rituximab + dexamethasone group vs 37% in the dexamethasone group (P = .02). The median follow-up time was 922 days. We found longer time to relapse (P = .03) and longer time to rescue treatment (P = .007...

  16. [Advance in thrombopoietic drugs used in treatment of children's immune thrombocytopenia].

    Ma, Jing-Yao; Wu, Run-Hui


    Immune thrombocytopenia (ITP) is a common acquired hemorrhagic disease. Conventional view considered its pathogenesis as the destruction of platelets induced by platelet associated antibodies, the target of treatment are inhibiting the production of antibodies and blocking the destruction of platelets in reticuloendothelial system, but they are ineffective in part of ITP patients, who transform to chronic/refractory ITP (C/RITP). As to children's C/RITP, the effect of first-line therapy is low, while the second-line therapy isn't effective definitely and has obvious side effects. The safe and effective second-line drugs to prevent disease progressing are urgently required. Recently, a pathogenesis that decrease the platelet production has been confirmed, thrombopoietic drugs, including thrombopoietin (TPO) and its receptor agonist (TRA), are under research and clinical application gradually. Recombinate human TPO (rhTPO) has accomplished Phase III clinical trails in adult C/RITP and tumor children. The Phase III clinical trails of romiplostim and eltrombopag, as the representative of TRA, in adult C/RITP have been performed. There are also two clinical trails of TRA for children's C/RITP, the efficacy and safety have been approved, with the convenience for using. In pediatric population, they have a good clinical application. In this article the research and development of thrombopoietic drugs and their perspective in pediatric clinical use are reviewed.

  17. Autoimmune hemolytic anemia and autoimmune thrombocytopenia at diagnosis and during follow-up of Hodgkin lymphoma.

    Dimou, Maria; Angelopoulou, Maria K; Pangalis, Gerassimos A; Georgiou, Georgios; Kalpadakis, Christina; Pappi, Vassiliki; Tsopra, Olga; Koutsoukos, Konstantinos; Zografos, Eleftherios; Boutsikas, George; Moschogianni, Maria; Vardounioti, Ioanna; Petevi, Kyriaki; Karali, Vassiliki; Kanellopoulos, Alexandros; Ntalageorgos, Themis; Yiakoumis, Xanthis; Bartzis, Vasiliki; Bitsani, Aikaterini; Pessach, Elias; Efthimiou, Anna; Korkolopoulou, Penelope; Rassidakis, George; Kyrtsonis, Marie-Christine; Patsouris, Efstratios; Meletis, John; Panayiotidis, Panayiotis; Vassilakopoulos, Theodoros P


    Autoimmune hemolytic anemia and thrombocytopenia (AIHA/AITP) frequently complicate the course of non-Hodgkin lymphomas, especially low-grade, but they are very rarely observed in Hodgkin lymphoma (HL). Consequently the frequency and the profile of patients with HL-associated AIHA/AITP have not been well defined. Among 1029 patients with HL diagnosed between 1990 and 2010, two cases of AIHA (0.19%) and three of AITP (0.29%) were identified at the presentation of disease. These patients were significantly older, and more frequently had features of advanced disease and non-nodular sclerosing histology, compared to the majority of patients, who did not have autoimmune cytopenias at diagnosis. ABVD combination chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) provided effective control of HL and the autoimmune condition as well. During approximately 6600 person-years of follow-up for the remaining 1024 patients, seven (0.7%) patients developed autoimmune cytopenias (three AITP, three AIHA, one autoimmune pancytopenia) for a 10- and 15-year actuarial incidence of 0.95% and 1.40%, respectively. Their features did not differ compared to the general population of adult HL. In this large series of consecutive, unselected patients, those who presented with autoimmune cytopenias had a particular demographic and disease-related profile. In contrast, patients developing autoimmune cytopenias during follow-up did not appear to differ significantly from those who did not.

  18. Structure-activity relationships of pyrazole derivatives as potential therapeutics for immune thrombocytopenias.

    Purohit, Meena K; Chakka, Sai Kumar; Scovell, Iain; Neschadim, Anton; Bello, Angelica M; Salum, Noruê; Katsman, Yulia; Bareau, Madeleine C; Branch, Donald R; Kotra, Lakshmi P


    Idiopathic or immune thrombocytopenia (ITP) is a serious clinical disorder involving the destruction of platelets by macrophages. Small molecule therapeutics are highly sought after to ease the burden on current therapies derived from human sources. Earlier, we discovered that dimers of five-membered heterocycles exhibited potential to inhibit phagocytosis of human RBCs by macrophages. Here, we reveal a structure-activity relationship of the bis-pyrazole class of molecules with -C-C-, -C-N- and -C-O- linkers, and their evaluation as inhibitors of phagocytosis of antibody-opsonized human RBCs as potential therapeutics for ITP. We have uncovered three potential candidates, 37, 47 and 50, all carrying a different linker connecting the two pyrazole moieties. Among these compounds, hydroxypyrazole derivative 50 is the most potent compound with an IC50 of 14 ± 9 μM for inhibiting the phagocytosis of antibody-opsonized human RBCs by macrophages. None of the compounds exhibited significant potential to induce apoptosis in peripheral blood mononuclear cells (PBMCs). Current study has revealed specific functional features, such as up to 2-atom spacer arm and alkyl substitution at one of the N(1) positions of the bivalent pyrazole core to be important for the inhibitory activity.

  19. Acute cholecystitis

    Halpin, Valerie


    Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae. About 95% of people with acute cholecystitis have gallstones.It is thought that blockage of the cystic duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.




    Full Text Available BACKGROUND Thrombocytopenia is one of the relatively common finding in haematological investigation. The causes of this varies from mild cases, viral fever to malignant conditions like leukaemia. Though abnormal platelet count is detected by automatic haematology analyser, confirmation is always done by peripheral smear examination. METHODS 2156 patients’ blood samples from OPD and inpatients are collected in CBC tubes and subjected to automatic haematology analyser (SYSMEX KX-21 and the results were analysed. In all these cases of low platelet count, repeat analysis was done with suitable anticoagulant 3.8% sodium citrate, finally smear examination was done as a confirmatory evidence. RESULTS 256 cases of thrombocytopenia were encountered out of 2156 patients’ samples. It accounted for 11.8% of blood samples that were run on the analyser. Age varied from 0-75 years with peak incidence in 15-30 years. It is seen more among males than females. In our study, viral infection, dengue fever formed the commonest cause and seen with peak incidence in rainy season from June to October. Rarer cases seen were leukaemia, hypersplenism and massive blood transfusion. Majority of the cases were presented with mild-to-moderate thrombocytopenia. Only 19% cases presented with severe thrombocytopenia (counts less than 40,000 cells per cu. mm. CONCLUSION An important approach to the diagnosis and successful treatment of thrombocytopenia is understanding the underlying pathophysiological process in the development of disease. Prompt investigations and identification may be crucial and sometimes lifesaving as in TTP, HIT or severe ITP. Notable progress has been made in the recent years in developing new treatment option for thrombocytopenia like ITP. Early diagnosis, treatment, vector control, community awareness are essential to decrease the incidence thrombocytopenia.

  1. Mechanism of thrombocytopenia in liver cirrhosis: Kinetics of indium-111 tropolone labelled platelets

    Aoki, Yoshinori; Hirai, Kenji; Tanikawa, Kyuichi (Kurume Univ., Fukuoka (Japan). 2. Dept. of Medicine)


    Using indium-111 tropolone-labelled platelets, a study of platelet kinetics was performed on the basis of the relationship between platelet count, platelet survival time, platelet dynamics, platelet-associated immunoglobulin G (PA-IgG) and splenic volume in 31 patients with liver cirrhosis and a platelet count of less than 100 x 10[sup 9]/1: The mean platelet count was 46.6 [+-] 25.3 x 10[sup 9]/1, and the mean platelet survival time was 6.50 [+-] 1.33 days. The mean uptake into the spleen was 43.2% [+-] 14.8% on the 1st day, and 53.7% [+-] 14.3% on the 7th day. The mean PA-IgG level was 107.6 [+-] 66.0 ng/10[sup 7] platelets in five patients with chronic active hepatitis who were studied as controls the mean platelet count was 197 [+-] 30 x 10[sup 9]/1, the mean platelet survival time 9.33 [+-] 0.78 days, and the mean PA-IgG 21.2 [+-] 2.9 ng/10[sup 7] platelets. The former two parameters were significantly higher, and the latter significantly lower. In liver cirrhosis, the platelet count showed a positive correlation with the platelet survival time and a negative correlation with PA-IgG and the splenic volume. These results suggest that the increases in both the splenic platelet pool and platelet destruction in the spleen through immunological mechanisms may influence thrombocytopenia in liver cirrhosis. (orig.).

  2. DNA Methyltransferase 3B Gene Promoter and Interleukin-1 Receptor Antagonist Polymorphisms in Childhood Immune Thrombocytopenia

    Margarita Pesmatzoglou


    Full Text Available Primary immune thrombocytopenia (ITP is one of the most common blood diseases as well as the commonest acquired bleeding disorder in childhood. Although the etiology of ITP is unclear, in the pathogenesis of the disease, both environmental and genetic factors including polymorphisms of TNF-a, IL-10, and IL-4 genes have been suggested to be involved. In this study, we investigated the rs2424913 single-nucleotide polymorphism (SNP (C46359T in DNA methyltransferase 3B (DNMT3B gene promoter and the VNTR polymorphism of IL-1 receptor antagonist (IL-1 Ra intron-2 in 32 children (17 boys with the diagnosis of ITP and 64 healthy individuals. No significant differences were found in the genotype distribution of DNMT3B polymorphism between the children with ITP and the control group, whereas the frequency of allele T appeared significantly increased in children with ITP (P = 0.03, OR = 2, 95% CI: 1.06–3.94. In case of IL-1 Ra polymorphism, children with ITP had a significantly higher frequency of genotype I/II, compared to control group (P = 0.043, OR = 2.60, 95% CI: 1.02–6.50. Moreover, genotype I/I as well as allele I was overrepresented in the control group, suggesting that allele I may have a decreased risk for development of ITP. Our findings suggest that rs2424913 DNMT3B SNP as well as IL-1 Ra VNTR polymorphism may contribute to the susceptibility to ITP.

  3. Hospitalizations in pediatric patients with immune thrombocytopenia in the United States

    Tarantino, Michael D.; Danese, Mark; Klaassen, Robert J.; Duryea, Jennifer; Eisen, Melissa; Bussel, James


    Abstract To examine utilization and outcomes in pediatric immune thrombocytopenia (ITP) hospitalizations, we used ICD-9 code 287.31 to identify hospitalizations in patients with ITP in the 2009 HCUP KID, an all-payer sample of pediatric hospitalizations from US community hospitals. Diagnosis and procedure codes were used to estimate rates of ITP-related procedures, comorbidity prevalence, costs, length of stay (LOS), and mortality. In 2009, there were an estimated 4499 hospitalizations in children aged 6 months–17 years with ITP; 43% in children aged 1–5 years; and 47% with emergency department encounters. The mean hospitalization cost was $5398, mean LOS 2.0 days, with 0.3% mortality (n = 13). With any bleeding (15.2%, including gastrointestinal 2.0%, hematuria 1.3%, intracranial hemorrhage [ICH] 0.6%), mean hospitalization cost was $7215, LOS 2.5 days, with 1.5% mortality. For ICH (0.6%, n = 27), mean cost was $40 209, LOS 8.5 days, with 21% mortality. With infections (14%, including upper respiratory 5.2%, viral 4.9%, bacterial 1.9%), the mean cost was $6928, LOS 2.9 days, with 0.9% mortality. Septic shock was reported in 0.3% of discharges. Utilization included immunoglobulin administration (37%) and splenectomies (2.3%). Factors associated with higher costs included age >6 years, ICH, hematuria, transfusion, splenectomy, and bone marrow diagnostics (p < 0.05). In conclusion, of the 4499 hospitalizations with ITP, mortality rates of 1.5%, 21%, and 0.9% were seen with any bleeding, ICH, and infection, respectively. Higher costs were associated with clinically significant bleeding and procedures. Future analyses may reveal effects of the implementation of more recent ITP guidelines and use of additional treatments. PMID:26941022

  4. Function of eltrombopag-induced platelets compared to platelets from control patients with immune thrombocytopenia.

    Haselboeck, Johanna; Kaider, Alexandra; Pabinger, Ingrid; Panzer, Simon


    Data on the in vivo function of platelets induced by the thrombopoietin receptor agonist eltrombopag are scarce. To assess a possible influence of eltrombopag we compared platelet function of eltrombopag-treated immune thrombocytopenia (ITP) patients (group 1; n=10) after treatment response to that from control ITP patients (group 2; n=12). We further analysed platelet function at baseline and after one, three, and four weeks of eltrombopag treatment and estimated daily changes of platelet function during the eltrombopag-induced platelet rise. The formation of platelet-monocyte aggregates (PMA), P-selectin expression [MFI], and platelet adhesion under high shear conditions (surface coverage, SC) in vivo and after in vitro addition of agonists (ADP, TRAP-6, Collagen) were similar between both groups after response to eltrombopag treatment. Only TRAP-6 induced a lower SC in the eltrombopag group (p=0.03). All platelet function parameters except for Collagen-induced P-selectin expression changed significantly during treatment with eltrombopag. PMA, naïve and after addition of ADP or TRAP-6 increased with increasing platelet counts. P-selectin expression decreased, when measured without and upon addition of ADP, increased in the presence of TRAP-6, and remained unchanged after addition of Collagen. SC increased during the eltrombopag-induced platelet rise. All significant changes of platelet function correlated to changes in platelet counts. Two patients developed venous thromboses during eltrombopag treatment, but no association with any distinct single platelet function parameter or combinations thereof was identifiable. Thus, eltrombopag-induced platelets function similar to those from control ITP patients without discernible increased hyper-reactivity.

  5. A case of refractory immune thrombocytopenia in pregnancy managed with elthrombopag

    Jyothis Purushothaman


    Full Text Available Immune thrombocytopenic purpura is a common acquired autoimmune disorder defined by a low platelet count secondary to accelerated platelet destruction or impaired thrombopoesis by anti-platelet antibodies. Thrombopoietin (TPO-mimetic drugs such as eltrombopag and romiplostim have been used successfully in many nonpregnant individuals with immune thrombocytopenia (ITP but studies based on its effects in pregnancy are limited. A 27-year-old multigravida who is a known case of ITP with bad obstetric history was referred to the Department of Obstetrics and Gynecology at 26 weeks of gestation with complaints of mucosal bleeding and recurrent abortions. After 2 weeks of hospital stay, the patient did not respond to treatment with steroid and immunosuppressant. There was a rapid decline in platelet count with mucosal bleeds for which she required frequent platelet transfusions. Due to high costs, short action periods, and other potential maternal and fetal side effects of intravenous immunoglobulin (IVIgG and anti-D, it was decided that TPO-mimetic drug eltrombopag would be given. After starting treatment with eltrombopag, the patient's platelet count could be maintained between 30,000/μl and 50,000/μl. At 36 weeks of gestation following preterm-induced vaginal delivery, she delivered a male active baby weighing 1.86 kg with an Apgar score of 8/10. After delivery, her platelet count was 60,000/μl. Eltrombopag is a thrombopoietin receptor agonist. It has been assigned to pregnancy category C by the Food and Drug Administration (FDA. There are no adequate and well-controlled studies of use of eltrombopag in pregnancy. In our case, the drug was given in the last trimester of pregnancy and the mother and baby were in good health at the time of discharge from the hospital and during follow-up.

  6. 肝素诱导血小板减少症%Heparin-induced thrombocytopenia

    贾海; 褚燕琦; 李炜; 袁继勇


    1例57岁男性患者因行溶栓术,给予尿激酶200000U,1次/6h泵入;肝素钠12 500 U入0.9%氯化钠注射液50ml进行24h微量泵泵入.溶栓治疗当日血小板计数为126×109/L,第3天为99×109/L,第4天降至65×109/L.考虑为肝素诱导血小板减少症,停用肝素钠,改为阿加曲班抗凝,并继续应用尿激酶行第2次溶栓术.停用肝素钠后血小板计数即回升,第2、4天分别为93×109/L、113×109/L,第5天恢复到术前水平.%A 57-year-old male patient received urokinase 200 000 U via pump every six hours and heparin sodium 12 500 U in 0. 9% chloride sodium 50 ml via minipump for 24 hours for thrombolytic therapy. In same day, the platelet level was 126 × 109/L and, on day 3 and 4, the platelet count respectively decreased to 99 × 109/L and 65 × 109/L. Heparin-induced thrombocytopenia was considered. Heparin sodium was stopped and switched to argatroban. The patient then underwent the second thrombolytic therapy with urokinase. The platelet count increased at once after heparin sodium discontinuation and, on days 2 and 4, his platelet level was 93 × 109/L and 113 × 109/L, respectively. His platelet count returned to a baseline level on day 5.

  7. Recombinant human thrombopoietin is an effective treatment for thrombocytopenia in hemophagocytic lymphohistiocytosis.

    Wang, Yini; Wang, Zhao; Wu, Lin; Zhang, Jia; Wang, Jingshi; Yan, Lijuan


    The aim of this study was to investigate the effectiveness and safety in the treatment of thrombocytopenia in hemophagocytic lymphohistiocytosis (HLH) by recombinant human thrombopoietin (rhTPO). A prospective randomized study was conducted between March 2010 and December 2011 in 40 patients with adult HLH whose blood platelet counts (BPC) were lower than 40 × 10(9)/L. The 40 patients were randomly assigned into the rhTPO group or control group based on sex, age, primary disease, and BPC (20 in each group). All patients were given conventional systemic therapy for HLH. The rhTPO group was administered by subcutaneous injection of rhTPO at a dose of 300 IU/kg Qd. The BPC, platelet transfusion, bleeding, and survival rate in the two groups were monitored and compared. There was no significant difference in BPC between the two groups before the treatment. Two weeks after the treatment, the BPC of the rhTPO group was significantly higher than that of the control group at every time point (P rhTPO group and control group, however, the number of patients presented with gastrointestinal bleeding, urinary tract bleeding, and pulmonary bleeding in the control group were higher than that in the rhTPO group (P = 0.013). The frequency of platelet transfusion in the control group (7.25 per patient, 145 in 19 patients) was significantly higher than that in the rhTPO group (2.25 per patient, 45 in 14 patients) (P rhTPO groups was shorter than that in the control group (the rhTPO group vs the control group: 13.43 ± 4.62 D vs 18.00 ± 3.98 D, P = 0.013). In the early stage of HLH treatment, rhTPO combined with conventional systemic therapy can restore the BPC to normal level within a shorter period of time, reduce the frequency of platelet transfusion and severe bleeding.

  8. A multicenter randomized controlled trial of recombinant human thrombopoietin treatment in patients with primary immune thrombocytopenia.

    Wang, Shujie; Yang, Renchi; Zou, Ping; Hou, Ming; Wu, Depei; Shen, Zhixiang; Lu, Xijing; Li, Yan; Chen, Xiequn; Niu, Ting; Sun, Hui; Yu, Li; Wang, Zhao; Zhang, Yin; Chang, Naibai; Zhang, Gaokui; Zhao, Yongqiang


    This multicenter, randomized trial assessed the efficacy and safety of a recombinant human thrombopoietin (rhTPO) in patients with persistent primary immune thrombocytopenia (ITP) who had failed glucocorticosteroid treatment. A total of 140 eligible patients were randomized to receive rhTPO + danazol (rhTPO group, 73 patients) or danazol (control group, 67 patients) alone. During the first phase, the increase in the mean maximal platelet counts (101.2 × 10(9)/L) and the area under curve (749.6) in the rhTPO group were significantly higher compared to control (33.3 × 10(9)/L and 316.2; P = 0.0060 and 0.0000, respectively). The major response rate (MRR) and total response rate (TRR) in the rhTPO group were 38.4 and 60.3 %, respectively, significantly higher than in control (MRR 7.9 %, P = 0.0003; TRR 36.5 %, P = 0.0104). In the control group, 45 patients with platelet counts rhTPO during the second phase and achieved MRR 31.1 % and TRR 66.7 %. The mean platelet counts in the rhTPO group were still approximately 50 × 10(9)/L on day 28 of the study. The overall incidence of rhTPO-related adverse events was 13.6 %. All the adverse events were generally mild. This study demonstrated that rhTPO was well tolerated, and it markedly increased platelet counts in chronic ITP patients. Stimulation of platelet production by rhTPO may provide a new therapeutic option for patients with ITP.

  9. Relationship between Th17 and Th22 in patients with primary immune thrombocytopenia

    Hai-Ping Tang; Jian-Guo Tan


    Objective:To investigate the relationship of Th17 and its cytokine interleukin-17 (IL-17), Th22 and its cytokines, IL-22, IL-6, tumor necrosis cytokines (TNF-α) and the pathogenesis and prognosis of primary immune thrombocytopenia (ITP) and to analyze the effects of glucocorticoids on Th17, Th22 and cytokine.Methods: Th17 and Th22 cells of 52 cases of ITP patients and 50 normal volunteers were measured with flow cytometry. The levels of IL-17, IL-22, IL-6 and TNF-α of two groups were measured with ELISA. The relationship of expressions and prognosis between Th17, Th22 and their cytokines in patients with ITP were analyzed.Results:The levels of Th17, Th22 ratio and IL-17, IL-22, IL-6, TNF-α of ITP group were higher than control groups. The levels of Th17, Th22 ratio and IL-17, IL-22, IL-6, TNF-α of glucocorticoids proportion group were lower than non-glucocorticoids therapy group. The levels of Th17, Th22 ratio and IL-17, IL-22, IL-6, TNF-αof complete remission (CR) group and partial response (PR) were lower than the no-remission group (NR), the differences were statistically significant.Conclusion:Th17 and Th22 may participate in the occurrence and progression of ITP, and their cytokines can be used as indicators of prognosis for patients with the disease. Glucocorticoids can play a therapeutic role through inhibiting the proportion of peripheral Th17 and Th22.

  10. Can we prevent blood dyscrasia (leucopenia, thrombocytopenia) and epileptic seizures induced by clozapine.

    Herceg, Miroslav; Muzinić, Lana; Jukić, Vlado


    Clozapine is associated with various haematological adverse effects, including leukopenia, neutropenia, agarnulocytosis, leukocytosis, anaemia, eosinophilia, thrombocytopenia and thrombocythaemia. Recognition and treatment of clozapine-related seizures also will become increasingly important as clozapine use grows in the 1990s. The decision to stop clozapine as a result of haematological adverse effects or seizures is a frustrating one for the clinician, and frequently disastrous for the patient. Cessation of treatment results in relapse. In case that patient is unresponsive to other antipsychotic, restarting clozapine should be consider, despite the risk involved. As the risk of a second agranulocytosis is much higher in those patients, various methods of militating against repeat blood dyscrasias have been treated, including granulocyte colony-stimulating factor and lithium. The decision to restart clozapine should be taken on case-by-case basis and should take into account the likely risks and benefits of restarting. Prior response to clozapine and magnitude of patient deterioration on stopping treatment are important factors to take into this consideration. Clozapine-related seizures did not preclude successful treatment with clozapine. A strategy that has been proposed to reduce the occurrence of seizures is the addition of an anticonvulsant agent. However, clozapine does induce a variety of adverse effects, most of which are of limited duration and either preventable or manageable if a number of simple clinical procedures are followed. With careful haematologyc control, the risk of agranulocytosis can be minimized and in case of clozapine related seizures recommendations include dose reduction, electroencephalogram (EEG), plasma-level monitoring and prophylactic antiepileptic treatment. Re-exposure to clozapine may rarely be attempted where there are facilities for very close and frequent monitoring.

  11. Thrombocytopenia in early pregnancy predicting partial haemolysis, elevated liver enzyme and low platelet count syndrome: a case report and review of literature

    Kavitha Nagandla


    Full Text Available The incidence of thrombocytopenia in pregnancy is 6-10% and is classically defined as a platelet count of less than 150,000/ L. Counts less than 100,000 to 150,000/L are considered mild, 50,000 to 100,000/L as moderate, and less than 50,000/L are considered as severe thrombocytopenia. It is the second most common hematological condition in pregnancy with anaemia being the leading cause. Thrombocytopenia may be related to disorders that are intrinsic to pregnancy such as gestational thrombocytopenia that is seen in three-fourths of all cases. The second common cause is hypertensive disorders in pregnancy more commonly seen in severe pre-eclampsia in 21% and in HELLP (haemolysis, elevated liver enzyme and low platelet count that accounts for 12% of thrombocytopenia cases in pregnancy. This case report revisits the diagnosis of partial HELLP under the background of preeclampsia that warrants aggressive treatment like complete HELLP syndrome to optimize the maternal and fetal outcome. [Int J Reprod Contracept Obstet Gynecol 2016; 5(8.000: 2847-2850

  12. Acute Kidney Failure

    ... out of balance. Acute kidney failure — also called acute renal failure or acute kidney injury — develops rapidly over ... 2015. Palevsky PM. Definition of acute kidney injury (acute renal failure). Accessed April ...

  13. Acute Pancreatitis and Pregnancy

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  14. Evaluation of the effect of partial splenic embolization on platelet values for liver cirrhosis patients with thrombocytopenia

    Chi-Ming Lee; Ting-Kai Leung; Hung-Jung Wang; Wei-Hsing Lee; Li-Kuo Shen; Jean-Dean Liu; Chun-Chao Chang; Ya-Yen Chen


    AIM: To investigate the effect of partial splenic embolization (PSE) on platelet values in liver cirrhosis patients with thrombocytopenia and to determine the effective embolization area for platelet values improvement.METHODS: Blood parameters and liver function indicators were measured on 10 liver cirrhosis patients (6 in Child-Pugh grade A and 4 in grade B) with thrombocytopenia (platelet values < 80 × 103/μL) before embolization. Computed tomography scan was also needed in advance to acquire the splenic baseline. After 2 to 3 d, angiography and splenic embolization were performed. A second computed tomography scan was made to confirm the embolization area after 2 to 3 wk of embolization. The blood parameters of patients were also examined biweekly during the 1 year follow-up period.RESULTS: According to the computed tomography images after partial splenic embolization, we divided all patients into two groups: low (< 30%), and high (≥ 30%) embolization area groups. The platelet values were increased by 3 times compared to baseline levels after 2 wk of embolization in high embolization area group. In addition, there were significant differences in platelet values between low and high embolization area groups. GPT values decreased significantly in all patients after 2 wk of embolization. The improvement in platelet and GPT values still persisted until 1 year after PSE.In addition, 3 of 4 (75%) Child-Pugh grade B patients progressed to grade A after 2 mo of PSE. The complication rate in < 30% and ≥ 30% embolization area groups was 50% and 100%, respectively.CONCLUSION: Partial splenic embolization is an effective method to improve platelet values and GPT values in liver cirrhosis patients with thrombocytopenia and the ≥ 30% embolization area is meaningful for platelet values improvement. The relationship between the complication rate and embolization area needs further studies.

  15. Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations (II): thrombocytopenia and skin manifestations.

    Cervera, R; Tektonidou, M G; Espinosa, G; Cabral, A R; González, E B; Erkan, D; Vadya, S; Adrogué, H E; Solomon, M; Zandman-Goddard, G; Shoenfeld, Y


    The objectives of the 'Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations' were to assess the clinical utility of the international consensus statement on classification criteria and treatment guidelines for the catastrophic APS, to identify and grade the studies that analyze the relationship between the antiphospholipid antibodies and the non-criteria APS manifestations, and to present the current evidence regarding the accuracy of these non-criteria APS manifestations for the detection of patients with APS. This article summarizes the studies analyzed on thrombocytopenia and skin manifestations, and presents the recommendations elaborated by the Task Force after this analysis.

  16. A patient with isochromosome 18q, radial-thumb aplasia, thrombocytopenia, and an unbalanced 10;18 chromosome translocation.

    Sahoo, Trilochan; Naeem, Rizwan; Pham, Kim; Chheng, Sou; Noblin, Sarah T; Bacino, Carlos A; Gambello, Michael J


    We report on the clinical and cytogenetic findings in a newborn with a de novo isochromosome 18q. Radial/thumb aplasia and thrombocytopenia were significant features in addition to multiple congenital anomalies. Comparison with reported cases suggests that the genes for such features are located on the 18q arm. An additional finding of a non-reciprocal translocation between chromosome 18p telomere and chromosome 10q telomere was also observed in a majority of cells examined. This additional rearrangement likely has minimal phenotypic consequences, but does raise the possibility that cryptic translocations of telomeric ends of the deleted arm in isochromosome cases may be more common than appreciated.

  17. Thrombocytopenia-associated multiple organ failure or severe haemolysis, elevated liver enzymes, low platelet count in a postpartum case

    Manish Jagia


    Full Text Available Thrombocytopenia-associated multiple organ failure (TAMOF is a thrombotic microangiopathic syndrome that includes thrombotic thrombocytopenic purpura, secondary thrombotic microangiopathy, and disseminated intravascular coagulation. We report a case of postpartum female who presented with TAMOF or severe Haemolysis, elevated liver enzymes, low platelet count (HELLP which was managed with plasma exchange. This case report is to make clinicians aware that TAMOF, severe HELLP, and other differential diagnosis in a postpartum case have a thin differentiating line and plasma exchange can be considered as one of the management options.

  18. A clinical comparative study on treatment of severe newly diagnosed immune thrombocytopenia by recombinant human thrombopoietin combined with glucocorticoid



    Objective To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of severe newly diagnosed primary immune thrombocytopenia (ITP) .Methods From June 2009 to December 2012,24 male patients and 38female patients with the diagnosis of severe primary ITP in our hospital were randomized into trial group (31cases) or control group (31 cases) ,the median age was 50 years (range:21-84 years) .Trial group was treated with rhTPO combined with glucocorticoid,and control group was

  19. Trends in the prevalence of thrombocytopenia among individuals iInfected with hepatitis C Virus in the United States, 1999-2008

    Kauf Teresa L


    Full Text Available Abstract Background Thrombocytopenia is associated with the natural history of hepatitis C virus (HCV infection and anti-viral therapy. Recent, national estimates of the clinical burden of thrombocytopenia among HCV-infected individuals in the United States are unavailable. Bi-yearly data from the 1999-2000 to 2007-2008 National Health and Nutrition Examination Surveys (NHANES were used to examine the prevalence of thrombocytopenia among HCV-infected individuals in the United States. Results Among 467 HCV-infected individuals in the survey (weighted population = 3,597,039, mean weighted age was 46.7 years (standard deviation = 15.5 and 61.7% were male. Overall, 7.6% met the study definition of TCP at the 150 × 109/L threshold; 4.5%, 2.0%, and 0.8% had platelet counts below 125, 100, and 75 × 109/L, respectively. The 2-year weighted prevalences of thrombocytopenia (150 × 109/L threshold from 1999-2008 were 4.9%, 8.6%, 6.5%, 4.1%, and 12.9%. The unadjusted biannual time trend (odds ratio was 1.16 (95% confidence interval = 0.82-1.64. In the two adjusted models, the odds by time ranged from 1.24-1.40, depending on whether the model included demographic or laboratory variables or both, but did not reach statistical significance. Age was positively and significantly related to thrombocytopenia status. Conclusions As the HCV-infected population ages, the prevalence of thrombocytopenia is expected to rise. This study provides limited evidence of such an effect at the national level.

  20. Thrombocytopenia as a prognostic factor in patients with severe sepsis in Intensive Care Unit Trombocitopenia como fator prognóstico em pacientes com sepse grave internados em Unidade de Terapia Intensiva

    Kawana Megumi Uehara


    Full Text Available Previous studies show that thrombocytopenia probably reflects the severity and course of subclinical pathological condition, and its correction seems to be associated with better prognosis. The objective of this study was to evaluate thrombocytopenia as a prognostic factor in patients with severe sepsis admitted to the ICU of Londrina University Hospital from June to December, 2008. Prospective observational study was conducted. We analyzed 54 patients aged 59.03 ± 19.17 years, 64.8% man. Data were obtained from the Database of ICU’s HU-UEL. The following variables were used: age, gender, period of observation, diagnosis of ICU admission, severity of illness assessed by APACHE II score (Acute Physiology and Chronic Health Evaluation II, presence of comorbidities, organ dysfunction assessed by scoring SOFA and laboratory data of platelet count. The average platelet count in all patients on admission to ICU was 209,018 ± 148,209/ mm3, and 26% of patients had thrombocytopenia during ICU stay. When compared platelet count between survivors and non survivors patients we observed significantly lower mean count in non survivors. Estudos mostram que a trombocitopenia provavelmente reflete a gravidade e o curso de uma condição patológica subjacente, e a sua correção parece estar associada a melhor prognóstico. O objetivo deste estudo foi avaliar a trombocitopenia como fator prognóstico em pacientes com sepse grave ou choque séptico à admissão internados em UTI do Hospital Universitário de Londrina durante o período de junho a dezembro de 2008. Foi realizado estudo observacional prospectivo. Foram analisados 54 pacientes com média de idade de 59,03 ± 19,17 anos, sendo 64,8% masculino. Os dados foram obtidos do Banco de Dados do CTI do HU-UEL. As variáveis desse banco utilizadas foram: idade, sexo, período de observação, diagnóstico de admissão na UTI, gravidade da doença avaliada pelo escore APACHE II (Acute Physiology and Chronic

  1. Treatment of patients with refractory immune thrombocytopenia: literature review and case report

    V. V. Ptushkin


    with severe bleeding. Patient received 1 mg/kg of romiplostim and a week later platelet count was 250  10 9/l. Successfully tumor resection was done. No romiplostim side effects or thrombotic complications during postoperative period were found. The obtained data together with similar case reports of successful surgery after TPO-agonists administration allow considering romiplostim as an effective method of thrombocytopenia therapy before surgery in ITP patients.

  2. Correlation Between HLA-A, B and DRB1 Alleles and Severe Fever with Thrombocytopenia Syndrome

    Zhang, Xiao-mei; Jiang, Xiao-lin; Pang, Bo; Song, Yong-hong; Wang, Jian-xing; Pei, Yao-wen; Zhu, Chuan-fu; Wang, Xian-jun; Yu, Xue-jie


    Objective Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne bunyavirus (SFTSV) in East Asian countries. The role of human leukocyte antigen (HLA) in resistance and susceptibility to SFTSV is not known. We investigated the correlation of HLA locus A, B and DRB1 alleles with the occurrence of SFTS. Methods A total of 84 confirmed SFTS patients (patient group) and 501 unrelated non-SFTS patients (healthy individuals as control group) from Shandong Province were genotyped by PCR-sequence specific oligonucleotide probe (PCR-SSOP) for HLA-A, B and DRB1 loci.Allele frequency was calculated and compared using χ2 test or the Fisher's exact test. A corrected P value was calculated with a bonferronis correction. Odds Ratio (OR) and 95% confidence intervals (CI) were calculated by Woolf’s method. Results A total of 11 HLA-A, 23 HLA-B and 12 HLA-DRB1 alleles were identified in the patient group, whereas 15 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles were detected in the control group. The frequencies of A*30 and B*13 in the SFTS patient group were lower than that in the control group (P = 0.0341 and 0.0085, Pc = 0.5115 and 0.252). The ORs of A*30 and B*13 in the SFTS patient group were 0.54 and 0.49, respectively. The frequency of two-locus haplotype A*30-B*13 was lower in the patient group than in the control group(5.59% versus 12.27%, P = 0.037,OR = 0.41, 95%CI = 0.18–0.96) without significance(Pc>0.05). A*30-B*13-DRB1*07 and A*02-B*15-DRB1*04 had strong associations with SFTS resistance and susceptibility respectively (Pc = 0.0412 and 0.0001,OR = 0.43 and 5.07). Conclusion The host HLA class I polymorphism might play an important role with the occurrence of SFTS. Negative associations were observed with HLA-A*30, HLA-B*13 and Haplotype A*30-B*13, although the associations were not statistically significant. A*30-B*13-DRB1*07 had negative correlation with the occurrence of SFTS; in contrast, haplotype A*02-B*15-DRB1

  3. [Clinical analysis of recombinant humanized thrombopoietin for treating 25 children with severe immune thrombocytopenia].

    Zheng, Jie; Ma, Jing-Yao; Su, Yan; Yang, Jing; Zhang, Rui-Dong; Zhou, Xuan; Wu, Run-Hui


    This study was aimed to evaluate the efficacy and safety of recombinant humanized thrombopoietin (rhTPO) for treating children with severe immune thrombocytopenia (ITP). A total of 25 patients with severe ITP who accepted rhTPO treatment for 14 days between December, 2009 and November, 2012 in Beijing Children's Hospital was retrospectively analyzed. The results showed that the median platelet counts of all 25 patients increased from the lowest level 4.0×10(9)/L (0×10(9)/L-10×10(9)/L) to the highest level 71×10(9)/L (14×10(9)/L-439×10(9)/L) on median 11 days (range from 3 days to 15 days). After rhTPO discontinuation, the platelet counts of patients gradually decreased. Complete response rate was 44% (11/25), response rate was 32% (8/25), non-response rate was 24% (6/25) and total response rate was 76% (19/25). The platelet count in the patients who showed complete response to rhTPO therapy reached the highest 112×10(9)/L (43×10(9)/L-439×10(9)/L) on median 12 days(range from 7 days to 15 days). The patients showed response to rhTPO treatment on median 4 days (range from 1 days to 11 days). The platelet count decreased gradually after the discontinuation of rhTPO administration but still significantly higher on 28 days than the level before the treatment (P rhTPO treatment showed response to γ-globulin after the discontinuation of rhTPO therapy. 2 patients showed mild clinical adverse reaction. It is concluded that rhTPO is an effective and safe treatment method for children with severe ITP. It will help the patient smoothly through the dangerous period of severe bleeding, but the platelet count decreases gradually after rhTPO discontinuation. Maintenance treatment is needed to consolidate the curative efficacy.

  4. Trombocitopenia fetal/neonatal aloinmune: Revisión a propósito de un caso Foetal/neonatal alloimmune thrombocytopenia: A review and case report

    P. Rodríguez Wilhelmi


    thrombocytopenia is the most common cause of severe thrombocytopenia in the newborn. It is an acute disorder which implies that foetal platelets are destroyed during the pregnancy due to a maternal alloimmune IgG antibody. More than 80% of Caucasians are HPA-1a specific. Intracranial haemorrhage, which occurs in 30% of cases, is the most serious complication, with a 10% mortality rate or a 20% rate of irreversible neurological sequels. The high risk of a recurrence of serious bleeding in future pregnances led us to consider prophylaxis or prenatal treatment. An early diagnosis of this process allows an effective therapy to be carried out based on the infusion of compatible phenotype HPA platelets or endovenous immunoglobulins. We present the case of a 27 year old pregnant woman, who in the 35th week of a second pregnancy was diagnosed using echography with a bilateral foetal hydrocephaly. After caesarean delivery in the 36th week, the newborn presented haematomas in the left shoulder and gluteus, macrocephalia with tension of the fontanellas and hemorrhagic cerebrospinal fluid after insertion of an external ventricular derivation catheter. The haemogram revealed a severe trombocytopenia (9 x 10(9/L. In the light of clinical suspicion of foetal/neonatal alloimmune thrombocytopenia, infusion was made of platelets from a non-phenotyped donor for the HPA-1a system, and an endovenous immunoglobulin treatment was followed, with a recovery of platelet counts, but with neurological sequels that are probably irreversible. The immunohaematologal study confirmed the negative HPA-1a maternal phenotype, the neonatal HPA-1a positive phenotype and the presence of anti-HPA-1a alloantibodies in the maternal serum. Nowadays, the prophylaxis and treatment continue to be a controversial issue that is open to discussion, as is the possibility of implementing antenatal screening.

  5. Spatial Analysis of Severe Fever with Thrombocytopenia Syndrome Virus in China Using a Geographically Weighted Logistic Regression Model

    Liang Wu


    Full Text Available Severe fever with thrombocytopenia syndrome (SFTS is caused by severe fever with thrombocytopenia syndrome virus (SFTSV, which has had a serious impact on public health in parts of Asia. There is no specific antiviral drug or vaccine for SFTSV and, therefore, it is important to determine the factors that influence the occurrence of SFTSV infections. This study aimed to explore the spatial associations between SFTSV infections and several potential determinants, and to predict the high-risk areas in mainland China. The analysis was carried out at the level of provinces in mainland China. The potential explanatory variables that were investigated consisted of meteorological factors (average temperature, average monthly precipitation and average relative humidity, the average proportion of rural population and the average proportion of primary industries over three years (2010–2012. We constructed a geographically weighted logistic regression (GWLR model in order to explore the associations between the selected variables and confirmed cases of SFTSV. The study showed that: (1 meteorological factors have a strong influence on the SFTSV cover; (2 a GWLR model is suitable for exploring SFTSV cover in mainland China; (3 our findings can be used for predicting high-risk areas and highlighting when meteorological factors pose a risk in order to aid in the implementation of public health strategies.

  6. Partial response to sorafenib treatment associated with transient grade 3 thrombocytopenia in a patient with locally advanced thyroid cancer

    Pitoia Fabian; Abelleira, Erika; Jerkovich, Fernando; Urciuoli, Carolina; Cross, Graciela, E-mail: [Division de Endocrinologia, Hospital de Clinicas, Universidad de Buenos Aires Buenos Aires (Argentina)


    Advanced radioactive refractory and progressive or symptomatic differentiated thyroid carcinoma (DTC) is a rare condition. Sorafenib was recently approved for the treatment of these patients. We present the case of a 67 year old woman diagnosed with DTC who underwent a total thyroidectomy with central, lateral-compartment neck dissection and shaving of the trachea and esophagus due to tumor infiltration. A local recurrence was detected 14 months later requiring, additionally, two tracheal rings resection. The patient received a cumulative {sup 131}I dose of 650 mCi and developed dysphagia and dyspnea 63 months after initial surgery. A {sup 18}FGD-PET/CT showed progression of the local mass associated to hypermetabolic pulmonary nodules. Sorafenib 800 mg/day was then prescribed. A dose reduction to 400 mg/day was necessary due to grade 3 thrombocytopenia that appeared four months after drug prescription. Platelet count went to normal after this dose reduction. Five months after initiation of sorafenib, a partial response of the local mass with significant intra-tumoral necrosis was observed. We conclude that sorafenib is a valid option for locally advanced DTC and that the platelet count should be evaluated regularly because it seems that thrombocytopenia might be more frequently observed in DTC than in other types of tumors. (author)

  7. Provision of HPA-1a (PlA1)-negative platelets for neonatal alloimmune thrombocytopenia: screening, testing, and transfusion protocol.

    Munizza, M; Nance, S; Keashen-Schnell, M A; Sherwood, W; Murphy, S


    HPA-1a-negative platelet products are not routinely available for newborns with alloimmune thrombocytopenia. In this article we describe a program established to identify normal pheresis donors who are HPA-1a-negative and to organize their future donations so that our regional blood center would always have an HPA-1a-negative platelet product available. The solid phase red cell adherence assay was used for initial screening of platelet pheresis products. HPA-1a-negative donors were confirmed with the platelet suspension immunofluorescence test using three anti-HPA-1a sera. Screening of 2600 plateletpheresis donor samples identified 40 HPA-1a-negative donors. Of these, 36 are active and are coded for recognition on the daily pheresis inventory sheet. Theoretically, assuming four donations per year and donors' cooperation with scheduling, these 36 donors would enable us to have at least one HPA-1a-negative product available every day. In addition, a decision tree for patient management using platelet serology and availability of HPA-1a-negative products was developed. The GTI-PAK trade mark 12 is the major technique used for serologic screening of mothers of patients thought to have neonatal alloimmune thrombocytopenia. By screening pheresis donors and developing a clinical decision tree, HPA-1a-negative products, a rare resource, can be fully utilized.

  8. Platelets and platelet alloantigens: Lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia

    Vadasz, Brian; Chen, Pingguo; Yougbaré, Issaka; Zdravic, Darko; Li, June; Li, Conglei; Carrim, Naadiya; Ni, Heyu


    Platelets play critical roles in hemostasis and thrombosis. Emerging evidence indicates that they are versatile cells and also involved in many other physiological processes and disease states. Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life threatening bleeding disorder caused by fetal platelet destruction by maternal alloantibodies developed during pregnancy. Gene polymorphisms cause platelet surface protein incompatibilities between mother and fetus, and ultimately lead to maternal alloimmunization. FNAIT is the most common cause of intracranial hemorrhage in full-term infants and can also lead to intrauterine growth retardation and miscarriage. Proper diagnosis, prevention and treatment of FNAIT is challenging due to insufficient knowledge of the disease and a lack of routine screening as well as its frequent occurrence in first pregnancies. Given the ethical difficulties in performing basic research on human fetuses and neonates, animal models are essential to improve our understanding of the pathogenesis and treatment of FNAIT. The aim of this review is to provide an overview on platelets, hemostasis and thrombocytopenia with a focus on the advancements made in FNAIT by utilizing animal models.

  9. Flow cytometric assessment of activation of peripheral blood platelets in dogs with normal platelet count and asymptomatic thrombocytopenia.

    Żmigrodzka, M; Guzera, M; Winnicka, A


    Platelets play a crucial role in hemostasis. Their activation has not yet been evaluated in healthy dogs with a normal and low platelet count. The aim of this study was to determine the influence of activators on platelet activation in dogs with a normal platelet count and asymptomatic thrombocytopenia. 72 clinically healthy dogs were enrolled. Patients were allocated into three groups. Group 1 consisted of 30 dogs with a normal platelet count, group 2 included 22 dogs with a platelet count between 100 and 200×109/l and group 3 consisted of 20 dogs with a platelet count lower than 100×109/l. Platelet rich-plasma (PRP) was obtained from peripheral blood samples using tripotassium ethylenediaminetetraacetic acid (K3-EDTA) as anticoagulant. Next, platelets were stimulated using phorbol-12-myristate-13-acetate or thrombin, stabilized using procaine or left unstimulated. The expression of CD51 and CD41/CD61 was evaluated. Co-expression of CD41/CD61 and Annexin V served as a marker of platelet activation. The expression of CD41/CD61 and CD51 did not differ between the 3 groups. Thrombin-stimulated platelets had a significantly higher activity in dogs with a normal platelet count than in dogs with asymptomatic thrombocytopenia. Procaine inhibited platelet activity in all groups. In conclusion, activation of platelets of healthy dogs in vitro varied depending on the platelet count and platelet activator.

  10. 左乙拉西坦相关血小板减少%Thrombocytopenia associated with levetiracetam

    赵丽平; 任华丽; 周颖; 崔一民


    左乙拉西坦(LEV)引起的血液系统不良反应包括白细胞减少、中性粒细胞减少、血小板减少及全血细胞减少,发生率为0.01%~ 0.13%.LEV相关血小板减少出现或加重的时间最短为用药后3 d,最长则可达到用药后60 d,同时还可伴有血红蛋白减少,或出现全血细胞减少.不良反应严重者血小板计数可降至1×109/L以下.除实验室检查发现的血小板计数减少外,临床还可出现黏膜出血、皮肤瘀斑、血尿等症状.LEV相关血小板减少的机制尚不清楚,骨髓抑制、免疫复合物形成、非免疫性直接破坏都有可能是LEV致血小板减少的机制.临床应用LEV后应密切观察相关症状和体征,定期检查血常规.一旦出现与血小板减少相关症状应及时停药,症状较轻者停药1周后可自行恢复,较重者可输注血小板,有严重出血症状者可短期给予糖皮质激素治疗.%Levetiracetam ( LEV )-induced hematological adverse reactions include leukopenia, neutropenia, thrombocytopenia, and pancytopenia; and the incidence was 0.01%-0. 13%. The shortest time to LEV-associated thrombocytopenia onset or aggravation is 3 days after drug administration and the longest time could reach to 60 days after drug use. Meanwhile, hypochromia or pancytopenia may occur. The platelet count could decrease to < 1 × 109/L in the serious patient. Besides the reduction of platelet count showed by laboratory test, mucosal bleeding, skin petechia, hematuria, and other symptoms may also develop. Although the mechanism of LEV-associated thrombocytopenia is unclear, marrow suppression, immune complex formation, and direct harm by nonimmune factors are thought to be related to it. Attention should be paid to the patients with symptoms and signs related to thrombocytopenia after LEV use and routine blood tests should be regularly performed. LEV should be withdrawn immediately if thrombocytopenia-related symptoms occur. Patient with more mild symptoms

  11. Bleeding manifestations and management of children with persistent and chronic immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study Group (ICIS).

    Neunert, Cindy E; Buchanan, George R; Imbach, Paul; Bolton-Maggs, Paula H B; Bennett, Carolyn M; Neufeld, Ellis; Vesely, Sara K; Adix, Leah; Blanchette, Victor S; Kühne, Thomas


    Long-term follow-up of children with immune thrombocytopenia (ITP) indicates that the majority undergo remission and severe thrombocytopenia is infrequent. Details regarding bleeding manifestations, however, remain poorly categorized. We report here long-term data from the Intercontinental Cooperative ITP Study Group Registry II focusing on natural history, bleeding manifestations, and management. Data on 1345 subjects were collected at diagnosis and at 28 days, 6, 12, and 24 months thereafter. Median platelet counts were 214 × 10(9)/L (interquartile range [IQR] 227, range 1-748), 211 × 10(9)/L (IQR 192, range 1-594), and 215 × 10(9)/L (IQR 198, range 1-598) at 6, 12, and 24 months, respectively, and a platelet count <20 × 10(9)/L was uncommon (7%, 7%, and 4%, respectively). Remission occurred in 37% of patients between 28 days and 6 months, 16% between 6 and 12 months, and 24% between 12 and 24 months. There were no reports of intracranial hemorrhage, and the most common site of bleeding was skin. In patients with severe thrombocytopenia we observed a trend toward more drug treatment with increasing number of bleeding sites. Our data support that ITP is a benign condition for most affected children and that major hemorrhage, even with prolonged severe thrombocytopenia, is rare.

  12. In vitro effects of mesenchymal stem cells on secreting function of T lymphocytes and CD4~+CD25~+T cells from patients with immune thrombo-cytopenia



    Objective To analyze in vitro the effect of mesenchymal stem cells(MSCs)on secreting cytokines by T lymphocytes and ratio of CD4+CD25+T cells from patients with immune thrombocytopenia(ITP).Methods Human bone marrow-derived MSCs were isolated by Ficoll Hypaque and cultured for proliferating to passage cells.Allogeneic T lymphocytes

  13. The Use of Thrombopoietin Receptor Agonists for Correction of Thrombocytopenia prior to Elective Procedures in Chronic Liver Diseases: Review of Current Evidence

    Kamran Qureshi


    Full Text Available Patients with chronic liver diseases (CLD undergo a range of invasive procedures during their clinical lifetime. Various hemostatic abnormalities are frequently identified during the periprocedural work-up; including thrombocytopenia. Thrombocytopenia of cirrhosis is multifactorial in origin, and decreased activity of thrombopoietin has been identified to be a major cause. Liver is an important site of thrombopoietin production and its levels are decreased in patients with cirrhosis. Severe thrombocytopenia (platelet counts < 60–75,000/µL is associated with increased risk of bleeding with invasive procedures. In recent years, compounds with thrombopoietin receptor agonist activity have been studied as therapeutic options to raise platelet counts in CLD. We reviewed the use of Eltrombopag, Romiplostim, and Avatrombopag prior to various invasive procedures in patients with CLD. These agents seem promising in raising platelet counts before elective procedures resulting in reduction in platelet transfusions, and they also enabled more patients to undergo the procedures. However, these studies were not primarily aimed at comparing bleeding episodes among groups. Use of these agents had some adverse consequences, importantly being the occurrence of portal vein thrombosis. This review highlights the need of further studies to identify reliable methods of safely reducing the provoked bleeding risk linked to thrombocytopenia in CLD.

  14. Thrombocytopenia-associated multiorgan failure occurring in an infant at the onset of type 1 diabetes successfully treated with fresh frozen plasma.

    Kumar, Revati; McSharry, Brent; Bradbeer, Peter; Wiltshire, Esko; Jefferies, Craig


    TAMOF is a devastating microangiopathy that can occur in association with the new onset of T1DM, and should be considered with the onset of thrombocytopenia, renal failure, and raised LDH. Treatment with fresh frozen plasma should be considered as a first-line option in such cases prior to plasma exchange.

  15. Acute immune thrombocytopenic purpura triggered by insect bite

    Namdev R


    Full Text Available Idiopathic Thrombocytopenic Purpura (ITP is a blood disorder characterized by an abnormal decrease in the number of platelets in the blood. Acute thrombocytopenic purpura is most commonly seen in young children, with a sudden onset, following a viral illness, vaccination or an insect bite. The report is a rare case of ITP, which was triggered by a honey-bee bite and caused continuous intermittent bleeding from the gingival sulcular region of the maxillary left permanent first molar, and ecchymotic spots on the forehead, scalp, and lower limbs. A complete hemogram revealed severe thrombocytopenia with platelet count as low as 15,000/mm3. The patient was immediately hospitalized and administered platelet replacement and medication. With this report, the authors, as dentists, emphasize the significance of recognition, early diagnosis, and referral of such patients with bleeding disorders to specialized centers, for prompt treatment.

  16. Acute gingival bleeding as a complication of dengue hemorrhagic fever

    Saif Khan


    Full Text Available Dengue fever is mosquito borne disease caused by dengue virus (DENV of Flaviviridae family. The clinical manifestations range from fever to severe hemorrhage, shock and death. Here, we report a case of 20-year-old male patient undergoing orthodontic treatment presenting with acute gingival bleeding with a history of fever, weakness, backache, retro orbital pain and ecchymosis over his right arm. The hematological investigations revealed anemia, thrombocytopenia and positive dengue non-structural protein-1 antigen and also positive immunoglobulin M and immunoglobulin G antibodies for DENV. Patient was diagnosed as a case of dengue hemorrhagic fever and was immediately referred for appropriate management. This case report emphasizes the importance of taking correct and thorough medical history.

  17. Recent Research Progress of Pregnancy with Thrombocytopenia%妊娠合并血小板减少的研究新进展



    Pregnancy with thrombocytopenia is a common disease during perinatal period, the incidence of which is about 10% . The platelet count in pregnancy less than 100 × 109/L by 2 checks( excluding the coagulation dysfunction ) is the diagnosis of thrombocytopenia. It can be caused by a variety of reasons,such as pregnancy associated thrombocytopenia, idiopathic thrombocytopenic purpura, hypertensive disorders in pregnancy, aplastic anemia, hypersplenism , and systemic lupus erythematosus. Pregnant women with thrombocytopenia should be given strict prenatal care. The focus of treatment is to actively prevent bleeding due to thrombocytopenia, and strive to give appropriate treatment, and active treatment to the comorbidities and complications during the prenatal stage.%妊娠合并血小板减少(PT)是围生期一种常见疾病,其发病率约为10%.孕期2次检测血小板计数<100×109/L(排除有凝血功能障碍者)即诊断为血小板减少.它可由多种原因引起,如妊娠相关性血小板减少、特发性血小板减少性紫癜、妊娠期高血压疾病、再生障碍性贫血、脾功能亢进、系统性红斑狼疮等.PT患者在孕期应进行严格的产前检查.处理的重点是积极预防由于血小板减少所致的出血,争取在产前给予相应的治疗,积极治疗合并症和并发症.

  18. Modification of solid phase red cell adherence assay for the detection of platelet antibodies in patients with thrombocytopenia.

    Vongchan, Preeyanat; Nawarawong, Weerasak; Linhardt, Robert J


    Platelet refractoriness is caused by HLA antibodies and platelet-specific antibodies. Current methods used to detect antiplatelet antibodies have limitations. Solid phase red cell adherence (SPRCA) lacks sensitivity and requires a second assay using chloroquine-treated intact platelets to specify the response due to anti-HLA. We modified SPRCA by using 2 types of antihuman platelet antibodies with different specificities toward platelet lysate and tested samples from 361 patients (69 with unexplained thrombocytopenia and 292 with poor response to platelet transfusions not explicable by alloimmunization or the clinical situation) and 50 from healthy volunteers. Our method compared favorably with platelet suspension direct immunofluorescence. All samples from healthy volunteers were negative; of the samples from the patient population, 240 were positive (147 samples had only antiplatelet and 3 samples had only anti-HLA antibodies). This modified technique had a sensitivity of 98% and a specificity of 91%.

  19. Effect of thrombopoietin-receptor agonists on circulating cytokine and chemokine levels in patients with primary immune thrombocytopenia (ITP)

    Gudbrandsdottir, Sif; Ghanima, Waleed; Nielsen, Claus H;


    with TPO-RAs (median age 50 years (inter-quartile range; IQR 20-69), median platelet counts 24 × 10(9)/L (IQR 15-47 × 10(9)/L), 28 females) and 16 healthy controls (nine females, median age 37 years, IQR 22-51 years) were collected before and during treatment, and analyzed for a panel of cytokines......BACKGROUND: Thrombopoietin-receptor-agonists (TPO-RAs) increase platelet production in Immune Thrombocytopenia (ITP) by stimulating Mpl. The effect of TPO-RAs on inflammatory cytokine production in ITP patients has not been well investigated. METHODS: Plasma samples from 48 ITP patients treated...... and chemokines by enzyme-linked immunosorbent assay and immuno-bead-based multiplex assay. RESULTS: Elevated levels of C-X-C motif chemokine 10 (CXCL10; p treatment...

  20. An Anti-Coagulation Conundrum: Implantation of Total Artificial Heart in a Patient with Heparin-Induced Thrombocytopenia Type II

    Cios, Theodore J.; Salamanca-Padilla, Yuliana; Guvakov, Dmitri


    Patient: Male, 44 Final Diagnosis: Heparin-induced thrombocytopenia Type II Symptoms: Congestive heart failure • short of breath Medication: — Clinical Procedure: LVAD explantation • TAH insertion Specialty: Anesthesiology Objective: Rare co-existance of disease or pathology Background: Heparin-induced thrombocytopenia (HIT) is a rare but life-threatening complication of heparin administration. It can present a major clinical dilemma for physicians caring for patients requiring life-saving urgent or emergent cardiac surgery. Studies have been published examining the use of alternative anticoagulants for patients undergoing cardiopulmonary bypass (CPB), however, evidence does not clearly support any particular approach. Presently, there are no large-scale, prospective randomized studies examining the impact of alternative anticoagulants on clinical outcomes for HIT-positive patients requiring cardiac surgery. Case Report: We present the case of a patient who underwent SynCardia Total Artificial Heart (TAH) implantation following a recent left ventricular assist device (LVAD) placement. The patient was receiving argatroban for type II HIT with anuric renal failure, and developed a thrombus which occluded the inflow cannula of the LVAD. Based on a published study and after establishing consensus with the surgical, anesthesiology, perfusion, and hematology teams, we decided to use tirofiban as an antiplatelet agent to inhibit the platelet aggregation induced by heparin, and ultimately used heparin as the anticoagulant for cardiopulmonary bypass. Conclusions: When selecting anticoagulation for a HIT-positive patient requiring CPB, so that benefits outweigh risks, it is of paramount importance that the decision be based on a multitude of factors. The team caring for the patient should have a shared mental model and be familiar with the pharmacology, devices used, and local practices. These three elements should be integrated with patient-specific comorbidities

  1. Acute abdomen

    Wig J


    Full Text Available 550 cases of acute abdomen have been analysed in detail includ-ing their clinical presentation and operative findings. Males are more frequently affected than females in a ratio of 3: 1. More than 45% of patients presented after 48 hours of onset of symptoms. Intestinal obstruction was the commonest cause of acute abdomen (47.6%. External hernia was responsible for 26% of cases of intestinal obstruction. Perforated peptic ulcer was the commonest cause of peritonitis in the present series (31.7% while incidence of biliary peritonitis was only 2.4%.. The clinical accuracy rate was 87%. The mortality in operated cases was high (10% while the over-all mortality rate was 7.5%.

  2. IL-33 Aggravates DSS-Induced Acute Colitis in Mouse Colon Lamina Propria by Enhancing Th2 Cell Responses.

    Zhu, Junfeng; Yang, Fangli; Sang, Lixuan; Zhai, Jingbo; Zhang, Xiaoqing; Yue, Dan; Li, Shengjun; Li, Yan; Lu, Changlong; Sun, Xun


    Interleukin- (IL-) 33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated diseases. IL-33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL-33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin- (IL-) 33 in dextran sulphate sodium- (DSS-) induced acute colitis in mice using recombinant mouse IL-33 protein (rIL-33). We found that DSS-induced acute colitis was aggravated by rIL-33 treatment. rIL-33-treated DSS mice showed markedly reduced levels of interferon- (IFN-)γ and IL-17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL-5 and IL-13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL-33 stimulated CD4(+)T cells and caused the cell to adopt a Th2-type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL-33 may be involved in pathogenesis of DSS-induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL-33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS-induced acute colitis.

  3. Acute Pancreatitis Concomitant Acute Coronary Syndrome

    Okay Abacı


    Full Text Available Acute pancreatitis is an inflammatory syndrome with unpredictable progression to systemic inflammation and multi-organ dysfunction. As in our case rarely, acute pancreatitis can be presented with the coexistance of acute coronary syndrome. To prevent a misdiagnosis of acute situation presented with chest or abdominal pain, physicians must be aware for coexisting pathophysiologies and take into account the differential diagnosis of all life-threatening causes such as cardiac ischemia or acute abdominal situations.

  4. Paroxysmal nocturnal hemoglobinuria: rare cause of acute renal failure

    Vilma Takayasu


    Full Text Available Paroxysmal nocturnal hemoglobinuria is a rare acquired disease, characterized by hemolytic anemia, recurrent infections, cytopenias, and vascular thrombosis. It occurs by non-malignant clonal expansion of one or more hematopoietic stem cells that acquired somatic mutations in PIG-A gene linked to chromosome X. This mutation results in lower erythrocyte expression of CD55 and CD59 surface proteins and consequently increased susceptibility to the complement system. The renal involvement is generally benign, resulting in mild impairment in urinary concentration. Acute renal failure requiring hemodialytic support accompanying PNH is rarely observed. The authors report a case of a 37-year-old male who presented with bicytopenia (hemolytic anemia and thrombocytopenia associated with acute renal failure requiring dialysis. Diagnosis was challenging because of the rarity and unfamiliarity with this entity, but was confirmed by flow cytometry. In the course of the disease, acute pyelonephritis with multiple renal abscesses was diagnosed requiring prolonged antibiotic therapy. Patient outcome was favorable after the control of hemolysis and the infection treatment.

  5. A case of thrombotic thrombocytopenic purpura induced by acute pancreatitis

    Arimoto M


    Full Text Available Miyoko Arimoto1, Yutaka Komiyama2, Fumiko Okamae1, Akemi Ichibe1, Setsuko Teranishi1, Hirohiko Tokunaga1, Keiko Nakaya3, Michie Fujiwara3, Manabu Yamaoka4, Shuji Onishi4, Rie Miyamoto5, Naoto Nakamichi5, Shosaku Nomura51Blood Transfusion Unit, Kansai Medical University Takii Hospital, 2Department of Clinical Sciences and Laboratory Medicine, Kansai Medical University, 3Clinical Medical Technology Unit, Kansai Medical University Takii Hospital, 4Blood Transfusion Unit, Kansai Medical University Hirakata Hospital, 5First Department of Internal Medicine, Kansai Medical University, Moriguchi, JapanAbstract: Thrombotic thrombocytopenic purpura (TTP is a multisystemic microvascular disorder that may be caused by an imbalance between unusually large von Willebrand factor multimers and the cleaving protease ADAMTS13. In acquired TTP, especially in secondary TTP with various underlying diseases, the diagnosis is difficult because there are many cases that do not exhibit severe deficiency of ADAMTS13 or raised levels of ADAMST13 inhibitors. It is well known that collagen disease, malignancy, and hematopoietic stem cell transplantation can be underlying conditions that induce TTP. However, TTP induced by acute pancreatitis, as experienced by our patient, has rarely been reported. Our patient completely recovered with treatments using steroids and plasma exchange (PE only. In cases where patients develop acute pancreatitis with no apparent causes for hemolytic anemia and thrombocytopenia, the possibility of TTP should be considered. Treatments for TTP including PE should be evaluated as soon as a diagnosis is made.Keywords: thrombotic thrombocytopenic purpura, ADAMTS13, acute pancreatitis, plasma exchange

  6. Lassa fever presenting as acute abdomen: a case series.

    Dongo, Andrew E; Kesieme, Emeka B; Iyamu, Christopher E; Okokhere, Peter O; Akhuemokhan, Odigie C; Akpede, George O


    Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Four patients died postoperatively, most before commencement of ribavirin, while the other three patients eventually recovered with appropriate antibiotic treatment including intravenous ribavirin. Surgeons working in West Africa should include Lassa fever in the differential diagnosis of acute abdomen, especially appendicitis. The presence of high grade fever, proteinuria and thrombocytopenia in patients with acute abdomen should heighten the suspicion of Lassa fever. Prolonged intra-operative bleeding should not only raise suspicion of the disease but also serve to initiate precautions to prevent nosocomial transmission.

  7. Iron metabolism and oxidative profile of dogs naturally infected by Ehrlichia canis: Acute and subclinical disease.

    Bottari, Nathieli B; Crivellenti, Leandro Z; Borin-Crivellenti, Sofia; Oliveira, Jéssica R; Coelho, Stefanie B; Contin, Catarina M; Tatsch, Etiane; Moresco, Rafael N; Santana, Aureo E; Tonin, Alexandre A; Tinucci-Costa, Mirela; Da Silva, Aleksandro S


    The aim of this study was to evaluate the oxidant profile and iron metabolism in serum of dogs infected by Ehrlichia canis. Banked sera samples of dogs were divided into two groups: negative control (n = 17) and infected by E. canis on acute (n = 24), and subclinical (n = 18) phases of the disease. The eritrogram, leucogram, and platelet counts were evaluate as well as iron, ferritin, and transferrin levels, latent iron binding capacity (LIBC), and transferrin saturation index (TSI) concentration. In addition, the advanced oxidation protein products (AOPP) and ferric reducing ability of plasma (FRAP) in sera were also analyzed. Blood samples were examined for the presence of E. canis by PCR techniques. History and clinical signals were recorded for each dog. During the acute phase of the disease, infected animals showed thrombocytopenia and anemia when compared to healthy animals (P canis showed changes in the iron metabolism and developed an oxidant status in consequence of disease pathophysiology.

  8. Hemolytic uremic syndrome as a primary manifestation of acute human immunodeficiency virus infection.

    Gomes, A M; Ventura, A; Almeida, C; Correia, M; Tavares, V; Mota, M; Seabra, J


    Hemolytic uremic syndrome may be associated with human immunodeficiency virus infection but it occurs in advanced stages of human immunodeficiency virus disease. As in other forms of hemolytic uremic syndrome plasmapheresis seems to be the treatment of choice. The authors present an unusual case of hemolytic uremic syndrome associated with acute human immunodeficiency virus infection in a 38 year-old black male. The patient was admitted with fever, asthenia, nausea, diarrhea, and reduced urinary output. He was found to have anemia, thrombocytopenia and severe renal failure. Hemolytic uremic syndrome was diagnosed and he was started on plasmapheresis and hemodialysis. Serological tests were consistent with acute human immunodeficiency virus infection: the enzyme linked immunosorbent assay for human immunodeficiency virus was weakly positive, Western Blot test was negative and human immunodeficiency virus RNA quantification was positive, with > 1,000,000 copies/microl. After 4 daily treatment sessions, patient's clinical condition improved and hemoglobin, platelets, lactic dehydrogenase and renal function normalized.

  9. Comparison of low-molecular-weight-heparin and unfractionated heparin for acute PTE

    CHEN Li-ying; YING Ke-jing; HONG Wu-jun; ZHOU Pan


    Objective: Acute pulmonary thromboembolism (PTE) is a serious high mortality pulmonary vascular disease whose effective treatment decreases morbidity and mortality. To determine if low-molecular-weight-heparin (LMWH) is clinically as efficient and safe as unfractionated heparin (UH) in patients with diagnosis of acute non-massive PTE, our study compares the efficacy, adverse effects and costs of LMWH and UH. Methods: One hundred and fourteen patients with non-massive acute PTE were randomly divided into LMWH (nadroparin calcium) and UH groups. Oxygenation index, D-dimer, fibrinogen (FG), lung ventilation/perfusion (V/Q) scan and computed tomography pulmonary angiography (CTPA) were observed before anticoagulation and on day 14 after anticoagulation. Results: In both groups, the ABG (arterial blood gas) analysis showed PaO2 and PaCO2 were elevated, P(A-a)O2 was decreased and oxygenation index (PaO2/FIO2) was elevated, D-dimer and fibrinogen were decreased,lung V/Q and CTPA showed embolized segments reduced (P<0.05). Hemorrhage and thrombocytopenia occurred in 3.5% of the LMWH group. Hemorrhage occurred in 5.3% and thrombocytopenia occurred in 7.0% of the UH group. The average cost in the LMWH group was RMB 1218.60 Yuan and RMB 1541.40 Yuan in the UH group. Conclusion: LMWH and UH are equally effective for treatment of non-massive acute PTE, but LMWH may have a lower prevalence of complications and is less expensive.

  10. Rates of clinically apparent heparin-induced thrombocytopenia for unfractionated heparin vs. low molecular weight heparin in non-surgical patients are low and similar

    Gerber Jonathan


    Full Text Available Abstract With the growing use of low-molecular-weight heparins (LMWH for the treatment and prevention of venous thromboembolism (VTE, it is important to provide an evidence-based comparison with unfractionated heparin (UFH concerning rates of heparin-induced thrombocytopenia (HIT. Such comparisons are essential in clinical decision-making and cost-modeling. In this paper we review data regarding non-surgical (medical patients. We conclude that the lack of uniform evaluation and standardized testing for HIT in the current literature precludes making a reliable estimate of the relative risk of HIT in UFH vs. LMWH in either the treatment or prevention of VTE in non-surgical patients. However, current data suggest that the risk of thrombocytopenia and HIT is low and similar for non-surgical patients who receive either LMWH or UFH.

  11. Severe Clinical Course in a Patient with Congenital Amegakaryocytic Thrombocytopenia Due to a Missense Mutation of the c-MPL Gene

    İkbal Ok Bozkaya


    Full Text Available Congenital amegakaryocytic thrombocytopenia (CAMT generally begins at birth with severe thrombocytopenia and progresses to pancytopenia. It is caused by mutations in the thrombopoietin receptor gene, the myeloproliferative leukemia virus oncogene (c-MPL. The association between CAMT and c-MPL mutation type has been reported in the literature. Patients with CAMT have been categorized according to their clinical symptoms caused by different mutations. Missense mutations of c-MPL have been classified as type II and these patients have delayed onset of bone marrow failure compared to type I patients. Here we present a girl with severe clinical course of CAMT II having a missense mutation in exon 4 of the c-MPL gene who was admitted to our hospital with intracranial hemorrhage during the newborn period.

  12. Pancytopenia with severe thrombocytopenia in a patient treated with twice-weekly LDL-apheresis by polyacrylate adsorption from whole blood.

    Nowack, Rainer; Wiedemann, Günther


    Pancytopenia with severe thrombocytopenia occurred in a patient treated with low-density lipoprotein (LDL)-apheresis by polyacrylate adsorption from whole blood, after treatment frequency had been increased from once to twice a week. Cell counts recovered with discontinuation of LDL-apheresis, but thrombocytopenia recurred after resumption of twice-weekly treatments. Thrombocyte counts remained stable following the replacement of polyacrylate adsorption from whole blood by double-filtration plasmapheresis. The complications' close coincidence with twice-weekly polyacrylate adsorption from whole blood suggests a causal relationship, although by a still unknown mechanism. Monitoring of thrombocytes should be advised in patients treated with LDL-apheresis by polyacrylate adsorption from whole blood.

  13. Acute neuromuscular weakness associated with dengue infection

    Harmanjit Singh Hira


    Full Text Available Background: Dengue infections may present with neurological complications. Whether these are due to neuromuscular disease or electrolyte imbalance is unclear. Materials and Methods: Eighty-eight patients of dengue fever required hospitalization during epidemic in year 2010. Twelve of them presented with acute neuromuscular weakness. We enrolled them for study. Diagnosis of dengue infection based on clinical profile of patients, positive serum IgM ELISA, NS1 antigen, and sero-typing. Complete hemogram, kidney and liver functions, serum electrolytes, and creatine phosphokinase (CPK were tested. In addition, two patients underwent nerve conduction velocity (NCV test and electromyography. Results: Twelve patients were included in the present study. Their age was between 18 and 34 years. Fever, myalgia, and motor weakness of limbs were most common presenting symptoms. Motor weakness developed on 2 nd to 4 th day of illness in 11 of 12 patients. In one patient, it developed on 10 th day of illness. Ten of 12 showed hypokalemia. One was of Guillain-Barré syndrome and other suffered from myositis; they underwent NCV and electromyography. Serum CPK and SGOT raised in 8 out of 12 patients. CPK of patient of myositis was 5098 IU. All of 12 patients had thrombocytopenia. WBC was in normal range. Dengue virus was isolated in three patients, and it was of serotype 1. CSF was normal in all. Within 24 hours, those with hypokalemia recovered by potassium correction. Conclusions: It was concluded that the dengue virus infection led to acute neuromuscular weakness because of hypokalemia, myositis, and Guillain-Barré syndrome. It was suggested to look for presence of hypokalemia in such patients.

  14. The Clinical Examination Analysis of Thrombocytopenia and the Particles in Blood%血小板减少及血液中微粒的临床检验分析



      目的:对血小板减少及血液中微粒的临床检验情况进行分析探讨.方法:随机抽取2010年1月-2012年8月临床部分收治的冠心病、急性脑梗死、慢性肾功能衰竭、急性白血病化疗后及健康体检者作为研究对象,对其分别采用流式细胞仪,以3 mm、0.8 mm的标准微球作内参对照展开血小板微粒检测,并对比分析检测结果.结果:冠心病、急性脑梗死、慢性肾功能衰竭者血浆中血小板微粒显著高于健康者(P0.05).结论:血小板微粒能够作为对血小板活化、预测和诊断血栓性疾病的一项重要指标,值得关注.%Objective:To discuss the clinical examination situation of thrombocytopenia and the particles in blood.Methods:Randomly selected clinical patients with coronary heart disease,acute cerebral infarction,chronic renal failure,acute leukemia after chemotherapy and health physical examination person in January 2010 to August 2012 as the research object,which respectively by flow cytometry instrument,to 3 mm,0.8 mm standard microspheres for control on platelet particle detection,and a comparative analysis of the test results.Results:The platelets particles in the blood in patients with coronary heart disease, acute cerebral infarction,chronic renal was significantly higher than healthy patients(P0.05).Conclusion:Platelet particles as an important index of platelet activation,forecast and diagnosis of thrombotic diseases is worth attention.

  15. Acute arterial occlusion - kidney

    Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... kidney can often result in permanent kidney failure. Acute arterial occlusion of the renal artery can occur after injury or trauma to ...

  16. Acute cerebellar ataxia

    Cerebellar ataxia; Ataxia - acute cerebellar; Cerebellitis; Post-varicella acute cerebellar ataxia; PVACA ... Acute cerebellar ataxia in children, especially younger than age 3, may occur several weeks after an illness caused by a virus. ...

  17. Deep vein thrombosis, ecythyma gangrenosum and heparin-induced thrombocytopenia occurring in a man with a heterozygous Factor V Leiden mutation

    Mariya Apostolova; Baoying Weng; Pote, Harry H.; Harold Ashcraft; Curtis Goldblatt; Paul V. Woolley


    Skin necrosis and limb gangrene are occasional thrombotic manifestations of anticoagulation therapy. We report a man heterozygous for the Factor V Leiden (FVL) mutation, and with a history of recurrent deep venous thrombosis, who initially presented with a necrotic skin lesion of the right flank while on warfarin therapy with a therapeutic international normalized ratio. Warfarin was discontinued and he received intravenous heparin. Thereafter he developed thrombocytopenia and pedal erythema ...

  18. Diversity and severity of adverse reactions to quinine: A systematic review.

    Liles, Nathan W; Page, Evaren E; Liles, Amber L; Vesely, Sara K; Raskob, Gary E; George, James N


    Quinine is a common cause of drug-induced thrombocytopenia and the most common cause of drug-induced thrombotic microangiopathy. Other quinine-induced systemic disorders have been described. To understand the complete clinical spectrum of adverse reactions to quinine we searched 11 databases for articles that provided sufficient data to allow evaluation of levels of evidence supporting a causal association with quinine. Three reviewers independently determined the levels of evidence, including both immune-mediated and toxic adverse reactions. The principal focus of this review was on acute, immune-mediated reactions. The source of quinine exposure, the involved organ systems, the severity of the adverse reactions, and patient outcomes were documented. One hundred-fourteen articles described 142 patients with definite or probable evidence for a causal association of quinine with acute, immune-mediated reactions. These reactions included chills, fever, hypotension, painful acral cyanosis, disseminated intravascular coagulation, hemolytic anemia, thrombocytopenia, neutropenia, acute kidney injury, rhabdomyolysis, liver toxicity, cardiac ischemia, respiratory failure, hypoglycemia, blindness, and toxic epidermal necrolysis. One hundred-two (72%) reactions were caused by quinine pills; 28 (20%) by quinine-containing beverages; 12 (8%) by five other types of exposures. Excluding 41 patients who had only dermatologic reactions, 92 (91%) of 101 patients had required hospitalization for severe illness; 30 required renal replacement therapy; three died. Quinine, even with only minute exposure from common beverages, can cause severe adverse reactions involving multiple organ systems. In patients with acute, multi-system disorders of unknown origin, an adverse reaction to quinine should be considered.

  19. The Development of Severe Neonatal Alloimmune Thrombocytopenia due to Anti-HPA-1a Antibodies Is Correlated to Maternal ABO Genotypes

    Maria Therese Ahlen


    Full Text Available Background. Maternal alloantibodies against HPA-1a can cross placenta, opsonize foetal platelets, and induce neonatal alloimmune thrombocytopenia (NAIT. In a study of 100, 448 pregnant women in Norway during 1995–2004, 10.6% of HPA-1a negative women had detectable anti-HPA-1a antibodies. Design and Methods. A possible correlation between the maternal ABO blood group phenotype, or underlying genotype, and severe thrombocytopenia in the newborn was investigated. Results. We observed that immunized women with blood group O had a lower risk of having a child with severe NAIT than women with group A; 20% with blood group O gave birth to children with severe NAIT, compared to 47% among the blood group A mothers (relative risk 0.43; 95% CI 0.25–0.75. Conclusion. The risk of severe neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies is correlated to maternal ABO types, and this study indicates that the observation is due to genetic properties on the maternal side.

  20. Japanese variant of multicentric castleman's disease associated with serositis and thrombocytopenia--a report of two cases: is TAFRO syndrome (Castleman- Kojima disease) a distinct clinicopathological entity?

    Masaki, Yasufumi; Nakajima, Akio; Iwao, Haruka; Kurose, Nozomu; Sato, Tomomi; Nakamura, Takuji; Miki, Miyuki; Sakai, Tomoyuki; Kawanami, Takafumi; Sawaki, Toshioki; Fujita, Yoshimasa; Tanaka, Masao; Fukushima, Toshihiro; Okazaki, Toshiro; Umehara, Hisanori


    Multicentric Castleman's disease (MCD) is a polyclonal lymphoproliferative disorder that manifests as marked hyper-γ-globulinemia, severe inflammation, anemia, and thrombocytosis. Recently, Takai et al. reported a new disease concept, TAFRO syndrome, named from thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. Furthermore, Kojima et al. reported Japanese MCD cases with effusion and thrombocytopenia (Castleman-Kojima disease). Here, we report two cases of MCD associated with marked pleural effusion, ascites, and thrombocytopenia, and discuss the independence of the TAFRO syndrome (Castleman-Kojima disease). Case 1: A 57-year-old woman had fever, anemia, anasarca, and some small cervical lymphadenopathy. Although she had been administered steroid therapy, and full-coverage antibiotics, her general condition, including fever, systemic inflammation, and anasarca, deteriorated steadily. We administered chemotherapy [CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone) regimen], but despite a transient improvement, she died due to septic shock. Case 2: A 73-year-old man with a history of aplastic anemia and remission presented with fever, severe inflammation, and anasarca. Prednisolone was administered (15 mg daily), and his hyperinflammation once improved. Nevertheless, his general condition, including pleural effusion and ascites, worsened, and C-reactive protein and interleukin-6 levels showed marked increases. The patient died due to multiorgan failure. Cases of TAFRO syndrome (Castleman-Kojima disease) are still rare. Therefore, it is necessary to conduct multicenter clinical surveys including similar cases, such as ours, to reach a consensus regarding diagnostic criteria, therapeutic strategy, and pathophysiological etiology for this syndrome.

  1. Regulation of platelet myosin light chain (MYL9) by RUNX1: implications for thrombocytopenia and platelet dysfunction in RUNX1 haplodeficiency

    Jalagadugula, Gauthami; Mao, Guangfen; Kaur, Gurpreet; Goldfinger, Lawrence E.; Dhanasekaran, Danny N.


    Mutations in transcription factor RUNX1 are associated with familial platelet disorder, thrombocytopenia, and predisposition to leukemia. We have described a patient with thrombocytopenia and impaired agonist-induced platelet aggregation, secretion, and glycoprotein (GP) IIb-IIIa activation, associated with a RUNX1 mutation. Platelet myosin light chain (MLC) phosphorylation and transcript levels of its gene MYL9 were decreased. Myosin IIA and MLC phosphorylation are important in platelet responses to activation and regulate thrombopoiesis by a negative regulatory effect on premature proplatelet formation. We addressed the hypothesis that MYL9 is a transcriptional target of RUNX1. Chromatin immunoprecipitation (ChIP) using megakaryocytic cells revealed RUNX1 binding to MYL9 promoter region −729/−542 basepairs (bp), which contains 4 RUNX1 sites. Electrophoretic mobility shift assay showed RUNX1 binding to each site. In transient ChIP assay, mutation of these sites abolished binding of RUNX1 to MYL9 promoter construct. In reporter gene assays, deletion of each RUNX1 site reduced activity. MYL9 expression was inhibited by RUNX1 short interfering RNA (siRNA) and enhanced by RUNX1 overexpression. RUNX1 siRNA decreased cell spreading on collagen and fibrinogen. Our results constitute the first evidence that the MYL9 gene is a direct target of RUNX1 and provide a mechanism for decreased platelet MYL9 expression, MLC phosphorylation, thrombocytopenia, and platelet dysfunction associated with RUNX1 mutations. PMID:20876458

  2. Trombocitopenia em cirurgia cardíaca: importância diagnóstica e prognóstica Thrombocytopenia in cardiac surgery: diagnostic and prognostic importance

    Ederlon Rezende


    Full Text Available OBJETIVO: Pacientes submetidos à cirurgia cardíaca estão mais propensos a desenvolver plaquetopenia. A trombocitopenia induzida por heparina acomete cerca de 5% dos pacientes. O objetivo foi avaliar a importância clínica da trombocitopenia grave em pacientes no pós-operatório de cirurgia cardíaca. MÉTODOS: Estudo prospectivo observacional que incluiu os pacientes de cirurgia cardíaca com plaquetas 6. A mortalidade na Unidade de Terapia Intensiva (UTI e hospitalar, o tempo de internação, os escores de gravidade e a incidência de tromboses foram comparados em pacientes com escore e" 6 (grupo 1 e 6, em pacientes no pós-operatório de cirurgia cardíaca, está associado a maior incidência de trombose, assim como o maior escore está relacionado à elevada mortalidade hospitalar.OBJECTIVE: Patients undergo to cardiac surgery have more probability to develop thrombocytopenia. The heparin induced thrombocytopenia happens in 5% of the patients. The aim from this study was to evaluate the clinical importance from the severe thrombocytopenia in postoperative cardiac surgical patients. METHODS: It was included cardiac surgical patients with platelets 6 (group 1 and 6, in postoperative cardiac surgical patients, it is associated to higher incidence of thrombosis as well as the greater score is related to higher hospital mortality rate.

  3. Acute Appendicitis

    Tind, Sofie; Qvist, Niels


    BACKGROUND: The classification of acute appendicitis (AA) into various grades is not consistent, partly because it is not clear whether the perioperative or the histological findings should be the foundation of the classification. When comparing results from the literature on the frequency...... patients were included. In 116 (89 %) of these cases, appendicitis was confirmed histological. There was low concordance between the perioperative and histological diagnoses, varying from 16 to 76 % depending on grade of AA. Only 44 % of the patients receiving antibiotics postoperatively had a positive...... peritoneal fluid cultivation. CONCLUSION: There was a low concordance in clinical and histopathological diagnoses of the different grades of appendicitis. Perioperative cultivation of the peritoneal fluid as a standard should be further examined. The potential could be a reduced postoperative antibiotic use...

  4. Rapid infusions of human normal immunoglobulin 50g/l are safe and well tolerated in immunodeficiencies and immune thrombocytopenia.

    Spadaro, Giuseppe; Vultaggio, Alessandra; Alberto Bosi, A; Reichert, Dietmar; Janssen, Jan; Lamacchia, Donatella; Nappi, Liliana; Pecoraro, Antonio; Milito, Cinzia; Ferraro, Andrea; Matucci, Andrea; Bacchiarri, Francesca; Carrai, Valentina; Hibbeler, Azra; Speckman, Elisabet; Guarnieri, Chiara; Bongiovanni, Serena; Quinti, Isabella


    Intravenous immunoglobulin (IVIg) is accepted as an effective and well-tolerated treatment for primary and secondary immunodeficiencies (ID) and immune thrombocytopenia (ITP). Adverse reactions of IVIg are usually mild, comprising transient flu-like symptoms, change in blood pressure and tachycardia. However IVIg therapy can be burdensome for both patients and healthcare facilities, since the infusion may take up to 4h to administer. The objective of our multicentre, prospective, open-label phase III trial was to evaluate the tolerability and safety of human normal immunoglobulin 50g/l (Ig VENA) at high intravenous infusion rates in adult patients with ID and ITP who had previously tolerated IVIg treatment, by progressively increasing infusion rate up to 8ml/kg/hr. 39 ID patients received three infusions, 5 ITP patients received up to a maximum of 5 infusions for a maximum of 5days. Overall 55 adverse events were reported in 18 patients, and all were mild and self-limiting. Two serious adverse events occurred in ID patients and 1 in an ITP patient; none was fatal or treatment-related. No clinically significant changes or abnormalities were observed in vital signs, laboratory results and HRQoL. In summary, in this study, more rapid IVIg infusions were well tolerated by ID and ITP patients, while maintaining their quality of life, helping to minimise the time spent in outpatient hospital visiting to potentially optimise adherence to treatment.

  5. Drug-induced hemolytic anemia and thrombocytopenia associated with alterations of cell membrane lipids and acanthocyte formation.

    Poulet, Frederique M; Penraat, Kelley; Collins, Nathaniel; Evans, Ellen; Thackaberry, Evan; Manfra, Denise; Engstrom, Laura; Geissler, Richard; Geraci-Erck, Maria; Frugone, Carlos; Abutarif, Malaz; Fine, Jay S; Peterson, Brianna L; Cummings, Brian S; Johnson, Robert C


    CXCR3 is a chemokine receptor, upregulated upon activation of T cells and expressed on nearly 100% of T cells in sites of inflammation. SCH 900875 is a selective CXCR3 receptor antagonist. Thrombocytopenia and severe hemolytic anemia with acanthocytosis occurred in rats at doses of 75, 100, and 150 mg/kg/day. Massively enlarged spleens corresponded histologically to extramedullary hematopoiesis, macrophages, and hemosiderin pigment and sinus congestion. Phagocytosed erythrocytes and platelets were within splenic macrophages. IgG and/or IgM were not detected on erythrocyte and platelet membranes. Ex vivo increased osmotic fragility of RBCs was observed. Lipid analysis of the RBC membrane revealed modifications in phosphatidylcholine, overall cholesterol, and/or sphingomyelin. Platelets exhibited slender filiform processes on their plasma membranes, analogous to those of acanthocytes. The presence of similar morphological abnormalities in acanthocytes and platelets suggests that possibly similar alterations in the lipid composition of the plasma membrane have taken place in both cell types. This phenotype correlated with alterations in plasma lipids (hypercholesterolemia and low triglycerides) that occurred after SCH 900875 administration, although other factors cannot be excluded. The increased cell destruction was considered triggered by alterations in the lipid profile of the plasma membranes of erythrocytes and platelets, as reflected morphologically.

  6. The ratio of Treg/Th17 cells correlates with the disease activity of primary immune thrombocytopenia.

    Lili Ji

    Full Text Available BACKGROUND: Primary immune thrombocytopenia (ITP is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. Regulatory T (Treg cells and T helper type 17 (Th17 cells are two subtypes of CD4(+ T helper (Th cells. They play opposite roles in immune tolerance and autoimmune diseases, while they share a common differentiation pathway. The imbalance of Treg/Th17 has been demonstrated in several autoimmune diseases. In this study, we aimed to investigate the ratio of the number of Treg cells to the number of Th17 cells in ITP patients and evaluate the clinical implications of the alterations in this ratio. METHODS: Thirty adult patients with newly diagnosed ITP enrolled in this study. Twelve patients had been clinically followed up for 12 months. The percentages of CD4(+CD25(hiFoxp3(+ Treg cells and CD3(+CD4(+IL-17-producing Th17 cells in these patients and healthy controls (n = 17 were longitudinally analyzed by flow cytometry. RESULTS: The percentage of Treg cells in ITP patients was significantly lower than that of healthy controls, and the percentage of Th17 cells increased significantly at disease onset. The ratio of Treg/Th17 correlated with the disease activity. CONCLUSION: The ratio of Treg/Th17 might be relevant to the clinical diversity of ITP patients, and this Treg/Th17 ratio might have prognostic role in ITP patients.

  7. Development of a Colloidal Gold Kit for the Diagnosis of Severe Fever with Thrombocytopenia Syndrome Virus Infection

    Xianguo Wang


    Full Text Available It is critical to develop a cost-effective detection kit for rapid diagnosis and on-site detection of severe fever with thrombocytopenia syndrome virus (SFTSV infection. Here, an immunochromatographic assay (ICA to detect SFTSV infection is described. The ICA uses gold nanoparticles coated with recombinant SFTSV for the simultaneous detection of IgG and IgM antibodies to SFTSV. The ICA was developed and evaluated by using positive sera samples of SFTSV infection (n=245 collected from the CDC of China. The reference laboratory diagnosis of SFTSV infection was based on the “gold standard”. The results demonstrated that the positive coincidence rate and negative coincidence rate were determined to be 98.4% and 100% for IgM and 96.7% and 98.6% for IgG, respectively. The kit showed good selectivity for detection of SFTSV-specific IgG and IgM with no interference from positive sera samples of Japanese encephalitis virus infection, Dengue virus infection, Hantavirus infection, HIV infection, HBV surface antigen, HCV antibody, Mycobacterium tuberculosis antibody, or RF. Based on these results, the ICS test developed may be a suitable tool for rapid on-site testing for SFTSV infections.

  8. A multicentre observational study for early diagnosis of Gaucher disease in patients with Splenomegaly and/or Thrombocytopenia.

    Motta, Irene; Filocamo, Mirella; Poggiali, Erika; Stroppiano, Marina; Dragani, Alfredo; Consonni, Dario; Barcellini, Wilma; Gaidano, Gianluca; Facchini, Luca; Specchia, Giorgina; Cappellini, Maria Domenica


    Gaucher disease (GD) is the most common lysosomal disorder resulting from deficient activity of the β-glucosidase enzyme that causes accumulation of glucosylceramide in the macrophage-monocyte system. Notably, because of non-specific symptoms and a lack of awareness, patients with GD experience long diagnostic delays. The aim of this study was to apply a diagnostic algorithm to identify GD type 1 among adults subjects referred to Italian haematology outpatient units because of splenomegaly and/or thrombocytopenia and, eventually, to estimate the prevalence of GD in this selected population. One hundred and ninety-six subjects (61 females, 135 males; mean age 47.8 ± 18.2 years) have been enrolled in the study and tested for β-glucosidase enzyme activity on dried blood spot (DBS). Seven of 196 patients have been diagnosed with GD, (5 females and 2 males) with mean age 31.8 ± 8.2 years, with a prevalence of 3.6% (with a prevalence of 3.6% (I95% CI 1.4-7.2; 1/28 patients) in this population. These results show that the use of an appropriate diagnostic algorithm and a simple diagnostic method, such as DBS, are important tools to facilitate the diagnosis of a rare disease even for not disease-expert physicians.

  9. Two novel RUNX1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndrome

    Jessica M. Schmit


    Full Text Available Here we report two new RUNX1 mutations in one patient with congenital thrombocytopenia that transformed into a high grade myelodysplastic syndrome with myelomonocytic features. The first mutation was a nucleotide base substitution from guanine to adenine within exon 8, resulting in a nonsense mutation in the DNA-binding inhibitory domain of the Runx1 protein. This nonsense mutation is suspected a de novo germline mutation since both parents are negative for the mutation. The second mutation identified was an in-frame six nucleotide base pair insertion in exon 5 of the RUNX1 gene, which is predicted to result in an insertion in the DNA-binding runt homology domain (RHD. This mutation is believed to be a somatic mutation as it was mosaic before allogeneic hematopoietic cell transplantation and disappeared after transplant. As no other genetic mutation was found using genetic screening, it is speculated that the combined effect of these two RUNX1 mutations may have exerted a stronger dominant negative effect than either RUNX1 mutation alone, thus leading to a myeloid malignancy.

  10. In vitro TNF blockade enhances ex vivo expansion of regulatory T cells in patients with immune thrombocytopenia

    Zhong, Hui; Bussel, James; Yazdanbakhsh, Karina


    Summary Tumour necrosis factor-α (TNF) is an inflammatory cytokine that is elevated in a number of autoimmune diseases including immune thrombocytopenia (ITP), a bleeding disorder characterized by low platelet counts. In vitro TNF blockade increases expansion of the regulatory T cell (Treg) IKZF2 (also termed Helios) subset in T cell-monocyte cocultures from healthy donors, but its role on proliferative responses of Tregs in ITP patients, who have altered immunoregulatory compartment, remains unclear. TNF in CD4+ T cells from patients with chronic ITP were elevated and negatively correlated with peripheral Treg frequencies, suggesting a possible inhibitory effect of TNF on ITP Tregs. In vitro antibody neutralization with anti-TNF in T cell-monocyte cocultures resulted in a robust expansion of pre-existing ITP Tregs, higher than in healthy controls. Similar to the effects of anti-TNF antibodies, TNF blockade with antibodies against TNFRSF1B (anti-TNFRSF1B, previously termed anti-TNFRII) almost doubled ITP Treg expansion whereas neutralization with anti-TNFRSF1A (anti-TNFRI) antibodies had no effect on proliferative responses of Tregs. In addition, TNFRSF1B levels on ITP Tregs were significantly elevated, which may explain the increased susceptibility of patient Tregs to the actions of TNF blockade. Altogether, these data raise the possibility that TNF blockers, through their ability to increase Treg proliferation, may be efficacious in ITP patients. PMID:25252160

  11. High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial.

    Wei, Yu; Ji, Xue-bin; Wang, Ya-wen; Wang, Jing-xia; Yang, En-qin; Wang, Zheng-cheng; Sang, Yu-qi; Bi, Zuo-mu; Ren, Cui-ai; Zhou, Fang; Liu, Guo-qiang; Peng, Jun; Hou, Ming


    This study compared the efficacy and safety of high-dose dexamethasone (HD-DXM) and conventional prednisone (PDN) on the largest cohort to date as first-line strategies for newly diagnosed adult primary immune thrombocytopenia (ITP). Patients enrolled were randomized to receive DXM 40 mg/d for 4 days (n = 95, nonresponders received an additional 4-day course of DXM) or prednisone 1.0 mg/kg daily for 4 weeks and then tapered (n = 97). One or 2 courses of HD-DXM resulted in a higher incidence of overall initial response (82.1% vs 67.4%, P = .044) and complete response (50.5% vs 26.8%, P = .001) compared with prednisone. Time to response was shorter in the HD-DXM arm (P < .001), and a baseline bleeding score ≥8 was associated with a decreased likelihood of initial response. Sustained response was achieved by 40.0% of patients in the HD-DXM arm and 41.2% in the PDN arm (P = .884). Initial complete response was a positive indicator of sustained response, whereas presence of antiplatelet autoantibodies was a negative indicator. HD-DXM was generally tolerated better. We concluded that HD-DXM could be a preferred corticosteroid strategy for first-line management of adult primary ITP. This study is registered at as #NCT01356511.

  12. Severe fever with thrombocytopenia syndrome virus inhibits exogenous Type I IFN signaling pathway through its NSs in vitro

    Li, Shilin; Jiao, Baihai; Wu, Jianqin; Zeng, Peibin; Chen, Limin


    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus (SFTS virus, SFTSV). At present there is still no specific antiviral treatment for SFTSV; To understand which cells support SFTSV life cycle and whether SFTSV infection activates host innate immunity, four different cell lines (Vero, Hela, Huh7.5.1, and Huh7.0) were infected with SFTSV. Intracellular/extracellular viral RNA and expression of IFNα, and IFNß were detected by real-time RT- PCR following infection. To confirm the role of non-structural protein (NSs) of SFTSV in exogenous IFNα-induced Jak/STAT signaling, p-STAT1 (Western Blot), ISRE activity (Luciferase assay) and ISG expression (real-time PCR) were examined following IFNα stimulation in the presence or absence of over-expression of NSs in Hela cells. Our study showed that all the four cell lines supported SFTSV life cycle and SFTSV activated host innate immunity to produce type I IFNs in Hela cells but not in Huh7.0, Huh7.5.1 or Vero cells. NSs inhibited exogenous IFNα-induced Jak/STAT signaling as shown by decreased p-STAT1 level, suppressed ISRE activity and down-regulated ISG expression. Suppression of the exogenous Type I IFN-induced Jak/STAT signaling by NSs might be one of the mechanisms of SFTSV to evade host immune surveillance. PMID:28234991

  13. Budd-Chiari syndrome and heparin-induced thrombocytopenia in polycythemia vera: Successful treatment with repeated TIPS and interferon alpha

    Akoum Riad


    Full Text Available Polycythemia vera (PV is a common cause of Budd-Chiari syndrome (BCS and portal vein thrombosis (PVT. The postpartum period is a precipitating cofactor. An additional heparin-induced thrombocytopenia/thrombosis (HIT/T leads to a life-threatening condition in which transjugular intrahepatic portosystemic shunting (TIPS seems to be the only life-saving procedure. We describe the case of a subacute BCS and PVT in the late postpartum period. The diagnosis was established using CT scan, MRI, and Doppler ultrasonography of abdominal vessels and the laboratory findings were compatible with PV. After a successful creation of TIPS, a HIT/T worsened the hemorrhagic and thrombotic picture. TIPS procedure was successfully repeated and heparin was replaced with Fondaparinux and then vitamin K antagonist. The treatment with interferon alpha-2A, started after the normalization of liver functions, resulted in a complete remission within 6 months. The JAK2 V617F mutation clone remained undetectable after 2 years′ follow-up.

  14. Model for the immune-mediated inner ear disease and expression of interferon-γ in the inner ear%免疫性内耳病模型的建立及其内耳干扰素-γ的表达

    马荧雪; 谭长强; 曹影; 王培蓓; 陈智斌


    目的:建立免疫性内耳病(IMIED)模型,并检测内耳干扰素-γ(IFN-γ)表达的变化情况.方法:将20只豚鼠按配对设计方法分为实验组和对照组.实验组采用钥孔戚血蓝蛋白(KLH)在已致敏的豚鼠圆窗龛局部免疫,对照组用PBS代替KLH免疫豚鼠;观察血清中特异性KLH抗体水平、听觉功能及内耳病理形态变化,并行酶免疫组化试验观察内耳IFN-γ的表达.结果:实验组免疫前后ABRⅢ波阈值的均值差异有统计学意义(P<0.05),免疫后实验组有7只动物(12耳)出现听损,且血清中特异性KLH抗体水平较免疫前明显升高(P<0.05);对照组免疫前后ABRⅢ波阈值的均值和血清KLH抗体水平的差异均无统计学意义(P>0.05);免疫后实验组ABRⅢ波阈值的均值和血清KLH抗体水平均高于对照组(P<0.05).实验组免疫后内耳组织中有炎症细胞浸润,部分豚鼠内耳有迷路积水.对照组豚鼠内耳组织中无明显IFN-γ表达,实验组IFN-γ表达主要分布在血管纹、螺旋韧带、螺旋神经节、Corti器及蜗轴小血管周围.结论:在已致敏的豚鼠圆窗龛局部免疫,诱导并造成IMIED模型的成功率较高.正常豚鼠内耳中几乎没有IFN-γ表达,而在IMIED豚鼠内耳中IFN-γ有显著表达,提示IMIED发生发展可能与IFN-γ表达有关.%Objective: To establish a model of immune-mediated inner ear disease( IMIED ) and to study the change of interferon- γ( IFN- γ ) expression in the inner ear. Methods: Twenty guinea pigs were divided into experimental group and control group with paired design. The round windows of systemically pre- sensitized guinea pigs were locally immunized with keyhole limpet hemocyanin( KLH ) in experimental group and PBS in the control group. Then the anti- KLH level and auditory function were determined before immunization and at 2 weeks after immunization. Tissue paraffin sections of temporal bone was made and observed by microscopy, and IFN- γ expression

  15. Acute Myopericarditis Mimicking Acute Myocardial Infarction

    Seval İzdeş


    Full Text Available Acute coronary syndromes among young adults are relatively low when compared with older population in the intensive care unit. Electrocardiographic abnormalities mimicking acute coronary syndromes may be caused by non-coronary syndromes and the differential diagnosis requires a detailed evaluation. We are reporting a case of myopericarditis presenting with acute ST elevation and elevated cardiac enzymes simulating acute coronary syndrome. In this case report, the literature is reviewed to discuss the approach to distinguish an acute coronary syndrome from myopericarditis. (Journal of the Turkish Society Intensive Care 2011; 9:68-70

  16. 利福平引起血小板减少14例临床分析%Analysis of the 14 Cases of Rifampicin Causing Thrombocytopenia

    杨铭; 岳冀; 李曦; 陈洪德; 周晓飞; 刘海燕


    Objective To investigate the mechanism, clinical manifestations and treatment of Rifampicin causing thrombocytopenia. Methods Retrospectively analyzed the 14 cases in Chengdu Tuberculosis Hospital from July 2008 to Oct 2010 in which patients accompanied thrombocytopenia after taking anti - tubercular medication, summarizing the experiences of clinical application. Results Among the 14 patients, there was no significant difference of Rifampicin causing drug- induced thrombocytopenia in age and gender. 12 of them arised thrombocytopenia in one month after taking drugs, some patients had the symptom of peripheral blood platelets reducing quickly in a short time, even with missing platelets, but clinical manifestations was dormant. The patients usually got better after stopping anti - tubercular medicaments. while the patients with smaller platelet counts below 30 × 109 / L, could recover after stopping anti -tubercular medicaments and getting hormones, gamma immumoglobulin and even supplying platelets. Conclusions During the process of anti - tubercular treatment, there may be drug- induced thrombocytopenia. The patients should be monitored carefully, especially in the first month after taking the anti - tubercular treatment. As far as the patients with the sign of thrombocytopenia were concerned, the most important and effective way is to stop medicines, especially Rifampicin. As for the patients with platelets counts below 30 × 109 / L, hormones, gamma immumoglobulin and platelets should be given except for stopping the anti - tubercular medicaments. The patients whose thrombocytopenia was surely caused by taking Rifampicin would not be taken it any more.%目的 探讨利福平引起血小板减少的机理及临床表现和处理.方法 回顾性分析成都市结核病防治院2008.07~2010.10使用抗结核药物治疗后血小板减少病例 14例,总结临床应用经验.结果 本组14例出现利福平药物引起的血小板减少,年龄

  17. 妊娠合并血小板减少89例临床分析%Clinical analysis of 89 thrombocytopenia in pregnancy

    王洪英; 齐小雪; 王跃莲


    目的 探讨妊娠合并血小板减少的病因、治疗及分娩方式.方法 回顾性分析我院2006年1月~2009年3月收治的89例妊娠合并血小板减少患者的临床资料.结果 妊娠期血小板减少的主要病因有妊娠相关性血小板减少症(PAT)65例(73.03%),妊娠期高血压疾病(HDCP)11例(12.36%),特发性血小板减少性紫癜(ITP)6例(6.74%),妊娠合并肝脏疾病5例(5.61%),系统性红宽狼疮合并妊娠2例(2.24%).PAT孕期不需特殊处理,妊娠结局良好,对血小板<50×109/L的12例患者分娩前给予地塞米松10~20mg/d,5例无效者分娩时输注血小板.结论 妊娠期血小板减少以PAT多见,孕期不需特殊处理.其次为妊娠期高血压疾病(HDCP).当血小板≤50×109/L分娩前给予地塞米松治疗,静脉点滴3~5d,无效者分娩时输注血小板,分娩方式以剖宫产为宜,产后出血发生率12.35%.%Objective To explore the causes,therapy and the way of delive of pregnant women with thromboeytopenia. Methods The data of 89 cases with thrombocytopenia during pregnancy were reviewed from Jan. 2006 to Mar. 2009. Results The main cause of thrombocytopenia during pregnancy were pregnancy associated thrombocytopenia (PAT) has 65 cases (73.03%), Hypertensive disorder complicating pregnancy(HDCP) has 11 cases(12.36%). Idiopathic thromboeytopenia(ITP) has 6 cases(6.74%). Hepatic disease in pregnancy has 5 cases (5.61% ,Systemic lupus erythematosus in pregnancy has 2cases (2.24%). Pregnancy associated thrombocytopenia need not to be specially treated during pregnancy, To the 12 patients whose platelet <50×109/L given dexamethasone 10~20mg/d treatment before delivery ,But five patients who has no effect intravenous platelet treatment during delivery. Conclusion Pregnancy associated thrombocytopenia is the common reason in thrombocytope-nia during pregnancy, Pregnancy associated thrombocytopenia need not to be specially treated during pregnancy. The second rea-son is hypertensive

  18. Presence of Essential Hypertension or Diabetes Mellitus Is a Predictor of Intracranial Bleeding in Elderly Patients: A Study of 108 Patients with Isolated Thrombocytopenia from a Single Reference Center

    Rajan Kapoor


    Full Text Available INTRODUCTION: Thrombocytopenia poses a significant problem in the elderly. Not only are there varied causes, but it is also associated with significant morbidity and mortality. We carried out a study to learn the causes of isolated thrombocytopenia in elderly patients and to correlate the severity of thrombocytopenia and bleeding manifestations with various etiologic factors and comorbidities. METHODS: A total of 108 patients above 50 years of age presenting with isolated thrombocytopenia (platelet counts of <100x109/L with normal hemoglobin and total leukocyte counts were enrolled in the study. Detailed history and clinical examinations were carried out for each patient. Complete blood counts were analyzed by automated cell counter. Peripheral smears were examined in all cases. HbsAg, anti-HCV, and anti-HIV testing by enzyme-linked immunosorbent assay was done in all patients. Wherever clinically indicated, bone marrow aspiration biopsy and cytogenetic studies were done. RESULTS: Out of 108 patients, 102 (94.4% presented with bleeding tendencies. Twenty-nine (26.8% presented with serious (World Health Organization grade 3/4 bleedings. Major findings were immune thrombocytopenic purpura in 79 (73.1%, myelodysplastic syndrome in 7 (6.5%, drug-induced thrombocytopenia in 7 (6.5%, and connective tissue disorder in 4 (3.7% cases. Ten patients presented with intracranial bleedings. Upon logistic regression analysis, comorbidities in the form of essential hypertension and diabetes mellitus were significantly associated with occurrence of intracranial bleeding. There was no correlation of serious bleedings with platelet counts. DISCUSSION AND CONCLUSION: Isolated thrombocytopenia in the elderly is associated with significant morbidity. Diligent clinical and laboratory evaluation is required to elucidate the cause of thrombocytopenia in the elderly. Comorbidities in this population are associated with serious bleedings and not low platelet counts as is

  19. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis

    Rose M. Ayoob


    Full Text Available The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males, mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies.

  20. Acute otitis externa.

    Hui, Charles Ps


    Acute otitis externa, also known as 'swimmer's ear', is a common disease of children, adolescents and adults. While chronic suppurative otitis media or acute otitis media with tympanostomy tubes or a perforation can cause acute otitis externa, both the infecting organisms and management protocol are different. This practice point focuses solely on managing acute otitis externa, without acute otitis media, tympanostomy tubes or a perforation being present.