Sample records for acute immune-mediated thrombocytopenia

  1. Oxaliplatin induced acute immune-mediated thrombocytopenia; a case report

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    İsmail Beypinar


    In conclusion, oxaliplatin induced immune-mediated thrombocytopenia is a rare side effect but a life threatening complication. A physician who uses oxaliplatin as a treatment option should keep in mind the possibility immune-mediated thrombocytopenia which may cause life-threatening bleeding. Especially the long term use of oxaliplatin (median >10 cycles may alert the physician for immune-mediated adverse effects.

  2. Piperacillin/tazobactam-induced immune-mediated thrombocytopenia in the intensive care unit. (United States)

    Boyce, K; Brar, H; Stabler, S N


    Drug-induced immune-mediated thrombocytopenia is a rare adverse event that remains a diagnostic challenge, especially in the critically ill population. There are only two previously reported cases of rapid and profound thrombocytopenia after administration of piperacillin/tazobactam. A 64-year-old man experienced several episodes of isolated thrombocytopenia after receiving piperacillin/tazobactam. Interestingly, the degree of thrombocytopenia varied with the amount of corticosteroid therapy the patient was receiving. Due to the complexity of thrombocytopenia in critically ill patients, other potential causes were extensively worked up and ruled out. We describe the first case of piperacillin/tazobactam-induced immune-mediated thrombocytopenia that was mitigated by the administration of corticosteroid therapy. This case highlights the importance of identifying potential drug-related causes of isolated thrombocytopenia. © 2016 John Wiley & Sons Ltd.

  3. Treatment of presumptive primary immune-mediated thrombocytopenia with mycophenolate mofetil versus cyclosporine in dogs. (United States)

    Cummings, F O; Rizzo, S A


    The objective of this study was to compare hospitalisation duration, survival times, adverse events and cost of therapy in dogs with presumptive primary immune-mediated thrombocytopenia undergoing therapy with mycophenolate mofetil and corticosteroids versus cyclosporine and corticosteroids. A retrospective study of medical case records of dogs with presumed primary immune-mediated thrombocytopenia was conducted. Data collected included signalment, presenting complaints, haematologic and biochemical profiles, vector-borne disease testing, thoracic and abdominal radiographs, abdominal ultrasound, medications administered, duration of hospitalisation, 30- and 60-day survival, adverse events and cost of therapy. Variables were compared between dogs treated solely with mycophenolate mofetil and corticosteroids or cyclosporine and corticosteroids. A total of 55 dogs with primary immune-mediated thrombocytopenia were identified. Eighteen were excluded because multiple immunosuppressive medications were used during treatment. Hospitalisation times, 30-day survival and 60-day survival times were similar between both groups. Dogs in the mycophenolate mofetil/corticosteroid group experienced fewer adverse events than the cyclosporine/corticosteroid group. Therapy with mycophenolate mofetil was less expensive than that with cyclosporine. These results suggest that using the combination of mycophenolate mofetil and corticosteroids appears to be as effective as cyclosporine and corticosteroids in the treatment of presumed primary immune-mediated thrombocytopenia in dogs. Adverse events were less common and cost of therapy was lower in the mycophenolate mofetil group. Additional larger prospective, controlled, double-masked, outcome-based, multi-institutional studies are required to substantiate these preliminary findings. © 2017 British Small Animal Veterinary Association.

  4. Systemic neosporosis in a dog treated for immune-mediated thrombocytopenia and hemolytic anemia. (United States)

    Magaña, Angie; Sánchez, Félix; Villa, Karina; Rivera, Liliana; Morales, Elizabeth


    A 4-year-old male Toy Poodle was presented to the Small Animal Veterinary Hospital of the Faculty of Veterinary Medicine of the Autonomous University of Mexico (FMVZ, UNAM) because of depression, lethargy, and hemorrhages involving several areas of the skin and around the eyes. Hematology data and a bone marrow analysis suggested hemolytic anemia and immune-mediated thrombocytopenia. The dog was treated with prednisone, and after one month the hematology variables improved. However, the dog's clinical condition inexplicably worsened and it was euthanized. On necropsy, there were no relevant findings. However, in histology, multifocal lymphoplasmacytic and histiocytic meningoencephalitis and necrosis, and a protozoan cyst in the cerebellum were identified. In addition, moderate multifocal lymphoplasmacytic and necrotizing pancreatitis, hepatitis, myocarditis, and diffuse lymphoplasmacytic enteritis were observed. Immunohistochemistry of the cerebellum, liver, pancreas, and intestine with a specific antibody against Neospora caninum confirmed the diagnosis of systemic neosporosis. The systemic neosporosis in this dog was most likely caused by reactivation of latent parasites due to prednisone administration during the one month of treatment. It should be kept in mind that in dogs being treated with immunosuppressants for immune-mediated conditions, opportunistic parasites, such as Toxoplasma gondii and N caninum, can be reactivated from a latent state, as it probably happened in the present case. © 2015 American Society for Veterinary Clinical Pathology.

  5. Acute profound thrombocytopenia with second exposure to eptifibatide associated with a strong antibody reaction (United States)



    We present a case of eptifibatide-induced acute profound thrombocytopenia in a 64-year-old male receiving eptifibatide for the second time during percutaneous coronary intervention. Although rare, short and self-limited episodes of acute and profound thrombocytopenia have been associated with eptifibatide exposure. The thrombocytopenia is thought to be immune mediated, and assays are available to test for eptifibatide-induced platelet antibodies. PMID:19172524

  6. Acute profound thrombocytopenia with second exposure to eptifibatide associated with a strong antibody reaction




    We present a case of eptifibatide-induced acute profound thrombocytopenia in a 64-year-old male receiving eptifibatide for the second time during percutaneous coronary intervention. Although rare, short and self-limited episodes of acute and profound thrombocytopenia have been associated with eptifibatide exposure. The thrombocytopenia is thought to be immune mediated, and assays are available to test for eptifibatide-induced platelet antibodies.

  7. Prevention of immune-mediated transfusion-related acute lung injury; from bloodbank to patient. (United States)

    Műller, Marcella C A; Porcelijn, Leendert; Vlaar, Alexander P J


    Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion related morbidity and mortality. Immune-mediated TRALI is caused by leucocyte and neutrophil antibodies in the transfused blood products that react with white blood cell antigens of the recipient, hereby inducing endothelial damage and lung injury. About two thirds of TRALI cases are thought to be immune-mediated. Both Human Leucocyte Antibodies (HLA Class I and II) and Human Neutrophil Antibodies (HNA) are involved in TRALI. Most antibodies result from allo-exposure of the blood donor, with multiparous donors having the highest incidence of antibodies. Detection of anti-leucocyte and anti-neutrophil antibodies is complex and many uncertainties still exist regarding the interpretation of the test results. In this review we discuss the evidence and effectiveness of measurements to prevent immune-mediated TRALI from a bloodbank and bedside perspective. From a bloodbank perspective various preventive measures have been implicated. In some countries bloodbanks have successfully implemented donor selection strategies, ranging from testing of allo-exposed donors for leucocyte antibodies to the exclusion of all females from donating high plasma volume products. Another strategy involves dilution of antibodies present by pooling of plasma donations of multiple donors. From a bedside view, the most important measure to prevent TRALI is to limit patients' exposure to allogenic bloodproducts. Furthermore recognition and awareness of the syndrome need to be heightened among clinicians.

  8. Acute renal failure and severe thrombocytopenia associated with metamizole

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    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.

  9. Acute renal failure and severe thrombocytopenia associated with metamizole. (United States)

    Redondo-Pachon, Maria Dolores; Enriquez, Ricardo; Sirvent, Ana Esther; Millan, Isabel; Romero, Alberto; Amorós, Francisco


    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 diagnosis 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.

  10. Eptifibatide-induced thrombocytopenia leading to acute stent thrombosis. (United States)

    Dézsi, Döme A; Bokori, György; Faluközy, József; Bujáky, Csaba; Fogarassy, György; Veress, Gábor; Aradi, Dániel


    A 71-year old female patient with inferior ST-elevation myocardial infarction underwent primary percutaneous coronary intervention (PCI) within 3 h of symptom onset. She was preloaded with 300 mg aspirin and 600 mg clopidogrel before PCI. Coronary angiogram showed occlusion of the right coronary artery. During PCI, eptifibatide was initiated due to the large thrombus burden. Few hours after the procedure, on eptifibatide infusion, a severe drop in platelet count was observed (from 210,000/μl to 35,000/μl) and the infusion was discontinued. One hour later, still under eptifibatide effect and with severe thrombocytopenia, acute stent thrombosis developed. Lack of prior heparin exposure, quick onset of thrombocytopenia made heparin induced thrombocytopenia improbable that was later excluded by specific immunoassay. However, platelet function testing suggested that eptifibatide induced thrombocytopenia was mediated by activating autoantibodies since platelet reactivity was paradoxically very high at the time of stent thrombosis but decreased radically with eptifibatide washout. The patient was successfully managed without further complications on the basis of platelet function data obtained in the subsequent days. This rare subtype of thrombocytopenia highlights that not only platelet count but also platelet function should be closely monitored in case of severe thrombocytopenia to better balance bleeding and thrombosis.

  11. Anemia and thrombocytopenia in acute and chronic renal failure. (United States)

    Dorgalaleh, Akbar; Mahmudi, Mohammad; Tabibian, Shadi; Khatib, Zahra Kashani; Tamaddon, Gholam Hossein; Moghaddam, Esmaeil Sanei; Bamedi, Taregh; Alizadeh, Shaban; Moradi, Eshagh


    Acute renal failure describes as a syndrome by rapid decline in the ability of the kidney to eliminate waste products, regulate acid-base balance, and manage water homeostasis. When this impairment is prolonged and entered chronic phase, erythropoietin secretion by this organ is decreasing and toxic metabolic accumulates and causes hematological changes include decrease of HCT, MCV and RBC and platelet counts. This study evaluates present of anemia and thrombocytopenia in patients with acute and chronic renal failure. This study conducted on 132 patients with renal impairment and also 179 healthy individuals as two separated control groups. Initially patients with renal problem were tested and after confirmation of impairment, patients were divided in two groups, acute with less than 3 months and chronic with more than 3 months renal failure, based on duration of the disease. Then complete blood count performed for each patient and finally obtained data were analyzed by SPSS software. Comparison between 96 patients with acute and 36 patients with chronic renal failure revealed that severity of anemia (HCT, Hb and MCV) between these two groups were statistically high in comparison with control groups (P > 0.05) but thrombocytopenia in patients with chronic renal failure was statistically different from control and the acute ones (P renal failure, to prevent the risk of bleeding, platelet count should be checked periodically.

  12. Eptifibatide-induced acute profound thrombocytopenia: a case report. (United States)

    Graidis, Christos; Golias, Christos; Dimitriadis, Dimokritos; Dimitriadis, Georgios; Bitsis, Theodosis; Dimitrelos, Ilias; Tsiakou, Afroditi; Charalabopoulos, Konstantinos


    The interactions among cells or among cells and components of the extracellular matrix, is a crucial pathophysiological process involving some molecules collectively known as adhesion molecules (CAMs). Glycoprotein IIb / IIIa receptors are only restricted to blood platelets and they bind fibrinogen and adhesion proteins such as fibronectin, vitronectin, von Willebrand factor to form cross bridges between adjacent platelets. IIb/IIIa receptor antagonists are an object of intense research activity for target therapy worldwide during the last decades. Three GPIIb/IIIa inhibitors, abciximab, tirofiban, and eptifibatide, have been approved for clinical use. Profound thrombocytopenia is an uncommon but clinically important complication of glycoprotein IIb/IIIa inhibitors. This case report discusses a forty-four-year-old male patient with acute coronary syndrome who underwent percutaneous coronary intervention and developed profound thrombocytopenia within 4 hours of first administration of eptifibatide. This report adds another case of eptifibatide-induced thrombocytopenia to the medical literature and endorses the importance of platelet count monitoring after initiating therapy with this agent.

  13. Piperidylmethyloxychalcone improves immune-mediated acute liver failure via inhibiting TAK1 activity. (United States)

    Park, Sun Hong; Kwak, Jeong-Ah; Jung, Sang-Hun; Ahn, Byeongwoo; Cho, Won-Jea; Yun, Cheong-Yong; Na, Chang Seon; Hwang, Bang Yeon; Hong, Jin Tae; Han, Sang-Bae; Kim, Youngsoo


    Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF. Post treatment with PMOC sequentially ameliorated hepatic inflammation, apoptosis of hepatocytes, severe liver injury and shock-mediated death in ALF-induced mice. As a mechanism, PMOC inhibited the catalytic activity of TGF-β-activated kinase 1 (TAK1) in a competitive manner with respect to ATP, displaced fluorescent ATP probe from the complex with TAK1, and docked at the ATP-binding active site on the crystal structure of TAK1. Moreover, PMOC inhibited TAK1 auto-phosphorylation, which is an axis in the activating pathways of nuclear factor-κB (NF-κB) or activating protein 1 (AP1), in the liver with ALF in vivo or in primary liver cells stimulated with TLR agonists in vitro. PMOC consequently suppressed TAK1-inducible NF-κB or AP1 activity in the inflammatory injury, an early pathogenesis leading to ALF. The results suggested that PMOC could contribute to the treatment of TLR/MyD88-associated ALF with the ATP-binding site of TAK1 as a potential therapeutic target.

  14. Acute Severe Thrombocytopenia Occurring After Administration of Eptifibatide Postpones Emergent Coronary Artery Surgery. (United States)

    Boettcher, Brent T; Olund, Timothy J; Pagel, Paul S


    Eptifibatide is a platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptor antagonist that inhibits fibrinogen binding to the activated GP IIb/IIIa site and prevents platelet-platelet interaction and clot formation. GP IIb/IIIa inhibitors improve outcome in patients undergoing percutaneous coronary intervention for acute coronary syndrome. Thrombocytopenia is a complication of GP IIb/IIIa inhibitors, but severe thrombocytopenia is unusual. Most reported cases of severe thrombocytopenia after eptifibatide occurred in patients with acute coronary syndrome. The authors describe a patient who developed acute profound thrombocytopenia after receiving eptifibatide before emergent coronary artery bypass graft surgery. A 67-year-old man with a normal platelet count (220 K/uL) developed atrial fibrillation, left bundle branch block, and respiratory insufficiency consistent with acute coronary syndrome two days after colectomy. He received eptifibatide during cardiac catheterization, where three-vessel coronary artery disease was encountered. Emergent coronary artery surgery was planned, but the platelet count before surgery was 2 K/uL. Eptifibatide was discontinued, surgery was postponed, and acute coronary syndrome was treated with intraaortic balloon counterpulsation. The authors describe the second reported case of eptifibatide-induced severe thrombocytopenia associated with cardiac surgery. In this case, discontinuation of eptifibatide and transfusion of apheresis platelets increased the platelet count (137 K/uL) the following day, and the patient subsequently underwent successful coronary artery surgery using cardiopulmonary bypass.

  15. Effect of high dose of steroid on plateletcount in acute stage of dengue Fever with thrombocytopenia. (United States)

    Shashidhara, K C; Murthy, K A Sudharshan; Gowdappa, H Basavana; Bhograj, Abhijith


    Dengue infection is the most rapidly spreading mosquito-borne viral disease in the world and an estimated 50 million dengue infections reported annually. The pathogenesis of Thrombocytopenia in dengue fever (DF) is not clearly understood. Increased peripheral destruction of antibody coated platelets and acute bone marrow suppression were strongly suspected as the possible mechanism. This often leads to life threatening dengue hemorrhagic fever (DHF) and Dengue shock syndrome (DSS). Steroids are used in the treatment of Idiopathic thrombocytopenic purpura to increase the platelet count which is mediated by auto antibodies .This hypothesis would support the use of steroids in dengue fever. The objective of this study was to test whether an intravenous high dose dexamethasone was efficacious in increasing the platelet count in acute stage of dengue fever with thrombocytopenia. During the study period between June 2010 - 2011 in JSS Hospital Mysore, 127 patients were screened for dengue fever with thrombocytopenia (dengue fever.

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

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    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.

  17. Thrombocytopenia and extracorporeal membrane oxygenation in adults with acute respiratory failure: a cohort study. (United States)

    Abrams, Darryl; Baldwin, Matthew R; Champion, Matthew; Agerstrand, Cara; Eisenberger, Andrew; Bacchetta, Matthew; Brodie, Daniel


    The association between extracorporeal membrane oxygenation (ECMO) use and the development of thrombocytopenia is widely presumed yet weakly demonstrated. We hypothesized that longer duration of ECMO support would be independently associated with worsened thrombocytopenia. We performed a single-center retrospective cohort study of 100 adults who received ECMO for acute respiratory failure. We used generalized estimating equations to test the association between days on ECMO and daily percentage of platelets compared to the first post-cannulation platelet count. We constructed a multivariable logistic regression model with backwards stepwise elimination to identify clinical predictors of severe thrombocytopenia (≤50,000/μL) while on ECMO. Days on ECMO was not associated with a decrease in platelet count in the unadjusted analysis (β -0.85, 95 % CI -2.05 to 0.36), nor after considering and controlling for days hospitalized prior to ECMO, APACHE II score, platelet transfusions, and potential thrombocytopenia-inducing medications (β -0.83, 95 % CI -1.9 to 0.25). Twenty-two subjects (22 %) developed severe thrombocytopenia. The APACHE II score and platelet count at the time of cannulation predicted the development of severe thrombocytopenia. The odds of developing severe thrombocytopenia increased 35 % for every 5-point increase in APACHE II score (OR 1.35, 95 % CI 0.94-1.94) and increased 35 % for every 25,000/μL platelets below a mean at cannulation of 188,000/μL (OR 1.35, 95 % CI 1.10-1.64). Duration of ECMO is not associated with the development of thrombocytopenia. The severity of critical illness and platelet count at the time of cannulation predict the development of severe thrombocytopenia while receiving ECMO for respiratory failure. Future studies should validate these findings, especially in cohorts with more venoarterial ECMO patients, and should characterize the association between thrombocytopenia and bleeding events while on ECMO.

  18. Successful management of acute thromboembolic disease complicated with heparin induced thrombocytopenia type II (HIT II: a case series

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    Trellopoulos George


    Full Text Available Abstract Heparin-induced thrombocytopenia type II (HIT II is a rare immune-mediated complication of heparin. The diagnosis of HIT is considered in patients exposed to heparin, presenting with thrombocytopenia and thrombosis. We present two cases with massive pulmonary embolism and HIT, successfully treated with the administration of fondaparinux, an alternative anticoagulant, combined with the insertion of an inferior vena cava filter for the prevention of new thromboembolic events. The two cases supplement the available data of the use of fondaparinux in patients with HIT and pulmonary embolism, before further large studies establish its efficacy and safety in this group of patients. Moreover, the management of these patients reveals the need for future evaluation of the combined therapy of alternative anticoagulant agents with the placement of vena cava filters.

  19. Acute profound thrombocytopenia associated with readministration of eptifibatide: case report and review of the literature. (United States)

    Russell, Kimberly N; Schnabel, Joseph G; Rochetto, Richard P; Tanner, Matthew C


    The glycoprotein IIb-IIIa inhibitor eptifibatide has been shown to be beneficial in the treatment of acute coronary syndromes and during percutaneous coronary intervention (PCI). Case reports of acute profound thrombocytopenia have been reported with eptifibatide, yet the true incidence of this reaction is unknown. We describe a 50-year-old woman with severe coronary artery disease who developed acute profound thrombocytopenia after readministration of eptifibatide. Eptifibatide was administered through hospital day 3, when it was discontinued in preparation for coronary angiography and PCI; the drug was restarted on day 5. On hospital day 6, she was noted to have a platelet count below 5 x 10(3)/mm,(3) indicating a profound decrease from a baseline of 456 x 10(3)/mm(3) on admission. Eptifibatide, heparin, vancomycin, and clopidogrel were potential causative agents. Anticoagulation and vancomycin were stopped, and her platelet count increased to 30 x 10(3)/mm(3) on day 7. Subsequent reexposure to heparin and vancomycin yielded no adverse effects. The patient's platelet count increased over the remainder of her hospitalization, and she was discharged home on day 19. Based on clinical presentation and negative heparin platelet factor 4 antibody test, eptifibatide was the most likely cause of thrombocytopenia. Use of the Naranjo adverse drug reaction probability scale indicated that eptifibatide was the probable cause of thrombocytopenia (score of 5); scores of 1 (possible) or 0 (doubtful) were derived with heparin, vancomycin, and clopidogrel. We conducted a literature search and compiled information from published case reports to describe the pattern of onset and recovery of eptifibatide-induced thrombocytopenia. In all patients receiving eptifibatide, routine platelet counts should be monitored at baseline and within 2-6 hours after starting the drug.

  20. [Transient dysfibrinogenemia and thrombocytopenia associated with recurrent acute pancreatitis in the course of isotretinoin therapy]. (United States)

    Aurousseau, M H; Levacher, S; Bénéton, C; Blaise, M; Pourriat, J L


    A 17 year-old young man developed two episodes of acute pancreatitis, separated by a 2 year interval and associated with isotretinoin therapy. In 1989, vesicular sludge without lithiasis was evidenced and in 1991, gall bladder stones were found by cholecystectomy. Concomitantly, transient dysfibrinogenemia and thrombopenia were present. It is interesting to note that far away from the use of isotretinoin, the patient suffered from another episode of acute pancreatitis without any coagulation disorder. The involvement of Roaccutane in cellular differentiation is discussed as well as its causal association with acquired dysfibrinogenemia and transient thrombocytopenia.

  1. Left main stent thrombosis complicated by eptifibatide-induced acute thrombocytopenia. (United States)

    Yang, Eric H; Perez, Edwin; Zhiroff, Katrine A; Burstein, Steven


    A 57-year-old man with a history of coronary artery disease and placement of an implantable cardioverter-defibrillator presented at our emergency room with an anterior ST-elevation myocardial infarction. Cardiac catheterization revealed an acutely occluded left main coronary artery, which was revascularized successfully with a bare-metal stent. Periprocedurally, the patient received aspirin, clopidogrel, unfractionated heparin, and eptifibatide. The patient was discharged a week later, but he returned to the emergency room the same day with recurrence of severe chest pain. Repeat cardiac catheterization revealed an acutely occluded stent, and the patient underwent repeat bare-metal stent placement and readministration of eptifibatide. On the next day, the patient's platelet count dropped acutely to less than 12,000/mm3. A test for heparin-induced thrombocytopenia antibody was negative. After discontinuation of eptifibatide, the patient's platelet count gradually returned to normal, and he was later discharged from the hospital with no complications. Eptifibatide-induced acute thrombocytopenia is a known but rare adverse effect. We review the handful of case reports in the medical literature, with emphasis on the prevalence, observed clinical course, and recently proposed physiologic mechanisms that probably are responsible for this phenomenon.

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

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    Tiehua Wang

    Full Text Available 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.This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies.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.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.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.

  3. Endometrial carcinoma and paraneoplastic immune thrombocytopenia

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    Hilmi Kodaz


    Conclusion: Autoimmune thrombocytopenia is a diagnosis of exclusion. Immune-mediated paraneoplastic syndrome include autoimmune thrombocytopenia is well known in hematological cancers, but it is rare in solid tumors. New developments in the treatment of primary cancer by clarification of paraneoplastic syndromes immunology should be considered.

  4. Immune-mediated liver failure

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    WANG Xiaojing


    Full Text Available The primary causative factors of liver failure include direct damage and immune-mediated liver injury. Increasing evidence suggests that immune-mediated injury plays a pivotal role in the pathogenesis of liver failure. The new concepts concerning the mechanisms of immune-mediated liver injury in liver failure are reviewed with relevant basic and clinical studies in both humans and animals. The innate and adaptive immunity, particularly the interaction of various immune cells and molecules, as well as apoptosis-related molecules, are discussed in detail.

  5. Thrombocytopenia on the first day of emergency department visit predicts higher risk of acute kidney injury among elderly patients. (United States)

    Chao, Chia-Ter; Tsai, Hung-Bin; Chiang, Chih-Kang; Huang, Jenq-Wen


    Few studies have addressed risk factors for acute kidney injury (AKI) in geriatric patients. We investigated whether thrombocytopenia was a risk factor for AKI in geriatric patients with medical illnesses. A prospective cohort study was conducted, by recruiting elderly (≥65 years) patients who visited the emergency department (ED) for medical illnesses during 2014. They all received hemogram for platelet count determination, and were stratified according to the presence of thrombocytopenia (platelets, thrombocytopenia and subsequent AKI after ED stay, using Cox proportional hazard modeling, with platelet count as a continuous variable or thrombocytopenia as a categorical variable. Of 136 elderly patients (mean age of 80.7 ± 8.2 years, 40% with chronic kidney disease, and 39% with diabetes) enrolled, 22.8% presented with thrombocytopenia, without differences in baseline renal function. After a mean ED stay of 4.4 ± 2.1 days, 41.9% developed AKI (52.6% Kidney Disease Improving Global Outcomes [KDIGO] grade 1, 24.6% grade 2, and 22.8% grade 3). Patients with higher AKI severity had stepwise lower platelet counts compared to those without AKI. The Cox proportional hazard model revealed that lower platelet count as a continuous variable (hazard ratio [HR] 0.984, 95% confidence interval [CI] 0.975-0.994) and as a categorical variable (presence of thrombocytopenia) (HR 1.86, 95% CI 1.06-3.27) increased the risk of AKI. The sensitivity analyses accounting for nephrotoxic medications use, including non-steroidal anti-inflammatory drugs, vancomycin, and contrast, yielded similar results. Thrombocytopenia is common among ED-visiting elderly, and the potential relationship between platelet counts and the risk of AKI suggests the utility of checking hemogram for those at-risk ofdeveloping adverse renal events. Thrombocytopenia on initial presentation might indicate an increased risk of AKI among elderly patients with medical illnesses.

  6. Rethinking platelet function: thrombocytopenia induced immunodeficiency in critical illness

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    Ostrowski, Sisse R; Johansson, Per Ingemar


    traditional innate immune cells, platelets are recruited immediately into injured and inflamed tissue, they release immune mediators, express and shed immunologically active membrane receptors, they interact with other immune cells and they recognize and clear pathogens. We hypothesize that thrombocytopenia...

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

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    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.

  8. Meloxicam-induced thrombocytopenia. (United States)

    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. © 2013 American College of Clinical Pharmacy.

  9. Two patients with acute thrombocytopenia following gold administration and five-year follow-up

    NARCIS (Netherlands)

    M.-D. Levin (Mark-David); M.B. van 't Veer (Mars); J.C. de Veld; H.M. Markusse


    textabstractThrombocytopenia is a well-known side effect following intramuscular gold therapy in patients with rheumatoid arthritis. Thrombocytopenia may occur at any time and it can be irreversible and sometimes fatal despite cytotoxic or immunosuppressive therapy. We describe two

  10. Acute renal failure, thrombocytopenia, and elevated liver enzymes after concurrent abuse of alcohol and cocaine

    Directory of Open Access Journals (Sweden)

    Alireza Hosseinnezhad


    Full Text Available Cocaine has been associated with known adverse effects on cardiac, cerebrovascular and pulmonary systems. However, the effect of cocaine on other organs has not been extensively reported. A middle age man presented with abdominal pain and nausea after inhalation of crack cocaine. On admission, he was found to be hypertensive and tachycardic. Physical examination revealed mild abdominal tenderness without rebound. Laboratory investigations were significant for acute kidney failure with elevated serum creatinine (3.72 mg/dL, thrombocytopenia (platelet count 74,000/UL, elevated alanine and aspartate transaminases (ALT 331 U/L; AST 462 U/L and elevated creatine phosphokinase (CPK 5885 U/L. Urine toxicology screening solely revealed cocaine. A clinical diagnosis of cocaine toxicity was made and patient was admitted to the intensive care unit because of multi organ failure. Despite downward trending of liver enzymes during the hospital course, he continued to have residual renal insufficiency and a low platelet count at the time of discharge. In a patient with history of recent cocaine use presenting with these manifestations, cocaine itself should be considered as a likely cause.


    Directory of Open Access Journals (Sweden)

    Ramasamy S


    Full Text Available BACKGROUND Snakebites and accidents caused by venomous arthropods are important public health problem. Envenomation by snakebite, independently of the species responsible for the bite, enforces medical emergencies since different organs and tissues can be affected at the same time. The hypothesis for pathogenesis of venom-induced AKI includes both a direct cytotoxic action of the venom on different renal structures and a secondary response of the whole organism resulting from systemic envenomation. The aim of the study is to assess the early predictors for acute kidney injury due to snakebite by comparing it with the patients who had not developed acute kidney injury after the snakebite. MATERIALS AND METHODS A prospective comparative study was undertaken at the Government Medical College Hospital, Salem, during the period of April 2015-March 2016. A total of 115 patients were included in the study in which 42 patients were having AKI due to snakebite and 73 patients were without AKI after snakebite. Haematological and biochemical investigations were performed in all patients, including haemoglobin, complete and differential leukocyte counts, platelet count, peripheral blood smear, bleeding and clotting times, Prothrombin Time (PT and Activated Partial Thromboplastin Time (APTT, blood urea, serum creatinine, serum electrolytes, liver function tests and urine examination. RESULTS Thrombocytopenia and albuminuria, which is to be considered as the major early marker for acute kidney injury among snakebite patients was found to be present in 85.7% and 100% in our patients with AKI whereas it was only 1.3% and 4.1% respectively among the patients without AKI and the difference was found to be statistically significant (p<.05. The survival rate was higher among the patients without AKI when compared to the patients with AKI and the difference is statistically significant (p<.05. CONCLUSION Early detection of AKI due to snakebite should be assessed by

  12. Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs. (United States)

    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.

  13. Eptifibatide-Induced Thrombocytopenia (United States)

    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. PMID:22412237

  14. Evaluation of scales and measurement instruments in immune-mediated polyneuropathies

    NARCIS (Netherlands)

    I.S.J. Merkies (Ingemar)


    textabstractImmune-mediated neuropathies mainly include Guillain-Barre syndrome (GBS) (most common form: acute inflammatory demyelinating polyneuropathy (AJDP)), chronic inflammatory demyelinating polyneuropathy (CIDP), neuropathy associated with monoclonal gammopathy of undetermined significance

  15. Immune-mediated brain pathology: from autoantibodies to microglia. (United States)

    Nestor, Jacquelyn; Gata-Garcia, Adriana; Arinuma, Yoshiyuki; Fujieda, Yuichiro; Kowal, Czeslawa; Diamond, Betty


    Cells and molecules of the immune system contribute to brain pathology as well as to brain homeostasis. We suggest that there are numerous anti-brain antibodies that can cause acute neuronal dysfunction if they penetrate brain parenchyma. Many of these acute immune-mediated insults may alter the homeostatic mechanisms in the brain and initiate pathologic events that no longer depend on the presence of the inciting antibody, but rather on microglial cell activation. This paradigm, if correct, suggests that there may be two potential moments of therapeutic intervention. The first moment is when antibody contacts cells of the central nervous system and the second is when microglia become activated and impair normal neuronal functions. In this review, we discuss data that support this model for immune-mediated pathology in both the adult brain and the developing fetal brain.

  16. Therapeutic Challenges in the Management of Acute Pulmonary Embolism in a Cancer Patient with Chemotherapy-induced Thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Abuajela Sreh


    Full Text Available This case demonstrates the therapeutic challenges encountered when managing an acute pulmonary embolism in a cancer patient with thrombocytopenia. A 64-year-old man with a history of lung cancer receiving chemotherapy was admitted to Walsall Manor Hospital with haemodynamic instability consistent with a pulmonary embolism, proven on computed tomographic pulmonary angiogram. His platelet count was noted to be 35×109/l (chemotherapy-induced thrombocytopenia. After discussions, he was deemed not suitable for thrombolysis based on risk versus benefits. The patient was initially transfused one adult dose of platelets and treated with half the therapeutic dose of low molecular weight heparin (LMWH. The same management plan was followed until the platelet count exceeded 50×10sup>9/l, after which the patient was established on the full therapeutic dose of LMWH. Clinically, the patient improved and was discharged. Three months after discharge, follow-up revealed sustained clinical improvement while the patient continued to be on the full therapeutic dose of LMWH with a stable platelet count.

  17. [Leptospirosis and thrombocytopenia]. (United States)

    Issa, N; Guisset, O; Mourissoux, G; Gabinski, C; Camou, F


    Leptospirosis is a worldwide zoonosis caused by the spirochete Leptospira interrogans. The spectrum of symptoms reported in leptospirosis is extremely broad. Thrombocytopenia is common during the acute phase of leptospirosis but its pathophysiological mechanism remains not well defined. We report a 56-year-old man hospitalized for severe sepsis with acute kidney injury and liver failure. Because of the recent flood of his house, we suspected leptospirosis. The diagnosis was rapidly confirmed. Blood tests revealed thrombocytopenia at 9 G/L associated with hyperferritinemia and hypertriglyceridemia. Cytological examination of bone marrow showed abundance of megakaryocytes and hemophagocytosis which confirmed the diagnosis of hemophagocytic syndrome. Clinical symptoms resolved and blood tests returned to normal values in the same time. We suggest that hemophogocytosis is a possible mechanism of thrombocytopenia in leptospirosis and that examination of bone marrow should be performed to confirm the diagnosis. Copyright © 2014. Published by Elsevier SAS.

  18. Acute thrombocytopenia in patients treated with amiodarone is caused by antibodies specific for platelet membrane glycoproteins (United States)

    Sahud, Mervyn A.; Caulfield, Michael; Clarke, Nigel; Koch, Robert; Bougie, Daniel; Aster, Richard


    Summary Amiodarone has been implicated as a cause of thrombocytopenia but the responsible mechanism is unknown. We performed studies in three patients to characterize the pathogenesis of this complication. No amiodarone-dependent, platelet-reactive antibodies were identified using conventional serological techniques. However, water-insoluble amiodarone solubilized in methanol and diluted to 1·0 mg/ml in aqueous buffer reproducibly promoted binding of IgG antibodies in patient serum to platelets. Solid phase assays identified drug-dependent antibodies specific for platelet gly coproteins (GP)Ia/IIa (integrin α2β1) in each patient and a second antibody specific for GPIIb/IIIa (αIIbβ3 integrin) in one patient. When studied by ion mobility analysis and transmission electron microscopy, the serologically active amiodarone preparation, a milky suspension, was found to consist of particles 2–30 nm in diameter, typical of a coacervate, a state characteristic of amiodarone in aqueous medium. The findings provide evidence that thrombocytopenia in the three patients studied was caused by drug-dependent antibodies specific for platelet glycoproteins GPIa/IIa and/or GPIIb/IIIa. We postulate that, in vivo, amiodarone may become incorporated into occult lipophilic domains in platelet glycoproteins, producing structural modifications that are immunogenic in some individuals, and that the resulting antibodies can cause platelet destruction in a person taking this drug. PMID:23952260

  19. Immune Thrombocytopenia (United States)

    ... information about platelet transfusions, go to the Health Topics Blood Transfusion article. Treating Infections Some infections can briefly lower ... experiences with clinical research. More Information Related Health Topics Blood ... Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Other ...

  20. Acute Trypanosoma cruzi infection is associated with anemia, thrombocytopenia, leukopenia, and bone marrow hypoplasia: reversal by nifurtimox treatment. (United States)

    Marcondes, M C; Borelli, P; Yoshida, N; Russo, M


    In the present work we show that acute infection of C3H mice with the CL strain of Trypanosoma cruzi is characterized by an exponential growth of parasites and high mortality accompanied by anemia, thrombocytopenia, leukopenia, and bone marrow hypoplasia. Administration of nifurtimox, a trypanocydal drug currently in clinical use at different days postinfection, modulates parasitemia and prevents mortality. More importantly, none of blood and bone marrow alterations were observed in nifurtimox-treated animals when treatment was initiated early in infection, one or seven days postinoculation. The bone marrow alterations were characterized by a decrease in the total number cells as well in the number of megakaryoblasts and erythroblasts. Transfer experiments of bone marrow cells from infected mice to noninfected lethally irradiated recipients revealed a poor marrow-repopulating activity. The colony forming units-spleen assay confirmed the depression of committed clonal progenitors cells and revealed a decreased number of granulocyte/macrophage, megacariocyte and erythrocyte colonies. In summary, this is the first report showing that acute T. cruzi infection results in profound alterations of the hematopoietic system and that these alterations can be prevented by nifurtimox treatment.

  1. Presumed primary immune-mediated neutropenia in 35 dogs: a retrospective study. (United States)

    Devine, L; Armstrong, P J; Whittemore, J C; Sharkey, L; Bailiff, N; Huang, A; Rishniw, M


    To describe, in a cohort of dogs with presumed primary immune-mediated neutropenia, the presenting clinical characteristics, haematology results, bone marrow characteristics, therapies used (drugs and doses), clinical response to treatment, relapse and outcome at six months and one year. Multi-institutional recruited retrospective descriptive case series with voluntary submissions. Presumed immune-mediated neutropenia was diagnosed based on a neutrophil concentration neutropenia based on a diagnostic bone marrow aspirate or biopsy, and exclusion of secondary immune-mediated neutropenia. Dogs meeting these diagnostic criteria between 2006 and 2013, and that had a haematocrit of ≥29% and minimum of two complete blood clounts performed after initiation of therapy, were included. Information on 35 dogs was included. Neutropenia was less than 0·5×109 cells/L in most cases (21 dogs), 0·5 to ·99×109 cells/L in 11, and 1.0 to 1·49×109 cells/L in three. Eight dogs had thrombocytopenia, which was severe (Neutropenia resolved in 32 of 33 dogs within two weeks of starting corticosteroid therapy and in all dogs within one month. Relapse of neutropenia occurred in 12 cases within one year. Initial response of presumed primary immune-mediated neutropenia cases to corticosteroid therapy can be excellent. Long-term monitoring for relapse is warranted because 34% of cases relapsed during or after taper of immunosuppressive medications. © 2017 British Small Animal Veterinary Association.

  2. 25-Hydroxyvitamin D and Peripheral Immune Mediators

    DEFF Research Database (Denmark)

    Thorsen, Steffen; Pipper, Christian; Skogstrand, Kristin


    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...

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Acute Kidney Injury, Recurrent Seizures, and Thrombocytopenia in a Young Patient with Lupus Nephritis: A Diagnostic Dilemma. (United States)

    Alvarado Verduzco, Hector; Acharya, Anjali


    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.

  5. Acute Kidney Injury, Recurrent Seizures, and Thrombocytopenia in a Young Patient with Lupus Nephritis: A Diagnostic Dilemma (United States)


    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. PMID:28044115

  6. Thrombocytopenia Is Associated With Multi-organ System Failure in Patients With Acute Liver Failure

    NARCIS (Netherlands)

    Stravitz, R. Todd; Ellerbe, Caitlyn; Durkalski, Valerie; Reuben, Adrian; Lisman, Ton; Lee, William M.

    BACKGROUND & AIMS: Acute liver failure (ALF) is a syndrome characterized by an intense systemic inflammatory response (SIRS) and multi-organ system failure (MOSF). Platelet-derived microparticles increase in proportion to the severity of the SIRS and MOSF, and are associated with poor outcome. We

  7. Anti-thymocyte serum as part of an immunosuppressive regimen in treating haematological immune-mediated diseases in dogs. (United States)

    Cuq, B; Blois, S L; Mathews, K A


    To report the outcomes associated with the use of rabbit anti-dog thymocyte serum in dogs with haematological immune-mediated diseases. Medical records from 2000 to 2016 of patients diagnosed with immune-mediated haemolytic anaemia, immune-mediated thrombocytopenia, pancytopenia and myelofibrosis were reviewed. All dogs had a severe or refractory disease and received rabbit anti-dog thymocyte serum. Lymphocyte counts were used to monitor the immediate anti-thymocyte effect of therapy; long-term patient outcome was recorded. A total of 10 dogs were included. All dogs except one had a notable decrease in their lymphocyte count after rabbit anti-dog thymocyte serum; four of nine had a decrease to less than 10% of the initial lymphocyte count and one dog reached 10·8%. All dogs were discharged from the hospital following their treatment. The dog with no alteration of lymphocyte count following therapy with rabbit anti-dog thymocyte serum had refractory immune mediated haemolytic anemia and was euthanised within two weeks. All other cases achieved clinical remission with immunosuppressive therapy eventually being tapered (3 of 10) or discontinued (6 of 10). Rabbit anti-dog thymocyte serum therapy might be of interest as an adjunctive therapy in refractory immune-mediated diseases and suppressed lymphocyte counts in most dogs. © 2017 British Small Animal Veterinary Association.

  8. Profound thrombocytopenia after primary exposure to eptifibatide

    Directory of Open Access Journals (Sweden)

    Nicholas B Norgard


    Full Text Available Nicholas B Norgard, Brian T BadgleyUniversity at Buffalo, School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY, USAAbstract: Eptifibatide is a glycoprotein IIb/IIIa receptor antagonist used to reduce the incidence of ischemic events in patients with acute coronary syndromes and those undergoing percutaneous coronary intervention. A minority of patients given eptifibatide develop acute, profound thrombocytopenia (<20,000 cells/mm3 within a few hours of receiving the drug. This case report discusses a patient who developed profound thrombocytopenia within hours of receiving eptifibatide for the first time. The Naranjo algorithm classified the likelihood that this patient’s thrombocytopenia was related to eptifibatide as probable. Profound thrombocytopenia is an uncommon but clinically important complication of eptifibatide. This case report emphasizes the importance of monitoring platelet counts routinely at baseline and within 2–6 hours of eptifibatide administration.Keywords: drug-induced thrombocytopenia, glycoprotein IIb/IIIa antagonists, eptifibatide, thrombocytopenia

  9. Glucocorticoid-dependent hypoadrenocorticism with thrombocytopenia and neutropenia mimicking sepsis in a Labrador retriever dog. (United States)

    Snead, Elisabeth; Vargo, Cheryl; Myers, Sherry


    Glucocorticoid-deficient hypoadrenocorticism (GDH) with immune-mediated-neutropenia (IMN) and -thrombocytopenia (IMT) were diagnosed in a 3-year-old Labrador retriever dog. Glucocorticoid-deficient hypoadrenocorticism is rare and diagnostically challenging as clinical signs and laboratory abnormalities are often nonspecific. Immune-mediated cytopenias and other autoimmune disorders, as part of an autoimmune polyglandular syndrome have been reported with hypoadrenocorticism in humans. This is the first reported case of hypoadrenocorticism and bicytopenia in a dog.

  10. Glucocorticoid-dependent hypoadrenocorticism with thrombocytopenia and neutropenia mimicking sepsis in a Labrador retriever dog


    Snead, Elisabeth; Vargo, Cheryl; Myers, Sherry


    Glucocorticoid-deficient hypoadrenocorticism (GDH) with immune-mediated-neutropenia (IMN) and -thrombocytopenia (IMT) were diagnosed in a 3-year-old Labrador retriever dog. Glucocorticoid-deficient hypoadrenocorticism is rare and diagnostically challenging as clinical signs and laboratory abnormalities are often nonspecific. Immune-mediated cytopenias and other autoimmune disorders, as part of an autoimmune polyglandular syndrome have been reported with hypoadrenocorticism in humans. This is ...

  11. Regulatory T cells in immune-mediated renal disease. (United States)

    Ghali, Joanna R; Wang, Yuan Min; Holdsworth, Stephen R; Kitching, A Richard


    Regulatory T cells (Tregs) are CD4+ T cells that can suppress immune responses by effector T cells, B cells and innate immune cells. This review discusses the role that Tregs play in murine models of immune-mediated renal diseases and acute kidney injury and in human autoimmune kidney disease (such as systemic lupus erythematosus, anti-glomerular basement membrane disease, anti-neutrophil cytoplasmic antibody-associated vasculitis). Current research suggests that Tregs may be reduced in number and/or have impaired regulatory function in these diseases. Tregs possess several mechanisms by which they can limit renal and systemic inflammatory immune responses. Potential therapeutic applications involving Tregs include in vivo induction of Tregs or inducing Tregs from naïve CD4+ T cells or expanding natural Tregs ex vivo, to use as a cellular therapy. At present, the optimal method of generating a phenotypically stable pool of Tregs with long-lasting suppressive effects is not established, but human studies in renal transplantation are underway exploring the therapeutic potential of Tregs as a cellular therapy, and if successful may have a role as a novel therapy in immune-mediated renal diseases. © 2015 Asian Pacific Society of Nephrology.

  12. Thrombocytopenia - drug induced (United States)

    Drug-induced thrombocytopenia; Immune thrombocytopenia - drug ... Drug-induced thrombocytopenia occurs when certain medicines destroy platelets or interfere with the body's ability to make enough of them. There ...

  13. Clinical observations in thrombocytopenia:

    NARCIS (Netherlands)

    M.C. Kappers-Klunne (Mies)


    textabstractWe investigated clinical and laboratory aspects in three different situations of thrombocytopenia in which an immune mechanism is active, i.e. thrombocytopenia caused by autoantibodies (thrombocytopenia induced by the anticoagulant drug heparin (HITT) and immune thrombocytopenic

  14. Immune-Mediated Diseases II Congress: summary. (United States)

    Shurin, Michael R; Smolkin, Yury S


    The remarkable progress in basic immunological research during the past 50 years can account for the emerging of medical or clinical immunology as a novel discipline, which may be defined as the application of basic immunology rules to the diagnosis, treatment, and prophylactics of patients with diseases in which immunological pathways may play an important etiological and/or pathogenetic role. The immune system has a central role not only in fighting infections, but also in many other diseases and disorders including cancer, AIDS, and organ transplantation. In addition, the immune system imbalance is responsible for primary and secondary immunodeficiencies, hypersensitive illnesses, such as asthma, dermatitis, and other allergies, as well as systemic and organ-specific autoimmune disorders, such as multiple sclerosis, lupus, rheumatoid arthritis and diabetes. Immune-mediated diseases such as autoimmune diseases and allergic diseases are important health problems in many countries. For instance, autoimmune diseases afflict up to 8% of the United States population; allergic diseases represent the sixth leading cause of chronic illness and disability in the United States, and the leading cause among children. Thus, immune-mediated diseases represent an enormous medical, social, and economical problem and require serious and instant attention from clinicians, scientists, pharmacists, and biotech professionals. The goal of the Second International Immune-Mediated Diseases (IMD) Congress was to advance medical and biomedical immunological sciences and clinical practice via the organization of multiple sessions and training courses as well as providing an environment for stimulating scientific discussions, the exchange of ideas, and consideration of novel clinical diagnostic and therapeutic approaches. Selected contributions from the participants of this Congress who are eager to share some of the academic and clinical enthusiasm are presented in this issue (and the

  15. Heparin-induced thrombocytopenia and thrombosis. (United States)

    Patel, Vipul P; Bong, Matthew; Di Cesare, Paul E


    Heparin-induced thrombocytopenia (HIT) and heparin induced thrombocytopenia with thrombosis (HITT) ar rare complications associated with use of unfractionate heparin (UFH) or low-molecular-weight heparin (LMWH) HIT is a benign clinical condition characterized by a mil drop in platelet count with no clinical significance. HIT is an immune-mediated reaction associated with a wide spread "hypercoagulable" state resulting in arterial an venous thrombosis. There is a higher incidence of HIT with UFH use than with LMWH use. Orthopedic surger patients are at higher risk for developing HITT than are patients who receive prophylactic heparin for cardiovascular surgery or medical reasons. Therapy for patients suspected of having HITT should begin with immedi ate discontinuation of heparin in any form followed by pharmacologic inhibition with thrombin (e.g., recombinant hirudin [lepirudin], argatroban, danaparoid sodium).

  16. The effect of Carica papaya leaves extract capsules on platelets count and hematocrit levels in acute febrile illness with thrombocytopenia patient

    Directory of Open Access Journals (Sweden)

    Abhishek Singhai


    Full Text Available Carica papaya leaves have been used in folk medicine for centuries. In addition to the nutritional value of its fruit, the leaves of C. papaya possess medicinal properties and are widely used in traditional medicines. This study was conducted to determine the effect of C. papaya leaves extract capsules (CPC in acute febrile illness with thrombocytopenia. An observational, prospective, uncontrolled, open label, single centre study in Indian patients. Total 80 patients were enrolled in the study. These subjects were randomized into two groups of 40, including the control and intervention groups (received two CPC three times daily. The result showed that CPC had significant increased the platelet count (p<0.05 and maintained stability of hematocrit in the normal level. Carica papaya leaf extract could be used as an additional or as a complementary drug in acute febrile illness patients with thrombocytopenia; it accelerates the increase in the platelet count and shorten the hospitalization thereby reducing the cost of hospitalization significantly.

  17. Profound thrombocytopenia after primary exposure to eptifibatide. (United States)

    Norgard, Nicholas B; Badgley, Brian T


    Eptifibatide is a glycoprotein IIb/IIIa receptor antagonist used to reduce the incidence of ischemic events in patients with acute coronary syndromes and those undergoing percutaneous coronary intervention. A minority of patients given eptifibatide develop acute, profound thrombocytopenia (eptifibatide for the first time. The Naranjo algorithm classified the likelihood that this patient's thrombocytopenia was related to eptifibatide as probable. Profound thrombocytopenia is an uncommon but clinically important complication of eptifibatide. This case report emphasizes the importance of monitoring platelet counts routinely at baseline and within 2-6 hours of eptifibatide administration.

  18. Thrombocytopenia in Pregnancy

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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



    Shilpa Anand Hakki


    BACKGROUND There is an alarming increase in the incidence of fever with thrombocytopenia especially during monsoon and peri-monsoon period. Infections with protozoa, bacteria and viruses can cause thrombocytopenia with or without disseminated intravascular coagulation. Commonly, dengue, malaria, scrub typhus and other rickettsial infections, meningococci, Leptospira and certain viral infections present as fever with thrombocytopenia. Occasionally, these patients can go on to devel...

  1. Rethinking platelet function: thrombocytopenia induced immunodeficiency in critical illness

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Johansson, Per Ingemar


    Thrombocytopenia in critical illness predicts a poor clinical outcome. Apart from its role in microvascular thrombus formation, it is widely anticipated that this association is indirect rather than causal. Emerging evidence however indicates that platelets are also immune competent cells. Like...... traditional innate immune cells, platelets are recruited immediately into injured and inflamed tissue, they release immune mediators, express and shed immunologically active membrane receptors, they interact with other immune cells and they recognize and clear pathogens. We hypothesize that thrombocytopenia...... per se results in immunodeficiency through loss of platelet-mediated immune functions, and propose that thrombocytopenia induced immunodeficiency in critical illness in part explain the negative predictive value of low or declining platelet count. We propose that rethinking the risks...

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Association of anticardiolipin, antiphosphatidylserine, anti-β2 glycoprotein I, and antiphosphatidylcholine autoantibodies with canine immune thrombocytopenia. (United States)

    Chen, Yu-Chen; Chi, Lang-Ming; Chow, Kuan-Chih; Chiou, Shiow-Her; Fan, Yi-Hsin; Ho, Shu-Peng; Hsu, Yu-Chen; Hwang, Yu-Chyi; Wu, Meng-Xing; Lee, Wei-Ming; Lin, Shiun-Long; Tsang, Chau-Loong; Mao, Frank Chiahung


    In humans, the presence of antiphospholipid antibodies (aPL) is frequently found in immune thrombocytopenia. The present study investigated whether aPL and any aPL subtypes are associated with canine thrombocytopenia, in particular, immune-mediated thrombocytopenia (immune thrombocytopenia) that usually manifests with severe thrombocytopenia. Sera were collected from 64 outpatient dogs with thrombocytopenia (Group I, platelet count 0 - 80 × 10(3)/uL), and 38 of which having severe thrombocytopenia (platelet count thrombocytopenia, n =20) or the absence of aPLT (subgroup IB, severe thrombocytopenia negative for aPLT, n =18). In addition, sera of 30 outpatient dogs without thrombocytopenia (Group II), and 80 healthy dogs (Group III) were analyzed for comparison. Indirect ELISAs were performed to compare serum levels of aPL subtypes, including anticardiolipin antibodies (aCL), antiphosphatidylserine antibodies (aPS), antiphosphatidylcholine (aPC), and anti-β2 glycoprotein I antibodies (aβ2GPI), and antiphosphatidylinositol antibodies (aPI), among different groups or subgroups of dogs. Among outpatient dogs, aCL, being highly prevalent in outpatient dogs with thrombocytopenia (63/64, 98 %), is an important risk factor for thrombocytopenia (with a high relative risk of 8.3), immune thrombocytopenia (relative risk 5.3), or severe thrombocytopenia negative for aPLT (relative risk ∞, odds ratio 19). In addition, aPS is a risk factor for immune thrombocytopenia or severe thrombocytopenia negative for aPLT (moderate relative risks around 2), whereas aPC and aβ2GPI are risk factors for immune thrombocytopenia (relative risks around 2). Of all the aPL subtypes tested here, aCL is highly associated with canine thrombocytopenia, including immune thrombocytopenia, severe thrombocytopenia negative for aPLT, and less severe thrombocytopenia. Furthermore, aPS is moderately associated with both canine immune thrombocytopenia and severe thrombocytopenia negative for a

  4. [Current treatment of primary immune thrombocytopenia]. (United States)

    Lozano, María L; Vicente, Vicente


    Primary immune thrombocytopenia, also termed immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by premature platelet destruction and impaired platelet production. Traditional treatment of ITP has predominantly consisted of immune suppression and/or modulation. However, the understanding of the immune mediated impairment of platelet production has led to the development of new treatments that target the thrombopoietin receptor, promoting formation of megakaryocytes and increasing platelet counts. Best practice for the management of ITP has not yet been established because data from comparative studies are lacking. While some disagreement might still remain among experts concerning therapy (when, who, and how should be treated), in recent years different evidence-based practice guidelines have been published to assist healthcare professionals in the diagnosis and treatment of ITP. This review describes the current treatment landscape of ITP. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  5. Genetics Home Reference: immune thrombocytopenia (United States)

    ... Facebook Twitter Home Health Conditions Immune thrombocytopenia Immune thrombocytopenia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Immune thrombocytopenia is a disorder characterized by a blood abnormality ...

  6. Pyrazinamide induced thrombocytopenia (United States)

    Kant, Surya; Verma, Sanjay Kumar; Gupta, Vaibhav; Anand, Sunish C.; Prasad, Rajendra


    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. PMID:20711377

  7. Mechanisms of conduction block in immune-mediated polyneuropathies

    NARCIS (Netherlands)

    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

  8. In vivo approaches for immune-mediated drug hypersensitivity research

    NARCIS (Netherlands)

    Kwast, L.M.


    Drug allergies, immune-mediated drug hypersensitivity reactions (IDHRs) or drug induced liver injury (DILI) are important causes of black box warnings and drug withdrawals, and thus a major problem in the development of drugs. Also drug induced liver injury Despite the high demand for preclinical

  9. Prognosis in canine idiopathic immune-mediated haemolytic anaemia

    NARCIS (Netherlands)

    Piek, Christine J.

    About 50% of dogs with idiopathic immune-mediated haemolytic anaemia (IMHA) dogs die in the first 2 weeks after diagnosis. It was shown that mortality risk is associated with the presence of hypercoagulability, inflammatory response, and liver and kidney failure. Evidence suggests that tissue

  10. Fetal thrombocytopenia : preventive strategies.

    NARCIS (Netherlands)

    Akker, Eline van den


    Intracranial haemorrhage (ICH) among term neonates is associated with neonatal death or lifelong disability. Between all the proposed aetiological mechanisms, including impairments in coagulation, hypoxic-ischemic injury and birth related trauma, thrombocytopenia seems to be the most important

  11. Thrombocytopenia and infections. (United States)

    Franchini, Massimo; Veneri, Dino; Lippi, Giuseppe


    Acquired thrombocytopenia recognizes a myriad of causes. Among these, infectious diseases play a relevant role since a low platelet count is commonplace along with other abnormal laboratory data. Areas covered: This narrative review, after a brief presentation of the possible pathogenic mechanisms, is focused on the most prevalent infections associated with thrombocytopenia, namely those attributable to hepatitis C virus (HCV), human immunodeficiency virus (HIV) and Helicobacter pylori. Expert commentary: An underlying HCV or HIV infection should always be suspected in patients at risk who present with isolated thrombocytopenia. The eradication of Helicobacter pylori is advisable in infected patients with secondary immune thrombocytopenia, because this will increase the platelet count in a substantial number of cases, thus avoiding more aggressive and prolonged treatments.

  12. Drug-induced thrombocytopenia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B


    OBJECTIVE: To analyse the clinical picture and the course of thrombocytopenia induced by non-cytotoxic drugs, and to evaluate a possible therapeutic effect of corticosteroids. METHODS: A retrospective analysis of 309 well-documented cases of drug-induced thrombocytopenia was performed. Data sources...... were reports from the files of the Danish Committee on Adverse Drug Reactions and discharge summaries. RESULTS: The median length of exposure to the offending drug, before development of thrombocytopenia, was 21 days. The median nadir platelet count was 11 x 10(9).l-1, and 74% of the patients had...... treatment was corticosteroids, which were administered in 53% of the cases. No difference in recovery between corticosteroid-treated and untreated patients was observed. No other clinical parameter affected the recovery rate. The mortality rate due to haemorrhage was 3.6%. CONCLUSION: Thrombocytopenia...

  13. How Is Thrombocytopenia Diagnosed? (United States)

    ... information about this procedure, go to the Health Topics Blood Transfusion article. Splenectomy A splenectomy is surgery to remove ... experiences with clinical research. More Information Related Health Topics Aplastic ... Thrombocytopenia Thrombotic Thrombocytopenic Purpura ...

  14. How Is Thrombocytopenia Treated? (United States)

    ... information about this procedure, go to the Health Topics Blood Transfusion article. Splenectomy A splenectomy is surgery to remove ... experiences with clinical research. More Information Related Health Topics Aplastic ... Thrombocytopenia Thrombotic Thrombocytopenic Purpura ...

  15. Living with Thrombocytopenia (United States)

    ... information about this procedure, go to the Health Topics Blood Transfusion article. Splenectomy A splenectomy is surgery to remove ... experiences with clinical research. More Information Related Health Topics Aplastic ... Thrombocytopenia Thrombotic Thrombocytopenic Purpura ...

  16. What Causes Thrombocytopenia? (United States)

    ... information about this procedure, go to the Health Topics Blood Transfusion article. Splenectomy A splenectomy is surgery to remove ... experiences with clinical research. More Information Related Health Topics Aplastic ... Thrombocytopenia Thrombotic Thrombocytopenic Purpura ...

  17. Living with Immune Thrombocytopenia (United States)

    ... information about platelet transfusions, go to the Health Topics Blood Transfusion article. Treating Infections Some infections can briefly lower ... experiences with clinical research. More Information Related Health Topics Blood ... Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Other ...

  18. Presumed immune-mediated hemolytic anemia in two foals with Rhodococcus equi infection. (United States)

    Johns, Imogen C; Desrochers, Anne; Wotman, Kathryn L; Sweeney, Raymond W


    To describe the clinical presentation, case management, and outcome in 2 foals with Rhodococcus equi infection associated with presumptive severe immune-mediated hemolytic anemia. Two foals diagnosed with R. equi pneumonia on the basis of tracheal wash cultures, thoracic radiographs, and thoracic ultrasonography were concurrently diagnosed with hemolytic anemia. Both foals required whole blood transfusions, and were treated with the antimicrobial combination of rifampin and a macrolide (eg, clarithromycin, erythromycin, or azithromycin). Dexamethasone was used to prevent further hemolysis in both foals, and to treat acute lung injury/acute respiratory distress syndrome in 1 of the foals. Both foals survived, and required prolonged antimicrobial therapy. Although extra-pulmonary disorders are commonly diagnosed in foals infected with R. equi, hemolytic anemia is rarely described. Dexamethasone is considered the treatment of choice for immune-mediated hemolytic anemia, but may be contra-indicated in foals with severe bacterial infections. In these foals, a relatively low dose and short duration of dexamethasone was utilized in an attempt to minimize immune suppression, although early discontinuation in 1 foal precipitated a second hemolytic crisis. © Veterinary Emergency and Critical Care Society 2011.

  19. Profound thrombocytopenia after primary exposure to eptifibatide


    Norgard, Nicholas; Badgley,Brian


    Nicholas B Norgard, Brian T BadgleyUniversity at Buffalo, School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY, USAAbstract: Eptifibatide is a glycoprotein IIb/IIIa receptor antagonist used to reduce the incidence of ischemic events in patients with acute coronary syndromes and those undergoing percutaneous coronary intervention. A minority of patients given eptifibatide develop acute, profound thrombocytopenia (<20,000 cells/mm3) within a few hours of receiving the drug. This c...

  20. [Serious side effects of frequently used antibiotics in childhood: biliary sludge or stones induced by ceftriaxone and thrombocytopenia induced by co-trimoxazole]. (United States)

    Voeten, M; Landstra, A M; Maseland, M H H; van Setten, P A


    Two patients, a girl and a boy, both aged 8.5 years, presented with serious side effects caused by ceftriaxone and co-trimoxazole, respectively. The first patientwas treated with ceftriaxone (100 mg/kg/day with a body weight of 35.6 kg) on suspicion of a neuroborreliosis, but developed an acute cholecystitis with cholelithiasis 3 weeks after the antibiotic had been withdrawn. He underwent a laparoscopic cholecystectomy. Ceftriaxone binds calcium in the biliary tract, forming biliary sludge or stones. The second patient developed thrombocytopenia during treatment with co-trimoxazole (58 mg/kg/day with a body weight of 25.4 kg) because of a urinary-tract infection. After discontinuation of the co-trimoxazole the thrombocytopenia resolved spontaneously. The pathophysiological mechanism involved may be either a direct toxic effect of trimethoprim or an immune-mediated reaction to sulfamethoxazole. According to current guidelines, the dosage of the drug was too high in both cases. It is important to ensure a correct dosage in children, since side effects are potentially dose-related.

  1. Thrombocytopenia in pregnancy. (United States)

    Cines, Douglas B; Levine, Lisa D


    Thrombocytopenia develops in 5% to 10% of women during pregnancy or in the immediate postpartum period. A low platelet count is often an incidental feature, but it might also provide a biomarker of a coexisting systemic or gestational disorder and a potential reason for a maternal intervention or treatment that might pose harm to the fetus. This chapter reflects our approach to these issues with an emphasis on advances made over the past 5 to 10 years in understanding and managing the more common causes of thrombocytopenia in pregnancy. Recent trends in the management of immune thrombocytopenia translate into more women contemplating pregnancy while on treatment with thrombopoietin receptor agonists, rituximab, or mycophenylate, which pose known or unknown risks to the fetus. New criteria to diagnose preeclampsia, judicious reliance on measurement of ADAMTS13 to make management decisions in suspected thrombotic thrombocytopenic purpura, new evidence supporting the efficacy and safety of anticomplement therapy for atypical hemolytic uremic syndrome during pregnancy, and implications of thrombotic microangiopathies for subsequent pregnancies are evolving rapidly. The goals of the chapter are to help the hematology consultant work through the differential diagnosis of thrombocytopenia in pregnancy based on trimester of presentation, severity of thrombocytopenia, and coincident clinical and laboratory manifestations, and to provide guidance for dealing with some of the more common and difficult diagnostic and management decisions. © 2017 by The American Society of Hematology.

  2. Thrombocytopenia in Systemic Lupus Erythematosus (United States)

    Jung, Jin-Hee; Soh, Moon-Seung; Ahn, Young-Hwan; Um, Yoo-Jin; Jung, Ju-Yang; Suh, Chang-Hee; Kim, Hyoun-Ah


    Abstract The aim of the study was to examine the clinical characteristics and prognosis according to severity of thrombocytopenia and response to treatment for thrombocytopenia in patients with systemic lupus erythematosus (SLE). We retrospectively evaluated 230 SLE patients with thrombocytopenia, and reviewed their clinical data and laboratory findings. Thrombocytopenia was defined as platelet counts under 100,000/mm3, and patients were divided into 3 thrombocytopenia groups according to severity: mild (platelet counts >50,000/mm3), moderate (>20,000/mm3, ≤50,000/mm3), and severe (≤20,000/mm3). Clinical characteristics, treatments, and prognoses were compared among the groups. Furthermore, complete remission of thrombocytopenia was defined as platelet counts >100,000/mm3 after treatment. There was no significant difference in clinical or laboratory findings among the groups according to severity of thrombocytopenia. However, hemorrhagic complications were more frequent in severe thrombocytopenia (P thrombocytopenia (odds ratio = 0.049, 95% confidence interval: 0.013–0.191, P thrombocytopenia in SLE patients can be a useful independent prognostic factor to predict survival. Moreover, complete remission of thrombocytopenia after treatment is an important prognostic factor. The severity of thrombocytopenia and response to treatment should be closely monitored to predict prognosis in SLE patients. PMID:26871854

  3. Thrombocytopenia in HIV

    African Journals Online (AJOL)


    Jun 15, 2007 ... necessary tests are done initially and the correct treatment started. ... megakaryocytes, stem cells and other immature cells in the bone marrow. .... treatment of. HIV-induced thrombocytopenia and there is a paucity of forthcoming trials on this topic since antiretrovirals have become commonly used.

  4. Thalidomide-associated thrombocytopenia

    NARCIS (Netherlands)

    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.

  5. Thrombocytopenia in HIV

    African Journals Online (AJOL)


    Jun 15, 2007 ... necessary tests are done initially and the correct treatment started. ... thrombocytopenia is prone to a more rapid acceleration of disease. ... Platelet life span is decreased in HIV-induced idiopathic thrompocytopenic purpura (ITP) and in. HIV patients without ITP. It seems as if HIV stimulates CD5+ cells.

  6. Inflammatory, immune-mediated adverse reactions related to soft tissue dermal fillers. (United States)

    Alijotas-Reig, Jaume; Fernández-Figueras, Maria Teresa; Puig, Lluís


    An increasing number of persons seek medical solutions for esthetic indications and for diverse pathological conditions, such as malformations, trauma, or cancer. Despite manufacturers' and different authors' claims that fillers are non-immunogenic or that complications are uncommon, unwanted adverse reactions do occur. To review the literature regarding the multiple types of immune-mediated adverse reactions related to medical dermal filler injections/prosthesis. A comprehensive MEDLINE, PubMed, and Google Scholar electronic database search was performed (2000-January 2012). Selected articles published before 2000 referring to general concerns regarding the studied topic were also included. The search provided almost 300 articles. Finally, 235 studies were selected and included. All known fillers present in the market have been shown to be able to provoke early- and late-onset inflammatory adverse reactions. Their true prevalence is unknown but appears to be significant. The majority of the late-onset adverse effects are inflammatory and immune-mediated in nature. Edema, granulomas, sarcoid-like disorders, and panniculitis are the findings most commonly seen. Rarely, systemic granulomatous and autoimmune diseases, and to lesser extent acute hypersensitivity reactions can be seen. All implanted, injected, and blood-contact biomaterials trigger a wide variety of adverse reactions that may appear early or late and range from local to systemic. Most fillers act more as adjuvants than as direct T-cell activators, on a background of genetic predisposition. Their treatment has not been the subject of well-designed studies. Management of both acute and systemic reactions is often difficult and requires anti-inflammatory and occasionally immunosuppressive therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Protective Effect of Akkermansia muciniphila against Immune-Mediated Liver Injury in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Wenrui Wu


    Full Text Available Accumulating evidence indicates that gut microbiota participates in the pathogenesis and progression of liver diseases. The severity of immune-mediated liver injury is associated with different microbial communities. Akkermansia muciniphila can regulate immunologic and metabolic functions. However, little is known about its effects on gut microbiota structure and function. This study investigated the effect of A. muciniphila on immune-mediated liver injury and potential underlying mechanisms. Twenty-two C57BL/6 mice were assigned to three groups (N = 7–8 per group and continuously administrated A. muciniphila MucT or PBS by oral gavage for 14 days. Mouse feces were collected for gut microbiota analysis on the 15th day, and acute liver injury was induced by Concanavalin A (Con A, 15 mg/kg injection through the tail vein. Samples (blood, liver, ileum, colon were assessed for liver injury, systemic inflammation, and intestinal barrier function. We found that oral administration of A. muciniphila decreased serum ALT and AST and alleviated liver histopathological damage induced by Con A. Serum levels of pro-inflammatory cytokines and chemokines (IL-2, IFN-γ, IL-12p40, MCP-1, MIP-1a, MIP-1b were substantially attenuated. A. muciniphila significantly decreased hepatocellular apoptosis; Bcl-2 expression increased, but Fas and DR5 decreased. Further investigation showed that A. muciniphila enhanced expression of Occludin and Tjp-1 and inhibited CB1 receptor, which strengthened intestinal barriers and reduced systemic LPS level. Fecal 16S rRNA sequence analysis indicated that A. muciniphila increased microbial richness and diversity. The community structure of the Akk group clustered distinctly from that of mice pretreated with PBS. Relative abundance of Firmicutes increased, and Bacteroidetes abundance decreased. Correlation analysis showed that injury-related factors (IL-12p40, IFN-γ, DR5 were negatively associated with specific genera

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

    DEFF Research Database (Denmark)

    Bisgaard, H; Bønnelykke, K; Stokholm, Jacob


    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......, and certain exposures may have detrimental effects in the earliest life, but no or even beneficial effects later. The human microbiome and infections are candidates as intermediary in the interaction between the host and the environment. The evidence seems inconsistent as infections as well as particular...... 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...

  10. Genetics Home Reference: X-linked thrombocytopenia (United States)

    ... Home Health Conditions X-linked thrombocytopenia X-linked thrombocytopenia Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description X-linked thrombocytopenia is a bleeding disorder that primarily affects males. ...

  11. Malaria-induced immune thrombocytopenia

    DEFF Research Database (Denmark)

    Sørensen, P G; Mickley, H; Schmidt, K G


    On return from Liberia, a previously healthy 36-year-old man showed signs of malaria accompanied by severe haemolysis and slight thrombocytopenia. We found evidence of a platelet-associated IgG being responsible for the thrombocytopenia, inasmuch as the direct platelet suspension immunofluorescen...

  12. How I manage neonatal thrombocytopenia

    National Research Council Canada - National Science Library

    Chakravorty, Subarna; Roberts, Irene


    ...‐onset thrombocytopenia in preterm neonates (>72 h) is nearly always due to post‐natally acquired bacterial infection and/or necrotizing enterocolitis, which rapidly leads to severe thrombocytopenia (platelet count < 50 × 10 9 /l...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Immune-mediated animal models of Tourette syndrome (United States)

    Hornig, Mady; Lipkin, W. Ian


    An autoimmune diathesis has been proposed in Tourette syndrome (TS) and related neuropsychiatric disorders such as obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism and anorexia nervosa. Environmental triggers including infection and xenobiotics are hypothesized to lead to the production of brain-directed autoantibodies in a subset of genetically susceptible individuals. Although much work has focused on Group A Streptococcus (GAS), the role of this common childhood infection remains controversial. Animal model studies based on immune and autoantibody findings in TS have demonstrated immunoglobulin (Ig) deposits and stereotypic movements and related behavioral disturbances reminiscent of TS following exposure to GAS and other activators of host anti-microbial responses, soluble immune mediators and anti-GAS or anti-neuronal antibodies. Demonstration of the ability to recreate these abnormalities through passive transfer of serum IgG from GAS-immunized mice into naïve mice and abrogation of this activity through depletion of IgG has provided compelling evidence in support of the autoimmune hypothesis. Immunologically-based animal models of TS are a potent tool for dissecting the pathogenesis of this serious neuropsychiatric syndrome. PMID:23313649

  16. The Role of Histone Demethylase Jmjd3 in Immune-Mediated Aplastic Anemia (United States)


    AWARD NUMBER: W81XWH-16-1-0055 TITLE: The Role of Histone Demethylase Jmjd3 in Immune- Mediated Aplastic Anemia PRINCIPAL INVESTIGATOR: Yi...Immune- Mediated Aplastic Anemia 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0055 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Yi Zhang 5d...anemia (AA) is a condition of bone marrow failure (BMF) characterized by blood pancytopenia and BM hypoplasia. In most cases, AA is an immune- mediated

  17. Eptifibatide-Induced Thrombocytopenia--When Inhibitor Turns Killer. (United States)

    Pothineni, Naga Venkata; Watts, Thomas E; Ding, Zufeng; Dai, Yao; Deshmukh, Abhishek J


    Eptifibatide is a commonly and widely used drug for management of acute coronary syndrome and during percutaneous coronary intervention. It is usually well tolerated with no major adverse effects. We report a rare case of life-threatening thrombocytopenia secondary to eptifibatide along with a literature review of available evidence.

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

    Directory of Open Access Journals (Sweden)

    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

  19. How Is Immune Thrombocytopenia Treated? (United States)

    ... information about platelet transfusions, go to the Health Topics Blood Transfusion article. Treating Infections Some infections can briefly lower ... experiences with clinical research. More Information Related Health Topics Blood ... Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Other ...

  20. How Is Immune Thrombocytopenia Diagnosed? (United States)

    ... information about platelet transfusions, go to the Health Topics Blood Transfusion article. Treating Infections Some infections can briefly lower ... experiences with clinical research. More Information Related Health Topics Blood ... Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Other ...

  1. Peritoneal EMH in a dog with immune-mediated hemolytic anemia. (United States)

    Brenner, Karen; Pohlman, Lisa; Muldowney, Ian; Petersen, Don; Schermerhorn, Thomas


    Extramedullary hematopoiesis (EMH) is the process by which normal blood cells are produced outside the bone marrow. In humans, EMH effusions are rare and are characterized by the presence of megakaryocytes, immature erythrocytes, immature leukocytes, or combinations of those cells. To the authors' knowledge, this is the first report to describe a case of peritoneal EMH effusion in a dog. A 5 yr old castrated male shorthaired dachshund presented with a 2 day history of pigmenturia and inappetence. A complete blood count revealed regenerative anemia with marked agglutination, spherocytosis, and an acute inflammatory leukogram characterized by a neutrophilia, regenerative left shift, and monocytosis. Ultrasound-guided aspiration of peritoneal effusion yielded a sample of high nucleated cellularity predominantly composed of mature and immature neutrophils and erythroid precursor cells. The patient was diagnosed with primary immune-mediated hemolytic anemia with concurrent EMH peritoneal effusion. The following case description and discussion explore the clinical findings associated with the unusual effusion and outline the possible pathogenesis by which the EMH effusion may have arisen in the dog.

  2. Ceftazidime-induced thrombocytopenia. (United States)

    Domingo-Chiva, E; Díaz-Rangel, M; Monsalve-Naharro, J Á; Cuesta-Montero, P; Catalá-Ripoll, J V; García-Martínez, E M


    Ceftazidime is an antibiotic belonging to the group of third generation cephalosporins, frequently used in clinical practice for its broad antibacterial spectrum. A case report is presented on a 78-year-old man who entered the intensive care unit due to respiratory failure secondary to nosocomial pneumonia in the postoperative period of a laparoscopic hepatic bisegmentectomy for a hepatocarcinoma. It required invasive mechanical ventilation and was treated with ceftazidime, developing a progressive decrease in platelet count after the onset of this drug and after re-exposure to it, not coinciding with the introduction of other drugs. The adverse reaction was reported to the Spanish pharmacosurveillance system and according to the Naranjo algorithm the causal relationship was probable. Since no case of ceftazidime-induced thrombocytopenia was found in the literature, we consider knowledge of it relevant as an adverse effect to be taken into account given its potential severity, especially when it cannot be explained by other causes. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Immune thrombocytopenia in the newborn

    Directory of Open Access Journals (Sweden)

    Murat Yurdakök


    Full Text Available The leading cause of moderate or severe thrombocytopenia in otherwise healthy appearing neonates is immune thrombocytopenia. Immune thrombocytopenia in the fetus or newborn may result from platelet alloantibodies against paternal antigens inherited by the fetus (alloimmune thrombocytopenia or platelet autoantibodies in the mother with immune thrombocytopenic purpura (ITP. Only 10% of human platelet antigen (HPA-1a negative mothers who are exposed to HPA-1a positive fetal platelets during pregnancy develop HPA-1a alloantibodies, and 30% of fetuses/neonates will develop thrombocytopenia and 20% of these cases being severe. The most serious complication of severe fetal and neonatal alloimmune thrombocytopenia (FNAIT is intracranial hemorrhage (ICH, which is detected in 10-20% of affected fetuses/neonates, with most cases occurring antenatally. ICH leads to neurological sequelae in 20%, and deaths in 5-10% cases. There is no evidence-based optimal treatment strategy. Platelet antibody titration in maternal plasma is not helpful for decision-making. The best indicator for current pregnancy is the outcome of the previous pregnancy. The risk of recurrence among subsequent HPA-positive sibling is close to 100% where the previous sibling was affected with antenatal intracranial ICH. The risk of ICH becomes higher with more severe and earlier onset in each subsequent pregnancy. Serial platelet counts should be obtained for the first 5-7 days of delivery to keep the platelet counts higher than 30,000/µL without active bleeding and higher that 50,000-100,000/µL with active bleeding. Intravenous immunoglobulin (IVIG is not alternative to platelet transfusions, since platelet counts don’t rise before 24-48 h. In platelet- transfused patients, IVIG can be given to potentially prolong the survival of the incompatible platelets. ITP during pregnancy is not considered a serious risk of perinatal bleeding, but may cause a moderate thrombocytopenia in neonate

  4. Neonatal thrombocytopenia: etiology, management and outcome

    NARCIS (Netherlands)

    Gunnink, Suzanne F.; Vlug, Roos; Fijnvandraat, Karin; van der Bom, Johanna G.; Stanworth, Simon J.; Lopriore, Enrico


    Thrombocytopenia is a very common hematological abnormality found in newborns, especially in preterm neonates. Two subgroups can be distinguished: early thrombocytopenia, occurring within the first 72 hours of life, and late thrombocytopenia, occurring after the first 72 hours of life. Early

  5. Preoperative predictors of thrombocytopenia in Caesarean delivery ...

    African Journals Online (AJOL)

    Preoperative predictors of thrombocytopenia in Caesarean delivery: is routine platelet count testing necessary? ... moderate thrombocytopenia. All asymptomatic patients, including those who were HIV positive, had platelet counts > 70 000/μl. Keywords: Caesarean delivery, HIV, obstetrics, pregnancy, thrombocytopenia ...

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Neonatal thrombocytopenia and platelets transfusion

    Directory of Open Access Journals (Sweden)

    Anil K Gupta


    Full Text Available Background: Neonates often develop thrombocytopenia at some time during hospital stay. Platelet transfusion are frequently given to them and are likely to result in unnecessary transfusion. Material and Methods: Thus, we analyzed thrombocytopenia in neonates, its prevalence, and relationship if any, between clinical condition and platelet transfusion in neonates, which would have been helpful in developing guidelines and/or protocols for platelet transfusion (and reducing the donor exposure in neonates. Results: A total of 870 neonates who were admitted in Neonatal Intensive Care Unit (NICU with various morbidities had platelets count done; of these, 146 (16.7% neonate revealed thrombocytopenia. Discussion: Low birth weight babies (P 0.009 and babies born with mother having hypertension (P 0.04 showed significant thrombocytopenia. Neonates with intrauterine growth retardation (IUGR diagnosed during antenatal screening showed lower platelet count (P 0.022. Neonates having associated illness, such as sepsis, gastrointestinal, and respiratory problems, and on vasopressor drugs were found to be associated with low platelet count. Conclusion: In our study, 16.40% of thrombocytopenic neonates required platelet transfusion either alone or with other blood component during their stay in NICU.

  8. Phosphate- or Citrate-Buffered Tirofiban Versus Unfractionated Heparin and its Impact on Thrombocytopenia and Clinical Outcomes in Patients With Acute Coronary Syndrome: A Post Hoc Analysis From the PRISM Trial. (United States)

    Adamo, Marianna; Ariotti, Sara; Costa, Francesco; Curello, Salvatore; Moschovitis, Aris; de Vries, Ton; White, Harvey D; Windecker, Stephan; Valgimigli, Marco


    The aim of this study was to investigate whether the 2 tirofiban formulations tested in the early and late phases of the PRISM (Platelet Receptor Inhibitor in Ischemic Syndrome Management) trial might differ with respect to risk for thrombocytopenia and clinical outcomes compared with unfractionated heparin (UFH). Citrate-buffered tirofiban is currently marketed as brand-name drug. However, tirofiban has recently been promoted in some countries as a generic drug with different formulations, such as phosphate-buffered product. In the PRISM trial 3,232 patients were randomly assigned to receive tirofiban or UFH. In the early phase, 879 patients were allocated to phosphate-buffered tirofiban and 874 patients to UFH group. After a protocol amendment due to a study drug instability report, citrate-buffered tirofiban replaced the phosphate-buffered formulation. Therefore, in the late phase, 737 and 742 patients were treated with citrate-buffered tirofiban and UFH, respectively. The relative risk for thrombocytopenia (nadir thrombocytopenia (nadir Thrombocytopenia was associated with a 5- to 10-fold increased risk for TIMI (Thrombolysis In Myocardial Infarction) bleeding and a 2-fold increased risk for net adverse cardiovascular events. Phosphate-buffered tirofiban, currently marketed as a generic drug, is associated with a higher rate of thrombocytopenia with a potentially increased risk for adverse clinical outcomes compared with citrate-buffered tirofiban. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. Immune-mediated hemolytic anemia: understanding the nemesis. (United States)

    McCullough, Sheila


    IMHA is one of the most common causes of anemia in small animals. Although treatment may be rewarding, many patients do not respond adequately to glucocorticoids alone and require additional immunosuppressive therapy. Some patients may succumb to acute severe anemia and die within the first few weeks of treatment; even if they survive, relapses may occur. IMHA is the nemesis; as our understanding of this disease increases and treatment options expand, it is hoped that survival rates will finally improve.

  10. Management of thrombocytopenia in advanced liver disease (United States)

    Gangireddy, VGR; Kanneganti, PC; Sridhar, S; Talla, S; Coleman, T


    Thrombocytopenia (defined as a platelet count thrombocytopenia (platelet count Thrombocytopenia can negatively impact the care of patients with severe liver disease by potentially interfering with diagnostic and therapeutic procedures. Multiple factors can contribute to the development of thrombocytopenia including splenic platelet sequestration, immunological processes, bone marrow suppression by chronic viral infection, and reduced levels or activity of the hematopoietic growth factor thrombopoietin. The present review focuses on the etiologies and management options for severe thrombocytopenia in the setting of advanced liver disease. PMID:25222481

  11. Iron deficiency thrombocytopenia: a case report. (United States)

    Shah, Binay Kumar; Shah, Tara


    To describe a rare case of thrombocytopenia secondary to iron deficiency. A 34-year-old woman presented with severe microcytic hypochromic anemia and thrombocytopenia. Her ferritin was 1 ng/dl. A diagnosis of iron deficiency anemia and thrombocytopenia was made and the patient was treated with packed red blood cell transfusion and intravenous iron. Thrombocytopenia rapidly improved to normal. This case showed that iron deficiency should be considered as a cause of thrombocytopenia in the appropriate setting after ruling out common causes. Copyright © 2011 S. Karger AG, Basel.

  12. Low-level light treatment ameliorates immune thrombocytopenia (United States)

    Yang, Jingke; Zhang, Qi; Wu, Mei X.


    Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP.

  13. Cytomegalovirus-associated encephalomyelitis in an immunocompetent adult: a two-stage attack of direct viral and delayed immune-mediated invasions. case report. (United States)

    Daida, Kensuke; Ishiguro, Yuta; Eguchi, Hiroto; Machida, Yutaka; Hattori, Nobutaka; Miwa, Hideto


    It is clinically rare to find cytomegalovirus (CMV)-associated encephalomyelitis in immunocompetent adults. Here, we present the case of an adult patient who developed acute transverse myelitis that was followed by immune-mediated disseminated encephalomyelitis. A 38-year-old man developed acute paraplegia with paresthesia below the level of the T7-8 dermatome. Both brain and spinal cord MRIs performed at admission appeared normal. Corticosteroid therapy was initiated, with the later addition of high-dose intravenous immunoglobulins. After polymerase chain reaction analysis indicated the presence of CMV DNA in his cerebrospinal fluid (CSF), anti-viral therapy was added. Forty days after symptom onset, despite an initial positive response to this therapy, he developed dysarthria and truncal ataxia. Repeated magnetic resonance imaging scans demonstrated progressively expanding lesions involving not only the spinal cord but also the cerebral white matter, suggestive of extensive immune-mediated demyelination involving the central nervous system (CNS), as is observed in acute disseminated encephalomyelitis (ADEM). This case report underscores the importance of careful patient observation following the initial diagnosis of a CMV-associated CNS infection, such as transverse myelitis, on the possibility that post-infectious ADEM may appear.

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

    DEFF Research Database (Denmark)

    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...

  15. High intravascular tissue factor expression in dogs with idiopathic immune-mediated haemolytic anaemia

    NARCIS (Netherlands)

    Piek, C.J.; Brinkhof, B.; Teske, E.; Rothuizen, J.; Dekker, A.; Penning, L.C.


    A high mortality occurs in dogs with idiopathic immune-mediated haemolytic anaemia (IMHA) during the first 2 weeks after the diagnosis. The aim of this study was to investigate the inflammatory response and coagulation abnormalities in dogs with IMHA in relation to the prognosis and to establish the

  16. A case of non-regenerative immune-mediated anemia treated by ...

    African Journals Online (AJOL)

    A 12-year-old female Shih Tzu dog was referred with diarrhea. Hematological examination indicated severe nonregenerative anemia. Bone marrow aspiration smears and core biopsy specimens revealed normal bone marrow. Based on those results, non-regenerative immune mediated anemia was diagnosed. The dog ...

  17. Hypocholesterolemia and nonregenerative, suspected immune-mediated, anemia: Report of 3 canine cases. (United States)

    Robbins, Rachel; Viviano, Katrina R


    This report describes hypocholesterolemia in 3 dogs with nonregenerative, suspected immune-mediated anemias. Common causes of hypocholesterolemia were ruled out, raising suspicion for a mechanistic link between anemia and hypocholesterolemia in dogs. As observed in humans with concurrent anemia and hypocholesterolemia, cholesterol concentrations increased to within the reference interval once the dogs' anemia resolved.

  18. Pathophysiology of immune-mediated demyelinating neuropathies--Part II: Neurology. (United States)

    Franssen, Hessel; Straver, Dirk C G


    In the second part of this review we deal with the clinical aspects of immune-mediated demyelinating neuropathies. We describe the relationship between pathophysiology and symptoms and discuss the pathophysiology of specific disease entities, including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, anti-myelin-associated glycoprotein neuropathy, and POEMS syndrome. Copyright © 2013 Wiley Periodicals, Inc.

  19. Houttuynia cordata modulates oral innate immune mediators: potential role of herbal plant on oral health. (United States)

    Satthakarn, S; Chung, W O; Promsong, A; Nittayananta, W


    Epithelial cells play an active role in oral innate immunity by producing various immune mediators. Houttuynia cordata Thunb (H. cordata), a herbal plant found in Asia, possesses many activities. However, its impacts on oral innate immunity have never been reported. The aim of this study was to determine the effects of H. cordata extract on the expression of innate immune mediators produced by oral epithelial cells. Primary gingival epithelial cells (GECs) were treated with various concentrations of the extract for 18 h. The gene expression of hBD2, SLPI, cytokines, and chemokines was measured using quantitative real-time RT-PCR. The secreted proteins in the culture supernatants were detected by ELISA or Luminex assay. Cytotoxicity of the extract was assessed using CellTiter-Blue Assay. H. cordata significantly induced the expression of hBD2, SLPI, IL-8, and CCL20 in a dose-dependent manner without cytotoxicity. The secreted hBD2 and SLPI proteins were modulated, and the levels of IL-2, IL-6, IL-8, and IFN-γ were significantly induced by the extract. Our data indicated that H. cordata can modulate oral innate immune mediators. These findings may lead to the development of new topical agents from H. cordata for the prevention and treatment of immune-mediated oral diseases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Thrombocytopenia in Small for Gestational Age Infants (United States)

    Christensen, Robert D.; Baer, Vickie L.; Henry, Erick; Snow, Gregory L.; Butler, Allison; Sola-Visner, Martha C.


    BACKGROUND Thrombocytopenia is common among small for gestational age neonates (SGA; birth weight thrombocytopenia are unclear, including the incidence, typical nadir, duration, association with preeclampsia, mechanism, and risk of death. METHODS Using nine years of multihospital records we studied SGA neonates with ≥2 platelet counts thrombocytopenia in 31% (905 of 2891) of SGA neonates vs. 10% of non-SGA matched-controls (pthrombocytopenia (DIC, early-onset sepsis, ECMO). This group had a 65% mortality rate. The remaining 803 did not have an obvious cause for their thrombocytopenia. We termed these the “thrombocytopenia of SGA”. They had a mortality rate of 2% (phalf of the patients. Severely SGA neonates (thrombocytopenia duration (ptripled. Thrombocytopenia was associated with SGA status more so than with the diagnosis of maternal preeclampsia. CONCLUSIONS SGA neonates with clearly recognized varieties of thrombocytopenia have a high mortality rate. In contrast the “thrombocytopenia of SGA” is a hyporegenerative condition of moderate severity and two weeks duration, associated with evidence of intrauterine hypoxia, and associated with a low mortality rate. PMID:26216323

  1. Thrombocytopenia in the pediatric burn patient. (United States)

    Warner, Petra; Fields, Amanda L; Braun, Lindsay C; James, Laura E; Bailey, J Kevin; Yakuboff, Kevin P; Kagan, Richard J


    Thrombocytopenia is initially seen in patients with burn injury as a transient occurrence during the first week after injury. Subsequent decreases occur later in the course of treatment and are commonly due to sepsis, dilutional effects, and medication exposure. Although studies have demonstrated that thrombocytopenia in the critically ill patients is associated with a worse prognosis, there is limited literature as to the significance of thrombocytopenia in the pediatric burn patients. In this study, the authors evaluate the prognostic implications of thrombocytopenia in the pediatric burn patients. They performed a 5-year retrospective chart of patients aged 18 years or younger with burns >20% TBSA admitted to their institution. Data collected included patient demographics, burn etiology and %TBSA involvement, length of stay, pertinent laboratory values, and in-hospital morbidity and mortality. Of the 187 patients studied, thrombocytopenia occurred in 112 patients. Eighty-two percent demonstrated thrombocytopenia within the first week of injury and 18% demonstrated additional episodes of thrombocytopenia after this time. A reactive thrombocytosis occurred in 130 (70%) patients. The incidence of thrombocytopenia could not be attributed to age, gender, or burn etiology. However, patients with thrombocytopenia were more likely to have inhalation injury and extensive TBSA involvement than those without (P thrombocytosis in the pediatric burn patient is associated with increased mortality risk and is influenced by the extent of burn, inhalation injury, and the development of sepsis.

  2. Eptifibatide-induced thrombocytopenia: with thrombosis and disseminated intravascular coagulation immediately after left main coronary artery percutaneous coronary angioplasty. (United States)

    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.

  3. The Differential Diagnosis of Thrombocytopenia in Pregnancy. (United States)

    Bergmann, Frauke; Rath, Werner


    Thrombocytopenia is, after anemia, the second most common abnormality of the complete blood count in pregnancy, with a reported frequency of 6.6% to 11.2%. It has many causes. Thrombocytopenia should be diagnostically evaluated as early as possible in pregnancy, so that the obstetrical management can be accordingly planned to minimize harm to the mother and child. As the various underlying diseases share clinical features and laboratory findings, the differential diagnosis is often a difficult interdisciplinary challenge. In this article, we review pertinent literature (2000-January 2015) retrieved by a selective search in PubMed. Gestational thrombocytopenia is the most common type, accounting for 75% of cases, followed by severe pre-eclampsia/HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count) in 15-22% and autoimmune thrombocytopenia (ITP) in 1-4%. Gestational thrombocytopenia and ITP differ in the bleeding history, the severity of thrombocytopenia, the frequency of neo - natal thrombocytopenia, and the rate of normalization of the platelet count after delivery. The HELLP syndrome and rarer microangiopathic hemolytic anemias (e.g., thrombotic thrombocytopenic purpura) can be differentiated on the basis of their main clinical features, such as hypertension/proteinuria and upper abdominal pain, the severity of hemolysis and thrombocytopenia, the degree of transaminase elevation, and the rapidity of postpartum remission of the clinical and laboratory findings. A stepwise diagnostic procedure should be followed to distinguish further causes, e.g., to differentiate thrombocytopenia due to infection, autoimmune disease, or drugs from thrombocytopenia due to a rare hereditary disease. The early interdisciplinary evaluation of thrombocytopenia in pregnancy is a prerequisite for the optimal care of the mother and child. The development of evidence-based recommendations for interdisciplinary management should be a goal for the near future.

  4. The Role of Innate Lymphoid Cells in Immune-Mediated Liver Diseases (United States)

    Liu, Meifang; Zhang, Cai


    Innate lymphoid cells (ILCs) are a recently identified group of innate immune cells lacking antigen-specific receptors that can mediate immune responses and regulate tissue homeostasis and inflammation. ILCs comprise group 1 ILCs, group 2 ILCs, and group 3 ILCs. These ILCs usually localize at mucosal surfaces and combat pathogens by the rapid release of certain cytokines. However, the uncontrolled activation of ILCs can also lead to damaging inflammation, especially in the gut, lung, and skin. Although the physiological and pathogenic roles of ILCs in liver diseases have been attracting increasing attention recently, there has been no systematic review regarding the roles of ILCs in immune-mediated liver diseases. Here, we review the relationships between the ILC subsets and their functions in immune-mediated liver diseases, and discuss their therapeutic potential based on current knowledge about the functional roles of these cells in liver diseases. PMID:28659927

  5. Immune mediated protection in multiple sclerosis: A role for neurokines in oligodendrocyte survival and macrophage modulation


    Hellings, Niels; Hendriks, Jerome; CARMANS, Sofie; Slaets, Leen; Dumont, Debora; Vanderlocht, Joris; Stinissen, Piet


    In multiple sclerosis (MS), immune mediated destruction of the myelin sheath, oligodendrocytes and axons leads to irreversible neurological deficits. Recent data show that immune responses in the central nervous system (CNS) may also confer protective effects. We recently demonstrated that autoreactive T cells and macrophages produce leukemia inhibitory factor (LIF), a member of the IL-6 family of neurokines. CD4+ T cells from relapsing remitting MS-patients show a reduced LIF production. Sti...

  6. Disseminated Scedosporium prolificans infection in a Labrador retriever with immune mediated haemolytic anaemia

    Directory of Open Access Journals (Sweden)

    Amanda Taylor


    Full Text Available Disseminated scedosporiosis is rare in dogs and is usually reported in German Shepherds with suspected heritable immunodeficiency. This is the first report of disseminated scedosporiosis due to Scedosporium prolificans in a Labrador retriever dog that was receiving immunosuppressive drug therapy for treatment of immune-mediated haemolytic anaemia. Despite cessation of immunosuppressive medications and an initial response to aggressive treatment with voriconazole and terbinafine the dog developed progressive disease with neurological signs necessitating euthanasia six months from diagnosis.

  7. Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Melo, Rossana C.N., E-mail: [Laboratory of Cellular Biology, Department of Biology, ICB, Federal University of Juiz de Fora, UFJF, Rua José Lourenço Kelmer, Juiz de Fora, MG 36036-900 (Brazil); Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 943, Boston, MA 02215 (United States); Weller, Peter F. [Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 943, Boston, MA 02215 (United States)


    Electron microscopy (EM)-based techniques are mostly responsible for our current view of cell morphology at the subcellular level and continue to play an essential role in biological research. In cells from the immune system, such as eosinophils, EM has helped to understand how cells package and release mediators involved in immune responses. Ultrastructural investigations of human eosinophils enabled visualization of secretory processes in detail and identification of a robust, vesicular trafficking essential for the secretion of immune mediators via a non-classical secretory pathway associated with secretory (specific) granules. This vesicular system is mainly organized as large tubular-vesicular carriers (Eosinophil Sombrero Vesicles – EoSVs) actively formed in response to cell activation and provides a sophisticated structural mechanism for delivery of granule-stored mediators. In this review, we highlight the application of EM techniques to recognize pools of immune mediators at vesicular compartments and to understand the complex secretory pathway within human eosinophils involved in inflammatory and allergic responses. - Highlights: • Application of EM to understand the complex secretory pathway in human eosinophils. • EM techniques reveal an active vesicular system associated with secretory granules. • Tubular vesicles are involved in the transport of granule-derived immune mediators.

  8. Thrombocytopenia in Children Infected with the Human ...

    African Journals Online (AJOL)

    Background: Human immunodeficiency virus (HIV) infection is associated with a myriad of hematopoietic abnormalities, of which thrombocytopenia (TP) is a common complication. The condition could predispose to life-threatening hemorrhage. Objectives: To determine the prevalence of thrombocytopenia among HIV- ...

  9. Gestational thrombocytopenia among pregnant Ghanaian women ...

    African Journals Online (AJOL)

    Background: Thrombocytopenia is a common problem during pregnancy that is not frequently detected and as a result is often inappropriately managed. The obvious concern with thrombocytopenia during pregnancy is the risk of significant bleeding at the time of delivery. This study was designed to determine the ...

  10. Genetics Home Reference: dyserythropoietic anemia and thrombocytopenia (United States)

    ... A main feature of this condition is a type of anemia called dyserythropoietic anemia, which is characterized by a ... and thrombocytopenia can usually be predicted by the type of GATA1 gene ... anemia and thrombocytopenia occur separately, each of the conditions ...

  11. Drug-induced immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Janković Slobodan


    Full Text Available Drug-induced immune thrombocytopenia (DIIT is a consequence of destruction or inadequate activation of platelets by immune system provoked by current or previous presence of a drug in human organism. Annual incidence of DIIT is around 1-2 cases on 100,000 inhabitants. There are four proposed mechanisms behind the DIIT: (1 binding of drug-dependent antibodies for platelets; (2 blocking of fibrinogen binding for glycoprotein receptors IIb/IIIa; (3 drug-independent antibodies against platelets; and (4 creation of drug-antibody immune complexes which further activate platelets and lead to thromboses. Regardless of the DIIT mechanism, it is of paramount importance that physicians think of drugs as possible causes when they encounter low platelet count in a patient. Key therapeutic measure is discontinuation of the offending drug, while platelet transfusion is used only after extreme drop of platelet count. Heparin-induced thrombocytopenia is an exception, because it also requires treatment of thromboses with direct thrombin inhibitors.

  12. Thrombocytopenia (United States)

    ... doctor will begin looking for its cause. Medical History Your doctor may ask about factors that can affect your platelets, such as: The medicines you take, including over-the-counter medicines and herbal remedies, and whether you drink beverages that contain ...

  13. Thrombocytopenia (United States)

    ... doctor will begin looking for its cause. Medical History Your doctor may ask about factors that can ... of bleeding. Two examples of such medicines are aspirin and ibuprofen. These medicines may thin your blood ...

  14. Prevalence of Vector-Borne Pathogens in Southern California Dogs With Clinical and Laboratory Abnormalities Consistent With Immune-Mediated Disease. (United States)

    Kidd, L; Qurollo, B; Lappin, M; Richter, K; Hart, J R; Hill, S; Osmond, C; Breitschwerdt, E B


    Studies investigating the prevalence of vector-borne pathogens in southern California dogs are limited. Occult infections might be misdiagnosed as idiopathic immune-mediated disease. (1) To determine the prevalence of vector-borne pathogens in southern California dogs with compatible clinical findings using PCR and serologic panels and (2) to determine whether testing convalescent samples and repeating PCR on acute samples using the same and different gene targets enhance detection. Forty-two client-owned dogs with clinical signs of vector-borne disease presenting to specialty practices in San Diego County. Combined prospective and retrospective observational study. Forty-two acute and 27 convalescent samples were collected. Acute samples were prospectively tested for antibodies to Rickettsia, Ehrlichia, Bartonella, Babesia, Borrelia, and Anaplasma species. PCR targeting Ehrlichia, Babesia, Anaplasma, hemotropic Mycoplasma, and Bartonella species was also performed. Retrospectively, convalescent samples were tested for the same organisms using serology, and for Ehrlichia, Babesia, Anaplasma, and Bartonella species using PCR. Acute samples were retested using PCR targeting Ehrlichia and Babesia species. Evidence of exposure to or infection with a vector-borne pathogen was detected in 33% (14/42) of dogs. Ehrlichia and Babesia species were most common; each was identified in 5 dogs. Convalescent serologic testing, repeating PCR, and using novel PCR gene targets increased detection by 30%. Repeated testing using serology and PCR enhances detection of infection by vector-borne pathogens in dogs with clinical signs of immune-mediated disease. Larger prevalence studies of emerging vector-borne pathogens in southern California dogs are warranted. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  15. Thrombocytopenia associates with the severity of inflammation and variables reflecting capillary leakage in Puumala Hantavirus infection, an analysis of 546 Finnish patients. (United States)

    Outinen, Tuula K; Laine, Outi K; Mäkelä, Satu; Pörsti, Ilkka; Huhtala, Heini; Vaheri, Antti; Mustonen, Jukka


    Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) in humans. Hantavirus infections are characterized by thrombocytopenia. Our objective was to assess the association of thrombocytopenia with disease severity in HFRS induced by Puumala hantavirus (PUUV). Altogether 546 patients treated for acute serologically confirmed PUUV infection during 1982-2013 at Tampere University Hospital, Finland, were examined. Blood platelet count was determined daily and analysed in relation to different variables reflecting disease severity. The patients were divided into two groups according to the minimum platelet count: severe thrombocytopenia (thrombocytopenia (≥69 × 10(9)/L). Thrombocytopenia (platelet count thrombocytopenia had longer stay (8 versus 7 days, p = 0.002) and greater weight gain (2.8 versus 2.0 kg, p thrombocytopenia (comparisons between medians). Maximum creatinine concentration did not differ between patients with or without severe thrombocytopenia (median 235 versus 214 μmol/L, p = 0.217). The severity of thrombocytopenia associates with the degree of inflammation and variables reflecting capillary leakage, but not with the severity of acute kidney injury in PUUV infected Finnish patients.

  16. Central and peripheral nervous system immune mediated demyelinating disease after allogeneic hemopoietic stem cell transplantation for hematologic disease. (United States)

    Delios, Anna Maria; Rosenblum, Marc; Jakubowski, Ann A; DeAngelis, Lisa M


    Immune mediated demyelinating disease (IMDD) after allogeneic hemopoietic stem cell transplant (HSCT) is rare and its etiology unclear. In this retrospective study, we identified patients who underwent HSCT between January 1992 and December 2010 and had IMDD post transplant. A total of 1,484 patients received HSCT and 7 (0.5 %) suffered from IMDD; five were men, and the median age was 54 years (range, 29-64 years). HSCT treated acute myeloid leukemia (n = 5), myelodysplastic syndrome (n = 1), and Waldenström macroglobulinemia (n = 1). All received an HLA matched donor graft, related (6), unrelated (1); from the bone marrow (1), peripheral blood stem cell (6); and T-cell depleted, ex vivo (6) or in vivo (1). The median time from transplant to neurologic symptoms was 120 days (range, 60-390 days). Three had acute demyelinating encephalomyelitis (ADEM), three acute inflammatory demyelinating polyradiculopathy (AIDP) and one autonomic neuropathy. Four of six patients tested had hemopoietic mixed chimerism prior to neurologic symptoms and low CD4(+) T-cell counts, median 76 (15-500 cells/μL). Two patients had simultaneous systemic graft versus host disease (GVHD). Two patients with ADEM had a spinal cord or brain biopsy which revealed demyelination. No patients had a viral etiology identified in the cerebrospinal fluid. Patients were treated with IV immunoglobulin, high dose steroids and/or rituximab. Five patients had a significant recovery. Response to immune modulators suggests an immune-based etiology. The incidence of de novo autoimmune disease after HSCT for hematological diseases is rare and may be difficult to differentiate from GVHD.

  17. [The clinical pathological characteristics and follow-up of 4 cases of immune-mediated necrotizing myopathy]. (United States)

    Zhang, Yingshuang; Sun, Aping; Chen, Lu; Dong, Rongfang; Zhong, Yanfeng; Fan, Dongsheng


    To characterize the clinical, electrophysiology and neuropathological features of 4 cases with immune-mediated necrotizing myopathy (IMNM). 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). 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. IMNM is characterized by heterogeneity at disease onset, severity and iInvolvement 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.

  18. Serum C-reactive protein concentrations in Nova Scotia Duck Tolling Retrievers with immune-mediated rheumatic disease. (United States)

    Bremer, Hanna Dorotea; Hillström, Anna; Kånåhols, Malin; Hagman, Ragnvi; Hansson-Hamlin, Helene


    Nova Scotia Duck Tolling Retrievers (NSDTRs) are a dog breed often affected by immune-mediated rheumatic disease (IMRD), a disorder characterised by chronic stiffness and joint pain. Most, but not all, dogs with IMRD, have antinuclear antibodies (ANA), which are also commonly present in the autoimmune disease systemic lupus erythematosus (SLE). The clinical and diagnostic findings of IMRD indicate that it is an SLE-related disorder. C-reactive protein (CRP), an acute phase protein, is a quantitative marker of inflammation for many diseases and is used for diagnosing and monitoring systemic inflammation in both humans and dogs. However, in human SLE, CRP concentrations are often elevated but correlate poorly with disease activity; they can be low in individual patients with active disease. The aim of the study was to investigate CRP in a group of NSDTRs with the SLE-related disorder IMRD. The hypothesis was that CRP concentrations would be increased in dogs with IMRD compared to healthy dogs, but that the increase would be mild. Serum CRP concentrations were measured in 18 IMRD-affected NSDTRs and 19 healthy control NSDTRs using two different canine-specific CRP assays. Dogs with IMRD and ANA had higher CRP concentrations than the control dogs, but the concentrations were below the clinical decision limit for systemic inflammation for most of the IMRD dogs. These results indicate that CRP concentrations were increased in dogs with IMRD and ANA, but the increase was mild, similar to what has been observed in human SLE.

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

    NARCIS (Netherlands)

    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

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

    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Immune Thrombocytopenia in a Child with Neuroblastoma

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    Hasan Tarkan Ikizoglu


    Full Text Available Thrombocytopenia is a frequent finding in patients with solid tumors. It is usually caused by bone marrow infiltration or by myelosuppression due to anticancer therapy; however immune thrombocytopenia (ITP associated with solid tumors is rare. Neuroblastoma is the most common extracranial solid tumor in children. Here we report the case of a two-year-nine-month-old patient with adrenal neuroblastoma who presented with ITP. Paraneoplastic ITP was considered in the differential diagnosis. Bone marrow infiltration and other causes of thrombocytopenia were excluded and the patient was treated with intravenous immunoglobulin and tumor resection. Platelet count increased rapidly after surgery and complete remission of ITP was achieved.

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

    DEFF Research Database (Denmark)

    Madsen, Caroline B; Lavrsen, Kirstine; Steentoft, Catharina


    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...... 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...

  4. Clinical and immunological studies in thrombocytopenia

    NARCIS (Netherlands)

    Veenhoven, Willem Adriaan


    In this thesis some of the problems concerning etiology and diagnosis of thrombocytopenia are studied. Special attention is paid to the detection of platelet antibodies and their significance in Werlhof's disease. ... Zie: Summary and conclusions

  5. Intravenous immunoglobulin for neonatal isoimmune thrombocytopenia.


    Derycke, M.; Dreyfus, M; Ropert, J C; Tchernia, G


    An infant with severe, isoimmune thrombocytopenia secondary to maternal anti-Pla 1 immunisation was treated successfully by intravenous gammaglobulin (400 mg/kg per day for five days). This treatment compared with Pla 1 negative platelet transfusions is discussed.

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

    NARCIS (Netherlands)

    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

  7. Investigation of corneal autoantibodies in horses with immune mediated keratitis (IMMK). (United States)

    Braus, B K; Miller, I; Kummer, S; Kleinwort, K J H; Hirmer, S; Hauck, S M; McMullen, R J; Kerschbaumer, M; Deeg, C A


    Immune mediated keratitis (IMMK) is primarily a non-ulcerative keratitis in horses causing intermittent ocular pain, eventually resulting in visual impairment. Affected horses typically respond to immunomodulatory treatment. However, the underlying cause of the disease remains enigmatic. The current study was undertaken to investigate the presence of autoantibodies in horses with immune mediated keratitis. Using 28 horses with IMMK and 27 healthy controls screening for serum autoantibodies against the corneal proteome using indirect immunofluorescence, one-dimensional (1DE) and two-dimensional electrophoresis (2DE) with subsequent western blot analysis was performed followed by mass spectrometric identification of bands or spots of interest. Indirect immunofluorescence did not reveal a difference in immune response towards corneal proteins between healthy horses and those with IMMK. Using western blot analysis some horses affected by IMMK (4/28) showed a single band (1D) or a single spot (2DE) (5/28) not detected in healthy controls. The corresponding spot was identified as maspin (SERPINB5), a protein responsible for the inhibition of corneal vascularisation, cell migration and cell adhesion to the extracellular matrix. Tests with a recombinant human protein commercially available did not verify blot findings, but the human protein may not be fully cross-reactive. Still, maspin might play a role in some cases of equine IMMK. Further research is needed to clarify the etiology of this disease. Copyright © 2017. Published by Elsevier B.V.

  8. Statin-associated immune-mediated myopathy: biology and clinical implications. (United States)

    Christopher-Stine, Lisa; Basharat, Pari


    In the last 6 years, our understanding of statin-associated myopathy expanded to include not only a toxic myopathy with limited and reversible side-effects but also an autoimmune variety in which statins likely induce an autoimmune myopathy that is both associated with a specific autoantibody and responsive to immunosuppression and immune modulation. This review widens the reader's understanding of statin myopathy to include an autoimmune process. Statin-associated immune-mediated myopathy provides an example of an environmental trigger (statins) directly implicated in an autoimmune disease associated with a genetic predisposition as well as potential risk factors including concomitant diseases and specific statins. Given a median exposure to statins of 38 months, providers should be aware that anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) myopathy may occur even after several years of statin exposure. It is important for the reader to understand the clinical presentation of statin-associated immune-mediated myopathy and the difference in its clinical presentation to that of statins as direct myotoxins. Prompt recognition of such an entity allows the clinician to immediately stop the offending agent if it has not already been discontinued as well as to recognize that statin rechallenge is not a likely option, and that prompt treatment with immunosuppression and/or immunomodulation is usually of enormous benefit to the patient in restoring muscle strength and physical function. VIDEO ABSTRACT.

  9. Preterm Birth Affects the Risk of Developing Immune-Mediated Diseases

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    Sybelle Goedicke-Fritz


    Full Text Available Prematurity affects approximately 10% of all children, resulting in drastically altered antigen exposure due to premature confrontation with microbes, nutritional antigens, and other environmental factors. During the last trimester of pregnancy, the fetal immune system adapts to tolerate maternal and self-antigens, while also preparing for postnatal immune defense by acquiring passive immunity from the mother. Since the perinatal period is regarded as the most important “window of opportunity” for imprinting metabolism and immunity, preterm birth may have long-term consequences for the development of immune-mediated diseases. Intriguingly, preterm neonates appear to develop bronchial asthma more frequently, but atopic dermatitis less frequently in comparison to term neonates. The longitudinal study of preterm neonates could offer important insights into the process of imprinting for immune-mediated diseases. On the one hand, preterm birth may interrupt influences of the intrauterine environment on the fetus that increase or decrease the risk of later immune disease (e.g., maternal antibodies and placenta-derived factors, whereas on the other hand, it may lead to the premature exposure to protective or harmful extrauterine factors such as microbiota and nutritional antigen. Solving this puzzle may help unravel new preventive and therapeutic approaches for immune diseases.

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

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    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.

  11. Aqueous immune mediators in malignant uveal melanomas in comparison to benign pigmented intraocular tumors. (United States)

    Usui, Yoshihiko; Tsubota, Kinya; Agawa, Tsuyoshi; Ueda, Shunichiro; Umazume, Kazuhiko; Okunuki, Yoko; Kezuka, Takeshi; Yamakawa, Naoyuki; Goto, Hiroshi


    To examine the usefulness of measuring immune mediators in aqueous humor samples for differentiating malignant uveal melanoma from benign pigmented intraocular tumors. Thirteen eyes of 13 patients with uveal melanoma were studied, and 13 eyes of 13 patients with benign pigmented intraocular tumors served as controls. Undiluted samples of aqueous humor were collected, and a cytometric bead array was used to determine the aqueous humor concentrations of 35 immune mediators comprising 14 interleukins (IL), interferon-γ, interferon-γ-inducible protein-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated on activation normal T cell expressed and secreted, monokine induced by interferon-γ, basic fibroblast growth factor, Fas ligand, granzyme A, granzyme B, eotaxin, interferon-inducible T-cell alpha chemoattractant, fractalkine, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, vascular endothelial growth factor, angiogenin, tumor necrosis factor-α, lymphotoxin-α, and CD40L. Aqueous humor levels of angiogenin, IL-8, and MCP-1 were significantly higher in eyes with malignant melanoma than in those with benign tumors (p melanoma from benign pigmented intraocular tumors, and may be a useful adjunct to histomorphology, diagnostic imaging, and other biomarkers for the diagnosis and appropriate clinical management of malignant uveal melanoma.

  12. Reactivation of hepatitis B virus during targeted therapies for cancer and immune-mediated disorders. (United States)

    Viganò, Mauro; Serra, Giuseppe; Casella, Giovanni; Grossi, Glenda; Lampertico, Pietro


    Targeted therapies have gained popularity in the treatment of several oncologic and immune-mediated diseases. Immunosuppression caused by these drugs has been associated to reactivation of hepatitis B virus (HBV) in both hepatitis B surface antigen (HBsAg) positive patients (overt infection) and HBsAg negative/anti-hepatitis B core antigen (anti-HBc) positive carriers (resolved infection), leading to premature discontinuation of therapy and potentially fatal hepatitis. This review summarizes the evidence of HBV reactivation in patients with overt or resolved HBV infection undergoing targeted therapies for cancer or immune-mediated disorders, providing recommendations for the management of these patients. The risk of HBV reactivation relies on the immunosuppressive potency and duration of these therapies, the underlying disease and the virological patient's profile. However, HBV reactivation is preventable by screening for HBV markers in all patients scheduled to receive targeted therapies, assessing the virological profile and patient's clinical state, followed by appropriate antiviral treatment or prophylaxis in those patients at high risk of HBV reactivation. Close monitoring of HBV carriers at low risk of reactivation is warranted with the aim to start antiviral therapy as soon as HBV reactivates.

  13. Anemia hemolítica imunomediada não regenerativa em um cão Nonregenerative immune-mediated hemolytic anemia in a dog

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    Leonardo Pinto Brandão


    Full Text Available Quadros hemolíticos não eritrorregenerativos são descritos em cães e podem ser decorrentes de doença medular primária, bem como, da destruição dos precursores eritróides medulares por imunoglobulinas. Um cão macho, de três anos de idade, sem raça definida, foi atendido no Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo apresentando sinais de anemia hemolítica aguda arregenerativa. Após a instituição de terapia imunossupressora (prednisona, houve remissão da hemólise sem, no entanto, sinais de eritrorregeneração. No décimo dia de tratamento, o mielograma demonstrou discreta hipoplasia e displasia eritróide, descartando a possibilidade de aplasia medular. Associou-se ciclofosfamida e azatioprina ao tratamento, tendo havido resposta eritrorregenerativa e recuperação dos valores hematológicos. A ocorrência deste caso de anemia hemolítica não eritrorregenerativa deve servir como alerta para a ocorrência desta condição mórbida, como também, da importância da utilização do mielograma como método auxiliar no diagnóstico de anemias arregenerativas.Nonregenerative forms of immune-mediated hemolytic anemia has been describe in dogs and are attributed to bone marrow diseases or immune-mediated destruction of erythroid progenitors. A 3-year-old, male mongrel dog was received at the Veterinary Hospital of the Faculdade of Medicina Veterinária e Zootecnia da Universidade de São Paulo (USP, Brazil showing signs of acute hemolytic anemia without erythroregeneration. After immunosuppressive therapy (prednisone the hemolysis was suppressed but the dog didn’t show hematologic signs of erythroid response. On the 10th day after treatment a bone marrow aspiration was performed and signs of hypoplasia and mild erythroid cell dysplasia were the main features observed, which could exclude the suspicious of marrow aplasia. After the addiction of cyclophosphamide and

  14. Influence of maternal age, gestational age and fetal gender on expression of immune mediators in amniotic fluid


    Weissenbacher Tobias; Laubender Rüdiger P; Witkin Steven S; Gingelmaier Andrea; Schiessl Barbara; Kainer Franziskus; Friese Klaus; Jeschke Udo; Dian Darius; Karl Katrin


    Abstract Background Variations in cytokine and immune mediator expression patterns in amniotic fluid due to gestational age, maternal age and fetal gender were investigated. Findings Amniotic fluid samples were obtained from 192 women, 82 with a mid-trimester amniocentesis (median gestational age 17 weeks) and 110 with a caesarean section not in labor (median gestational age 39 weeks). Amniotic fluid was screened by commercial ELISAs for the TH1/TH2/TH17 cytokines and immune mediators IL-1 be...

  15. Coexistence of Cushing syndrome from functional adrenal adenoma and Addison disease from immune-mediated adrenalitis. (United States)

    Colucci, Randall; Jimenez, Rafael E; Farrar, William; Malgor, Ramiro; Kohn, Leonard; Schwartz, Frank L


    A 56-year-old woman presented with an incidental adrenal adenoma and physical examination findings that included moderate obesity, a slight cervicothoracic fat pad ("buffalo hump"), increased supraclavicular fat pads, and white abdominal striae. Biochemical workup revealed elevated levels of 24-hour urinary free cortisol but normal serum morning cortisol and suppressed levels of corticotropin, suggestive of adrenal-dependent Cushing syndrome. The resected adrenal gland revealed macronodular cortical hyperplasia with a dominant nodule. Other findings included an absent cortisol response to corticotropin stimulation, presence of serum anti-21-hydroxylase antibodies, and mononuclear cell infiltration--consistent with adrenalitis. The findings represent, to the authors' knowledge, the first known case of a patient with coexistent functional cortisol-secreting macronodular adrenal tumor resulting in Cushing syndrome and immune-mediated adrenalitis resulting in Addison disease.

  16. Pseudo-hypoproteinemia in a hyperbilirubinemic dog with immune-mediated hemolytic anemia. (United States)

    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. © 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.

  17. Biology of anti-TNF agents in immune-mediated inflammatory diseases: therapeutic implications. (United States)

    Levy, Roger A; Guzman, Renato; Castañeda-Hernández, Gilberto; Martinez-Vazquez, Manuel; Damian, Guilherme; Cara, Carlos


    Biologics are increasingly being used to modify the course of immune-mediated inflammatory diseases. Some main agents are monoclonal antibodies and a fusion-protein that target TNF. This group includes adalimumab, infliximab, certolizumab pegol, golimumab and etanercept. Although the efficacy of anti-TNFs is supported by numerous randomized clinical trials, their pharmacokinetics depend on many factors, in particular immunogenicity, which can cause marked and rapid clearance and a consequent decrease in efficacy. Kinetics involve receptors that recognize the Fc fragment of the antibody and are responsible for various processes. Pharmacological advances permit optimizing the pharmacokinetics of anti-TNFs. In this review, we examine the kinetics of anti-TNF biologics, and consequent therapeutic implications, and overview some latest developments in the field. First draftsubmitted: 17 May 2016; Accepted for publication: 15 September2016; Published online: 14 October 2016.

  18. Biologic Therapy in Immune Mediated Inflammatory Disease: Basic Science and Clinical Concepts. (United States)

    Molinelli, E; Campanati, A; Ganzetti, G; Offidani, A


    During the last decades, the advent of biological therapies has revolutionized the management of several immune-mediated inflammatory disorders, as inflammatory bowel diseases, autoimmune arthritis and psoriasis, which significantly impact both quality of life and health care economics. Biological therapies currently available can be divided into two main categories: the tumor necrosis factor-α antagonists (infliximab, adalimumab, etanercept, golimumab, certolizumab pegol) and interleukin 12/23 monoclonal antibodies (ustekinumab). Biologics, reducing TNFα bioavailability or inhibiting proximal regulators of inflammatory cascade, represent an established therapeutic strategy of inflammatory autoimmune diseases, with remarkable efficacy and a safety profile that is extensively examined and monitored. The biology and the immunological effects of TNFα, IL-12, IL-23 and related signalling pathways are accurately summarized. The dosing regimens, methods of administration, pharmacodynamics profiles, and side effects of the currently licensed TNFα antagonists and IL12/IL23 inhibitor are discussed in detail.

  19. Molecular tracking of antigen-specific T cell clones in neurological immune-mediated disorders (United States)

    Muraro, Paolo A.; Wandinger, Klaus-Peter; Bielekova, Bibiana; Gran, Bruno; Marques, Adriana; Utz, Ursula; McFarland, Henry F.; Jacobson, Steve; Martin, Roland


    Summary T cells recognizing self or microbial antigens may trigger or reactivate immune-mediated diseases. Monitoring the frequency of specific T cell clonotypes to assess a possible link with the course of disease has been a difficult task with currently available technology. Our goal was to track individual candidate pathogenic T cell clones, selected on the basis of previous extensive studies from patients with immune-mediated disorders of the CNS, including multiple sclerosis, HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/ TSP) and chronic Lyme neuroborreliosis. We developed and applied a highly specific and sensitive technique to track single CD4+ and CD8+ T cell clones through the detection and quantification of T cell receptor (TCR) α or β chain complementarity-determining region 3 transcripts by real-time reverse transcriptase (RT)-PCR. We examined the frequency of the candidate pathogenic T cell clones in the peripheral blood and CSF during the course of neurological disease. Using this approach, we detected variations of clonal frequencies that appeared to be related to clinical course, significant enrichment in the CSF, or both. By integrating clono-type tracking with direct visualization of antigen-specific staining, we showed that a single T cell clone contributed substantially to the overall recognition of the viral peptide/MHC complex in a patient with HAM/ TSP. T cell clonotype tracking is a powerful new technology enabling further elucidation of the dynamics of expansion of autoreactive or pathogen-specific T cells that mediate pathological or protective immune responses in neurological disorders. PMID:12477694

  20. Serum and cerebrospinal fluid immune mediators in children with autistic disorder: a longitudinal study. (United States)

    Pardo, Carlos A; Farmer, Cristan A; Thurm, Audrey; Shebl, Fatma M; Ilieva, Jorjetta; Kalra, Simran; Swedo, Susan


    The causes of autism likely involve genetic and environmental factors that influence neurobiological changes and the neurological and behavioral features of the disorder. Immune factors and inflammation are hypothesized pathogenic influences, but have not been examined longitudinally. In a cohort of 104 participants with autism, we performed an assessment of immune mediators such as cytokines, chemokines, or growth factors in serum and cerebrospinal fluid (n = 67) to determine potential influences of such mediators in autism. As compared with 54 typically developing controls, we found no evidence of differences in the blood profile of immune mediators supportive of active systemic inflammation mechanisms in participants with autism. Some modulators of immune function (e.g., EGF and soluble CD40 ligand) were increased in the autism group; however, no evidence of group differences in traditional markers of active inflammation (e.g., IL-6, TNFα, IL-1β) were observed in the serum. Further, within-subject stability (measured by estimated intraclass correlations) of most analytes was low, indicating that a single measurement is not a reliable prospective indicator of concentration for most analytes. Additionally, in participants with autism, there was little correspondence between the blood and CSF profiles of cytokines, chemokines, and growth factors, suggesting that peripheral markers may not optimally reflect the immune status of the central nervous system. Although the relatively high fraction of intrathecal production of selected chemokines involved in monocyte/microglia function may suggest a possible relationship with the homeostatic role of microglia, control data are needed for further interpretation of its relevance in autism. These longitudinal observations fail to provide support for the hypothesized role of disturbances in the expression of circulating cytokines and chemokines as an indicator of systemic inflammation in autism., NCT

  1. Rapamycin is highly effective in murine models of immune-mediated bone marrow failure. (United States)

    Feng, Xingmin; Lin, Zenghua; Sun, Wanling; Hollinger, Maile K; Desierto, Marie J; Keyvanfar, Keyvan; Malide, Daniela; Muranski, Pawel; Chen, Jichun; Young, Neal S


    Acquired aplastic anemia, the prototypical bone marrow failure disease, is characterized by pancytopenia and marrow hypoplasia. Most aplastic anemia patients respond to immunosuppressive therapy, usually with anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In this study, we tested efficacy of rapamycin as a new or alternative treatment in mouse models of immune-mediated bone marrow failure. Rapamycin ameliorated pancytopenia, improved bone marrow cellularity, and extended animal survival in a manner comparable to the standard dose of cyclosporine. Rapamycin effectively reduced Th1 inflammatory cytokines interferon-γ and tumor necrosis factor-α, increased the Th2 cytokine interleukin-10, stimulated expansion of functional regulatory T cells, eliminated effector CD8+ T cells (notably T cells specific to target cells bearing minor histocompatibility antigen H60), and preserved hematopoietic stem and progenitor cells. Rapamycin, but not cyclosporine, reduced the proportion of memory and effector T cells and maintained a pool of naïve T cells. Cyclosporine increased cytoplasmic nuclear factor of activated T-cells-1 following T-cell receptor stimulation, whereas rapamycin suppressed phosphorylation of two key signaling molecules in the mammalian target of rapamycin pathway, S6 kinase and protein kinase B. In summary, rapamycin was an effective therapy in mouse models of immune-mediated bone marrow failure, acting through different mechanisms to cyclosporine. Its specific expansion of regulatory T cells and elimination of clonogenic CD8+ effectors support its potential clinical utility in the treatment of aplastic anemia. Copyright© 2017 Ferrata Storti Foundation.

  2. Central and peripheral nervous system immune-mediated demyelinating disease after allogeneic hematopoietic stem cell transplantation. (United States)

    Stefanou, M I; Bischof, F


    We aimed to evaluate clinical and diagnostic features of central and peripheral immune-mediated demyelinating disease (CPID) in allogeneic hematopoietic stem cell transplantation (aHSCT) recipients. CPID refers to the late-onset, immune-mediated neurological complications following aHSCT, when other frequent differential diagnoses have been ruled out, and when symptoms and signs of systemic GvHD manifestations are absent. Case records at the University of Tuebingen, between 2001 and 2015, were screened to identify patients with CPID after aHSCT. Seven patients who developed CPID after aHSCT were identified. The average time interval from aHSCT until onset of CPID was 2.6 (±2.8) years (mean±SD). The most prevalent manifestations of CPID were optic neuritis and/or myelitis and polyneuropathy. Cerebrospinal fluid analyses involved elevated protein concentration and lymphocytic pleocytosis, while oligoclonal bands in CSF, but not in serum, were detected in 28% of cases. Aquaporin-4-antibodies were consistently absent. MRI studies showed features suggestive of demyelination processes, with cerebral and/or spinal cord white-matter involvement, and features compatible with cerebral vasculitis. Corticosteroids, Immunoglobulins, Cyclophosphamide, Rituximab and Interferon beta-1a showed marginal treatment responses, whereas plasma exchange resulted in marked clinical improvement in two treated patients. A chronic disease-course with persisting neurological deficits was prevalent. CPID may comprise a rare complication of aHSCT, which manifests as optic neuritis and/or myelitis and is accompanied by sensorimotor polyneuropathy. A concomitant systemic manifestation of GvHD is not mandatory for CPID diagnosis. Usually, CPID exhibits a chronic, persisting disease course. Thus, clinical awareness is required, as early diagnosis and aggressive treatment may be prognostically advantageous. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Relationship between recurrent vulvovaginal candidosis and immune mediators in vaginal fluid. (United States)

    Weissenbacher, Tobias M; Witkin, Steven S; Gingelmaier, Andrea; Scholz, Christoph; Friese, Klaus; Mylonas, Ioannis


    Recurring vulvovaginal candidosis (RVVC) is a common vaginal discharge, affecting 75% of all women at least once in their life. In 5% of these women, this infection is recurring. Recent studies have focused on determining the importance of vaginal-associated immunity. To investigate the effects of immune mediators and the probability of an immune defect as well as localized allergic responses due to candida, we examined the cytokines IL-4, IL-5, IL-13 as well as prostaglandin E(2) (PgE(2)), candida-specific IgE and total-IgE in patients with a clinical diagnosis of RVVC. In 104 symptomatic and 41 asymptomatic patients, regarding clinical symptoms of RVVC, vaginal fluids were measured by ELISA for the immune mediators IL-4, IL-5, IL-13, PgE(2), candida-specific IgE and total-IgE. Polymerase chain reactions as well as culture were used for candida detection. Concerning IL-5, IL-13 and total-IgE no statistically significant difference was found. Those women with a history of RVVC and who were currently symptomatic had elevated concentrations of IL-4 (pvaginal fluids compared to women with no clinical symptoms. Those three interleukins showed no significant differences between symptomatic patients who were positive or negative for Candida albicans or Candida glabrata. These findings indicate that women with clinical vaginal symptoms have a localized vaginal immunosuppression which might be the cause of their symptoms. Greatly elevated vaginal PgE(2) levels can be a consequence of a localized allergic response. An allergic reaction to candida components may be the cause of the allergic response in those women with high levels of candida-specific IgE. In women with elevated PgE(2), treatment with an antihistamine or prostaglandin synthesis inhibitor might be beneficial.

  4. Alleviating anemia and thrombocytopenia in myelofibrosis patients. (United States)

    Cervantes, Francisco; Correa, Juan-Gonzalo; Hernandez-Boluda, Juan Carlos


    Anemia and thrombocytopenia are frequent clinical manifestations of myelofibrosis as well as important prognostic factors of the disease. Concerning the treatment of anemia, the first step should be the correction of reversible contributing factors, such as possible iron, folate and vitamin B12 deficiency. Then, treatment options include erythropoiesis stimulating agents, androgens, immunomodulating drugs, corticosteroids, and splenectomy. Anemia responses may also be observed in some patients treated with JAK inhibitors. However, most patients eventually fail to such therapies and become transfusion dependent. Some of the aforementioned therapies can also improve thrombocytopenia, but the responses are usually observed in patients with moderate platelet count decrease. Allogeneic hematopoietic stem cell transplantation, the only curative treatment of myelofibrosis, can be an alternative for selected patients with cytopenias who are refractory to conventional therapies. However, for the majority of patients, the management of anemia and severe thrombocytopenia remains an unmet need.

  5. Hepatitis and thrombocytopenia: markers of dengue mortality. (United States)

    Krishnamoorthy, Smitha; Bhatt, Arun N; Mathew, Celine Thalappillil; Ittyachen, Abraham M


    Dengue fever is of great concern to public health in India as it contributes significantly to the burden of healthcare. The aim of our study was to measure mortality in dengue and its association with hepatitis and thrombocytopenia. Our study was performed in a tertiary care setting in the state of Kerala in southern India. Adult patients admitted in the year 2013 were included. Among 1308 confirmed dengue patients, the mortality rate was 1.76%. Hepatitis and thrombocytopenia were present in over 80% of all patients, but severe hepatitis was seen in 11.4% and severe thrombocytopenia in 9.3%. These were markers of fatal outcome. Other factors significantly associated with mortality were age >60 years, male sex, diabetes and the presence of any co-morbidity.

  6. Genetics Home Reference: thrombocytopenia-absent radius syndrome (United States)

    ... Email Facebook Twitter Home Health Conditions TAR syndrome Thrombocytopenia-absent radius syndrome Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Thrombocytopenia-absent radius (TAR) syndrome is characterized by the ...

  7. Mononeuritis multiplex in acquired amegakaryocytic thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Firosh Khan


    Full Text Available Mononeuritis multiplex involves inflammation of two or more nerves, typically in unrelated parts of the body. It has been well described in bleeding disorders like idiopathic thrombocytopenic purpura (ITP and Hemophilia. Acquired amegakaryocytic thrombocytopenia (AAT is a bleeding diathesis characterized by thrombocytopenia but with reduced number of megakaryocytes in the bone marrow, as against ITP. Though AAT is a well described entity, peripheral nervous system manifestations have not been described so far. We report a young man who has presented with bleeding diathesis and mononeuritis multiplex due to AAT. The mechanism of development of mononeuritis multiplex and treatment options are discussed.


    Directory of Open Access Journals (Sweden)

    Ravindra Kumar Sudarsi


    Full Text Available BACKGROUND AND OBJECTIVES The aetiologies of thrombocytopenia are diverse. Various studies on thrombocytopenia done in the past have related to specific aetiologies. This study attempts to determine the common aetiologies of thrombocytopenia and bleeding manifestations in adult patients admitted under Department of Medicine. METHODS Patients older than 18 years of age who were first time found to have thrombocytopenia at admission under Department of Medicine between 1st October 2014 and 31st September 2015 were followed up during their stay in hospital and the diagnosis made, bleeding manifestations, and requirement of platelet transfusions were recorded. RESULTS 200 patients were included in the study. Dengue/dengue-like fever was the diagnosis made in 30% of patients followed by malaria (22%, undiagnosed aetiology (9%, HELLP (6%, snake bite and sepsis 5% each, ITP and megaloblastic anaemia 4.5% each, haematological malignancies and CTD 3% each, and other rare causes formed the rest. Bleeding secondary to thrombocytopenia was seen in 36 patients. 22.2% of them were diagnosed as dengue, 19.4% had malaria, 16.7% had ITP, 11.1% of patients with HELLP, 8.3% each had malignancy and undiagnosed viral infections, 5.6% each had CTD and MDS, and 2.8% had aplastic anaemia. Dengue fever was responsible for thrombocytopenia-related bleeding in 8 cases, ITP in 6 cases, malaria in 7 cases, HELLP in 4 cases, malignancy and undiagnosed aetiology 3 cases each, CTD and MDS 2 cases each, and aplastic anaemia in 1 case. The common bleeding manifestations were GIT (Melena, petechial rash, and menorrhagia occurring in 33.3%, 22.2% and 13.8% of total number of patients respectively. 30.5% of those who had bleeding secondary to thrombocytopenia had platelet count <5000/μL. 68.7% of those with platelet count <5000/μL had bleeding manifestation. 36.6% of those who had bleeding secondary to thrombocytopenia had platelet count 5,000-10,000/μL. 65.0% of those with

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

    NARCIS (Netherlands)

    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,

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

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

    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

  13. Isolated Thrombocytopenia in Thai Children: Etiology and Result of Bone Marrow Aspiration Study

    Directory of Open Access Journals (Sweden)

    Kamon Phuakpet


    Full Text Available Background: Isolated thrombocytopenia (IT refers to an entity of low platelet count without abnormalities of other lineages. Previous studies revealed that the main cause of IT in children without atypical features i.e. hepa- tosplenomegaly or adenopathy was immune thrombocytopenia (ITP, while acute leukemia and aplastic anemia (AA were other possible causes. However, there was no previous study in Thailand to identify the cause of IT. Objective: To study the bone marrow aspiration (BMA result in Thai children with IT and to identify the cause of IT in Thai children. Methods: This was a retrospective chart review of children younger than 15 years old with IT who were diag- nosed at Siriraj Hospital during January 1996 to December 2010. All patients had BMA to identify the cause of thrombocytopenia. Demographic data, clinical manifestation, laboratory results including BMA finding, diagnosis and initial treatment were collected and analyzed. Results: One hundred and twenty-nine patients were enrolled to the study. All patients had normal or increased megakaryocytes in their bone marrow, and none of them had more than 5% of blast cells. Most patients (97.7% were diagnosed as acute ITP while 2.3% were diagnosed with neonatal alloimmune thrombocytopenia. None of the patients had acute leukemia or AA. Conclusion: The BMA result of most patients in this study was compatible to that of ITP, that is none of the patients had acute leukemia or AA. The most common cause of IT in Thai children is acute ITP. This result sug- gested that BMA in children with IT before starting treatment is not necessary.

  14. Use of mycophenolate mofetil to treat immune-mediated skin disease in 14 dogs - a retrospective evaluation. (United States)

    Ackermann, Amanda L; May, Elizabeth R; Frank, Linda A


    Mycophenolate mofetil (MMF) is a lymphocytotoxic immunosuppressive agent used in human and companion animal medicine for the treatment of immune-mediated disease. Mycophenolate mofetil is reported to have reduced myelotoxicity and hepatotoxicity when compared to azathioprine. It was hypothesized that treatment with MMF as a secondary agent with glucocorticoids would be effective in treating immune-mediated skin disease. In addition, adverse effects associated with the drug are reported. Fourteen dogs from a hospital population diagnosed with immune-mediated skin disease. A retrospective review of medical records from 2010 to 2015 was used to identify dogs with immune-mediated skin disease that were treated with MMF. All dogs were treated with MMF (mean dose 14.7 mg/kg twice daily) in conjunction with glucocorticoids. Ten of 14 cases showed positive results, with complete remission in eight cases and partial remission in two cases. Mean time to remission was 5.7 weeks. Therapy was discontinued in one case (perianal fistula) due to lack of response. Adverse events were noted in six cases and included diarrhoea (n = 6), haematochezia (n = 2), vomiting (n = 3) and papilloma formation (n = 1). Therapy was discontinued in two cases with diarrhoea. Mycophenolate mofetil was discontinued in an additional case because of a diagnosis of neoplasia. All other adverse events were self-limiting or easily medically managed. No hepatotoxicity or bone marrow suppression was noted. This study supports the use of MMF as a second-line immunotherapeutic in immune-mediated skin disease in dogs. © 2016 ESVD and ACVD.

  15. Venous Thromboembolism in Patients With Thrombocytopenia

    DEFF Research Database (Denmark)

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


    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. O...

  16. Infections and Thrombocytopenia in Chronic Idiopathic ...

    African Journals Online (AJOL)

    This is a case report to study the association between episodes of thrombocytopenia and bacterial infections in a patient with chronic idiopathic thrombocytopenic purpura (ITP).The case was a 31 year old female patient, with a history of chronic ecchymosis, melaena stool and menorrhagia, who presented at the female ...

  17. Molecular mechanisms of drug-induced thrombocytopenia

    NARCIS (Netherlands)

    Burgess, J 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


    Directory of Open Access Journals (Sweden)

    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.

  19. Thrombocytopenia induced by dabigatran: two case reports. (United States)

    Kang, Hyun Goo; Lee, Seung Jae; Chung, Ji Yeon; Cheong, Jin Sung


    Vitamin K inhibitors (e.g. warfarin) and indirect thrombin inhibitors (e.g. heparin) are widely used to prevent thromboembolic disorders (e.g. myocardial infarction, venous thromboembolism, and stroke). These agents have been mainstays of anticoagulation for people older than 60 years. However, their administration is associated with a risk of bleeding and requires careful monitoring of patients. Novel oral anticoagulants (NOACs), such as dabigatran, are significantly safer in preventing thromboembolism than warfarin and heparin (sporadically causes thrombocytopenia) and are more specific for their target protein, thrombin. The major advantage of dabigatran, a direct thrombin inhibitor, is that it reversibly inhibits both free and clot-bound thrombin by tight binding affinity and the predictable pharmacodynamic effect. A few studies, however, reported that dabigatran can cause thrombocytopenia, although the underlying mechanism remains unclear. Thus, an antidote for dabigatran was developed to prevent thrombocytopenia. In this report, we discuss two cases of thrombocytopenia and purpura after dabigatran treatment. A 73-year-old man showed hemorrhagic necrotic skin lesions on his neck and right hand. He was administered dabigatran (220 mg/day) for cerebral infarction for three days and his platelet count decreased abruptly (6000/μL). This suggested that dabigatran had caused thrombocytopenia and purpura; therefore, dabigatran administration was discontinued. The results of a blood test, performed 14 days after stopping dabigatran treatment, showed that the platelet count had recovered to the normal range of more than 150,000/μL. A 75-year-old woman had taken warfarin continuously for 8 years. However, she had a new cerebral infarction. Therefore, warfarin treatment was replaced with dabigatran (300 mg/day). Her platelet count decreased (41,000/μL) significantly and dabigatran treatment was discontinued. The blood test results show that platelet counts

  20. Use of thrombopoietin receptor agonists in childhood immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    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

  1. Urothelial Cancer With Occult Bone Marrow Metastases and Isolated Thrombocytopenia

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    Ajjai Alva


    Full Text Available Bladder cancer rarely presents clinically with a myelophthisic picture from diffuse bone marrow infiltration especially in the absence of detectable skeletal metastases. A 75-year old man presented with newly diagnosed urothelial cell carcinoma of the bladder. Pathology from transurethral resection of bladder tumor demonstrated muscle-invasive disease. Pre-therapy imaging including CT abdomen/pelvis, CXR and bone scan demonstrated liver lesions concerning for metastatic disease but no skeletal metastases. Labs were notable for isolated thrombocytopenia, hypercalcemia and acute kidney injury prompting hospitalization. Hematologic work-up including bone marrow aspiration and biopsy revealed diffuse infiltration of the bone marrow by urothelial cancer. The case illustrates the importance of fully investigating otherwise unexplained clinical findings in patients with clinically localized urothelial cancer prior to curative intent surgery.

  2. Urothelial Cancer With Occult Bone Marrow Metastases and Isolated Thrombocytopenia. (United States)

    Alva, Ajjai; Davis, Elizabeth; Chinnaiyan, Arul M; Dhanasekaran, Saravana; Mehra, Rohit


    Bladder cancer rarely presents clinically with a myelophthisic picture from diffuse bone marrow infiltration especially in the absence of detectable skeletal metastases. A 75-year old man presented with newly diagnosed urothelial cell carcinoma of the bladder. Pathology from transurethral resection of bladder tumor demonstrated muscle-invasive disease. Pre-therapy imaging including CT abdomen/pelvis, CXR and bone scan demonstrated liver lesions concerning for metastatic disease but no skeletal metastases. Labs were notable for isolated thrombocytopenia, hypercalcemia and acute kidney injury prompting hospitalization. Hematologic work-up including bone marrow aspiration and biopsy revealed diffuse infiltration of the bone marrow by urothelial cancer. The case illustrates the importance of fully investigating otherwise unexplained clinical findings in patients with clinically localized urothelial cancer prior to curative intent surgery.

  3. Complete Penile Necrosis in a Patient With Heparin-induced Thrombocytopenia: A Case Report

    Directory of Open Access Journals (Sweden)

    Anne-Sophie Blais


    Full Text Available Penile necrosis is a rare condition that has been mostly described in association with diabetes mellitus and end-stage renal disease. We report an unusual case of acute penile necrosis because of heparin-induced thrombocytopenia. A 75-year-old man presented with acute renal failure and experienced cardiac complications during the hospitalization. The patient was treated twice with intravenous heparin. He developed symptoms of penile necrosis 4 days after the reintroduction of heparin. At that moment, the platelet count dropped by 61%, and the analysis of heparin-pf4 antibodies was positive for heparin-induced thrombocytopenia. The patient underwent a total penectomy and a perineal urethrostomy.

  4. The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia (United States)

    Rocha, Andreia Maria Camargos; Souza, Cláudia; Rocha, Gifone Aguiar; de Melo, Fabrício Freire; Clementino, Nelma Cristina Diogo; Marino, Marília Campos Abreu; Bozzi, Adriana; Silva, Maria Luiza; Martins Filho, Olindo Assis; Queiroz, Dulciene Maria Magalhães


    Th17 cells have been associated with immune-mediated diseases in humans but it has still not been determined whether they play a role in immune thrombocytopenia. We evaluated representative cytokines of the Th17, Th1, Th2 and Treg cell commitment in the serum of patients with chronic immune thrombocytopenia, as well as the cell source of IL-17A. Higher levels of IL-17A and Th17-related cytokines, and an increased percentage of IL-17A producing CD4+ and neutrophils were observed in patients. The levels of cytokines involved in Th1 cell commitment IFN-γ, IL-2, IL12-p70 and the percentages of Th1 cells were also increased, but IL-4 was not detected. Although the concentrations of IL-10 were higher, the levels of TGF-β were similar in both groups. In conclusion, our results point to a putative role for Th-17 cells/IL-17A cytokine in the pathogenesis of chronic immune thrombocytopenia. PMID:21972211

  5. Etiology and complications of thrombocytopenia in hospitalized medical patients. (United States)

    Fountain, Eric M; Arepally, Gowthami M


    To determine incidence, risk factors, hematologic complications, and prognostic significance of thrombocytopenia in the general medicine population, we performed a single-institutional, retrospective study of all adult patients admitted to a general medical ward from January 1st, 2014 to December 31st, 2014 with hospital-acquired thrombocytopenia. Those with moderate thrombocytopenia, defined as a platelet count nadir of 50% relative decline, were compared to those with less severe thrombocytopenia. Of the 7420 patients admitted, 465 (6.3%) developed hospital-acquired thrombocytopenia. Infection and moderate thrombocytopenia were present in 56 and 23%, respectively. Severe sepsis and antibiotic use were both associated with moderate thrombocytopenia, and proton pump inhibitor use was statistically significant in both univariate and multivariate analysis. Hematologic complications were more frequent with moderate thrombocytopenia, including frequency of HIT testing and red blood cell transfusions. Outcome metrics including transfer to an intensive care unit (OR 6.78), death during admission (OR 6.85), and length of stay (10.6 vs. 5.1 days) were all associated with moderate thrombocytopenia. Thrombocytopenia is associated with poor prognosis, and the association between moderate thrombocytopenia and proton pump inhibitor use is relatively novel and should be validated in prospective studies.

  6. Gradual thrombocytopenia induced by long-term trastuzumab exposure. (United States)

    Miarons, M; Velasco, M; Campins, L; Fernández, S; Gurrera, T; Lopez-Viaplana, L


    Unexplained thrombocytopenia is a common clinical problem, and the possibility of drug-induced thrombocytopenia must be considered. Moreover, chemotherapy agents are known to typically cause thrombocytopenia by suppressing haematopoiesis, but they can also cause immune thrombocytopenia in which the mechanism involves antibody-mediated platelet destruction. We report a case of severe thrombocytopenia related to trastuzumab administration in which the patient exhibits a slow drift downward in platelet counts with repeated cycles of trastuzumab. A 70-year-old woman received a diagnosis of breast cancer and was treated with trastuzumab. She was confirmed to have a severe trastuzumab-induced thrombocytopenia after the 4th cycle. Retreatment with trastuzumab was not attempted. Considering that trastuzumab is being increasingly used and that severe thrombocytopenia is a potentially life-threatening complication, its association must be seriously considered. © 2016 John Wiley & Sons Ltd.


    Directory of Open Access Journals (Sweden)

    Roberto Stasi


    Full Text Available Thrombocytopenia is a well recognized complication of infections, including those from hepatotropic viruses. Thrombocytopenia may actually be the only manifestation of vital hepatitis, which should therefore be considered in the differential diagnosis of primary immune thrombocytopenia (ITP. The mechanisms of thrombocytopenia associated with viral hepatitis vary widely depending on the specific infectious agent and the severity of liver disease. Most of the studies have described thrombocytopenia in association with chronic hepatitis C virus (HCV infection, the most common cause of chronic infection worldwide. Studies have shown that treatment of HCV infection often results in substantial improvement or complete recovery of the thrombocytopenia. In patients with thrombocytopenia associated with HCV-related chronic liver disease, the use of eltrombopag, a thrombopoietin receptor agonist, normalizes platelet levels thereby permitting the initiation of antiviral therapy.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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.

  10. Severe Fever with Thrombocytopenia Syndrome Virus Infection Associated with Hemophagocytic Lymphohistiocytosis as Poor Prognostic Factor (United States)

    Park, Sunmin; Kim, Juwon; Kim, Hyo Youl; Uh, Young; Kim, Young Keun


    Abstract Background Severe fever with thrombocytopenia (SFTS) is an emerging infectious disease caused by a novel bunyavirus designated SFTS virus (SFTSV) with a high fatality rate. Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated life-threatening disease triggered by infections, neoplasms and noninfectious inflammatory diseases. A few HLH associated with SFTSV were reported. According to the diagnostic criteria of HLH, 11 patients with SFTS were reviewed. Methods During last 2 years (2015–2016), 11 SFTS patients were diagnosed at the Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, South Korea. Clinical features were analyzed using diagnostic criteria of 2004-HLH trial. We described if the prognosis of SFTSV-infected patients was associated with clinical features of HLH. Results Of 11 patients, four patients were fulfillled the diagnostic criteria of 2004-HLH trial (five of eight criteria). Two patients were fulfilled the four criteria. Five patients were fulfilled three or less criteria. Three of six patients who fulfilled four or more criteria were died. There was no mortality in five patients who fulfilled three or less criteria. Hemophagocytosis in bone marrow (BM) was observed in all six patients who were taken BM study. Conclusion In SFTS, HLH was severe clinical feature and it might be associated with poor prognosis. Disclosures All authors: No reported disclosures.

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

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    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.

  12. Immune-Mediated and Hypoxia-Regulated Programs: Accomplices in Resistance to Anti-angiogenic Therapies. (United States)

    Croci, Diego O; Mendez-Huergo, Santiago P; Cerliani, Juan P; Rabinovich, Gabriel A


    In contrast to mechanisms taking place during resistance to chemotherapies or other targeted therapies, compensatory adaptation to angiogenesis blockade does not imply a mutational alteration of genes encoding drug targets or multidrug resistance mechanisms but instead involves intrinsic or acquired activation of compensatory angiogenic pathways. In this article we highlight hypoxia-regulated and immune-mediated mechanisms that converge in endothelial cell programs and preserve angiogenesis in settings of vascular endothelial growth factor (VEGF) blockade. These mechanisms involve mobilization of myeloid cell populations and activation of cytokine- and chemokine-driven circuits operating during intrinsic and acquired resistance to anti-angiogenic therapies. Particularly, we focus on findings underscoring a role for galectins and glycosylated ligands in promoting resistance to anti-VEGF therapies and discuss possible strategies to overcome or attenuate this compensatory pathway. Finally, we highlight emerging evidence demonstrating the interplay between immunosuppressive and pro-angiogenic programs in the tumor microenvironment (TME) and discuss emerging combinatorial anticancer strategies aimed at simultaneously potentiating antitumor immune responses and counteracting aberrant angiogenesis.

  13. Monocyte scintigraphy in rheumatoid arthritis: the dynamics of monocyte migration in immune-mediated inflammatory disease.

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    Rogier M Thurlings

    Full Text Available BACKGROUND: Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA, a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man. METHODS/PRINCIPAL FINDINGS: We developed a technique that enabled us to analyze the migration of labelled autologous monocytes in RA patients using single photon emission computer tomography (SPECT. We isolated CD14+ monocytes by CliniMACS in 8 patients and labeled these with technetium-99m (99mTc-HMPAO. Monocytes were re-infused into the same patient. Using SPECT we calculated that a very small but specific fraction of 3.4 x 10(-3 (0.95-5.1 x 10(-3 % of re-infused monocytes migrated to the inflamed joints, being detectable within one hour after re-infusion. CONCLUSIONS/SIGNIFICANCE: The results indicate monocytes migrate continuously into the inflamed synovial tissue of RA patients, but at a slow macrophage-replacement rate. This suggests that the rapid decrease in synovial macrophages that occurs after antirheumatic treatment might rather be explained by an alteration in macrophage retention than in monocyte influx and that RA might be particularly sensitive to treatments targeting inflammatory cell retention.

  14. The protective effects of extra virgin olive oil on immune-mediated inflammatory responses. (United States)

    Casas, Rosa; Estruch, Ramon; Sacanella, Emilio


    The increasing interest in the Mediterranean diet (MeDiet) hinges on the relevant role it plays in inflammatory diseases. Several clinical, epidemiological and experimental evidences suggest that consumption of the MeDiet reduces the incidence of certain pathologies related to oxidative stress, chronic inflammation and immune system diseases such as cancer, atherosclerosis and cardiovascular disease (CVD). These reductions can be partially attributed to extra virgin olive oil (EVOO) consumption which has been described as a key bioactive food because of its high nutritional quality and its particular composition of fatty acids, vitamins and polyphenols. Indeed, the beneficial effects of EVOO have been linked to its fatty acid composition, which is very rich in monounsaturated fatty acids (MUFA), and has moderate saturated and polyunsaturated fatty acids (PUFA). The current knowledge available on the beneficial effects of EVOO and its phenolic compounds, specifically its biological properties and antioxidant capacity against immune-mediated inflammatory responses (atherosclerosis, rheumatoid arthritis, diabetes, obesity, cancer, inflammatory bowel disease or neurodegenerative disease, among others) in addition to its potential clinical applications. The increasing body of studies carried out provides compelling evidence that olive polyphenols are potential candidates to combat chronic inflammatory states. Copyright© Bentham Science Publishers; For any queries, please email at

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

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    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.

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

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    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.

  17. AAO: Autoimmune and Autoinflammatory (Disease) in Otology: What is New in Immune-Mediated Hearing Loss. (United States)

    Vambutas, Andrea; Pathak, Shresh


    Autoinflammatory diseases are a family of immune-mediated, rare diseases, some of which, exhibit sensorineural hearing loss (SNHL), suggesting potentially similar mechanisms of molecular pathogenesis between autoinflammatory-mediated hearing loss and autoimmune inner ear disease (AIED) may exist. The purpose of this review is to compare the clinical features of autoimmune and autoinflammatory diseases that affect hearing, discuss the limitations of our knowledge, and highlight potential new disease mechanisms and therapeutics. Pubmed Literature Review; Google Scholar Literature review. A focused comparison of AIED with a number of autoinflammatory diseases that manifest with sensorineural hearing loss was performed. The pathogenesis of these diseases is reviewed in the context of the innate and adaptive immune system, cytokine expression and genetic polymorphisms. AIED, since first described by Cogan and Lehnhardt and first clinically characterized by McCabe, has remained an enigmatic disease, with limited advances in both new diagnostics and new therapeutics. Since the discovery of autoinflammatory diseases, a number of systemic autoimmune diseases have either been re-classed as autoinflammatory diseases or identified to have features of autoinflammatory disease. AIED has clinical features of both autoimmune and autoinflammatory disease. It is critical that autoinflammatory diseases be correctly identified, as failure to do so may result in systemic amyloidosis and kidney damage.

  18. Immunological HCV-Associated Thrombocytopenia: Short Review

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    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.

  19. Anti-IL-23 and Anti-IL-17 Biologic Agents for the Treatment of Immune-Mediated Inflammatory Conditions. (United States)

    Frieder, Jillian; Kivelevitch, Dario; Haugh, Isabel; Watson, Ian; Menter, Alan


    Advancements in the immunopathogenesis of psoriasis have identified interleukin (IL)-23 and IL-17 as fundamental contributors in the immune pathways of the disease. Leveraging these promising therapeutic targets has led to the emergence of a number of anti-IL-23 and -17 biologic agents with the potential to treat multiple conditions with common underlying pathology. The unprecedented clinical efficacy of these agents in the treatment of psoriasis has paved way for their evaluation in diseases such as psoriatic arthritis, Crohn's disease, rheumatoid arthritis, in addition to other immune-mediated conditions. Here we review the IL-23/IL-17 immune pathways and discuss the key clinical and safety data of the anti-IL-23 and anti-IL-17 biologic agents in psoriasis and other immune-mediated diseases. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  20. Severe thrombocytopenia related to trastuzumab infusion


    Mantzourani, Marina; Gogas, Helen; Katsandris, Aikaterini; Meletis, John


    Summary Background Trastuzumab is a humanized, monoclonal antibody that interferes with the HER2/neu receptor and binds selectively to the HERB2 protein which causes uncontrolled proliferation of malignant breast cells. Case Report We report a case of severe thrombocytopenia related to trastuzumab administration. Three days after the first dose of single-agent trastuzumab, the patient was admitted to the hospital with nose bleeding, petechiae and platelet counts of 5?109/L. Conclusions The pa...

  1. Postdiarrhoeal haemolytic uraemic syndrome without thrombocytopenia

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    Alejandro Balestracci


    Conclusions: The prevalence of non-thrombocytopenic D+ HUS was 5.6% and most cases occurred with mild forms of the disease; however, the need for dialysis in one of them indicated that normalisation of platelet count is not always an accurate marker for disease remittance. Our results also confirm that the time of onset of D+ HUS in patients without thrombocytopenia is usually delayed with respect to the initial intestinal symptoms; thus, heightened diagnostic suspicion is necessary.

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

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    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.

  3. The Association of Specific Constituents of the Fecal Microbiota with Immune-Mediated Brain Disease in Dogs. (United States)

    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.

  4. Treatment of immune-mediated temporal lobe epilepsy with GAD antibodies. (United States)

    Malter, M P; Frisch, C; Zeitler, H; Surges, R; Urbach, H; Helmstaedter, C; Elger, C E; Bien, C G


    Temporal lobe epilepsy with antibodies (abs) against the glutamic acid decarboxylase 65 isoform (GAD-TLE) is known as an immune-mediated neurological syndrome. Here we evaluate the therapy response to various immunotherapies and epilepsy surgery in this syndrome. All patients with GAD-TLE and follow-up data and stored serum and CSF samples, identified and treated at the Bonn centre from 2002 to 2010, were studied retrospectively. Seizure freedom for ≥1 year and reduction of ≥50%, i.e. therapy response, were assessed. GAD-ab titres and neuropsychological performances were documented prior and after individual interventions. Thirteen patients with GAD-TLE were identified with the following seizure responses: corticosteroids (5 responders out of 11 treated patients); i.v. immunoglobulins (1/5), apheresis therapy (1/8); and natalizumab (1/1), selective amygdala-hippocampectomy (2/3). None of the patients achieved sustained seizure freedom apart from one patient. This patient was on antiepileptic drug treatment after discontinuation of immunotherapy. The seizure response to immunotherapies in patients with GAD-TLE was poor. Corticosteroids were the most effective regarding seizure response. Especially the poor effects of apheresis therapies support the idea that GAD-abs are not directly pathogenic. None of three patients was seizure-free after temporal lobe surgery suggesting that GAD-TLE patients respond worse than others to this type of intervention. Our results reflect the chronic course of the disease with low likelihood for patients with GAD-TLE to attain long-term seizure freedom. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  5. New strategies for immune-mediated anti-viral drug and vaccine development. (United States)

    Chen, Chiann-Chyi; Ron, Yacov


    Substantial progress in the development of new anti-viral drugs has taken place in recent years. Most of these new drugs belong to three groups of compounds, nucleoside analogs, thymidine kinase-dependent nucleotide analogs and specific viral enzyme inhibitors. Although these drugs revolutionized the treatment of several viral diseases, the involvement of the immune system is crucial for complete recovery and prevention of re-infection. New advances in the understanding of immune regulation mechanisms, mainly the role of cytokines, led to the development of several new immunologically-based anti-viral drugs and treatments. The most studied group of immunomodulators is the cytokines, some of which were shown to act as potent stimulators of immune responses. Other, non-cytokine immune modulators have also been successfully employed in both humans and experimental animals as anti-viral drugs of which several are currently in clinical trials. Advances in genetic engineering and transgenic mouse technologies facilitated the production of humanized as well as authentic human anti-viral monoclonal antibodies. Some of these antibodies proved to be clinically efficacious and are commercially produced as anti-viral drugs. As is often the case in anti-viral treatments, a combination of conventional and an immune-mediated anti-viral drugs or a combination therapy involving immunomodulators, therapeutic vaccines, immune intervention and even gene therapy might prove most efficacious as a treatment for a particular virus. Most of the advances made in anti-viral treatments have also been applied to the development of new vaccines. Some of the classical attenuated viruses are being replaced by recombinant attenuated viruses. Recombinant viral vaccines containing genes encoding other viral antigens and/or cytokines are being tested as new vaccines. Several chimeric viral vaccines have proven efficacious in experimental animals and are now in different phases of clinical trials

  6. Targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia (United States)

    Lee, Jong-Min; Chan, Kaimin; Kan, Yuet Wai; Johnson, Jeffrey A.


    A basic leucine zipper transcription factor, NF-E2-related factor 2 (Nrf2), plays a critical role in the cellular defense mechanism by mediating a coordinate up-regulation of antioxidant responsive element-driven detoxification and antioxidant genes. Here, we report that targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia due to increased sequestration of damaged erythrocytes. Splenomegaly and spleen toxicity in Nrf2-/- mice raised a possibility of hemolytic anemia and splenic extramedullary hematopoiesis in Nrf2-/- mice. In support of this, hematology analysis revealed that Nrf2-/- mice suffer from anemia with abnormal red cell morphologies (i.e., Howell-Jolly bodies, acantocytes, and schistocytes). In addition, Nrf2-/- erythrocytes were more sensitive to H2O2-induced hemolysis, and erythrocyte-bound IgG levels were markedly increased in Nrf2-/- mice compared with Nrf2+/+ mice. Because IgG bound to erythrocytes in the presence of oxidative damage in erythrocytes (regardless of Nrf2 genotype), these data support that Nrf2-/- erythrocytes have higher levels of damage compared with Nrf2+/+ cells. Finally, Nrf2-/- mice showed increased levels of erythrocyte-bound IgG compared with Nrf2+/+ mice after H2O2 injection in vivo, suggesting that the decreased glutathione and increased H2O2 render the Nrf2-/- mice more susceptible to toxicity. Taken together, these observations indicate that a chronic increase in oxidative stress due to decreased antioxidant capacity sensitizes erythrocytes and causes hemolytic anemia in Nrf2-/- mice, suggesting a pivotal role of Nrf2-antioxidant responsive element pathway in the cellular antioxidant defense system. PMID:15210949

  7. Thrombocytopenia during Pregnancy and Its Outcome – A Prospective Study

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    Pallavi Satish Vishwekar


    Full Text Available Background: Thrombocytopenia is second to anemia as the most common hematological abnormality during pregnancy. Accurate etiological diagnosis is essential for optimal therapeutic management and thus can prevent maternal and fetal morbidity and mortality. Aims and Objectives: To determine various etiologies of maternal thrombocytopenia, their complications and fetomaternal outcome compared with normal pregnancy. Material and Methods: A prospective study was carried out in tertiary hospital, 1460 pregnant women who attended the Antenatal clinic regularly were enrolled. All were screened for thrombocytopenia in third trimester (after 28 weeks, women with normal platelet (n=1350 were taken in control group and those with low counts less than 150 x109/L (n=130 were included in study group. Etiology and fetomaternal outcome of thrombocytopenia in third trimester of pregnancy were evaluated and compared. Results: Gestational thrombocytopenia was the commonest etiology (68.46%. Incidence of thrombocytopenia due to severe preeclampsia and Hemolysis, Elevated Liver enzymes, Low Platelet (HELLP syndrome in study group was 18.46% and 7.69% of them had medical cause like malarial or dengue fever. Major causes were Gestational Thrombocytopenia (GT, Idiopathic Thrombocytopenic Purpura (ITP, preeclampsia, HELLP syndrome, malaria, and dengue. Maternal complications due to bleeding tendencies like placental abruption, postpartum hemorrhage were evident in the study population. Fetal complications were significantly higher in study group. Early neonatal thrombocytopenia depended on etiology rather than severity of maternal thrombocytopenia. Conclusions: Outcome of pregnancy with moderate to severe thrombocytopenia depends mainly on the etiology of thrombocytopenia. Adverse outcomes are especially seen with pregnancy complicated by preeclampsia and HELLP syndrome. Fetomaternal outcome is favorable in gestational thrombocytopenia. Thus accurate etiological

  8. Heparin-induced thrombocytopenia presenting as unilateral lower limb paralysis following lumbar spine surgery: case report. (United States)

    Smith, Brandon W; Joseph, Jacob R; Park, Paul


    Heparin-induced thrombocytopenia (HIT) is a state of thrombocytopenia with a paradoxically elevated thrombotic potential after exposure to heparin. Severe cases can present with multiorgan involvement with direct and secondary effects. Although HIT has been reported following other surgeries, to the authors' knowledge there has not been a report of HIT after spinal surgery. The present case details the course of a patient who underwent elective lumbar surgery followed by delayed presentation of shortness of breath due to multiple pulmonary embolisms and right lower-extremity paralysis due to extensive iliofemoral clot burden with acute compartment syndrome. The patient was treated with intravenous argatroban for extensive thrombosis and also required open thrombectomy and fasciotomies for treatment of compartment syndrome. Although the patient eventually experienced motor recovery, residual sensory deficits persisted at last follow-up. In this report, the pathophysiology, clinical presentation, and treatment of HIT are reviewed.

  9. Severe Symptomatic Hypophosphatemia With Thrombocytopenia in a Child With Diabetic Ketoacidosis

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    Full Text Available Introduction Although asymptomatic hypophosphatemia is a common finding in diabetic ketoacidosis (DKA, severe symptomatic hypophosphatemia is an uncommon complication. Case Presentation We report a 16-year-old female child with DKA, who developed thrombocytopenia, rhabdomyolysis, muscle weakness, and acute renal failure due to severe hypophosphatemia. She was managed with intravenous fluids, insulin infusion, phosphate therapy, and dialysis. After two weeks of hospitalization, the patient was discharged home with no squeal. Conclusions In critically ill patients, the symptoms of hypophosphatemia may not be apparent, but clinicians should be vigilant about this complication during therapy. In cases of severe symptoms (e.g., cardiopulmonary distress, anemia and thrombocytopenia, or rhabdomyolysis, phosphate therapy under close surveillance is warranted.

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

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    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

  11. Thrombocytopenia in leptospirosis and role of platelet transfusion

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    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

  12. Thrombocytopenia in neonatal sepsis: Incidence, severity and risk factors

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    Ree, Isabelle M. C.; Fustolo-Gunnink, Suzanne F.; Bekker, Vincent; Fijnvandraat, Karin J.; Steggerda, Sylke J.; Lopriore, Enrico


    Thrombocytopenia is a frequent problem in neonatal sepsis and is among the most predictive, independent risk factors for sepsis-associated mortality. This study aims to clarify the occurrence, severity and duration of thrombocytopenia in neonatal sepsis. A cohort study was carried out among all

  13. Management of thrombocytopenia due to liver cirrhosis: A review (United States)

    Hayashi, Hiromitsu; Beppu, Toru; Shirabe, Ken; Maehara, Yoshihiko; Baba, Hideo


    Thrombocytopenia is a common complication in liver disease and can adversely affect the treatment of liver cirrhosis, limiting the ability to administer therapy and delaying planned surgical/diagnostic procedures because of an increased risk of bleeding. Multiple factors, including splenic sequestration, reduced activity of the hematopoietic growth factor thrombopoietin, bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents, and antiviral treatment with interferon-based therapy, can contribute to the development of thrombocytopenia in cirrhotic patients. Of these factors, the major mechanisms for thrombocytopenia in liver cirrhosis are (1) platelet sequestration in the spleen; and (2) decreased production of thrombopoietin in the liver. Several treatment options, including platelet transfusion, interventional partial splenic embolization, and surgical splenectomy, are now available for severe thrombocytopenia in cirrhotic patients. Although thrombopoietin agonists and targeted agents are alternative tools for noninvasively treating thrombocytopenia due to liver cirrhosis, their ability to improve thrombocytopenia in cirrhotic patients is under investigation in clinical trials. In this review, we propose a treatment approach to thrombocytopenia according to our novel concept of splenic volume, and we describe the current management of thrombocytopenia due to liver cirrhosis. PMID:24627595

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

    Directory of Open Access Journals (Sweden)

    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].

  15. Thrombocytopenia in Haart naive HIV infected patients attending the ...

    African Journals Online (AJOL)

    Background: Haematological abnormalities are common in HIV infected patients. Thrombocytopenia has been associated with progression of disease. The presence of thrombocytopenia is significantly associated with decreased survival and is a predictor of mortality. Objective: To determine the prevalence of ...

  16. Incidence and risk factors for thrombocytopenia in the intensive care ...

    African Journals Online (AJOL)

    Background. In Western countries, incidence of thrombocytopenia in intensive care units (ICUs) has been found to be 13 - 44%. We chose to study the incidence, risk factors and transfusion requirements of thrombocytopenia in tertiary care ICUs in northern India. Objective. To study the incidence and risk factors of ...

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

    DEFF Research Database (Denmark)

    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...... that the RA and CD networks have predictive power by demonstrating that proteins in these networks, not encoded in the confirmed list of disease associated loci, are significantly enriched for association to the phenotypes in question in extended GWAS analysis. Finally, we test our method in 3 non...

  18. Analysis of polymorphisms in 16 genes in type 1 diabetes that have been associated with other immune-mediated diseases

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    Walker Neil M


    Full Text Available Abstract Background The identification of the HLA class II, insulin (INS, CTLA-4 and PTPN22 genes as determinants of type 1 diabetes (T1D susceptibility indicates that fine tuning of the immune system is centrally involved in disease development. Some genes have been shown to affect several immune-mediated diseases. Therefore, we tested the hypothesis that alleles of susceptibility genes previously associated with other immune-mediated diseases might perturb immune homeostasis, and hence also associate with predisposition to T1D. Methods We resequenced and genotyped tag single nucleotide polymorphisms (SNPs from two genes, CRP and FCER1B, and genotyped 27 disease-associated polymorphisms from thirteen gene regions, namely FCRL3, CFH, SLC9A3R1, PADI4, RUNX1, SPINK5, IL1RN, IL1RA, CARD15, IBD5-locus (including SLC22A4, LAG3, ADAM33 and NFKB1. These genes have been associated previously with susceptibility to a range of immune-mediated diseases including rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, Graves' disease (GD, psoriasis, psoriatic arthritis (PA, atopy, asthma, Crohn disease and multiple sclerosis (MS. Our T1D collections are divided into three sample subsets, consisting of set 1 families (up to 754 families, set 2 families (up to 743 families, and a case-control collection (ranging from 1,500 to 4,400 cases and 1,500 to 4,600 controls. Each SNP was genotyped in one or more of these subsets. Our study typically had approximately 80% statistical power for a minor allele frequency (MAF >5% and odds ratios (OR of 1.5 with the type 1 error rate, α = 0.05. Results We found no evidence of association with T1D at most of the loci studied 0.02 P ADAM33, rs2787094, was any evidence of association obtained, P = 0.0004 in set 1 families (relative risk (RR = 0.78, but further support was not observed in the 4,326 cases and 4,610 controls, P = 0.57 (OR = 1.02. Conclusion Polymorphisms in a variety of genes previously associated with

  19. Recent advances in understanding and management of acquired thrombocytopenia. (United States)

    Nagalla, Srikanth; Sarode, Ravindra


    There are numerous congenital and acquired causes of thrombocytopenia. Thrombocytopenia could be a result of decreased bone marrow production, increased consumption, increased destruction, splenic sequestration or a combination of these causes. In this review, we have focused on some of the serious acquired causes of thrombocytopenia. There have been some significant advances in our understanding of the pathophysiology, diagnostic testing, and treatment of immune thrombocytopenia, heparin-induced thrombocytopenia, thrombotic thrombocytopenic purpura, and atypical hemolytic uremic syndrome over the past five years. These advances have resulted in a significant decrease in mortality and morbidity of patients with these disorders. Despite these advances, we are still faced with numerous unanswered questions in the pathophysiology and management of these complex thrombocytopenic disorders.

  20. TAVI induces an elevation of hemostasis-related biomarkers, which is not causative for post-TAVI thrombocytopenia. (United States)

    Sedaghat, Alexander; Falkenberg, Nora; Sinning, Jan-Malte; Kulka, Hannah; Hammerstingl, Christoph; Nickenig, Georg; Oldenburg, Johannes; Pötzsch, Bernd; Werner, Nikos


    Thrombocytopenia after transcatheter aortic valve implantation (TAVI) has been evaluated in several studies, but the pathomechanisms behind this phenomenon are not well described. Here, we assess the influence of TAVI on hemostasis-related biomarkers and their potential role in post-TAVI thrombocytopenia. We assessed perioperative platelet counts in 307 patients undergoing transfemoral TAVI. Additionally, hemostasis-related biomarkers including thrombin-anti-thrombin complex (TAT), prothrombin activation fragment 1+2 (F1+2), plasmin-α₂-antiplasmin complex (PAP), and d-dimer were assessed in a subcohort of 35 patients. The course of these parameters was correlated with platelet counts and compared in patients with and without a relevant thrombocytopenia, i.e., a decline in platelet count of ≥50% compared to baseline. Levels of TAT (8.6±8.7μg/l), PAP (992±597μg/l), and d-dimer (1.43±1.66mg/l) were elevated above normal range before TAVI. TAT, F1+2, and d-dimer significantly increased after TAVI, and d-dimer as well as PAP remained elevated until day 7, indicating TAVI-induced increased thrombin formation associated with secondary fibrinolysis. Post-TAVI thrombocytopenia occurred in 17.9% of patients and was associated with a significantly higher incidence of post-TAVI complications, e.g. acute kidney injury and vascular complications. No impact of activated coagulation on thrombocytopenia was observed. TAVI induces an increase in hemostasis-related biomarkers, which persists until 1week after the procedure. The frequent finding of post-TAVI thrombocytopenia appears not to be linked to increased thrombin formation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. 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...

  2. Sustained response to combination therapy in a patient with chronic hepatitis C and thrombocytopenia secondary to alpha-interferon. (United States)

    Jiménez-Sáenz, M; Rojas, M; Piñar, A; Salas, E; Rebollo, J; Carmona, I; Herrerías-Esteban, J M; Herrerías-Gutiérrez, J M


    Recent data suggest that hepatitis C viral (HCV) infection may induce a significant autoimmune reaction to platelets, but the mechanism is unknown. Many patients with chronic hepatitis C, in fact, have high levels of platelet-associated immunoglobulin G (PAIgG) and HCV-RNA is present in the platelets of 100% of those patients with thrombocytopenia and high PAIgG levels. Hepatitis C virus infection has been associated with the development of thrombocytopenic purpura, sometimes triggered during interferon (IFN) therapy. In such cases, the treatment of the underlying disease is a difficult problem to solve. We report the case of a patient with chronic hepatitis C, who developed life-threatening thrombocytopenic purpura after a prolonged course of IFN-alpha2b over a 4-year period. Treatment with anti-immunoglobulin gammaglobulin (Polyglobin; Química Farmaceutica Bayer, Barcelona, Spain) had a transient effect on the platelet count, but prolonged therapy with prednisone was necessary for definitive relief of the haematological complication. Two years later, the patient was treated with combined therapy, including ribavirin (1200 mg/day) and IFN-alpha2b (5 mU, t.i.w.) for 12 months. This therapy induced a sustained response, both biochemical and virological, without haematological complications. This observation suggests that ribavirin may be of benefit in the treatment of immune-mediated thrombocytopenia in patients with chronic hepatitis C, preventing the harmful effect of IFN-alpha but also allowing both drugs to be combined so as to increase the probability of sustained remission of the liver disease.

  3. Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study. (United States)

    Linkins, L A; Warkentin, T E; Pai, M; Shivakumar, S; Manji, R A; Wells, P S; Wu, C; Nazi, I; Crowther, M A


    Essentials Heparin-induced thrombocytopenia (HIT) is a thrombogenic condition that is difficult to treat. We evaluated rivaroxaban as a treatment option in patients with suspected or confirmed HIT. One patient had recurrent thrombosis and 9/10 patients with thrombocytopenia had platelet recovery. Rivaroxaban may be an effective and safe treatment option for HIT. Background Rivaroxaban is a direct oral anti-Xa inhibitor that has the potential to greatly simplify treatment of heparin-induced thrombocytopenia (HIT). Objectives To evaluate the efficacy and safety of rivaroxaban in this patient population, we conducted a multicenter, single-arm, prospective cohort study of patients with suspected or confirmed HIT. Patients/Methods Twenty-two consecutive adults with suspected or confirmed HIT received rivaroxaban 15 mg bid until a local HIT assay result was available. Participants with a positive local assay result continued rivaroxaban 15 mg bid until platelet recovery (or until day 21 if they had acute thrombosis at study entry), then stepped down to rivaroxaban 20 mg daily until day 30. Results and Conclusions The primary outcome measure, incidence of new symptomatic, objectively-confirmed venous and arterial thromboembolism at 30 days, occurred in one HIT-positive participant (4.5%; 95% confidence interval [CI], 0-23.5%) and one HIT-positive participant required limb amputation despite platelet recovery. Platelet recovery was achieved in nine out of 10 HIT-positive patients with thrombocytopenia. Rivaroxaban appears to be effective for treating patients with confirmed HIT, although the small number of patients enrolled limits precision. © 2016 International Society on Thrombosis and Haemostasis.

  4. Interferon gamma effect on immune mediator production in human nerve cells infected by two strains of Toxoplasma gondii. (United States)

    Mammari, Nour; Vignoles, Philippe; Halabi, Mohamad Adnan; Dardé, Marie-Laure; Courtioux, Bertrand


    Interferon gamma (IFN-γ) is the major immune mediator that prevents toxoplasmic encephalitis in murine models. The lack of IFN-γ secretion causes reactivation of latent T. gondii infection that may confer a risk for severe toxoplasmic encephalitis. We analyse the effect of IFN-γ on immune mediator production and parasite multiplication in human nerve cells infected by tachyzoites of two T. gondii strains (RH and PRU). IFN-γ decreased the synthesis of MCP-1, G-CSF, GM-CSF and Serpin E1 in all cell types. It decreased IL-6, migration inhibitory factor (MIF) and GROα synthesis only in endothelial cells, while it increased sICAM and Serpin E1 synthesis only in neurons. The PRU strain burden increased in all nerve cells and in contrast, RH strain replication was controlled in IFN-γ-stimulated microglial and endothelial cells but not in IFN-γ-stimulated neurons. The proliferation of the PRU strain in all stimulated cells could be a specific effect of this strain on the host cell. © N. Mammari et al., published by EDP Sciences, 2015.

  5. Effects of Food Additives on Immune Cells As Contributors to Body Weight Gain and Immune-Mediated Metabolic Dysregulation

    Directory of Open Access Journals (Sweden)

    Heitor A. Paula Neto


    Full Text Available Food additives are compounds used in order to improve food palatability, texture, and shelf life. Despite a significant effort to assure safety of use, toxicological analysis of these substances, generally, rely on their direct toxicity to target organs (liver and kidney or their genotoxic effects. Much less attention is paid to the effects of these compounds on cells of the immune system. This is of relevance given that metabolic dysregulation and obesity have a strong immune-mediated component. Obese individuals present a state of chronic low-grade inflammation that contributes to the establishment of insulin resistance and other metabolic abnormalities known as the metabolic syndrome. Obesity and metabolic syndrome are currently recognized as worldwide epidemics that pose a profound socioeconomic impact and represent a concern to public health. Cells of the immune system contribute to both the maintenance of “lean homeostasis” and the metabolic dysregulation observed in obese individuals. Although much attention has been drawn in the past decades to obesity and metabolic syndrome as a result of ingesting highly processed food containing large amounts of fat and simple sugars, mounting evidence suggest that food additives may also be important contributors to metabolic derangement. Herein, we review pieces of evidence from the literature showing that food additives have relevant effects on cells of the immune system that could contribute to immune-mediated metabolic dysregulation. Considering their potential to predispose individuals to develop obesity and metabolic syndrome, their use should be taken with caution or maybe revisited.

  6. Interferon gamma effect on immune mediator production in human nerve cells infected by two strains of Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Mammari Nour


    Full Text Available Interferon gamma (IFN-γ is the major immune mediator that prevents toxoplasmic encephalitis in murine models. The lack of IFN-γ secretion causes reactivation of latent T. gondii infection that may confer a risk for severe toxoplasmic encephalitis. We analyse the effect of IFN-γ on immune mediator production and parasite multiplication in human nerve cells infected by tachyzoites of two T. gondii strains (RH and PRU. IFN-γ decreased the synthesis of MCP-1, G-CSF, GM-CSF and Serpin E1 in all cell types. It decreased IL-6, migration inhibitory factor (MIF and GROα synthesis only in endothelial cells, while it increased sICAM and Serpin E1 synthesis only in neurons. The PRU strain burden increased in all nerve cells and in contrast, RH strain replication was controlled in IFN-γ-stimulated microglial and endothelial cells but not in IFN-γ-stimulated neurons. The proliferation of the PRU strain in all stimulated cells could be a specific effect of this strain on the host cell.

  7. Influence of maternal age, gestational age and fetal gender on expression of immune mediators in amniotic fluid. (United States)

    Weissenbacher, Tobias; Laubender, Rüdiger P; Witkin, Steven S; Gingelmaier, Andrea; Schiessl, Barbara; Kainer, Franziskus; Friese, Klaus; Jeschke, Udo; Dian, Darius; Karl, Katrin


    Variations in cytokine and immune mediator expression patterns in amniotic fluid due to gestational age, maternal age and fetal gender were investigated. Amniotic fluid samples were obtained from 192 women, 82 with a mid-trimester amniocentesis (median gestational age 17 weeks) and 110 with a caesarean section not in labor (median gestational age 39 weeks). Amniotic fluid was screened by commercial ELISAs for the TH1/TH2/TH17 cytokines and immune mediators IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF alpha, GRO-alpha, MIP1alpha, MIP1beta, Histone, and IP10. Analysis was by Bonferroni correction for multiple comparisons. None of the 15 examined cytokines revealed any differences in expression patterns regarding fetal gender. Significant differences were found in IL-4, IL-10, IL-12, TNF- alpha, GRO-alpha and MIP1-beta with respect to gestational age and in GRO-alpha regarding maternal age. Cytokines utilized as biomarkers in the diagnosis of intrauterine infections are not influenced in their expression pattern by fetal gender but may vary with respect to maternal age and gestational age.

  8. Imbalanced immune homeostasis in immune thrombocytopenia. (United States)

    Yazdanbakhsh, Karina


    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. How do we approach thrombocytopenia in critically ill patients? (United States)

    Thachil, Jecko; Warkentin, Theodore E


    A low platelet count is a frequently encountered haematological abnormality in patients treated in intensive treatment units (ITUs). Although severe thrombocytopenia (platelet count thrombocytopenia is associated with organ failure and adverse prognosis. The aetiology for thrombocytopenia in ITU is often multifactorial and correcting one aetiology may not normalise the low platelet count. The classical view for thrombocytopenia in this setting is consumption associated with thrombin-mediated platelet activation, but other concepts, including platelet adhesion to endothelial cells and leucocytes, platelet aggregation by increased von Willebrand factor release, red cell damage and histone release, and platelet destruction by the complement system, have recently been described. The management of severe thrombocytopenia is platelet transfusion in the presence of active bleeding or invasive procedure, but the risk-benefit of prophylactic platelet transfusions in this setting is uncertain. In this review, the incidence and mechanisms of thrombocytopenia in patients with ITU, its prognostic significance and the impact on organ function is discussed. A practical approach based on the authors' experience is described to guide management of a critically ill patient who develops thrombocytopenia. © 2016 John Wiley & Sons Ltd.

  10. Thrombocytopenia in hospitalized patients with severe clostridium difficile infection. (United States)

    Fountain, Eric M; Moses, Maggie C; Park, Lawrence P; Woods, Christopher W; Arepally, Gowthami M


    Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhea and colitis. The incidence and prognostic significance of thrombocytopenia as related to mode of acquisition (hospital vs. community), NAP1/027 strain, and disease severity has not been examined. We performed a single-institution retrospective analysis of all adult inpatients from 2013 to 2014 diagnosed with CDI during their hospitalization to document the incidence/prevalence of thrombocytopenia and associated outcomes. Severe disease was defined by a composite endpoint of inpatient death, death within 30 days of discharge, presence of septic shock, or need for colectomy during hospitalization. Of the 533 patients diagnosed with CDI, moderate thrombocytopenia (platelet count thrombocytopenia developed in 3 % of patients after admission. Thrombocytopenia was more common in hospital-acquired disease and associated with increased length of stay, but was not associated with treatment failure. Those with moderate thrombocytopenia were more likely to have severe disease, after controlling for white blood cell count, albumin, and creatinine. Moderate thrombocytopenia is associated with poor prognosis and is a potential risk stratification tool for severe CDI.

  11. Thrombocytopenia in pregnancy – pathogenesis and diagnostic approach

    Directory of Open Access Journals (Sweden)

    Anna Jodkowska


    Full Text Available Thrombocytopenia (TP affects 7-10% of pregnant women. It occurs 4 times more frequently in pregnancy than in the non-pregnant women population. Women with thrombocytopenia in pregnancy are a heterogeneous and poorly known group.There are several possible causes of thrombocytopenia in pregnancy. The most common are: gestational thrombocytopenia (GE (60-75%, preeclampsia (PE and HELLP (hemolysis, elevated liver enzymes, low platelets syndrome associated TP (21%, and idiopathic immune thrombocytopenia (ITP (3-10%. Although thrombocytopenia diagnosed in pregnancy in most cases has a mild course, it has also been reported to be associated with a higher rate of preterm birth and premature detachment of the placenta. Some cases of severe thrombocytopenia with systemic involvement are associated with high risk of serious perinatal complications and require early diagnosis, careful clinical monitoring and medical treatment.The differential diagnosis and proper assessment of clinical risk of TP during pregnancy may be of great concern. The article discusses these issues, focusing on pathophysiology of TP in pregnancy.


    Directory of Open Access Journals (Sweden)



    Full Text Available INTRODUCTION: Fever is the cardinal manifestation of infection. Platelets are necessary to prevent bleeding manifestations. Certain infections cause thrombocytopenia and bleeding manifestations. AIMS AND OBJECTIVES: To study the incidence of bleeding manifestations in i nfections which cause fever and thrombocytopenia. MATERIALS AND METHODS: INCLUSION CRITERIA: Patients who were admitted with fever and thrombocytopenia, aged above 12 years, in S.V.R.R.G.G.H, Tirupati were taken for the study. EXCLUSION CRITERIA: Patients who are admitted with thrombocytopenia and without fever were excluded. Patients who are admitted with fever and normal platelet count were excluded. RESULTS AND CONCLUSI ON: Fever with thrombocytopenia is the commonest presenting problem in the medical war ds. In the present study the commonest infectious etiology of fever with thrombocytopenia was malaria fever (36%, followed by undiagnosed fevers (28%, dengue fever (26%, typhoid fever (6% and scrub typhus (4%. In the present study bleeding manifestati ons were seen in 16 cases (32% and bleeding manifestations were not seen in 34 cases (68%. The commonest bleeding manifestation was cutaneous, followed by hematemesis, malena, bleeding gums, hematuria and epistaxis. Bleeding manifestation was commonly se en in thrombocytopenia with dengue fever (14%, followed by malaria (8%, undiagnosed cases (8% and typhoid (2%.

  13. Risk factors for ganciclovir-induced thrombocytopenia and leukopenia. (United States)

    Matsumoto, Kazuaki; Shigemi, Akari; Ikawa, Kazuro; Kanazawa, Naoko; Fujisaki, Yuko; Morikawa, Norifumi; Takeda, Yasuo


    Ganciclovir is a nucleoside guanosine analogue that exhibits therapeutic activity against human cytomegalovirus infection, and is primarily excreted via glomerular filtration and active tubular secretion. The adverse effects induced by ganciclovir therapy are generally of a hematological nature and include thrombocytopenia and leukopenia. Low marrow cellularity and elevated serum creatinine have been identified as risk factors for ganciclovir-induced neutropenia. However, the risk factors for thrombocytopenia have yet to be determined. Therefore, this study investigated patients administered ganciclovir to determine the risk factors for thrombocytopenia and leukopenia. Thrombocytopenia occurred in 41 of these patients (30.6%). Multivariate logistic regression analysis identified three independent risk factors for thrombocytopenia: cancer chemotherapy (odds ratio (OR)=3.1), creatinine clearance (ganciclovir dose (≥12 mg/kg/d) (OR=15.1). Leukopenia occurred in 36 patients (28.6%), and white blood cell count (ganciclovir dose (≥12 mg/kg/d) (OR=7.8) were identified as risk factors. These results demonstrated that several factors influenced the occurrence of ganciclovir-induced thrombocytopenia and leukopenia, and suggest that special attention should be paid to patients receiving cancer chemotherapy with a low creatinine clearance (ganciclovir-induced thrombocytopenia.

  14. Incidence of thrombocytopenia in the neonatal intensive care unit. (United States)

    Gupta, Aparajita; Mathai, S S; Kanitkar, Madhuri


    Thrombocytopenia is the commonest haematological abnormality encountered in the neonatal intensive care unit (NICU). The incidence in neonates varies greatly, depending upon the population studied. The aim of the present study was to study the incidence of thrombocytopenia in the neonates admitted to the NICU. The study was carried out in 258 consecutive eligible neonates from August 2007 to August 2009. Neonates were placed in two risk groups for thrombocytopenia, viz. high risk and low risk, depending upon the presentation, maternal history and any antenatal/perinatal events. Platelet counts were done on the first, third and fifth day of admission and thereafter every 72 hours till counts were normal. Low counts were collaborated with a peripheral blood smear. The overall incidence of thrombocytopenia in the study group was 70% (182/258). The incidence in the high-risk group was 93.7% cases (134/143) and in the low-risk group was 41.7% (48/115). This difference was statistically significant. Factors associated with thrombocytopenia were sepsis, extreme low birth weight, intra-uterine growth restriction, birth asphyxia and pre-eclampsia in mothers. The most common severe bleeding manifestation was pulmonary haemorrhage. The overall mortality in babies with thrombocytopenia was 33% despite > 90% of these cases having received platelet transfusion. Of these pulmonary haemorrhage was the main cause of death in five cases. It is concluded that thrombocytopenia is very common in the NICU and should be actively looked for so that it can be managed appropriately.

  15. Thrombocytopenia in neonatal sepsis: Incidence, severity and risk factors. (United States)

    Ree, Isabelle M C; Fustolo-Gunnink, Suzanne F; Bekker, Vincent; Fijnvandraat, Karin J; Steggerda, Sylke J; Lopriore, Enrico


    Thrombocytopenia is a frequent problem in neonatal sepsis and is among the most predictive, independent risk factors for sepsis-associated mortality. This study aims to clarify the occurrence, severity and duration of thrombocytopenia in neonatal sepsis. A cohort study was carried out among all neonates with proven culture positive sepsis that were admitted to a tertiary NICU between 2006 and 2015 (n = 460). The occurrence, severity and duration of thrombocytopenia were recorded, as well as major bleedings and potential risk factors for mortality in neonatal sepsis. Sepsis was diagnosed in 460 of 6551 neonates (7%). Severe thrombocytopenia (platelets ≤50*109/L) occurred in 20% (92/460) of septic neonates. The median time for platelets to rise >100*109 was 6.0 days (interquartile range 4.0-7.0). On multivariate analysis, maternal hypertension, intravascular thrombosis and Gram negative (as opposed to Gram positive) sepsis were independently associated with thrombocytopenia in neonatal sepsis. In severe thrombocytopenia, 10% (9/92) suffered a severe IVH, compared to 5% (20/356) in neonates with platelets >50*109/L (p = 0.125). 10% (9/92) suffered a pulmonary hemorrhage, compared to 2% (9/368) in neonates with platelets >50*109/L (p = 0.001). On multivariate analysis, thrombocytopenia and Gram negative (as opposed to Gram positive) sepsis were independently associated with neonatal mortality. Thrombocytopenia is independently associated with maternal hypertension, intravascular thrombosis and Gram negative sepsis. Thrombocytopenia in neonatal sepsis increases the risk of mortality nearly four-fold, with another six-fold increase in mortality in case of Gram negative sepsis.

  16. Anterior Chamber-Associated Immune Deviation (ACAID: An Acute Response to Ocular Insult Protects from Future Immune-Mediated Damage?

    Directory of Open Access Journals (Sweden)

    Robert E. Cone


    Full Text Available The “immune privilege” that inhibits immune defense mechanisms that could lead to damage to sensitive ocular tissue is based on the expression of immunosuppressive factors on ocular tissue and in ocular fluids. In addition to this environmental protection, the injection of antigen into the anterior chamber or infection in the anterior chamber induces a systemic suppression of potentially damaging cell-mediated and humoral responses to the antigen. Here we discuss evidence that suggests that Anterior Chamber-Associated Immune Deviation (ACAID a is initiated by an ocular response to moderate inflammation that leads to a systemic immunoregulatory response. Injection into the anterior chamber induces a rise in TNF-α and MCP-1 in aqueous humor and an infiltration of circulating F4/80 + monocytes that home to the iris. The induction of ACAID is dependent on this infiltration of circulating monocytes that eventually emigrate to the thymus and spleen where they induce regulatory T cells that inhibit the inductive or effector phases of a cell-mediated immune response. ACAID therefore protects the eye from the collateral damage of an immune response to infection by suppressing a future potentially damaging response to infection.

  17. Refractory Immunological Thrombocytopenia Purpura and Splenectomy in Pregnancy

    Directory of Open Access Journals (Sweden)

    Santiago Bernal-Macías


    Full Text Available Thrombocytopenia is defined as a platelet count of less than 100,000 platelets per microlitre (mcL. Thrombocytopenia develops in approximately 6-7% of women during pregnancy and at least 3% of these cases are caused by immunological platelet destruction. Herein, we present a pregnant woman who develops at the first trimester autoimmune thrombocytopenia purpura associated with positive antiphospholipid antibodies. The disease was refractory to pharmacological treatments but had a favourable response to splenectomy. The patient carried the pregnancy to term without complication and gave birth to a healthy baby girl.

  18. Treatment and Prevention of Heparin-Induced Thrombocytopenia (United States)

    Dans, Antonio L.; Moores, Lisa K.; Bona, Robert; Davidson, Bruce L.; Schulman, Sam; Crowther, Mark


    Background: Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke. Methods: The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: Among the key recommendations for this article are the following: For patients receiving heparin in whom clinicians consider the risk of HIT to be > 1%, we suggest that platelet count monitoring be performed every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first) (Grade 2C). For patients receiving heparin in whom clinicians consider the risk of HIT to be < 1%, we suggest that platelet counts not be monitored (Grade 2C). In patients with HIT with thrombosis (HITT) or isolated HIT who have normal renal function, we suggest the use of argatroban or lepirudin or danaparoid over other nonheparin anticoagulants (Grade 2C). In patients with HITT and renal insufficiency, we suggest the use of argatroban over other nonheparin anticoagulants (Grade 2C). In patients with acute HIT or subacute HIT who require urgent cardiac surgery, we suggest the use of bivalirudin over other nonheparin anticoagulants or heparin plus antiplatelet agents (Grade 2C). Conclusions: Further studies evaluating the role of fondaparinux and the new oral anticoagulants in the treatment of HIT are needed. PMID:22315270

  19. Correlation study between platelet count, leukocyte count, nonhemorrhagic complications, and duration of hospital stay in dengue fever with thrombocytopenia (United States)

    Jayanthi, Hari Kishan; Tulasi, Sai Krishna


    Introduction: Dengue is one of the common diseases presenting as fever with thrombocytopenia, also causing significant morbidity and complications. Objectives: Though the correlation between platelet count, bleeding manifestations and hemorrhagic complications has been extensively studied, less is known about the correlation between platelet count and non hemorrhagic complications. This study was done to see the correlation between platelet count and non hemorrhagic complications, duration of hospital stay and additive effect of leucopenia with thrombocytopenia on complications. Methods: Our study is prospective observational study done on 99 patients who had dengue fever with thrombocytopenia. Correlations were obtained using scatter plot and SPSS software trail version. Results: Transaminitis (12.12%) was the most common complication followed by acute renal injury (2%). In our study we found that, as the platelet count decreased the complication rate increased (P = 0.0006). In our study duration of hospital increased (P is 0.00597) with decreasing platelet count when compared to other study where there was no correlation between the two. There was no correlation between thrombocytopenia with leucopenia and complications (P is 0.292), similar to other study. Conclusion: Platelet count can be used to predict the complication and duration of hospital stay and hence better use of resources. PMID:27453855

  20. IL1RN VNTR and IL2-330 polymorphic genes are independently associated with chronic immune thrombocytopenia. (United States)

    Rocha, Andreia Maria Camargos; De Souza, Cláudia; Rocha, Gifone Aguiar; De Melo, Fabrício Freire; Saraiva, Isadora Sofia Borges; Clementino, Nelma Cristina Diogo; Marino, Marília Campos Abreu; Queiroz, Dulciene Maria Magalhães


    Chronic Immune Thrombocytopenia (cITP) is an acquired immune-mediated disease associated with a T-helper cell type 1 (Th1) immune polarization, whose genetic risk factors, however, are largely unknown. We investigated polymorphisms in promoter regions of genes that code molecules involved in proinflammatory immune response [IL1B-31T/C, IL1RN variable number tandem repeats (VNTR), IL2-330T/G, and TNF-307G/A] as well as in genes that code Toll like receptors (TLR) (TLR2 Arg753Gln, TLR4 Asp299Gly and TLR5 Arg(392stop)) in 122 patients with cITP and 541 blood donors. The frequencies of the IL1RN polymorphic allele 2 (P = 0·001) and of the IL2-330 polymorphic allele G (P =0·004) were significantly higher in cITP patients than in blood donors. In logistic analysis adjusting for age and gender, the polymorphisms remained independently associated with cITP. Enhanced serum concentrations of interleukin (IL)-1α and IL-1β were observed in cITP (P IL2-330G allele. Here we demonstrated that IL2-330G and IL1RN*2 are independently associated with cITP and are functional in vivo, which strongly suggests that they contribute to the pathogenesis of cITP. © 2010 Blackwell Publishing Ltd.

  1. Refractory primary immune thrombocytopenia with subsequent del(5q) MDS

    DEFF Research Database (Denmark)

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


    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...

  2. Thrombocytopenia induced by noncytotoxic drugs in Denmark 1968-91

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B


    OBJECTIVES: To analyse the distribution of noncytotoxic drugs reported as cause of thrombocytopenia during a 24-year period, and to draw attention to the most commonly involved drugs in modern clinical practice. DESIGN/SETTING: Retrospective study of spontaneous case reports from the Danish...... reporting system on adverse drug reactions. SUBJECTS: A total of 309 critically reviewed cases of drug-induced thrombocytopenia reported during the period from 1968 to the end of 1991. RESULTS: Sodiumaurothiomalate and the combination sulfamethoxazole with trimethoprim were the most commonly reported single...... numerously reported. The still-growing list of thrombocytopenia-inducing agents contained 110 different drugs. At present, 20% of reported cases concern drugs not previously registered as causing thrombocytopenia in Denmark. Twenty-five per cent of all cases were caused by drugs which appeared only...

  3. Fetal and neonatal thrombopoietin levels in alloimmune thrombocytopenia

    NARCIS (Netherlands)

    Porcelijn, L.; Folman, C. C.; de Haas, M.; Kanhai, H. H. H.; Murphy, M. F.; von dem Borne, A. E. G. Kr; Bussel, J. B.


    Thrombopoietin (Tpo) is the main hematopoietic growth factor for platelet production. Plasma Tpo levels in autoimmune thrombocytopenic patients are normal or slightly elevated. Although thrombocytopenia exists, Tpo levels are not increased because the produced megakaryocytes and platelets can bind

  4. What Are the Signs and Symptoms of Thrombocytopenia? (United States)

    ... information about this procedure, go to the Health Topics Blood Transfusion article. Splenectomy A splenectomy is surgery to remove ... experiences with clinical research. More Information Related Health Topics Aplastic ... Thrombocytopenia Thrombotic Thrombocytopenic Purpura ...

  5. Subdural Hematoma in Grave’s Disease Induced Thrombocytopenia.

    Directory of Open Access Journals (Sweden)

    Sunil Kumar


    Full Text Available Subdural hematoma (SDH usually occurs secondary to trauma, in bleeding disorders it may occur spontaneously. It is a rare complication of immune thrombocytopenia. Here we report a case of 45 years female presenting with presenting with complaints of headache, palpitation and menorrhagia and later diagnosed to be a case of Grave's disease with thrombocytopenia with sub dural hematoma. No such case reports are available in literature.

  6. Noninvasive Sampling of Mucosal Lining Fluid for the Quantification of In Vivo Upper Airway Immune-mediator Levels

    DEFF Research Database (Denmark)

    Wolsk, Helene Mygind; Chawes, Bo L.; Thorsen, Jonathan


    (often used by other techniques). The mucosal lining fluid is sampled on a strip of filter paper placed at the anterior part of the inferior turbinate and left for 2 min of absorption. Analytes are eluted from the filter papers, and the extracted protein-based eluates are analyzed...... to that specific panel or sampling site. The technique was first implemented in 7-year-old children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) cohort with allergic rhinitis. It was thereafter used in the longitudinal COPSAC2010 birth cohort, sampled at 1 month, 2 years, and 6......This protocol describes noninvasive sampling of undisturbed upper airway mucosal lining fluid. It also details the extraction procedure used prior to the analysis of immune mediators in fluid eluates for the study of the airway topical immune signature, without the need for stimulation procedures...

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

    DEFF Research Database (Denmark)

    Paes, Geert; Paepe, Dominique; Meyer, Evelyne


    hyperlipemic dogs (group 3), 10 dogs with lymphoma (group 4), 8 dogs with an infection (group 5) and 13 healthy dogs (group 6) were included. In all dogs, blood smear examination, in-saline auto-agglutination test, Coombs' test, COFT and ROFT were performed. In the COFT, OF5, OF50 and OF90 were defined......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....... Since the classic osmotic fragility test (COFT) is time-consuming and requires specialized equipment, an easy and less labour-intensive rapid osmotic fragility test (ROFT) has been used in some countries, but its diagnostic value has not yet been investigated. This study aimed to evaluate erythrocyte...

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

    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

  9. Acute Idiopathic Thrombocytopenic


    Basavaraj Bhagawati; Rahul Hegde


    Acute thrombocytopenic purpura is the most common of thrombocytopenias of the childhood. Clinical Features include petechial lesions on oral mucosa, gingival bleeding and occassionally hemorrhage into tissues. Serious complications like intracranial bleeding are also reported. This paper describes a case, presenting in our dental OPD and reviews on published guidelines.

  10. A 7-year case of furosemide-induced immune thrombocytopenia. (United States)

    Ochoa, Pamella S; Fisher, Tye


    Immune thrombocytopenia has been attributed to many causes. Several drugs have been implicated as culprits in causing drug-induced thrombocytopenia. Although the mechanism for this type of thrombocytopenia is not well understood, at least three types of antibodies appear to be involved: drug-dependent antibodies, hapten-dependent antibodies, and drug-induced platelet-reactive autoantibodies. In this report, we describe a case in which furosemide was identified as the probable cause of drug-induced thrombocytopenia in an 84-year-old man with chronic symptomatic idiopathic thrombocytopenia for seven years before discovery. The patient's platelet count and daily furosemide dose, both intravenous and oral, were documented throughout his medical history. A dose-dependent change in platelet count was observed in association with the furosemide dose. His platelet count increased on discontinuation of furosemide and beginning of torsemide. Several months after discontinuation of furosemide, his platelet count increased to a 9-year high of 206 × 10³/mm³ from a low of 36 × 10³/mm³ while receiving furosemide therapy. Based on the observations of this case report, clinicians should more readily consider furosemide as a potential cause of thrombocytopenia. © 2013 Pharmacotherapy Publications, Inc.

  11. [Heparin-induced thrombocytopenia: recent data]. (United States)

    Gruel, Y; Rollin, J; Leroux, D; Pouplard, C


    Despite less frequent, heparin-induced thrombocytopenia (HIT) remains a severe complication of treatment with heparin, and is important to diagnose and manage appropriately. HIT results from an atypical immune response to heparin, with the synthesis of IgG antibodies specific to heparin-modified platelet factor 4 (PF4) which activate platelets, leukocytes and the endothelium. This activation explains that low platelet count is associated with thrombotic events in 50% of patients. The diagnosis of HIT is sometimes evoked because of atypical manifestations (i.e. cutaneous necrosis, amnesia, hypotension or dyspnea following intravenous injection of heparin). Biological assays are always necessary to confirm HIT in case of clinical suspicion, and specific rapid tests are now available for detecting anti-PF4 antibodies. However, their specificity is poor and functional assays such as serotonin release assay or platelet aggregation test are often necessary. Argatroban that is a direct antithrombin drug can be used in patients with severe renal failure and will be preferred to danaparoid sodium in this situation. Fondaparinux is not licensed for treating confirmed HIT and can only be used in case of suspicion. The early detection of HIT is based on the monitoring of platelet count recommended in surgical patients receiving a low molecular weight heparin and in all patients treated with unfractionated heparin. Copyright © 2013. Published by Elsevier SAS.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Cutaneous Alternaria infectoria infection in a dog in association with therapeutic immunosuppression for the management of immune-mediated haemolytic anaemia

    NARCIS (Netherlands)

    Dedola, C.; Stuart, A.P.G.; Ridyard, A.E.; Else, R.W.; van den Broek, A.H.M.; Choi, J.S.; de Hoog, G.S.; Thoday, K.L.


    A 4-year-old, ovariohysterectomized, English springer spaniel on immunosuppressive therapy was re-examined for the review of its immune-mediated haemolytic anaemia and the recent development of skin lesions. For the 3 months since hospital discharge, the dog had been receiving 1.3 mg/kg prednisolone

  14. Improving and standardising assessment of patients with immune-mediated neuropathies: Peripheral Neuropathy outcome measures Standardisation study (PeriNomS study – part 1)

    NARCIS (Netherlands)

    S.I. van Nes (Sonja)


    textabstractIn this thesis, the outline and the results of the fi rst part of the Peripheral Neuropathy outcome measures Standardisation (PeriNomS) study are described. The PeriNomS study aims to improve and standardise the assessment of patients with immune-mediated neuropathies. These disorders

  15. [Two-year incidence of new immune-mediated inflammatory diseases in patients with inflammatory bowel disease: A study in the AQUILES cohort]. (United States)

    Marín-Jiménez, Ignacio; Gisbert, Javier P; Pérez-Calle, José L; García-Sánchez, Valle; Tabernero, Susana; García-Vicuña, Rosario; Romero, Cristina; Juliá, Berta; Vanaclocha, Francisco; Cea-Calvo, Luis


    To describe the 2-year incidence of new immune-mediated inflammatory diseases (spondylarthritis, uveitis, psoriasis) in the cohort of patients with inflammatory bowel disease (IBD) included in the AQUILES study. Over a 2-year period, 341 patients with IBD (53% women, mean age 40 years) diagnosed with Crohn's disease (60.5%), ulcerative colitis (38.1%) and indeterminate colitis (1.4%) were followed up. New diagnoses made during follow-up were based on reports of the corresponding specialists (rheumatologists, ophthalmologists, and dermatologists). A total of 22 new diagnoses of immune-mediated inflammatory diseases were established in 21 patients (cumulative incidence of 6.5%, 95% confidence interval [CI] 3.7-9.2, incidence rate of 26 cases per 10,000 patient-years). Most diagnoses were new cases of spondylarthritis (n=15). The cumulative incidence of new diagnoses of immune-mediated inflammatory diseases was similar in patients with Crohn's disease (5.8%, 95% CI 3.4-9.9) and in patients with ulcerative colitis (7.7%, 95% CI 4.2-13.6). On multivariate analysis, the incidence of new immune-mediated inflammatory diseases was significantly associated with a family history of IBD (odds ratio=3.6, 95% CI 1.4-9.4) and the presence of extraintestinal manifestations of IBD (odds ratio=1.8, 95% CI .7-5.2). In patients with IBD, the incidence of new immune-mediated inflammatory diseases at 2 years of follow-up was 6.5%. These diseases were more frequent in patients with extraintestinal manifestations of IBD and a family history of IBD. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  16. Thrombocytopenia induced by a taurine-containing energy drink: an adverse reaction to herbal medicine

    Directory of Open Access Journals (Sweden)

    Federico Pasin


    Full Text Available Thrombocytopenia is a well-recognized adverse effect of many drugs. The association of thrombocytopenia with herbal remedies, nutritional supplements, foods and beverages, complementary or alternative medicines, has been rarely described. There are reports of thrombocytopenia caused by quinine-containing beverages, cow�s milk, cranberry juice, Jui, a Chinese herbal tea, Lupinus termis bean and tahini. A definite evidence of a causal association with thrombocytopenia is warranted; nevertheless not always there is provided probable or possible evidence in the association with thrombocytopenia. We report the first case, to our knowledge, of thrombocytopenia induced by taurine, present in an energy drink prescribed to our patient as tonic treatment.

  17. Venous Thromboembolism in Patients With Thrombocytopenia: Risk Factors, Treatment, and Outcome. (United States)

    Baelum, Jens Kristian; Moe, Espen Ellingsen; Nybo, Mads; Vinholt, Pernille Just


    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. To identify VTE risk factors and describe treatment and outcome (bleeding episodes and mortality) in patients with thrombocytopenia. Patients with thrombocytopenia (platelet count thrombocytopenia. Also, patients with thrombocytopenia may be VTE risk stratified based on platelet count and comorbidities. Finally, patients having thrombocytopenia with VTE seem to be safely treated with anticoagulants without increased occurrence of bleeding.

  18. Pathophysiology of acute small bowel disease with CT correlation

    Energy Technology Data Exchange (ETDEWEB)

    Sarwani, N., E-mail: nsarwani@hmc.psu.ed [Department of Radiology, Section of Abdominal Imaging, Penn State Milton Hershey Medical Center, Hershey, PA (United States); Tappouni, R.; Tice, J. [Department of Radiology, Section of Abdominal Imaging, Penn State Milton Hershey Medical Center, Hershey, PA (United States)


    The objective of this article is to review the pathophysiology of acute small bowel diseases, and to correlate the mechanisms of disease with computed tomography (CT) findings. Disease entities will be classified into the following: immune mediated and infectious causes, vascular causes, mechanical causes, trauma, and others. Having an understanding of acute small bowel pathophysiology is a useful teaching tool, and can lead to imaging clues to the most likely diagnosis of acute small bowel disorders.

  19. Thrombocytopenia: diagnosis with flow cytometry and antiplatelet antibodies. (United States)

    Guerra, João Carlos de Campos; Kanayama, Ruth Hissae; Nozawa, Sonia Tsukasa; Ioshida, Márcia Regina; Takiri, Irina Yoko; Lazaro, Robson José; Hamerschlak, Nelson; Rosenfeld, Luiz Gastão Mange; Guerra, Celso Carlos de Campos; Bacal, Nydia Strachman


    To identify antiplatelet antibodies by flow cytometry (direct method) in patients with thrombocytopenia. Between January 1997 and March 2004 a total of 15100 patients were referred to the Centro de Hematologia de São Paulo for hematological investigation of several diagnoses (anemia, leukopenia, thrombocytopenia, coagulation abnormalities, adenomegaly, leukemia and others). Of those, 1057 were referred because of thrombocytopenia and were divided into two groups: Group Idiopathic thrombocytopenic purpura, with no identifiable cause; and Group Other thrombocytopenia, which included low normal platelet counts cause to be established, hepatitis C and HIV infection, hypersplenism, EDTA-induced artifacts, laboratory error, and other causes. Flow cytometry immunophenotyping was done in 115 cases to identify platelet autoantibodies (direct method). Of the total number of patients, 1057 (7%) presented low platelet counts, 670 were females (63.4%) and age range of one to 75 years. Of the 115 cases (9.7%) submitted to immunophenotyping, the results were positive in 40% and the test was inconclusive in 5%. Idiopathic thrombocytopenic purpura was found in 52% of patients, more often in women. Hepatitis C virus infection was found in 7% and HIV infection in 1%. Low normal platelet counts were found in 17%, laboratory errors in 6%, and laboratory artifacts in 1% of cases. Platelet autoantibodies were found in 76.9% of all idiopathic thrombocytopenic purpura cases. It was negative in 83.3% of the low normal counts. antiplatelet autoantibodies when present help to diagnose idiopathic thrombocytopenic purpura. When absent, suggest other causes of thrombocytopenia.

  20. Adherence to systemic therapies for immune-mediated inflammatory diseases in Lebanon: a physicians’ survey from three medical specialties

    Directory of Open Access Journals (Sweden)

    Ammoury A


    Full Text Available Alfred Ammoury,1 Jad Okais,2 Mireille Hobeika,3 Raymond B Sayegh,4 Rani H Shayto,5 Ala I Sharara5 1Division of Dermatology, St George Hospital University Medical Center, 2Division of Rheumatology, St Joseph University, 3AbbVie Levant, 4Division of Gastroenterology, St Joseph University, 5Department of Internal Medicine, Division of Gastroenterology, American University of Beirut Medical Center, Beirut, Lebanon Background: Immune-mediated inflammatory diseases (IMIDs are chronic conditions that may cause tissue damage and disability, reduced quality of life and increased mortality. Various treatments have been developed for IMIDs, including immune modulators and targeted biologic agents. However, adherence remains suboptimal. Methods: An adherence survey was used to evaluate physicians’ beliefs about adherence to medication in IMID and to evaluate if and how they manage adherence. The survey was distributed to 100 randomly selected physicians from three different specialties. Results were analyzed by four academic experts commissioned to develop an action plan to address practical and perceptual barriers to adherence, integrating it into treatment goals to maximize outcomes in IMID, thereby elevating local standards of care. Results: Eighty-two physicians participated in this study and completed the questionnaire. Most defined adherence as compliance with prescribed treatment. Although the majority of surveyed physicians (74% did not systematically measure adherence in their practice, 54% identified adherence as a treatment goal of equal or greater importance to therapeutic endpoints. Lack of time and specialized nursing support was reported as an important barrier to measuring adherence. The expert panel identified four key areas for action: 360° education (patient–nurse–physician, patient–physician communication, patient perception and concerns, and market access/cost. An action plan was developed centered on education and awareness

  1. Immune thrombocytopenia (ITP): a rare association of lymph node tuberculosis. (United States)

    Surana, Anuj P; Shelgikar, Kishor M; Melinkeri, Sameer; Phadke, Arvind


    Although various haematologic abnormalities are known to occur with tuberculosis, association of immune thrombocytopenia with tuberculosis is uncommon. We report a case of retroperitoneal lymph node tuberculosis who presented with ITP. A 76 year old female was admitted to our hospital with oral mucosal bleed and petechial lesions over extremities and abdomen. A diagnosis of immune thrombocytopenia (ITP) was established. Intravenous Anti-D immunoglobulin and Dexamethasone therapy was started, but failed to elicit any sustained platelet response. CT abdomen revealed multiple retroperitoneal lymph nodes with central necrosis. Histopathology (HPE) of these revealed caseating lymphadenitis suggestive of tuberculosis. After 2 months of anti-tuberculous therapy, the platelet counts returned to normal and patient was off all therapy for ITP thereby suggesting likely association between tuberculosis and immune thrombocytopenia.

  2. Relapsed hydroxychloroquine induced thrombocytopenia in a systemic lupus erythematosus patient. (United States)

    Antón Vázquez, Vanesa; Pascual, Luis; Corominas, Héctor; Giménez Torrecilla, Isabel

    Hydroxychloroquine is used in the long-term therapy of systemic lupus erythematosus (SLE). Although considered to be a safe treatment, side effects have been documented. An uncommon side effect is thrombocytopenia. In order to establish the diagnosis of thrombocytopenia secondary to Hydroxychloroquine, non-pharmacological causes must be ruled out and it is necessary to determine a recurrence after re-exposure to the drug. We present one case of severe thrombocytopenia occurring in a patient with SLE undergoing treatment with Hydroxychloroquine. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  3. Heparin-associated thrombocytopenia: an update. (United States)

    Fondu, P


    The use of heparin may be complicated by two types of thrombocytopenia (HAT): type I occurs early, is transient, and has no clinical relevance, while type II may lead to very severe manifestations (arterial or venous thromboses and more rarely bleedings), that are still underestimated by some clinicians. HAT-type II most frequently develops after use of therapeutic doses of unfractionated heparin (UH) but has also been described less frequently after use of very low doses of UH, of low molecular weight heparins (LMWH), and even of polysulfated glycosaminoglycosans devoid of anticoagulant action. The estimation of the incidence of HAT-type II and of related thromboses is a very difficult matter. Recent observations suggest that thromboses (notably venous) may be more frequent than previously estimated. HAT-type II pathophysiology includes the formation of immune complexes at the surface of platelets; the antigen has been shown to be most often platelet factor 4 bound to heparin while the antibody is recognized by platelet Fc gamma RII receptors. Thromboses result most probably from activation of both platelets (leading to the formation of microparticles) and endothelial cells. Several biological tests are presently available for diagnosing HAT-type II but none of them has been shown to be ideal. The prevention of HAT-type II requires history taking preference of LMWH to UH, early start of oral anticoagulation, and platelet monitoring from the fifth day of heparin therapy. The therapy of HAT-type II implies immediate discontinuation of heparin and avoidance of platelet transfusions, unless severe bleeding occurs. If further antithrombotic treatment is deemed necessary (probably in all cases), several options are possible but presently, the most recommended ones are Org 10172 or Ancrod; embolectomy or thrombolysis may also be required if a new thrombotic event has developed. A very difficult dilemma concerns patients previously sensitized to heparin and who present a

  4. Genetic Associations in Acquired Immune-Mediated Bone Marrow Failure Syndromes: Insights in Aplastic Anemia and Chronic Idiopathic Neutropenia

    Directory of Open Access Journals (Sweden)

    Irene Mavroudi


    Full Text Available Increasing interest on the field of autoimmune diseases has unveiled a plethora of genetic factors that predispose to these diseases. However, in immune-mediated bone marrow failure syndromes, such as acquired aplastic anemia and chronic idiopathic neutropenia, in which the pathophysiology results from a myelosuppressive bone marrow microenvironment mainly due to the presence of activated T lymphocytes, leading to the accelerated apoptotic death of the hematopoietic stem and progenitor cells, such genetic associations have been very limited. Various alleles and haplotypes of human leucocyte antigen (HLA molecules have been implicated in the predisposition of developing the above diseases, as well as polymorphisms of inhibitory cytokines such as interferon-γ, tumor necrosis factor-α, and transforming growth factor-β1 along with polymorphisms on molecules of the immune system including the T-bet transcription factor and signal transducers and activators of transcription. In some cases, specific polymorphisms have been implicated in the outcome of treatment on those patients.

  5. Genetic Associations in Acquired Immune-Mediated Bone Marrow Failure Syndromes: Insights in Aplastic Anemia and Chronic Idiopathic Neutropenia (United States)

    Mavroudi, Irene; Papadaki, Helen A.


    Increasing interest on the field of autoimmune diseases has unveiled a plethora of genetic factors that predispose to these diseases. However, in immune-mediated bone marrow failure syndromes, such as acquired aplastic anemia and chronic idiopathic neutropenia, in which the pathophysiology results from a myelosuppressive bone marrow microenvironment mainly due to the presence of activated T lymphocytes, leading to the accelerated apoptotic death of the hematopoietic stem and progenitor cells, such genetic associations have been very limited. Various alleles and haplotypes of human leucocyte antigen (HLA) molecules have been implicated in the predisposition of developing the above diseases, as well as polymorphisms of inhibitory cytokines such as interferon-γ, tumor necrosis factor-α, and transforming growth factor-β1 along with polymorphisms on molecules of the immune system including the T-bet transcription factor and signal transducers and activators of transcription. In some cases, specific polymorphisms have been implicated in the outcome of treatment on those patients. PMID:22956967

  6. Immune-mediated agranulocytosis caused by the cocaine adulterant levamisole: a case for reactive metabolite(s) involvement. (United States)

    Wolford, Angela; McDonald, Thomas S; Eng, Heather; Hansel, Steven; Chen, Yue; Bauman, Jonathan; Sharma, Raman; Kalgutkar, Amit S


    The United States Public Health Service Administration is alerting medical professionals that a substantial percentage of cocaine imported into the United States is adulterated with levamisole, a veterinary pharmaceutical that can cause blood cell disorders such as severe neutropenia and agranulocytosis. Levamisole was previously approved in combination with fluorouracil for the treatment of colon cancer; however, the drug was withdrawn from the U.S. market in 2000 because of the frequent occurrence of agranulocytosis. The detection of autoantibodies such as antithrombin (lupus anticoagulant) and an increased risk of agranulocytosis in patients carrying the human leukocyte antigen B27 genotype suggest that toxicity is immune-mediated. In this perspective, we provide an historical account of the levamisole/cocaine story as it first surfaced in 2008, including a succinct review of levamisole pharmacology, pharmacokinetics, and preclinical/clinical evidence for levamisole-induced agranulocytosis. Based on the available information on levamisole metabolism in humans, we propose that reactive metabolite formation is the rate-limiting step in the etiology of agranulocytosis associated with levamisole, in a manner similar to other drugs (e.g., propylthiouracil, methimazole, captopril, etc.) associated with blood dyscrasias. Finally, considering the toxicity associated with levamisole, we propose that the 2,3,5,6-tetrahydroimidazo[2,1-b]thiazole scaffold found in levamisole be categorized as a new structural alert, which is to be avoided in drug design.

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

    DEFF Research Database (Denmark)

    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....

  8. Symptom burden profile in myelofibrosis patients with thrombocytopenia: Lessons and unmet needs. (United States)

    Scotch, Allison H; Kosiorek, Heidi; Scherber, Robyn; Dueck, Amylou C; Slot, Stefanie; Zweegman, Sonja; Boekhorst, Peter A W Te; Commandeur, Suzan; Schouten, Harry; Sackmann, Federico; Fuentes, Ana Kerguelen; Hernández-Maraver, Dolores; Pahl, Heike L; Griesshammer, Martin; Stegelmann, Frank; Döhner, Konstanze; Lehmann, Thomas; Bonatz, Karin; Reiter, Andreas; Boyer, Francoise; Etienne, Gabriel; Ianotto, Jean-Christophe; Ranta, Dana; Roy, Lydia; Cahn, Jean-Yves; Harrison, Claire N; Radia, Deepti; Muxi, Pablo; Maldonado, Norman; Besses, Carlos; Cervantes, Francisco; Johansson, Peter L; Barbui, Tiziano; Barosi, Giovanni; Vannucchi, Alessandro M; Paoli, Chiara; Passamonti, Francesco; Andreasson, Bjorn; Ferrari, Maria L; Rambaldi, Alessandro; Samuelsson, Jan; Birgegard, Gunnar; Xiao, Zhijian; Xu, Zefeng; Zhang, Yue; Sun, Xiujuan; Xu, Junqing; Kiladjian, Jean-Jacques; Zhang, Peihong; Gale, Robert Peter; Mesa, Ruben A; Geyer, Holly L


    Myelofibrosis is a myeloproliferative neoplasm associated with progressive cytopenias and high symptom burden. MF patients with thrombocytopenia have poor prognosis but the presence of thrombocytopenia frequently precludes the use of JAK2 inhibitors. In this study, we assessed quality of life and symptom burden in 418 MF patients with (n=89) and without (n=329) thrombocytopenia using prospective data from the MPN-QOL study group database, including the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and Total Symptom Score (MPN10). Thrombocytopenia, defined as platelet count thrombocytopenia were more likely to have anemia (86% vs. 67%, p=0.04), leukopenia (40% vs. 20%, p=0.04), and transfusion requirements (51% vs. 20%, p=0.002) but few differences in symptoms when compared to patients with moderate thrombocytopenia. These results suggest that MF patients with thrombocytopenia experience greater symptomatic burden than MF patients without thrombocytopenia and may benefit from additional therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

    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...

  10. The potential of antimicrobials to induce thrombocytopenia in critically ill patients

    DEFF Research Database (Denmark)

    Johansen, Maria Egede; Jensen, Jens Ulrik Stæhr; Bestle, Morten Heiberg


    Antimicrobial-induced thrombocytopenia is frequently described in the literature among critically ill patients. Several antimicrobials have been implicated, although experimental evidence to demonstrate causality is limited. We report, using a randomized trial, the potential of antimicrobials...... to induce thrombocytopenia....

  11. High level increase in liver enzymes and severe thrombocytopenia in a male case of anorexia nervosa

    Directory of Open Access Journals (Sweden)

    Mojgan Karahmadi


    Conclusions: Improvement of initial clinical symptoms and recovery of liver enzymes and thrombocytopenia after the treatment suggested that liver dysfunction and thrombocytopenia may be observed in AN patients and should be taken care of by physicians.

  12. Tuberculous splenic abscess in a neonate with thrombocytopenia

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  13. Massive hemorrhage due to hemodialysis-associated thrombocytopenia. (United States)

    Vicks, S L; Gross, M L; Schmitt, G W


    Marked declines in platelet numbers were noted in association with hemodialysis. This resulted in gastrointestinal bleeding and the need for packed RBC and platelet transfusions. This hemodialysis-associated thrombocytopenia was ameliorated by changing the dialyzer in use. The gastrointestinal bleeding stopped and the need for platelet transfusions was obviated. The degree of platelet loss during hemodialysis is probably affected by the composition of the dialyzer membrane used as well as other factors. Hemodialysis-associated thrombocytopenia may be a contributing factor in the increased bleeding tendency noted in hemodialysis patients.

  14. Heparin and heparin-induced thrombocytopenia

    African Journals Online (AJOL)


    Jun 15, 2007 ... South Africa Platelet transfusion should. NOT be given as this may exacerbate the thrombosis, and warfarin should not be used until the platelet count has recovered. Warfarin may acutely increase the prothrombotic state due to dropping the protein C (natural anticoagulant) level. Vitamin K administration is.

  15. A plant cell-expressed recombinant anti-TNF fusion protein is biologically active in the gut and alleviates immune-mediated hepatitis and colitis. (United States)

    Ilan, Yaron; Gingis-Velitski, Svetlana; Ben Ya'aco, Ami; Shabbat, Yehudit; Zolotarov, Lidya; Almon, Einat; Shaaltiel, Yoseph


    The orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) (n=6) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human antibody IgG1 domain. To evaluate the immune modulatory effect of the oral administration of plant cells expressing PRX-106. Mice treated with Concanavalin A (ConA) to induce immune hepatitis was orally treated with cells expressing PRX-106 containing 0.5 or 5μg PRX 106. In the colitis model, TNBS-colitis was induced in mice followed by the oral administration of plant cells expressing PRX-106. The immune modulatory effect was determined through follow-up to assess the clinical effect, histology, and serum cytokine levels and by FACS analysis for lymphocyte subsets. The oral administration of BY-2 cells expressing PRX-106 alleviated immune-mediated liver injury. Serum AST and ALT levels decreased and were comparable to those of mice that had received high-dose steroids. The beneficial effect was also observed as a marked decrease in hepatic necrosis. In the colitis model, the oral administration of BY-2 plant cells expressing PRX-106 alleviated weight loss associated with immune-mediated colitis and improved bowel histology. A reduction in I-IkB-alpha phosphorylation in treated mice was also observed. These effects were associated with a significant alteration in the distribution of CD4+CD25+FOXP3+ cells. Plant cells expressing recombinant anti-TNF fusion protein show biological activity when orally administered, exerting an immune modulatory effect through the alleviation of immune-mediated hepatitis and immune-mediated colitis. Copyright © 2016 Elsevier GmbH. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Immune thrombocytopenia with multi-organ dysfunction syndrome as a rare presentation of scrub typhus: a case report. (United States)

    Ittyachen, Abraham M; Abraham, Saramma P; Krishnamoorthy, Smitha; Vijayan, Anuroopa; Kokkat, Jayamohan


    Scrub typhus is an acute infectious illness caused by Orientia tsutsugamushi. It is endemic to a part of the world known as the "tsutsugamushi triangle". Humans are accidental hosts in this zoonotic disease. About a third of patients admitted with scrub typhus have evidence of multi-organ dysfunction. Multi-organ dysfunction secondary to scrub typhus carries a high mortality rate. We report a 65-year old lady who was admitted in a Tertiary Care Center in the state of Kerala in India, with 7 day history of fever, myalgia and reduced urine output. Head to foot examination revealed the presence of an eschar on her chest. One week prior to the onset of her illness she had gone trekking through a hilly forest area. She was clinically suspected to have scrub typhus, which was later confirmed with laboratory tests. She developed multi-organ dysfunction syndrome secondary to this illness. Though there was an improvement in the multi-organ dysfunction, thrombocytopenia alone failed to improve. Bone marrow study was done which was suggestive of immune thrombocytopenia. Patient was given a course of steroids with which the thrombocytopenia improved. Failure of platelet count to normalize even after there has been a general improvement of other markers of multi-organ dysfunction in scrub typhus should prompt the clinician to consider other potential causes of thrombocytopenia. An unusual finding as this calls for further research to understand the molecular mechanisms behind such an event. Further, considering the close similarity in clinical presentation of several tropical illnesses, meticulous history taking and a detailed physical examination needs to be emphasized.

  18. Vasospasm following aneurysmal subarachnoid hemorrhage: Thrombocytopenia a marker

    Directory of Open Access Journals (Sweden)

    Ashish Aggarwal


    Full Text Available Background: Symptomatic vasospasm (SV is often seen after aneurysmal subarachnoid hemorrhage (aSAH. The pathophysiology suggests that platelets initiate the process and are consumed. This is likely to result in thrombocytopenia. The objective of this study was to find out if thrombocytopenia preceded or followed SV and to analyze the relationship between the two. Materials and Methods: The platelet counts of 74 patients were studied on day 1, 3, 5, 7, 9, 11, and 14 following aSAH. Clinical symptoms and raised velocities on transcranial Doppler were studied on the same days to determine SV. The relationship of platelet counts and SV were analyzed. Results: Thirty-nine (52.7% patients developed SV. Platelet counts dropped on postictal day (PID 3-7 and SV was commonly seen on PID 5-9. The median platelet counts were significantly lower in patients with SV when compared to those without SV. Platelet count 5 times for a patient with relative thrombocytopenia especially on PID 5-9. Additionally, it appears that thrombocytopenia precedes vasospasm and may be an independent predictor. However, this requires further studies for validation.

  19. Severe fetal thrombocytopenia in Rhesus D alloimmunized pregnancies

    NARCIS (Netherlands)

    van den Akker, Eline S. A.; de Haan, Timo R.; Lopriore, Enrico; Brand, Anneke; Kanhai, Humphrey H. H.; Oepkes, Dick


    The objective of the study was to evaluate the incidence of fetal thrombocytopenia and association with hydrops in Rhesus D alloimmunization. The study was a retrospective chart review of 914 intrauterine transfusions in 314 pregnancies performed between 1988 and 2005 in a single institution. The

  20. Familial thrombocytopenia associated with platelet autoantibodies and chromosome breakage

    NARCIS (Netherlands)

    Helmerhorst, F. M.; Heaton, D. C.; Crossen, P. E.; von dem Borne, A. E.; Engelfriet, C. P.; Natarajan, A. T.


    An extended family is described in which three members had thrombocytopenia. These affected members had chromosomal changes resembling those found in Fanconi's anaemia, though they lacked the development defects associated with that syndrome. One had bone-marrow hypoplasia and died of squamous cell

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

    DEFF Research Database (Denmark)

    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...

  2. Thrombocytopenia during pregnancy in women with HIV infection ...

    African Journals Online (AJOL)

    Thrombocytopenia (TCP) (platelet count <150 ×. 109/L) during pregnancy often causes anxiety among both patients and healthcare practitioners. It occurs in 5 - 8% of pregnancies, the prevalence depending on whether it is associated with medical disorders or not.[1,2] Gestational TCP (gTCP), also known as incidental or ...

  3. The diagnostic value of thrombopoietin level measurements in thrombocytopenia

    NARCIS (Netherlands)

    Porcelijn, L.; Folman, C. C.; Bossers, B.; Huiskes, E.; Overbeeke, M. A.; van der Schoot, C. E.; de Haas, M.; von dem Borne, A. E.


    It has been reported that blood trombopoietin (TPO) levels can discriminate between thrombocytopenia due to increased platelet destruction and decreased platelet production. With our TPO ELISA and a glycocalicin ELISA we analysed a large group of patients in detail and could confirm and amplify the

  4. [Immune-mediated inflammatory diseases in patients with inflammatory bowel disease. Baseline data from the Aquiles study]. (United States)

    Marín-Jiménez, Ignacio; García Sánchez, Valle; Gisbert, Javier P; Lázaro Pérez Calle, José; Luján, Marisol; Gordillo Ábalos, Jordi; Tabernero, Susana; Juliá, Berta; Romero, Cristina; Cea-Calvo, Luis; García-Vicuña, Rosario; Vanaclocha, Francisco


    To determine the prevalence of immune-mediated inflammatory diseases (IMID) in a cohort of patients with inflammatory bowel disease (IBD) enrolled in hospital gastroenterology outpatients units for the AQUILES study, a prospective 2-year follow-up study. We included patients ≥18 years old with a prior or new diagnosis of IBD (Crohn disease [CD], ulcerative colitis [UC] or indeterminate colitis). Diagnoses were collected in a cross-sectional manner from the clinical records at enrollment of a new patient in the study. We included 526 patients (mean age 40.2 years; 47.3% men, 52.7% women), 300 with CD (57.0%), 218 with UC (41.4%) and 8 with indeterminate colitis. Other types of IMID were present in 71 patients (prevalence: 13.5%, 95% CI: 10.8-16.7): 47 were spondyloarthropathies (prevalence: 8.9%); 18 psoriasis (3.4%); 5 pyoderma gangrenosum (1.0%), and 11 uveitis (2.1%). The prevalence of IMID was higher in patients with CD than in those with UC (17.0% [95% CI: 13.2-21.7] vs 9.2% [95% CI: 6.0-13.8], p=0.011). In the multivariate analysis, the variables associated with the presence of IMID were diagnosis of CD (OR=1.8 [95% CI: 1.1-3.2]) and duration of IBD ≥4 years (OR=2.1 [95% CI: 1.1-4.1] in those with disease duration 4-8 years, and OR=2.1 [95% CI: 1.2-3.9] in those with ≥8 years vs. 4 years since disease onset. Copyright © 2013 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  5. Predicting Outcome in dogs with Primary Immune-Mediated Hemolytic Anemia: Results of a Multicenter Case Registry. (United States)

    Goggs, R; Dennis, S G; Di Bella, A; Humm, K R; McLauchlan, G; Mooney, C; Ridyard, A; Tappin, S; Walker, D; Warman, S; Whitley, N T; Brodbelt, D C; Chan, D L


    Outcome prediction in dogs with immune-mediated hemolytic anemia (IMHA) is challenging and few prognostic indicators have been consistently identified. An online case registry was initiated to: prospectively survey canine IMHA presentation and management in the British Isles; evaluate 2 previously reported illness severity scores, Canine Hemolytic Anemia Score (CHAOS) and Tokyo and to identify independent prognostic markers. Data from 276 dogs with primary IMHA across 10 referral centers were collected between 2008 and 2012. Outcome prediction by previously reported illness-severity scores was tested using univariate logistic regression. Independent predictors of death in hospital or by 30-days after admission were identified using multivariable logistic regression. Purebreds represented 89.1% dogs (n = 246). Immunosuppressive medications were administered to 88.4% dogs (n = 244), 76.1% (n = 210) received antithrombotics and 74.3% (n = 205) received packed red blood cells. Seventy-four per cent of dogs (n = 205) were discharged from hospital and 67.7% (n = 187) were alive 30-days after admission. Two dogs were lost to follow-up at 30-days. In univariate analyses CHAOS was associated with death in hospital and death within 30-days. Tokyo score was not associated with either outcome measure. A model containing SIRS-classification, ASA classification, ALT, bilirubin, urea and creatinine predicting outcome at discharge was accurate in 82% of cases. ASA classification, bilirubin, urea and creatinine were independently associated with death in hospital or by 30-days. Markers of kidney function, bilirubin concentration and ASA classification are independently associated with outcome in dogs with IMHA. Validation of this score in an unrelated population is now warranted. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  6. Acute disseminated encephalomyelitis in dengue viral infection. (United States)

    Wan Sulaiman, Wan Aliaa; Inche Mat, Liyana Najwa; Hashim, Hasnur Zaman; Hoo, Fan Kee; Ching, Siew Mooi; Vasudevan, Ramachandran; Mohamed, Mohd Hazmi; Basri, Hamidon


    Dengue is the most common arboviral disease affecting many countries worldwide. An RNA virus from the flaviviridae family, dengue has four antigenically distinct serotypes (DEN-1-DEN-4). Neurological involvement in dengue can be classified into dengue encephalopathy immune-mediated syndromes, encephalitis, neuromuscular or dengue muscle dysfunction and neuro-ophthalmic involvement. Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination. This monophasic illness is characterised by multifocal white matter involvement. Many dengue studies and case reports have linked ADEM with dengue virus infection but the association is still not clear. Therefore, this article is to review and discuss concerning ADEM in dengue as an immune-medicated neurological complication; and the management strategy required based on recent literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Severe thrombocytopenia induced by iodinated contrast after coronary angiography: The use of gadolinium contrast and intravascular ultrasound as an alternative to guide percutaneous coronary intervention. (United States)

    Cubero-Gómez, José María; Guerrero Márquez, Francisco J; Diaz-de la-Llera, Luis; Fernández-Quero, Mónica; Guisado-Rasco, Agustín; Villa-Gil-Ortega, Manuel


    Acute contrast-induced thrombocytopenia is a rare event with the use of modern low osmolarity iodinated contrast media. The pathophysiological mechanism that causes platelet counts to drop has not been identified, but an immunological mechanism is suspected due to cytotoxicity after previous exposure to contrast. We report the case of a 47-year-old male patient with acute severe thrombocytopenia due to iodinated contrast media exposure. His platelet count after the procedure with the highest amount of contrast was zero, which is the lowest reported platelet count to date. Percutaneous coronary revascularization under both intravascular ultrasound and gadolinium contrast guidance was performed without complications. The most feared complication after the use of gadolinium is nephrogenic systemic fibrosis, especially in patients on hemodialysis. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Thrombocytopenia in pregnancy with different diagnoses: Differential clinical features, treatments, and outcomes. (United States)

    Wang, Xiaoyue; Xu, Yan; Luo, Wenxiang; Feng, Hui; Luo, Yizhou; Wang, Yanli; Liao, Hui


    To investigate the clinical features and perinatal treatment of thrombocytopenia induced by different causes during pregnancy.Clinical data from 195 pregnant women with thrombocytopenia attending 2 tertiary hospitals from January 2014 to October 2016 were retrospectively studied. The obtained data were analyzed with SPSS 19.0 software.There were 117 (60.0%), 55 (28.2%), and 23 cases (11.8%) of pregnancy-associated thrombocytopenia (PAT), idiopathic thrombocytopenia (ITP), and hypertensive disorder in pregnancy (PIH), respectively. The percentage of nulliparous women, gestational age at delivery, date of diagnosis of thrombocytopenia, and delivery mode significantly differed between the patients in these 3 groups (P thrombocytopenia in pregnancy are diverse, and the clinical features vary widely. Timely analysis is needed to determine the primary cause of thrombocytopenia, and appropriate therapy should then be selected to effectively improve the prognosis of pregnancies.

  9. Extensive Intracardiac and Deep Venous Thromboses in a Young Woman with Heparin-Induced Thrombocytopenia and May-Thurner Syndrome

    Directory of Open Access Journals (Sweden)

    Yekaterina Kim


    Full Text Available A 38-year-old woman with a history of recurrent deep venous thromboses (DVTs on chronic anticoagulation presented with acute left leg swelling. The patient was diagnosed with an acute left lower extremity (LLE DVT in the setting of May-Thurner syndrome for which treatment with unfractionated heparin was started. Her hospital course was complicated by a new diagnosis of heparin-induced thrombocytopenia (HIT, with an incidental discovery of a large tricuspid valve mobile mass on a transthoracic echocardiogram (TTE. Subsequent imaging confirmed multiple right atrial thrombi along with LLE venous stent thrombosis and a new right LE acute DVT. Anticoagulation with argatroban for HIT thrombosis was started. She underwent a right atrial percutaneous thrombectomy and bilateral lower extremity thrombectomy with directed angioplasty and stent placement. This presentation is a rare manifestation of HIT with extensive intracardiac and deep venous thrombi, with successful staged interventions.

  10. Acute disseminated encephalomyelitis preceding measles exanthema. (United States)

    Nardone, Raffaele; Golaszewski, Stefan; Trinka, Eugen; Tezzon, Frediano; Zuccoli, Giulio


    We report a case of acute disseminated encephalomyelitis preceding measles virus infection. Brain magnetic resonance imaging revealed signal intensity abnormalities in the basal ganglia and cortex consistent with acute disseminated encephalomyelitis. Fever and the first Koplik spots appeared 8 and 10 days later, respectively. This case supports the hypothesis that the immune-mediated demyelinating process may occur before the symptomatic phase of a viral infection. Therefore, children without history of infectious disorders should also have acute disseminated encephalomyelitis included in the differential considerations.

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

    Directory of Open Access Journals (Sweden)

    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

  12. Periodontal manifestations of acute autoimmune thrombocytopenic purpura. A case report. (United States)

    Ripamonti, U; Petit, J C; Penfold, G; Lemmer, J


    Purpuric hemorrhages are usually the result of thrombocytopenia, but are also seen in vascular disorders such as vitamin C deficiency, Henoch-Schonlein purpura, and von Willebrand's disease. The progressive purpuric hemorrhages in the oral mucosae and skin in a case of acute autoimmune thrombocytopenic purpura (AITP) in a young adult are described. Localized hemorrhagic periodontal lesions of doubtful interpretation proved to be the first clinical signs of the underlying thrombocytopenia. The diagnosis is confirmed by finding thrombocytopenia with normal or increased numbers of megakaryocytes in the bone marrow. Treatment must be started before the onset of serious complications such as cerebral hemorrhages.

  13. RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury

    NARCIS (Netherlands)

    Fischer, Julius C.; Bscheider, Michael; Eisenkolb, Gabriel; Lin, Chia Ching; Wintges, Alexander; Otten, Vera; Lindemans, Caroline A.; Heidegger, Simon; Rudelius, Martina; Monette, Sébastien; Rodriguez, Kori A.Porosnicu; Calafiore, Marco; Liebermann, Sophie; Liu, Chen; Lienenklaus, Stefan; Weiss, Siegfried; Kalinke, Ulrich; Ruland, Jürgen; Peschel, Christian; Shono, Yusuke; Docampo, Melissa; Velardi, Enrico; Jenq, Robert R; Hanash, Alan M; Dudakov, Jarrod A; Haas, Tobias; van den Brink, Marcel R M; Poeck, Hendrik


    The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Hepatitis B infection is associated with an increased incidence of thrombocytopenia in healthy adults without cirrhosis. (United States)

    Joo, E-J; Chang, Y; Yeom, J-S; Lee, Y-G; Ryu, S


    The association between HBV infection and incident thrombocytopenia among subjects without cirrhosis or splenomegaly is unknown. Therefore, we sought to elucidate the association between HBV infection and the development of thrombocytopenia in a large cohort of apparently healthy men and women. A cohort study was performed in 122 200 participants without liver cirrhosis or splenomegaly who underwent comprehensive health examinations and were followed until December 2014. HBV infection was defined by the presence of hepatitis B surface antigen (HBsAg) at baseline. Thrombocytopenia was defined as a platelet count thrombocytopenia. HBsAg was positive in 4857 of 122 200 subjects (4.0%) at baseline. During 883 983 person-years of follow-up, 2037 incident cases of thrombocytopenia were identified (incident rate 2.3 per 1000 person-years). HBsAg-positive subjects had a higher incidence of thrombocytopenia than did healthy controls (11.2 vs 1.9 per 1000 person-years, respectively). The multivariate-adjusted hazard ratio (95% CI) for incident thrombocytopenia comparing HBsAg-positive to HBsAg-negative subjects was 5.71 (5.10-6.38). Strong associations between HBsAg positivity and thrombocytopenia were consistently observed across prespecified subgroups. In this large cohort study of an apparently healthy population, HBsAg positivity was strongly and independently associated with incident thrombocytopenia, indicating that mechanisms of thrombocytopenia other than portal hypertension may exist in healthy HBV carriers. © 2016 John Wiley & Sons Ltd.

  16. [Retrospective analysis of patients with thrombocytopenia after patent ductus arteriosus interventional occlusion]. (United States)

    Liao, Qi-wei; Zhang, Wei-hua; Guang, Xue-feng; Lu, Yi-bing


    To explore the risk factors of patent ductus arteriosus (PDA) patients with thrombocytopenia after PDA interventional occlusion. Thrombocytopenia occurred in 14 out of 350 patients underwent PDA occlusion. Age, gender, body weight, PDA size, occluder size, mean pulmonary arterial pressure, the dose of heparin, the manufacturer of occluder, residual shunt after operation were analyzed. The recovery time of different grades of thrombocytopenia was observed. Multivariate logistic regression showed that the PDA size (OR = 2.238, P < 0.05), the dose of heparin (OR = 3.247, P < 0.05), residual shunt after operation (OR = 1.912, P < 0.01) were the independent risk factors of thrombocytopenia after PDA occlusion. The recovery time of mild thrombocytopenia was (7 ± 2) days without treatment. The recovery time of moderate thrombocytopenia was (12 ± 4) days with glucocorticoids treatment. The recovery time of severe thrombocytopenia was (21 ± 7) days with platelet transfusion. The occluder size, dose of heparin, residual shunt are the independent risk factors of thrombocytopenia after PDA interventional occlusion. Recover time of thrombocytopenia after PDA interventional occlusion is closely related to the severity of thrombocytopenia.

  17. Levamisole Reduces the Thrombocytopenia Associated with Myxovirus Vaccination (United States)

    Pineau, S.; Belbeck, L. W.; Moore, S.


    Mature dogs were vaccinated with a myxovirus vaccine. At this time, half of the dogs were also given a subcutaneous injection of levamisole hydrochloride (2.2 mg/kg). Blood platelets were counted daily. The dogs that had received only the vaccine showed, after 48 hours, a 48% decrease in platelets. Levamisole reduced the thrombocytopenia associated with myxovirus vaccination. Levamisole could have a protective effect on platelets by preventing their aggregation induced by viral neuraminidase. PMID:7363270

  18. Differentiation of severe fever with thrombocytopenia syndrome from scrub typhus. (United States)

    Kim, Min-Chul; Chong, Yong Pil; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han


    We developed a severe fever with thrombocytopenia syndrome (SFTS) differentiation score in the cohort including 21 patients with SFTS and 91 patients with scrub typhus. This scoring using criteria (score > 1) of altered mental status, leukopenia, prolonged aPTT, and normal CRP provided 100% sensitivity and 97% specificity for SFTS. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail:


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    Manoj Kumar Sahu


    Full Text Available BACKGROUND Valproate shows the most promising efficiency in treating mood as well as anxiety disorders; however, thrombocytopenia is one of the most common side effects associated with it. The perceived novelty and under recognition of the platelet lowering effects of valproate is illustrated by various case reports of thrombocytopenia associated with valproate in psychiatric populations. AIMS Present study aims is to investigate the relationship between platelet count & VPA therapy, age, and duration of medication. SETTINGS AND DESIGN It was a longitudinal observational study conducted at Department of Psychiatry, Pt. JNM Medical College, Raipur. METHODS AND MATERIAL The sample consisted of patients of either sex, aged between 18 to 65 years who were prescribed valproate therapy by the treating doctor. Patients were evaluated at baseline, at every month up to three months and at six months. The platelet counts were determined using an automatic haematology analyser. STATISTICAL ANALYSIS Correlation statistics were used to analyse the collected data. CONCLUSION Most of the time thrombocytopenia is mild and transient which resolves spontaneously. Regular monitoring of platelet level is required in the high risk groups.

  20. A diagnostic approach that may help to discriminate inherited thrombocytopenia from chronic immune thrombocytopenia in adult patients. (United States)

    Fiore, Mathieu; Pillois, Xavier; Lorrain, Simon; Bernard, Marie-Agnès; Moore, Nicholas; Sié, Pierre; Viallard, Jean-François; Nurden, Paquita


    Inherited thrombocytopenia (IT) is a heterogeneous group of rare diseases that are often confused with immune thrombocytopenia (ITP). The objective of this study was to supply clinicobiological elements that allow a distinction to be drawn between IT and chronic ITP. We then compared 23 adult patients with IT and 9 patients with chronic ITP. Our study revealed six discriminating criteria: (i) an age of discovery thrombocytopenia: PPV = 100.0% [82.4; 100.0], (iii) a personal history of bleeding: PPV = 100% [76.8; 100.0], (iv) a mean platelet volume >11 fL: PPV = 93.3% [68.1; 99.8], (v) an excess of giant platelets on blood smear: 100.0% [76.8; 100.0], and (vi) a percentage >44% of platelets with a surface area >4 µm(2) in electron microscopy: PPV = 83.3% [58.6; 96.4]. If at least three of these criteria were combined, it was possible to distinguish IT from chronic ITP with 91.3% [72.0; 98.9] sensitivity and PPV = 100.0% [66.4; 100.0] specificity. The secondary objective of this study was to assess the prevalence of potential IT diagnosis in patients with chronic thrombocytopenia of uncertain origin. Applying our diagnostic approach to a series of 20 cases allowed us to estimate that 40% of them could be suffering from IT. Finally, our diagnostic approach may help to correctly distinguish IT from chronic ITP, particularly in the context of macrothrombocytopenia.

  1. [Clinical analysis of pregnancy complicated with severe thrombocytopenia]. (United States)

    Wang, Da-peng; Liang, Mei-ying; Wang, Shan-mi


    To investigate the etiology and perinatal outcome of pregnancies complicated with extremely severe thrombocytopenia [at least two times of platelets count (PLT) pregnancy]. Clinical data, including basic information, etiology, management and outcomes of pregnant women with extremely severe thrombocytopenia, admitted to Peking University People's Hospital from January 2004 to March 2009, were retrospectively collected. The management of these cases varied according to different etiology and the symptoms: (1) PLT were maintained > 20 × 10(9)/L and hemoglobulin > 70 g/L in those women without spontaneous bleeding; (2) PLT transfusion would be required when PLT 70 g/L and PLT > 30 × 10(9)/L before cesarean section or delivery; (4) Predinisone and/or intravenous immunoglobulin G (IVIG) would be given in women complicated with idiopathic thrombocytopenic purpura (ITP) when PLT pregnancy. Among the 26 women, half received regular prenatal check in our hospital and the average gestations at diagnosis was 24 weeks and the other half without regular prenatal visits and the average gestations at diagnosis was 32 weeks. Etiology was identified in 24 out of the 26 women, including 14 (54%) ITP, 5 myelodysplastic syndrome (MDS), 4 chronic aplastic anaemia (CAA) and 1 systemic lupus erythematosus (SLE). (2) MANAGEMENT: All of the 26 women received blood products. Among the 14 ITP cases, 6 received predinisone and IVIG and 8 only took predinisone. Nine of the 26 patients (35%) had pregnant complications, among which 6 (6/9) were preeclampsia. The overall average gestation at delivery was 36 weeks. Only 2 delivered vaginally with the average blood loss of 83 ml and 23 cesarean sections were performed with the average blood loss of 410 ml. (3) Perinatal outcomes: There were 26 perinatal babies, among which 1 died intrauterine and 25 were born alive (12 preterm infants). The average birth weight was 2877 g. Neonatal severe thrombocytopenia presented in 2 newborns whose mother

  2. Rapid and durable response to intravenous immunoglobulin in delayed heparin-induced thrombocytopenia: a case report. (United States)

    Lei, Brandon Z; Shatzel, Joseph J; Sendowski, Merav


    Heparin-induced thrombocytopenia (HIT) results in platelet consumption and a virulent thrombotic state, which generally responds to cessation of heparin and initiation of anticoagulation. Rarely, delayed HIT can occur and/or persist after heparin is discontinued. A 47-year-old male developed delayed HIT with severe thrombocytopenia and thrombosis after cardiac surgery. Thrombocytopenia developed and persisted after heparin cessation and did not improve despite sequential use of argatroban followed by bivalirudin. Treatment with intravenous immunoglobulin (IVIg) was well tolerated and resulted in rapid resolution of thrombocytopenia. There are few case reports on the management of delayed HIT with severe and prolonged thrombocytopenia. The risk for thrombosis and bleeding in the setting of an undefined time course increases uncertainty in management. This case, along with others accumulating in the literature, suggest that IVIg may be effective in treating delayed HIT with persistent thrombocytopenia. © 2016 AABB.

  3. Thrombocytopenia in neonates with polycythemia: incidence, risk factors and clinical outcome. (United States)

    Vlug, Roos D; Lopriore, Enrico; Janssen, Marleen; Middeldorp, Johanna M; Rath, Mirjam E A; Smits-Wintjens, Vivianne E H J


    Polycythemia occurs in 1 to 5% of neonates and is associated with complications, including an increased risk of thrombocytopenia. To evaluate incidence, risk factors, management and outcome of thrombocytopenia in neonates with polycythemia. All neonates with polycythemia admitted to our neonatal intensive care unit between 2006 and 2013 were included in this retrospective study. We evaluated the incidence of thrombocytopenia (platelet count polycythemia and is independently associated with growth restriction. Increased hematocrit is associated with decreased platelet count.

  4. Heparin-Related Thrombocytopenia Triggered by Severe Status of Systemic Lupus Erythematosus and Bacterial Infection

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    Satoshi Suzuki


    Full Text Available A patient with severe lupus nephritis developed thrombocytopenia during treatment with high-dose steroids. In addition to viral- or disease-induced cytopenia, the pathology was believed to arise from diverse contributing factors, such as thrombotic microangiopathy and heparin-related thrombocytopenia (HIT. By combining plasma exchange therapy and intravenous cyclophosphamide, we successfully controlled the SLE activity and improved the thrombocytopenia. An antecedent bacterial infection or SLE activity is believed to have contributed to the concurrent HIT.

  5. Lupus anticoagulant hypoprothrombinemia syndrome associated with severe thrombocytopenia in a child. (United States)

    Foord, Aimee; Baca, Nicole; Buchbinder, David; Mahajerin, Arash


    Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) comprises lupus anticoagulant, acquired hypoprothrombinemia, and often mild thrombocytopenia or normal platelets. It is usually associated with autoimmunity or postviral illness. We describe a case of a 10-year-old boy with oral bleeding and severe thrombocytopenia initially suggestive of immune thrombocytopenia. Secondary to bleeding, evaluation demonstrated prolonged coagulation tests and subsequently revealed the presence of lupus anticoagulant and hypoprothrombinemia, along with marked autoimmunity, suggestive of LAHPS. He was treated with intravenous immunoglobulin and hydroxychloroquine. This case report and discussion highlight the diagnostic and therapeutic challenges associated with LAHPS and coincident severe thrombocytopenia. © 2016 Wiley Periodicals, Inc.

  6. Transient Elastography for Spleen Stiffness Measurement in Patients With Cirrhosis: Role in Degree of Thrombocytopenia. (United States)

    Chien, Cheng-Hung; Lin, Yi-Lan; Chien, Rong-Nan; Hu, Ching-Chih; Yen, Cho-Li; Lee, Tsung-Shih; Hsieh, Po-Jen; Lin, Chih-Lang


    The purpose of our study was to evaluate the relationship between spleen stiffness measured by transient elastography and the degree of thrombocytopenia in patients with liver cirrhosis. A total of 67 patients with liver cirrhosis were prospectively enrolled in the study. All patients underwent single-day hematologic and biochemical tests, sonography, and transient elastography of the liver and spleen. Thrombocytopenia was categorized as mild (platelet count, 75,000-150,000/μL), moderate (50,000-75,000/μL), and severe (thrombocytopenia was significantly correlated with spleen stiffness (P = .001) and spleen size (P = .002) but not with liver stiffness (P = .086). In patients without splenomegaly, spleen stiffness values were significantly higher in patients with thrombocytopenia than in those without thrombocytopenia (P = .035). In patients with splenomegaly, spleen stiffness values were significantly higher in patients with moderate to severe thrombocytopenia than in those with a normal platelet count or mild thrombocytopenia (P = .007). Compared to liver stiffness, spleen stiffness showed a better and statistically significant correlation with platelet count and spleen size in patients with cirrhosis. The degree of thrombocytopenia was directly correlated with spleen stiffness, irrespective of the presence of splenomegaly. The clinical phenomenon of unexpected thrombocytopenia may be explained by a subtle or irreversible change in spleen stiffness.

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

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    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.

  8. Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis (United States)

    Beers, D. R.; Ho, B. K.; Siklos, L.; Alexianu, M. E.; Mosier, D. R.; Mohamed, A. H.; Otsuka, Y.; Kozovska, M. E.; McAlhany, R. E.; Smith, R. G.; hide


    Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.

  9. Thrombocytopenia in common variable immunodeficiency patients – clinical course, management, and effect of immunoglobulins (United States)

    Siedlar, Maciej; Kowalczyk, Danuta; Szaflarska, Anna; Błaut-Szlósarczyk, Anita; Zwonarz, Katarzyna


    Common variable immunodeficiency (CVID) is a primary immunodeficiency of humoral immunity with heterogeneous clinical features. Diagnosis of CVID is based on hypogammaglobulinaemia, low production of specific antibodies, and disorders of cellular immunity. The standard therapy includes replacement of specific antibodies with human immunoglobulin, prophylaxis, and symptomatic therapy of infections. High prevalence of autoimmunity is characteristic for CVID, most commonly: thrombocytopaenia and neutropaenia, celiac disease, and systemic autoimmune diseases. The study included seven children diagnosed with CVID and treated with immunoglobulin substitution from 2 to 12 years. Thrombocytopenia was diagnosed prior to CVID in four children, developed during immunoglobulin substitution in three children. In one boy with CVID and thrombocytopaenia, haemolytic anaemia occurred, so a diagnosis of Evans syndrome was established. Therapy of thrombocytopaenia previous to CVID included steroids and/or immunoglobulins in high dose, and azathioprine. In children with CVID on regular immunoglobulin substitution, episodes of acute thrombocytopaenia were associated with infections and were treated with high doses of immunoglobulins and steroids. In two patients only chronic thrombocytopaenia was noted. Splenectomy was necessary in one patient because of severe course of thrombocytopaenia. The results of the study indicated a supportive role of regular immunoglobulin substitution in patients with CVID and chronic thrombocytopaenia. However, regular substitution of immunoglobulins in CVID patients did not prevent the occurrence of autoimmune thrombocytopaenia episodes or exacerbations of chronic form. In episodes of acute thrombocytopaenia or exacerbations of chronic thrombocytopaenia, infusions of immunoglobulins in high dose are effective, despite previous regular substitution in the replacing dose. PMID:26155188

  10. Thrombocytopenia in common variable immunodeficiency patients - clinical course, management, and effect of immunoglobulins. (United States)

    Pituch-Noworolska, Anna; Siedlar, Maciej; Kowalczyk, Danuta; Szaflarska, Anna; Błaut-Szlósarczyk, Anita; Zwonarz, Katarzyna


    Common variable immunodeficiency (CVID) is a primary immunodeficiency of humoral immunity with heterogeneous clinical features. Diagnosis of CVID is based on hypogammaglobulinaemia, low production of specific antibodies, and disorders of cellular immunity. The standard therapy includes replacement of specific antibodies with human immunoglobulin, prophylaxis, and symptomatic therapy of infections. High prevalence of autoimmunity is characteristic for CVID, most commonly: thrombocytopaenia and neutropaenia, celiac disease, and systemic autoimmune diseases. The study included seven children diagnosed with CVID and treated with immunoglobulin substitution from 2 to 12 years. Thrombocytopenia was diagnosed prior to CVID in four children, developed during immunoglobulin substitution in three children. In one boy with CVID and thrombocytopaenia, haemolytic anaemia occurred, so a diagnosis of Evans syndrome was established. Therapy of thrombocytopaenia previous to CVID included steroids and/or immunoglobulins in high dose, and azathioprine. In children with CVID on regular immunoglobulin substitution, episodes of acute thrombocytopaenia were associated with infections and were treated with high doses of immunoglobulins and steroids. In two patients only chronic thrombocytopaenia was noted. Splenectomy was necessary in one patient because of severe course of thrombocytopaenia. The results of the study indicated a supportive role of regular immunoglobulin substitution in patients with CVID and chronic thrombocytopaenia. However, regular substitution of immunoglobulins in CVID patients did not prevent the occurrence of autoimmune thrombocytopaenia episodes or exacerbations of chronic form. In episodes of acute thrombocytopaenia or exacerbations of chronic thrombocytopaenia, infusions of immunoglobulins in high dose are effective, despite previous regular substitution in the replacing dose.

  11. IVIg for Treatment of Severe Refractory Heparin-Induced Thrombocytopenia. (United States)

    Padmanabhan, Anand; Jones, Curtis G; Pechauer, Shannon M; Curtis, Brian R; Bougie, Daniel W; Irani, Mehraboon S; Bryant, Barbara J; Alperin, Jack B; Deloughery, Thomas G; Mulvey, Kevin P; Dhakal, Binod; Wen, Renren; Wang, Demin; Aster, Richard H


    Heparin-induced thrombocytopenia (HIT) complicated by severe thrombocytopenia and thrombosis can pose significant treatment challenges. Use of alternative anticoagulants in this setting may increase bleeding risks, especially in patients who have a protracted disease course. Additional therapies are lacking in this severely affected patient population. We describe three patients with HIT who had severe thromboembolism and prolonged thrombocytopenia refractory to standard treatment but who achieved an immediate and sustained response to IVIg therapy. The mechanism of action of IVIg was evaluated in these patients and in five additional patients with severe HIT. The impact of a common polymorphism (H/R 131) in the platelet IgG receptor FcγRIIa on IVIg-mediated inhibition of platelet activation was also examined. At levels attained in vivo, IVIg inhibits HIT antibody-mediated platelet activation. The constant domain of IgG (Fc) but not the antigen-binding portion (Fab) is required for this effect. Consistent with this finding, IVIg had no effect on HIT antibody binding in a solid-phase HIT immunoassay (platelet factor 4 enzyme-linked immunoassay). The H/R131 polymorphism in FcγRIIa influences the susceptibility of platelets to IVIg treatment, with the HH131 genotype being most susceptible to IVIg-mediated inhibition of antibody-induced activation. However, at high doses of IVIg, activation of platelets of all FcγRIIa genotypes was significantly inhibited. All three patients did well on long-term anticoagulation therapy with direct oral anticoagulants. These studies suggest that IVIg treatment should be considered in patients with HIT who have severe disease that is refractory to standard therapies. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  12. Argatroban in the management of heparin-induced thrombocytopenia

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    Luciano Babuin


    Full Text Available Luciano Babuin, Vittorio PengoClinical Cardiology, Department of Cardiac Thoracic and Vascular Sciences, University of Padua School of Medicine, Padova, ItalyAbstract: Heparin-induced thrombocytopenia (HIT is an immunoglobulin-mediated serious complication of heparin therapy characterized by thrombocytopenia and high risk for venous and arterial thrombosis: HIT and thrombosis syndrome (HITTS. Argatroban, a direct thrombin ­inhibitor, is indicated as the anticoagulant for the treatment and prophylaxis of thrombosis in patients with HIT and in patients undergoing percutaneous coronary intervention (PCI who have HIT. The aim of this review is to examine the pharmacological characteristics and the clinical efficacy and safety of this drug in adults with HIT, including those undergoing PCI. Briefly, 2 prospective multicenter, nonrandomized, open-label studies evaluated the efficacy and safety of argatroban as an anticoagulant in patients with HIT or HITTS. Both studies showed that the incidence of the primary efficacy end point, a composite of all-cause death, all-cause amputation, or new thrombosis, was reduced in argatroban-treated patients vs control subjects with HIT or HITTS. In both studies, bleeding rates were similar between the groups. Argatroban was evaluated as the anticoagulant therapy in 3 prospective, multicenter, open-label studies in HIT patients who underwent PCI. The studies were similar in design with respect to patient inclusion and exclusion criteria, the argatroban dosing regimen, and primary efficacy outcomes. The investigators performed a pooled analysis of these studies, which showed that most (≥95% patients achieved a satisfactory outcome from the procedure and adequate ­anticoagulation (coprimary end points.Keywords: argatroban, thrombocytopenia, thrombosis

  13. Interferon-β therapy and risk of thrombocytopenia in multiple sclerosis patients. (United States)

    Koudriavtseva, Tatiana; Plantone, Domenico; Renna, Rosaria; Mandoj, Chiara; Giannarelli, Diana; Mainero, Caterina


    Thrombocytopenia is a well-described adverse event of several disease-modifying therapies (DMT) in multiple sclerosis (MS). On the other hand, an increased prevalence of MS has been reported in patients with immune thrombocytopenia. In this retrospective, cross-sectional, case-control study we evaluated in a heterogeneous MS cohort: (1) the prevalence of thrombocytopenia in comparison with sex- and age-matched controls; (2) the relationship between thrombocytopenia and patients' demographic, clinical characteristics; (3) the risk for thrombocytopenia in relation to DMT. 187 consecutive MS patients [51 males, mean age (±SD) 44.5 ± 10.7 years] and 200 controls (56 males, mean age 45.5 ± 12 years) were included. Thrombocytopenia was defined as platelet count lower than normal laboratory values (130-400 × 10(9)/L). The prevalence of thrombocytopenia was significantly higher in MS patients than in controls (7 vs. 2.5 %, p = 0.04). Thrombocytopenia was present only in relapsing-remitting MS cases, and significantly associated with lower EDSS (p = 0.002) and with a trend for shorter disease duration (p = 0.06). It was more frequent in patients on high-dose interferon-β therapy compared with those on low-dose interferon-β therapy, other therapies or untreated patients (p = 0.02). High-dose interferon-β therapy was associated with more than eightfold increase in the risk for thrombocytopenia (odds ratio 8.60, 95 % confidence interval: 1.01-74.48 adjusted for EDSS, disease duration and type of disease). The prevalence of thrombocytopenia was increased in MS patients treated with DMT. High-dose interferon-β therapy is the variable most strongly associated with thrombocytopenia.

  14. Three parameters, plasma thrombopoietin levels, plasma glycocalicin levels and megakaryocyte culture, distinguish between different causes of congenital thrombocytopenia

    NARCIS (Netherlands)

    van den Oudenrijn, Sonja; Bruin, Marrie; Folman, Claudia C.; Bussel, James; de Haas, Masja; von dem Borne, Albert E. G. Kr


    Fourteen children with congenital thrombocytopenia were analysed in order to unravel the mechanisms underlying their thrombocytopenia and to evaluate the value of new laboratory tests, namely measurement of plasma thrombopoietin (Tpo) and glycocalicin (GC) levels and analysis of megakaryocytopoiesis

  15. Drug-specific characteristics of thrombocytopenia caused by non-cytotoxic drugs

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B


    OBJECTIVE: To analyse drug-specific clinical characteristics and to investigate the possible influence of epidemiological and other factors on thrombocytopenia induced by selected non-cytotoxic drugs. METHODS: A retrospective analysis of drug-induced thrombocytopenia reported to the Danish...

  16. Health-related quality of life in children with newly diagnosed immune thrombocytopenia

    NARCIS (Netherlands)

    Heitink-Pollé, Katja M. J.; Haverman, Lotte; Annink, Kim V.; Schep, Sarah J.; de Haas, Masja; Bruin, Marrie C. A.


    Despite its generally transient and benign course, childhood immune thrombocytopenia has a large impact on health-related quality of life. Recently published guidelines state that quality of life should be taken into account while making decisions on management in childhood immune thrombocytopenia.

  17. Spontaneous reflex sympathetic dystrophy (Sudeck's atrophy) syndrome associated with idiopathic thrombocytopenia. (United States)

    Hidaka, T; Suzuki, K; Hara, M; Kawagoe, M; Nakamura, H


    A 37-year-old woman developed reflex sympathetic dystrophy (RSD) (Sudeck's atrophy) syndrome in the right foot. Simultaneously, she had idiopathic thrombocytopenia. There was no history of injury or bone fracture before onset of RSD. Spontaneous RSD associated with idiopathic thrombocytopenia has rarely been described. A possible relationship between the 2 conditions is discussed.

  18. Early-Onset Thrombocytopenia in Small-For-Gestational-Age Neonates: A Retrospective Cohort Study

    NARCIS (Netherlands)

    Fustolo-Gunnink, S. F.; Vlug, R. D.; Smits-Wintjens, V. E. H. J.; Heckman, E. J.; te Pas, A. B.; Fijnvandraat, K.; Lopriore, E.


    Thrombocytopenia is a common finding in small for gestational age (SGA) neonates and is thought to result from a unique pathophysiologic mechanism related to chronic intrauterine hypoxia. Our objective was to estimate the incidence and severity of early-onset thrombocytopenia in SGA neonates, and to

  19. Persistent immune thrombocytopenia heralds the diagnosis of Mycobacterium chimaera prosthetic valve endocarditis

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    Keith A. Sacco


    Full Text Available A 63 year old female was admitted for investigation of worsening renal insufficiency. During hospitalization she developed persistent immune thrombocytopenia refractory to supportive or immunosuppressive treatment. She was diagnosed with Mycobacterium chimaera prosthetic valve endocarditis and thrombocytopenia resolved with anti-mycobacterial therapy.

  20. Heparin-induced thrombocytopenia among patients of a comprehensive cancer center

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    Weixin Wu


    Full Text Available Most clinical studies of heparin-induced thrombocytopenia have not included cancer patients who have high risk of thromboembolism, frequent exposure to heparin, and many potential causes of thrombocytopenia other than heparin-induced thrombocytopenia. To estimate the incidence and prevalence of heparin-induced thrombocytopenia in cancer patients, we identified cases based on diagnostic codes, anti-heparin antibody testing, and clinical characteristics (4T score at a comprehensive cancer center between 1 October 2008 and 31 December 2011. We estimated that the prevalence of heparin-induced thrombocytopenia to be 0.02% among all cancer patients and 0.24% among cancer patients exposed to heparin. The annual incidence of heparin-induced thrombocytopenia was 0.57 cases per 1000 cancer patients exposed to heparin. Of the 40 cancer patients with the International Classification of Diseases (Ninth Revision; ICD-9 code for heparin-induced thrombocytopenia, positive anti-heparin antibody, and 4T score ≥4, 5 (12.5% died of related thromboembolic or hemorrhagic complications. In a multivariate logistic regression model, male gender was a significant (p = 0.035 factor, and non-hematological malignancy was a significant (p = 0.017 factor associated with anti-heparin antibody positivity. Future studies may further examine the risk factors associated with heparin-induced thrombocytopenia in larger cohorts.

  1. Drug-induced thrombocytopenia after anticoagulation with rivaroxaban. (United States)

    Pop, Marianne K; Farokhi, Farhad; Iduna, Lela


    A 66-year-old man presented to the emergency department with complaints of dark-colored stool and rash developing over the last couple of days. The patient was started on rivaroxaban and flecainide for months prior for atrial fibrillation. Upon arrival, he was awake, alert, and oriented with a blood pressure of 111/63mmHg, heart rate of 68 beats per minute, and oxygen saturation of 96% on room air. A review of systems was unremarkable with the exception of skin rash and light-headedness. The patient's initial laboratory results were significant for red blood cell (RBC) count of 4.05×10 6 /mcL, hemoglobin of 12.1g/dL, hematocrit of 35.6%, and platelet count of 1×103/mcL. Aggressive hydration was started in the ED, initially with two 1-L boluses of normal saline followed by an infusion of 10mL/h. One unit of platelets was transfused. Rivaroxaban and flecainide were held on admission. Twenty-four hours after admission, the patient was initiated on immune globulin (IVIG) Gammagard (Baxter, West Lake, CA), 75g on 3 consecutive days and steroids for possible immune thrombocytopenia. His platelet count steadily improved over the 6-day period to 119×103/mcL on the day of hospital discharge. This is the second reported case of possible rivaroxaban-induced thrombocytopenia. Copyright © 2018. Published by Elsevier Inc.

  2. Resolution of Dialyzer Membrane-Associated Thrombocytopenia with Use of Cellulose Triacetate Membrane: A Case Report

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    Feyisayo Olafiranye


    Full Text Available Blood and dialyzer membrane interaction can cause significant thrombocytopenia through the activation of complement system. The extent of this interaction determines the biocompatibility of the membrane. Although the newer synthetic membranes have been shown to have better biocompatibility profile than the cellulose-based membranes, little is known about the difference in biocompatibility between synthetic membrane and modified cellulose membrane. Herein, we report a case of a patient on hemodialysis who developed dialyzer-membrane-related thrombocytopenia with use of synthetic membrane (F200NR polysulfone. The diagnosis of dialyzer membrane-associated thrombocytopenia was suspected by the trend of platelet count before and after dialysis, and the absence of other possible causes of thrombocytopenia. We observed significant improvement in platelet count when the membrane was changed to modified cellulose membrane (cellulose triacetate. In patients at high risk for thrombocytopenia, the modified cellulose membrane could be a better alternative to the standard synthetic membranes during hemodialysis.

  3. Prolonged thrombocytopenia in a child with severe neonatal alloimmune reaction and Noonan syndrome. (United States)

    Salva, Inês; Batalha, Sara; Maia, Raquel; Kjollerstrom, Paula


    Fetomaternal alloimmune thrombocytopenia (FMAIT) caused by maternal antibodies is the leading cause of severe neonatal thrombocytopenia. A 1-month-old Caucasian girl was referred to our Hematology Clinic for persistent thrombocytopenia diagnosed after a bleeding episode. Diagnostic tests suggested FMAIT. Mild thrombocytopenia persisted for 18 months, and subsequent findings of dysmorphic facies, short stature and mild pulmonary stenosis led to the hypothesis of Noonan syndrome (NS), which was confirmed by genetic test. Other hematological abnormalities were excluded and she had no further bleeding episodes. This case illustrates the possibility of different diagnoses with the same clinical manifestations. The persistence of thrombocytopenia longer than expected associated with typical physical features led to the diagnosis of NS.

  4. Thrombocytopenia is associated with an increased risk of cancer during treated HIV disease

    DEFF Research Database (Denmark)

    Borges, Alvaro Humberto Diniz; Lundgren, Jens D; Ridolfo, Annalisa


    patients, including 1168 non-AIDS-defining events [crude incidence 18.6/1000 PYFU, 95% confidence interval (CI) 17.5-19.6] and 735 AIDS-defining events (crude incidence 11.7/1000 PYFU, 95% CI 10.8-12.5). Patients with thrombocytopenia (platelet count ≤100 × 10/l) had a slightly increased incidence of AIDS...... (aIRR 2.20, 95% CI 1.61-3.01), but not cardiovascular disease (aIRR 0.66, 95% CI 0.32-1.34), was significantly higher in patients with thrombocytopenia. The association between thrombocytopenia and cancer remained unaltered in sensitivity analyses requiring repeated platelet counts to confirm...... thrombocytopenia and lagging platelets by 1 year prior to clinical events.CONCLUSION: Patients with thrombocytopenia had increased incidence of AIDS-defining and non-AIDS-defining events, but the association with the latter, in particular cancer, was stronger. Future studies should investigate whether...

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

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    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.

  6. Thrombocytopenia as a thrombotic risk factor in patients with antiphospholipid antibodies without disease criteria. (United States)

    Demetrio Pablo, Rosalia; Muñoz, Pedro; López-Hoyos, Marcos; Calvo, Vanesa; Riancho, Leyre; Martínez-Taboada, Victor Manuel


    The antiphospholipid syndrome (APS) is an acquired immune disorder defined by the presence of thrombosis (arterial and/or venous) and/or pregnancy morbidity along with the presence of positive antiphospholipid antibodies (aPL). There is a clear relationship between aPL and some events not included in the clinical criteria, including haematologic. a) to study the probability of developing clinical APS in patients with positive aPL and thrombopenia; b) to identify potential risk factors for thrombosis, and c) to study the association between thrombocytopenia and aPL. A retrospective study of 138 patients with positive aPL without fulfilling clinical criteria for APS. Thrombocytopenia was defined as a platelet count≤100,000/μl. Patients with other causes of thrombocytopenia were excluded. Seventeen of the 138 (12%) patients in the study had thrombocytopenia. The mean platelet count was 60,000/μl. The risk of developing thrombocytopenia was higher in smokers (OR 2.8; P=.044), in those with lupus anticoagulant (OR 13.5; P<.001) and those with higher burden of aPL (OR 50.8; P<.001). After a mean follow-up of 146±60.3 months, 5 patients with thrombocytopenia (29.4%) developed thrombosis. In our series, the incidence of thrombocytopenia is 12%. aPL-positive patients who develop thrombocytopenia have a potential risk of developing thrombosis. Tobacco could be a risk factor for thrombocytopenia. Autoantibodies load is a risk factor for the development of thrombocytopenia. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

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

    DEFF Research Database (Denmark)

    Brorsson, Caroline Anna; Pociot, Flemming


    ) in autoimmune gastritis, transglutaminase (TGA) in celiac disease, and 21-hydroxylase (21-OHA) in autoimmune hypoadrenalism. In addition to the MHC region, we identify SNPs in five susceptibility loci (IFIH1, PTPN22, SH2B3, BACH2, and CTLA4) as significantly associated with more than one autoantibody at a false......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...... 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...

  8. Anti-inflammatory activity of extra virgin olive oil polyphenols: which role in the prevention and treatment of immune-mediated inflammatory diseases? (United States)

    Santangelo, Carmela; Vari, Rosaria; Scazzocchio, Beatrice; De Sanctis, Patrizia; Giovannini, Claudio; D'Archivio, Massimo; Masella, Roberta


    Altered inflammatory response characterizes chronic immune-mediated inflammatory diseases (IMID) such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, and psoriasis. Accumulating evidence indicates that regular consumption of extra virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, is associated with a reduced risk of developing chronic degenerative disorders such cardiovascular diseases, type 2 diabetes and cancer. The beneficial effects on health of EVOO have been attributed, besides to the monounsaturated fats content, to the presence of phenolic compounds that have antioxidant, anti-inflammatory and immunomodulatory properties. The purpose of this review is to provide an overview of the effects of EVOO polyphenols on IMID highlighting the potential mechanisms of action. In particular, the activity of the major EVOO phenolic compounds, including oleuropein, hydroxytyrosol, tyrosol, and oleochantal, in modulating the disease associated inflammatory perturbations will be discussed. Copyright© Bentham Science Publishers; For any queries, please email at

  9. ADEM: literature review and case report of acute psychosis presentation. (United States)

    Nasr, J T; Andriola, M R; Coyle, P K


    Acute disseminated encephalomyelitis is a monophasic, immune-mediated disorder that produces multifocal demyelinating lesions within the central nervous system. It is characterized clinically by the acute onset of neurologic abnormalities, including varying degrees of mental state changes ranging from drowsiness to coma. It is unusual for the illness to present as an isolated acute psychosis. The case of a 14-year-old female with biopsy-confirmed acute disseminated encephalomyelitis, who was initially diagnosed with an acute psychiatric disorder, is presented, and published reports on this unusual manifestation are reviewed. A Medline database search was performed from 1965 to 1999, using the terms acute disseminated encephalomyelitis, postvaccinal encephalomyelitis, postinfectious encephalomyelitis, and measles encephalomyelitis, combined with the terms psychosis, psychiatric disorder, and behavioral disorder. Selected cross-referenced reports were also reviewed. Nine patients were identified who presented with acute psychosis. We conclude that, although rare, acute disseminated encephalomyelitis can present as an acute psychosis. This immune-mediated condition should be included in the differential diagnosis of neurologic disorders presenting as a psychiatric illness.

  10. In Vitro Infection of Human Nervous Cells by Two Strains of Toxoplasma gondii: A Kinetic Analysis of Immune Mediators and Parasite Multiplication (United States)

    Mammari, Nour; Vignoles, Philippe; Halabi, Mohamad Adnan; Darde, Marie Laure; Courtioux, Bertrand


    The severity of toxoplasmic infection depends mainly on the immune status of the host, but also on the Toxoplasma gondii strains, which differ by their virulence profile. The relationship between the human host and T. gondii has not yet been elucidated because few studies have been conducted on human models. The immune mechanisms involved in the persistence of T. gondii in the brains of immunocompetent subjects and during the reactivation of latent infections are still unclear. In this study, we analyzed the kinetics of immune mediators in human nervous cells in vitro, infected with two strains of T. gondii. Human neuroblast cell line (SH SY5Y), microglial (CMH5) and endothelial cells (Hbmec) were infected separately by RH (type I) or PRU (type II) strains for 8 h, 14 h, 24 h and 48 h (ratio 1 cell: 2 tachyzoites). Pro-inflammatory protein expression was different between the two strains and among different human nervous cells. The cytokines IL-6, IL-8 and the chemokines MCP-1 and GROα, and SERPIN E1 were significantly increased in CMH5 and SH SY5Y at 24 h pi. At this point of infection, the parasite burden declined in microglial cells and neurons, but remained high in endothelial cells. This differential effect on the early parasite multiplication may be correlated with a higher production of immune mediators by neurons and microglial cells compared to endothelial cells. Regarding strain differences, PRU strain, but not RH strain, stimulates all cells to produce pro-inflammatory growth factors, G-CSF and GM-CSF. These proteins could increase the inflammatory effect of this type II strain. These results suggest that the different protein expression profiles depend on the parasitic strain and on the human nervous cell type, and that this could be at the origin of diverse brain lesions caused by T. gondii. PMID:24886982

  11. Acute Disseminated Encephalomyelitis Following Typhoid Fever: A Case Report

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    R Adhikari


    Full Text Available The involvement of central nervous system in children with typhoid fever is common. Acute disseminated encephalomyelitis is a rare immune mediated and demyelinating disease of the central nervous system that usually affects children. We report a 7-year-old child with typhoid fever who developed acute cerebellar syndrome due to acute disseminated encephalomyelitis.Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-4, 55-58 DOI:

  12. MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia. (United States)

    Rauch, Philipp J; Ellegast, Jana M; Widmer, Corinne C; Fritsch, Kristin; Goede, Jeroen S; Valk, Peter J M; Löwenberg, Bob; Takizawa, Hitoshi; Manz, Markus G


    Although the molecular pathways that cause acute myeloid leukemia (AML) are increasingly well understood, the pathogenesis of peripheral blood cytopenia, a major cause of AML mortality, remains obscure. A prevailing assumption states that AML spatially displaces nonleukemic hematopoiesis from the bone marrow. However, examining an initial cohort of 223 AML patients, we found no correlation between bone marrow blast content and cytopenia, questioning the displacement theory. Measuring serum concentration of thrombopoietin (TPO), a key regulator of hematopoietic stem cells and megakaryocytes, revealed loss of physiologic negative correlation with platelet count in AML cases with blasts expressing MPL, the thrombopoietin (scavenging) receptor. Mechanistic studies demonstrated that MPLhi blasts could indeed clear TPO, likely therefore leading to insufficient cytokine levels for nonleukemic hematopoiesis. Microarray analysis in an independent multicenter study cohort of 437 AML cases validated MPL expression as a central predictor of thrombocytopenia and neutropenia in AML. Moreover, t(8;21) AML cases demonstrated the highest average MPL expression and lowest average platelet and absolute neutrophil counts among subgroups. Our work thus explains the pathophysiology of peripheral blood cytopenia in a relevant number of AML cases. © 2016 by The American Society of Hematology.

  13. Atorvastatin induced thrombocytopenia: A case report and review of literature

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    Saibal Moitra


    Full Text Available A 65-year-old hypertensive male, with co-existing benign prostatic hyperplasia for last 5 years was on tab telmisartan 40 mg and tab tamsulosin 0.4 mg, both once daily. He was found dyslipidemic on a routine investigation and was put on tab atorvastatin 10 mg once daily. The patient developed a petechial rash and bleeding from gums within a week of starting atorvastatin, and his platelet count dropped to 15,000/cmm. Atorvastatin was suspected to be the offender as no other causes of thrombocytopenia could be implicated. Atorvastatin was discontinued and intravenous steroid and platelet transfusion given. Platelet count improved gradually and became normal after 10 days. Causality assessment as per the Naranjo algorithm revealed a "probable association" with atorvastatin therapy.

  14. Romiplostim as early treatment of immune thrombocytopenia with severe immunodeficiency

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    Francesca Palandri


    Full Text Available Immunosuppressive agents are the standard therapeutic approach for immune thrombocytopenia (ITP. Their prolonged use may increase the risk of infectious complications, particularly when the patient is already at higher infectious risk. In this setting, the use of drugs with a mechanism of action alternative to immunosuppression, like thrombopoietin receptor agonists (TRAs, may find particular indication. We report the unique case of a patient with severe immunodeficiency and ITP, who experienced a serious infectious complication while on steroids treatment, and who was successfully treated with Romiplostim second- line. The present experience supports the effectiveness and safety of TRAs as early treatment of ITP patients with drug-induced immunodeficiency or with active infections.

  15. A retrospective study of the risk factors for linezolid-induced thrombocytopenia and anemia. (United States)

    Hanai, Yuki; Matsuo, Kazuhiro; Ogawa, Miki; Higashi, Ayaka; Kimura, Itsuki; Hirayama, Shinobu; Kosugi, Takayoshi; Nishizawa, Kenji; Yoshio, Takashi


    Myelosuppression is major treatment-related adverse events of linezolid therapy and result in treatment termination in some cases. We aimed to identify the risk factors for linezolid-induced thrombocytopenia and anemia. We retrospectively retrieved demographic and laboratory data from the medical records of 221 Japanese patients who were undergoing linezolid therapy. Thrombocytopenia and anemia were defined as an unexplained reduction of >30% in the patient's platelet count and hemoglobin level, respectively, from the baseline. Thrombocytopenia developed in 48.4% of patients, and anemia developed in 10.4% of patients during linezolid therapy. In multivariate analysis, creatinine clearance (adjusted odds ratio = 0.94 [0.92-0.95], P thrombocytopenia. Patients with creatinine clearance rates of thrombocytopenia. In addition, a high incidence of linezolid-induced thrombocytopenia was even detected among the patients that had received linezolid therapy for 15 days. In conclusion, we recommend that among patients receiving linezolid therapy the platelet counts of those with risk factors for linezolid-induced thrombocytopenia should be monitored closely throughout treatment, and the hemoglobin levels of patients that receive linezolid for >15 days should be carefully monitored on a weekly basis to detect anemia. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  16. Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis. (United States)

    Machlus, Kellie R; Wu, Stephen K; Vijey, Prakrith; Soussou, Thomas S; Liu, Zhi-Jian; Shacham, Eran; Unger, T J; Kashyap, Trinayan; Klebanov, Boris; Sola-Visner, Martha; Crochiere, Marsha; Italiano, Joseph E; Landesman, Yosef


    Selinexor is the first oral selective inhibitor of nuclear export compound tested for cancer treatment. Selinexor has demonstrated a safety therapy profile with broad antitumor activity against solid and hematological malignancies in phases 2 and 3 clinical trials (#NCT03071276, #NCT02343042, #NCT02227251, #NCT03110562, and #NCT02606461). Although selinexor shows promising efficacy, its primary adverse effect is high-grade thrombocytopenia. Therefore, we aimed to identify the mechanism of selinexor-induced thrombocytopenia to relieve it and improve its clinical management. We determined that selinexor causes thrombocytopenia by blocking thrombopoietin (TPO) signaling and therefore differentiation of stem cells into megakaryocytes. We then used both in vitro and in vivo models and patient samples to show that selinexor-induced thrombocytopenia is indeed reversible when TPO agonists are administered in the absence of selinexor (drug holiday). In sum, these data reveal (1) the mechanism of selinexor-induced thrombocytopenia, (2) an effective way to reverse the dose-limiting thrombocytopenia, and (3) a novel role for XPO1 in megakaryopoiesis. The improved selinexor dosing regimen described herein is crucial to help reduce thrombocytopenia in selinexor patients, allowing them to continue their course of chemotherapy and have the best chance of survival. This trial was registered at as #NCT01607905. © 2017 by The American Society of Hematology.

  17. Thrombocytopenia model with minimal manipulation of blood cells allowing whole blood assessment of platelet function. (United States)

    Tiedemann Skipper, Mette; Rubak, Peter; Halfdan Larsen, Ole; Hvas, Anne-Mette


    In vitro models of thrombocytopenia are useful research tools. Previously published models have shortcomings altering properties of platelets and other blood components. The aim of the present study was to develop a whole blood method to induce thrombocytopenia with minimal manipulation, and to describe platelet function in induced thrombocytopenia in individuals with healthy platelets. Hirudin anticoagulated blood was obtained from 20 healthy volunteers. One part of the blood was gently centrifuged at 130g for 15 minutes. The platelet-rich plasma was replaced with phosphate-buffered saline to establish thrombocytopenia. Various levels of thrombocytopenia were achieved by combining different volumes of baseline whole blood and thrombocytopenic blood. Platelet counts were measured by flow cytometry (Navios, Beckman Coulter) and routine haematological analyser (Sysmex XE-5000). Platelet function was analysed by impedance aggregometry (Multiplate® Analyzer, Roche) and by flow cytometry (Navios, Beckman Coulter) using collagen, adenosine diphosphate, thrombin receptor activating peptide-6 and ristocetin as agonists. Median baseline platelet count was 227×10(9)/l. The in vitro model yielded median platelet counts at 51×10(9)/l (range 26-93×10(9)/l). We observed minor, yet significant, changes in platelet size and maturity from baseline to modelled thrombocytopenia. In the thrombocytopenic samples, significant and positive linear associations were found between platelet count and platelet aggregation across all agonists (all p-valuesthrombocytopenia was established and validated. This new model serves as a useful future tool, particularly to explore platelet function in patients with thrombocytopenia.

  18. Thrombocytopenia as an adverse effect of complementary and alternative medicines, herbal remedies, nutritional supplements, foods, and beverages. (United States)

    Royer, Derek J; George, James N; Terrell, Deirdra R


    Thrombocytopenia is a well-recognized adverse effect of many drugs. However, the association of thrombocytopenia with complementary/alternative medicines, herbal remedies, nutritional supplements, foods, and beverages has been rarely described, except for reports of thrombocytopenia caused by quinine-containing beverages. To systematically identify all published reports of thrombocytopenia associated with these substances and to assess the evidence supporting their causal association with thrombocytopenia. Eleven databases were searched to identify relevant published reports. A priori criteria were defined for article selection and assessment. Each selected article was independently assessed by the three authors to document the presence of the criteria and determine the level of evidence for a causal association of the reported substance with thrombocytopenia. Twenty-seven articles were identified that reported the occurrence of thrombocytopenia with 25 substances (other than quinine). However, only six articles describing five substances (cow's milk, cranberry juice, Jui [Chinese herbal tea], Lupinus termis bean, and tahini [pulped sesame seeds]) reported clinical data supporting definite evidence of a causal association with thrombocytopenia. Four articles provided probable evidence for four additional substances, and five articles provided possible evidence for five additional substances. In the remaining articles, the association with thrombocytopenia was unlikely or the articles were excluded from review. Reports of thrombocytopenia describing definite or probable evidence for an association of a complementary/alternative medicines, herbal remedies, nutritional supplements, foods, and beverages are rare. Whether the occurrence of thrombocytopenia with these substances is uncommon or unrecognized is unknown.

  19. The Incidence, Clinical Outcomes, and Risk Factors of Thrombocytopenia in Intra-Abdominal Infection Patients: A Retrospective Cohort Study (United States)

    Wu, Qin; Ren, Jianan; Wang, Gefei; Li, Guanwei; Gu, Guosheng; Wu, Xiuwen; Li, Yuan; Chen, Jun; Zhao, Yunzhao; Li, Jieshou


    Background Studies on the incidence and risk factors of thrombocytopenia among intra-abdominal infection patients remain absent, hindering efficacy assessments regarding thrombocytopenia prevention strategies. Methods 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. Results 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. Conclusions 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. PMID:26808492

  20. Prevalence of Thrombocytopenia among Chinese Adult Antiretroviral-naïve HIV-positive Patients (United States)

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


    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 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 of 50–199 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 = 0.018), 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

  1. A successful method for severe gestational thrombocytopenia: A rare case study

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    Adnan İncebıyık


    Full Text Available In a normally progressing pregnancy, especially in thethird trimester thrombocyte numbers reduce by about10%. The reason for this reduction is thought to be thehemodilution and increased consumption in pregnancy.Generally, it is recognized by chance during routine bloodcount and it is the second most common hematologicanomaly during pregnancy. Once thrombocytopenia isdiagnosed in pregnancy, research must be done to determinewhether it is a life-threatening risk factor in terms ofthe mother-fetus-infant. The majority of thrombocytopeniaseen in pregnancy is gestational thrombocytopenia. Thispaper examines an active labor, normal birthing case witha thrombocyte count of 7916/mm3.Key words: Gestational thrombocytopenia, idiopathicthrombocytopenic purpura, normal birth

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

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    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.

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

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    Joonhee Cho

    Full Text Available 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.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.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-6.17β-estradiol and IL-6 may act synergistically to promote sex bias in experimental DILI by reducing Tregs. Modulating Treg numbers may provide a therapeutic approach to DILI.

  4. Drug utilization of biological drugs in the treatment of chronic Immune-Mediated Inflammatory Diseases (IMIDs: an observational study on Italian patients

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    Paolo Faccendini


    Full Text Available Drug utilization of biological drugs in the treatment of chronic Immune-Mediated Inflammatory Diseases (IMIDs: an observational study on Italian patientsObjectives:The aim of this analysis was to provide an estimate of drug utilization indicators (dose escalation and dose tapering related to biologic drugs in the chronic treatment of adult patients with Immune-Mediated Inflammatory Diseases (IMIDs.Methods:We conducted an observational retrospective cohort analysis using the Policlinico di Tor Vergata (PTV database. We considered all biologic drugs dispensed by the PTV hospital pharmacy between January 2010 and December 2015:abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab (originator and biosimilar, tocilizumab, and ustekinumab were included. Drug dose escalation and dose tapering were calculated and compared with their Defined Daily Dose (DDD.Results:A total of 1803 patients with IMID and biologic drug prescription were analyzed (male: 51.2%. The majority of patients were in the class 36-50 years (n = 612. The median follow-up was 33.8 months (IQR 14.43-56.20. Dermatology was the ward with the largest number of patients (n = 882; 48.9%, followed by rheumatology (n = 619; 34.3% and gastroenterology (n = 302; 16.8%. Dose escalation was observed in 406 patients (22.5%. Infliximab biosimilar (n = 51 was the biological drug with the highest dose escalation rate (86.3%, followed by infliximab originator (n = 28; 60.3% and ustekinumab (37.8%. Etanercept was the biological drug with the lowest dose escalation rate (7.4%, followed by golimumab (12.2% and adalimumab (13.8%. In 677 patients (37.5% a dose tapering was observed. Etanercept showed the highest rate of patients with dose tapering (41.6%, followed by adalimumab (33.6%.Conclusions:The results of this analysis show that dose modification is quite common in PTV clinical practice. Considering the strong focus on the pharmaceutical expenditure and the need of cost containment

  5. Bactrim Induced Hemolysis and Thrombocytopenia in a Patient with Pernicious Anemia

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    Aijan Ukudeyeva


    Full Text Available This case report presents a 87-year-old female who had a history of pernicious anemia and was given Bactrim, which suppressed folic acid and caused a more profound anemia, thrombocytopenia and hemolysis.

  6. Severe Malarial Thrombocytopenia: A Risk Factor for Mortality in Papua, Indonesia (United States)

    Lampah, Daniel A.; Yeo, Tsin W.; Malloy, Michael; Kenangalem, Enny; Douglas, Nicholas M.; Ronaldo, Donny; Sugiarto, Paulus; Simpson, Julie A.; Poespoprodjo, Jeanne Rini; Anstey, Nicholas M.; Price, Ric N.


    Background The significance of thrombocytopenia to the morbidity and mortality of malaria is poorly defined. We compared the platelet counts and clinical correlates of patients with and those without malaria in southern Papua, Indonesia. Methods Data were collated on patients presenting to a referral hospital between April 2004 and December 2012. Results Platelet measurements were available in 215 479 patients (23.4%), 66 421 (30.8%) of whom had clinical malaria. Patients with Plasmodium falciparum monoinfection had the lowest platelet counts and greatest risk of severe thrombocytopenia (platelet count, thrombocytopenia alone had an adjusted OR of 2.77 (95% CI, 2.20–3.48), and those with both risk factors had an adjusted OR of 13.76 (95% CI, 10.22–18.54; P thrombocytopenia identifies both children and adults at increased risk of death from falciparum or vivax malaria, particularly in those with concurrent severe anemia. PMID:25170106

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

    NARCIS (Netherlands)

    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

  8. International consensus report on the investigation and management of primary immune thrombocytopenia

    NARCIS (Netherlands)

    Provan, Drew; Stasi, Roberto; Newland, Adrian C.; Blanchette, Victor S.; Bolton-Maggs, Paula; Bussel, James B.; Chong, Beng H.; Cines, Douglas B.; Gernsheimer, Terry B.; Godeau, Bertrand; Grainger, John; Greer, Ian; Hunt, Beverley J.; Imbach, Paul A.; Lyons, Gordon; McMillan, Robert; Rodeghiero, Francesco; Sanz, Miguel A.; Tarantino, Michael; Watson, Shirley; Young, Joan; Kuter, David J.


    Previously published guidelines for the diagnosis and management of primary immune thrombocytopenia (ITP) require updating largely due to the introduction of new classes of therapeutic agents, and a greater understanding of the disease pathophysiology. However, treatment-related decisions still

  9. Perinatal outcome in normal pregnant women with incidental thrombocytopenia at delivery

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    Ying-Hsuan Lin


    Conclusions: The results indicate that women who suffered from incidental thrombocytopenia at delivery but did not have other diseases during pregnancy were not at increased risk for adverse pregnancy outcomes.

  10. Screening in pregnancy for fetal or neonatal alloimmune thrombocytopenia: systematic review

    NARCIS (Netherlands)

    Kamphuis, M. M.; Paridaans, N.; Porcelijn, L.; de Haas, M.; van der Schoot, C. E.; Brand, A.; Bonsel, G. J.; Oepkes, D.


    Background Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, which may lead to intracranial haemorrhage (ICH), with neurological damage as a consequence. In the absence of screening, FNAIT is only diagnosed after bleeding symptoms, with preventive options

  11. Assessing thrombocytopenia in the intensive care unit: the past, present, and future. (United States)

    Zarychanski, Ryan; Houston, Donald S


    Thrombocytopenia is common among patients admitted to the intensive care unit (ICU). Multiple pathophysiological mechanisms may contribute, including thrombin-mediated platelet activation, dilution, hemophagocytosis, extracellular histones, ADAMTS13 deficiency, and complement activation. From the clinical perspective, the development of thrombocytopenia in the ICU usually indicates serious organ system derangement and physiologic decompensation rather than a primary hematologic disorder. Thrombocytopenia is associated with bleeding, transfusion, and adverse clinical outcomes including death, though few deaths are directly attributable to bleeding. The assessment of thrombocytopenia begins by looking back to the patient's medical history and presenting illness. This past information, combined with careful observation of the platelet trajectory in the context of the patient's clinical course, offers clues to the diagnosis and prognosis. Management is primarily directed at the underlying disorder and transfusion of platelets to prevent or treat clinical bleeding. Optimal platelet transfusion strategies are not defined, and a conservative approach is recommended. © 2016 by The American Society of Hematology. All rights reserved.

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

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    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.

  13. Benefit of transfusion-related acute lung injury risk-minimization measures--German haemovigilance data (2006-2010). (United States)

    Funk, M B; Guenay, S; Lohmann, A; Henseler, O; Heiden, M; Hanschmann, K M O; Keller-Stanislawski, B


    Based on the frequency of immune-mediated and non-immune-mediated transfusion-related acute lung injury (TRALI), the effect of risk-minimization measures was evaluated during a period of 5 years (2006-2010). Risk-minimization measures were implemented in 2008/2009, consisting of exclusion of female donors with a history of pregnancy or exclusion of female donors with human leucocyte antigen (HLA)/human neutrophil alloantigen (HNA) antibodies. TRALI was confirmed according to the criteria of the International Haemovigilance Network. Based upon the results of donor testing of white-blood-cell antibodies (WBC-Ab) against HLA or HNAs, confirmed cases were classified as immune- or non-immune-mediated TRALI. Reporting rates were calculated on the basis of the annually transfused blood components, and pre- and post-implementation periods were compared. In total, 60 immune-mediated (75%) and 20 non-immune-mediated (25%) TRALI reactions were confirmed. A total of 68 (64 women and four men) donors were involved: seven red-blood-cell concentrates donors (13%), six platelet concentrate donors (10%), and 48 fresh frozen plasma (FFP) donors (77%). The reporting rate of immune-mediated TRALI caused by FFP decreased continuously; from 12·71 per million units in 2006/2007 to 6·81 per million units in 2008/2009 and no case in 2010. The comparison of the pre- and the post-implementation period demonstrated a significantly reduced risk of TRALI events comparing 2006/2007 with 2010 (P-value: <0·01). Furthermore, no case of TRALI-induced fatality occurred after the implementation of risk-minimization measures. © 2011 The Author(s). Vox Sanguinis © 2011 International Society of Blood Transfusion.

  14. Presentation, management and outcome of heparin-induced thrombocytopenia after valvular heart surgery. (United States)

    Arangalage, Dimitri; Lepage, Laurent; Faille, Dorothée; Cimadevilla, Claire; Dilly, Marie-Pierre; Papy, Emmanuelle; Alhenc-Gelas, Martine; Ghodbane, Walid; Nataf, Patrick; Iung, Bernard; Steg, Philippe Gabriel; Vahanian, Alec; Ajzenberg, Nadine; Messika-Zeitoun, David


    The use of heparin exposes patients to heparin-induced thrombocytopenia, which is a challenging issue for both diagnosis and patient management. We sought to describe the clinical presentation, management and outcome of a series of patients diagnosed with heparin-induced thrombocytopenia after heart valve surgery. All consecutive patients diagnosed with heparin-induced thrombocytopenia during the postoperative period of heart valve surgery over a 6-year period were prospectively enrolled in a single-centre registry. Clinical and biological data were collected. In-hospital and mid-term outcomes were assessed. Information regarding the occurrence of all medical events including death, recurrence of thromboembolic events and/or thrombocytopenia was collected. We identified 93 patients (incidence proportion = 2.8%). Most patients (82%) were asymptomatic with isolated thrombocytopenia at the time of diagnosis. The other main circumstance of diagnosis was the occurrence of thromboembolic events in 17 patients (6 strokes, 10 prosthetic valve thrombosis and 1 peripheral embolic event). The in-hospital mortality rate was 1%. No thrombolysis, interventional procedure or redo surgery was performed. Danaparoid sodium was used as heparin replacement therapy in most cases (96%) and leading to complete and uneventful thrombus resolution in all cases with only one possibly related major bleeding complication. During a mean follow-up of 36 ± 20 months, no patient presented recurrence of any heparin-induced thrombocytopenia-related complication. In this contemporary series of patients, heparin-induced thrombocytopenia incidence was low and isolated thrombocytopenia was the most frequent presentation. Conservative management with early diagnosis and substitutive anticoagulation therapy introduction was associated with a low rate of clinical events and a remarkably good outcome with a low mortality rate. © The Author 2016. Published by Oxford University Press on behalf of the

  15. Clinical features and outcome of pregnancy with SLE-associated thrombocytopenia. (United States)

    Xu, Xue; Liang, Mei-Ying; Wang, Jian-Liu; Chen, Shi


    To analyze the course of maternal diseases and compare pregnancy outcomes in patients with systemic lupus erythematosus (SLE)-associated thrombocytopenia to patients without. Medical charts of 77 pregnancies in 73 SLE patients were systematically reviewed. Patients were divided into two groups according to the presence or absence of thrombocytopenia. Patients who are new onset SLE during pregnancy were also been studied. Thrombocytopenia was found in 18 (23.3%) of the pregnancies. SLE patients with thrombocytopenia during pregnancy had higher percentage of disease flaring (11/18 versus 14/59, p = 0.003) and SLE-Pregnancy Disease Activity Index (7.89 ± 6.192 versus 2.41 ± 3.3.89, p = 0.001) compared to patients without. Also, patients with thrombocytopenia had a higher percentage of pulmonary, cardiac and multiple organ system involvement. There was a statistically significant difference in preeclampsia and early onset hypertensive disorder induced before 34 weeks as well as the rate of live birth less than 34 weeks (33.3% versus 6.8%, p = 0.003 & 38.9% versus 13.6%, p = 0.018 & 16.7% versus 1.7%, p = 0.038). Patients with thrombocytopenia suffered from higher rate of pregnancy loss (22.2% versus 3.4%, p = 0.024) and neonatal death (33.3% versus 1.7%, p = 0.000). In our study there were 17 patients with new-onset of SLE during pregnancy. The hematological system manifestation occurred in all of them and there was a significant increase in the incidence of thrombocytopenia (n = 12, 70.6%). Thrombocytopenia in SLE during pregnancy indicates higher disease activity, severe organ damage, early onset preeclampsia and higher pregnancy loss.

  16. Triad of Iron Deficiency Anemia, Severe Thrombocytopenia and Menorrhagia—A Case Report and Literature Review


    Ibrahim, Ramy; Khan, Areej; Raza, Shahzad; Kafeel, Muhammad; Dabas, Ridhima; Haynes, Elizabeth; Gandhi, Anjula; Majumder, Omran L.; Zaman, Mohammad


    Introduction Thrombocytosis is a common disorder in patients diagnosed with iron deficiency anemia. The decreased platelet counts commonly found iron deficiency anemia is rarely reported in clinical practice. The exact mechanism of the occurrence of thrombocytopenia in iron deficiency anemia remains unclear. In this case report we discuss a triad of symptoms seen in the African American population: Iron deficiency anemia, menorrhagia and thrombocytopenia. Case presentation A 40 year old multi...

  17. Chemotherapy induced thrombocytopenia treated by four types of platelets concentrates

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    Nikolić Ljubinka I.


    Full Text Available Introduction: Serious adverse event of anticancer chemotherapy is glanulocytopenia and thrombocytopenia which can decrease efficiency of final therapy results. After many years, platelet concentrates transfusion (PCT is still researching problem without sure standpoint. The aim: To determine whether there is a difference in the clinical efficiency in the use of 4 types of platelet applied for transfusion; - to ascertain whether platelet count increase expressed as corrected count increment (CCI, is a better parameter for the evaluation of platelet transfusion efficiency than the bleeding time (Bt, as the only readily assessable in vivo platelet function related parameter. Subjects and methods: This paper is a part of academic (noncommercial IV phase observational nointervetion study. Investigation included 78 patients diagnosed with malignant lymphoma and metastatic solid tumors, transfused by platelet concentrates. Patients were devided into 4 groups, based on the type of platelet concentrates used for transfusion. Results: Patients, were transfused with total number of 647 PC units (235 units were non-leukodepleted and 412 units were leukodepleted. Mean number of PC transfusions per patient was 8.3 PC units, and 4.8 PC unit per one transfusion episode. Before PCT: platelets values were: 18.1 x109/L ±13.1, Bt 8.4±6.1min, and after PCT were 28.2 x109/L ±22.1, 4.7±4.4 min respectively ((p<0.01. Mean CCI value was 13.8±30.4. CCI was corrected in 196/129 PCT and Bt in 122/129 PCT. After supportive therapy using PCs Bt was corrected and became similar in all 4 groups. Discussion: Clinical output is the most important parameter for treatment decision because many patients can tolerate prolonged periods of profound thrombocytopenia without serious bleeding problems. Conclusion: In all 4 investigated groups of patients bleeding time was a far better parameter compared with CCI for the PC therapy efficiency. Authors suggest to be careful and follow

  18. Prevalence and etiological classification of thrombocytopenia among a group of pregnant women in Erbil City, Iraq

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    Rawand Pouls Shamoon


    Full Text Available Objective: To determine the prevalence and define the causes of pregnancy-associated thrombocytopenia. Materials and Methods: A total of 850 pregnant women at different ages of gestation were screened for thrombocytopenia. A control group of 150 age-matched non-pregnant women were tested for platelet count. Newborns of thrombocytopenic women were tested within 24 hours of delivery and reassessment of the women's platelets was done within 7-10 days post-delivery. Results: The mean platelet count in pregnant women was significantly lower than in non-pregnant women (221±59.9/mm3 vs. 273±66.9/mm3. Thrombocytopenia affected 8% of cases, with peak incidence during the third trimester. Gestational thrombocytopenia was found to be the principal cause (73.8%; hypertensive disorders caused thrombocytopenia in 23% of cases and two cases (4% were due to immune thrombocytopenic purpura. No maternal or fetal complications were noted. The mean platelet count of 51 newborns of thrombocytopenic women was 240±7.1. Two newborns (4% had low platelet counts. Conclusion: The majority of thrombocytopenias were mild gestational and occurred in late pregnancy. No maternal or neonatal bleeding complications were observed.

  19. Long-term complications of splenectomy in adult immune thrombocytopenia. (United States)

    Thai, Lan-Huong; Mahévas, Matthieu; Roudot-Thoraval, Françoise; Limal, Nicolas; Languille, Laetitia; Dumas, Guillaume; Khellaf, Mehdi; Bierling, Philippe; Michel, Marc; Godeau, Bertrand


    The recent large decrease in splenectomy use for chronic immune thrombocytopenia (ITP) is partly due to still-unsolved questions about long-term safety. We performed the first single-center exposed/unexposed cohort study evaluating the long-term incidence of splenectomy complications in patients with primary ITP. Overall, 83 patients who underwent splenectomy more than 10 years ago (exposed) were matched with 83 nonsplenectomized patients (unexposed) on the date of ITP diagnosis ±5 years, age and gender. After a median follow-up of 192 months (range 0.5-528), 43 patients (52%) achieved overall response after splenectomy. Splenectomized patients experienced more venous thromboembolism (VTE) than controls (n = 13 vs n = 2, P = 0.005). On multivariate analysis, splenectomy was an independent risk factor of VTE (hazard ratio = 4.006, P = 0.032 [95% confidence interval: 1.13-14.21]). Splenectomized patients presented more severe infections on long-term follow-up: all required hospitalization, and 5/26 (19%) infections led to severe sepsis or septic shock and to death for 3 cases (none in controls). However, the incidence of malignancy was similar in both groups, as was cardiovascular risk, which appeared to be related more to ITP than splenectomy. Finally, splenectomy did not significantly decrease overall survival. Despite the risk of thrombosis and severe sepsis, splenectomy remains an effective and curative treatment for ITP.

  20. State of the art - how I manage immune thrombocytopenia. (United States)

    Cooper, Nichola


    The management of patients with immune thrombocytopenia (ITP) is rapidly evolving. Over the last 15 years, a number of novel treatments have improved practice, with many steroid-sparing agents and a reduction in the progression to splenectomy. Although this has improved clinical care, many therapeutic challenges remain. There is no diagnostic test, no biomarkers to direct treatment and few comparative studies to help management decisions. Development of up to date guidelines is difficult with little high-grade evidence. First line treatment continues to be steroids and intravenous immunoglobulins (IVIG) although both are often poorly tolerated and not curative. Common second line treatments include rituximab, immunosuppressive agents, such as azathioprine and mycophenolate mofetil, and the thrombopoietin receptor agonists romiplostim and eltrombopag. There are no comparative studies to decide between these agents and treatment is generally individualized, depending on comorbidity. Use of splenectomy has declined and is generally reserved for patients with chronic disease, although the exact position of splenectomy is subject to debate. Further understanding of the cause of disease in individual patients may help guide treatment. Randomized controlled studies of common treatments and novel treatments for refractory patients are urgently needed. © 2017 John Wiley & Sons Ltd.

  1. Acute disseminated encephalomyelitis: current knowledge and open questions. (United States)

    Steiner, Israel; Kennedy, Peter G E


    Acute disseminated encephalomyelitis (ADEM) is usually an acute, multi-focal, and monophasic immune-mediated disease of the central nervous system. The disorder is mainly a condition of the pediatric age group, but neurologists are also involved in the management of adult patients. The lack of defined diagnostic criteria for ADEM underlies the limited understanding of its epidemiology, etiology, pathogenesis, course, prognosis, therapy, as well as the association with, and distinction from, multiple sclerosis. The present review summarizes current knowledge and outlines unanswered questions the answers to which should be eventually provided through a synergistic combination of clinical and basic research.


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    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

  3. Thrombotic microangiopathies and acute kidney injury induced by ...

    African Journals Online (AJOL)

    Thrombotic microangiopathy (TMA) is a rare, but potentially lethal condition requiring rapid recognition, diagnosis and initiation of therapy. Here, we present two cases of women with hemolytic anemia, thrombocytopenia and acute kidney injury shortly after surgical termination of pregnancy. Histological examination of their ...

  4. Thrombotic thrombocytopenic purpura: a case presenting with acute ischemic colitis. (United States)

    See, Joseph R H; Sabagh, Tarek; Barde, Christopher J


    Thrombotic thrombocytopenic purpura (TTP) consists of the pentad of thrombocytopenia, hemolytic anemia, fever, neurologic abnormalities, and renal disease. We present a case report of acute TTP following a bout of ischemic colitis. This report reminds the clinician that ischemic colitis can be an atypical presentation of TTP. The prompt recognition and treatment of this disease process resulted in a good prognosis for our patient.


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    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.

  6. An improbable and unusual case of thrombotic thrombocytopenia purpura

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    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.

  7. Behavioral effects of the benzodiazepine-positive allosteric modulator SH-053-2'F-S-CH₃ in an immune-mediated neurodevelopmental disruption model. (United States)

    Richetto, Juliet; Labouesse, Marie A; Poe, Michael M; Cook, James M; Grace, Anthony A; Riva, Marco A; Meyer, Urs


    Impaired γ-aminobutyric acid (GABA) signaling may contribute to the emergence of cognitive deficits and subcortical dopaminergic hyperactivity in patients with schizophrenia and related psychotic disorders. Against this background, it has been proposed that pharmacological interventions targeting GABAergic dysfunctions may prove useful in correcting such cognitive impairments and dopaminergic imbalances. Here, we explored possible beneficial effects of the benzodiazepine-positive allosteric modulator SH-053-2'F-S-CH₃, with partial selectivity at the α2, α3, and α5 subunits of the GABAA receptor in an immune-mediated neurodevelopmental disruption model. The model is based on prenatal administration of the viral mimetic polyriboinosinic-polyribocytidilic acid [poly(I:C)] in mice, which is known to capture various GABAergic, dopamine-related, and cognitive abnormalities implicated in schizophrenia and related disorders. Real-time polymerase chain reaction analyses confirmed the expected alterations in GABAA receptor α subunit gene expression in the medial prefrontal cortices and ventral hippocampi of adult poly(I:C) offspring relative to control offspring. Systemic administration of SH-053-2'F-S-CH₃ failed to normalize the poly(I:C)-induced deficits in working memory and social interaction, but instead impaired performance in these cognitive and behavioral domains both in control and poly(I:C) offspring. In contrast, SH-053-2'F-S-CH₃ was highly effective in mitigating the poly(I:C)-induced amphetamine hypersensitivity phenotype without causing side effects in control offspring. Our preclinical data suggest that benzodiazepine-like positive allosteric modulators with activity at the α2, α3, and α5 subunits of the GABAA receptor may be particularly useful in correcting pathological overactivity of the dopaminergic system, but they may be ineffective in targeting multiple pathological domains that involve the co-existence of psychotic, social, and cognitive

  8. Spontaneous, Immune-Mediated Gastric Inflammation in SAMP1/YitFc Mice, a Model of Crohn’s-Like Gastritis (United States)

    Reuter, Brian K.; Pastorelli, Luca; Brogi, Marco; Garg, Rekha R.; McBride, James A.; Rowlett, Robert M.; Arrieta, Marie C.; Wang, Xiao-Ming; Keller, Erik J.; Feldman, Sanford H.; Mize, James R.; Cominelli, Fabio; Meddings, Jonathan B.; Pizarro, Theresa T.


    Background & Aims Crohn’s disease (CD) can develop in any region of the gastrointestinal tract, including the stomach. The etiology and pathogenesis of Crohn’s gastritis are poorly understood, treatment approaches are limited, and there are not many suitable animal models for study. We characterized the features and mechanisms of chronic gastritis in SAMP1/YitFc (SAMP) mice, a spontaneous model of CD-like ileitis, along with possible therapeutic approaches. Methods Stomachs from specific pathogen-free and germ-free SAMP and AKR mice (controls) were evaluated histologically; the presence of Helicobacter spp. was tested in fecal pellets by PCR analysis. In vivo gastric permeability was quantified by fractional excretion of sucrose and epithelial tight junction protein expression was measured by quantitative reverse transcription PCR analysis. The effects of a proton pump inhibitor (PPI) or corticosteroids were measured and the ability of pathogenic immune cells to mediate gastritis was assessed in adoptive transfer experiments. Results SAMP mice developed Helicobacter-negative gastritis, characterized by aggregates of mononuclear cells, diffuse accumulation of neutrophils, and disruption of epithelial architecture; SAMP mice also had increased in gastric permeability compared with controls, without alterations in expression of tight junction proteins. The gastritis and associated permeability defect observed in SAMP mice were independent of bacterial colonization and reduced by administration of corticosteroids but not a PPI. CD4+ T cells isolated from draining mesenteric lymph nodes of SAMP mice were sufficient to induce gastritis in recipient SCID mice. Conclusions In SAMP mice, gastritis develops spontaneously and has many features of CD-like ileitis. These mice are a useful model to study Helicobacter-negative, immune-mediated Crohn’s gastritis. PMID:21704001

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

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    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.

  10. Chronic social stress in pigs impairs intestinal barrier and nutrient transporter function, and alters neuro-immune mediator and receptor expression (United States)

    Li, Yihang; Song, Zehe; Kerr, Katelyn A.; Moeser, Adam J.


    Psychosocial stress is a major factor driving gastrointestinal (GI) pathophysiology and disease susceptibility in humans and animals. The mechanisms governing susceptibility to stress-induced GI disease remain poorly understood. In the present study, we investigated the influence of chronic social stress (CSS) in pigs, induced by 7 d of chronic mixing/crowding stress, on intestinal barrier and nutrient transport function, corticotropin releasing factor (CRF) signaling and immunological responses. Results from this study showed that CSS resulted in a significant impairment of ileal and colonic barrier function indicated by reduced transepithelial electrical resistance (TER) in the ileum and increased FD4 flux in the ileum (by 0.8 fold) and colon (by 0.7 fold). Ileal sodium glucose linked transporter 1 (SGLT-1) function, measured as glucose-induced changes in short-circuit current (Isc), was diminished (by 52%) in CSS pigs, associated with reduced body weight gain and feed efficiency. Although reductions in SGLT-1 function were observed in CSS pigs, mRNA expression for SGLT-1, villus heights were increased in CSS pigs. Corticotropin releasing factor (CRF) mRNA was upregulated (by 0.9 fold) in the ileum of CSS pigs but not in the colon. Urocortin 2 (Ucn2) mRNA was upregulated (by 1.5 fold) in the colon of CSS pigs, but not in the ileum. In CSS pigs, a downregulation of pro-inflammatory cytokines mRNA (IL1B, TNFA, IL8, and IL6) was observed in both ileum and colon, compared with controls. In contrast CSS induced a marked upregulation of mRNA for IL10 and mast cell chymase gene (CMA1) in the ileum and colon. Together, these data demonstrate that chronic stress in pigs results in significant alterations in intestinal barrier and nutrient transport function and neuro-immune mediator and receptor expression. PMID:28170426

  11. Differential profiles of immune mediators and in vitro HIV infectivity between endocervical and vaginal secretions from women with Chlamydia trachomatis infection: a pilot study. (United States)

    Sperling, Rhoda; Kraus, Thomas A; Ding, Jian; Veretennikova, Alina; Lorde-Rollins, Elizabeth; Singh, Tricia; Lo, Yungtai; Quayle, Alison J; Chang, Theresa L


    Chlamydia trachomatis infection is one of the most prevalent bacterial STIs in the USA and worldwide, and women with C. trachomatis infection are at increased risk of acquiring HIV. Because immune activation at the genital mucosa facilitates HIV/SIV infection, C. trachomatis-mediated cytokine induction may contribute to increased HIV transmission in asymptomatic women. To begin to elucidate the mechanisms, we longitudinally analyzed profiles of innate immune factors and HIV infectivity in genital secretions from anatomically specific sites in asymptomatic women during C. trachomatis infection and post-antibiotic treatment. We found higher levels of cytokines and chemokines in endocervical secretions than vaginal secretions. Compared with the convalescent state, G-CSF, IL-1α, and RANTES were elevated in endocervical secretions, IFN-γ and TNF-α were elevated in vaginal secretions, and IFNγ, IL-1β, and MIP1-α were elevated in cervicolavage fluid (CVL), before adjustment of multiple comparisons. Elevated endocervical levels of IP-10 and MCP-1 were associated with the use of hormonal contraception in infected women after successful treatment, suggesting the role of hormonal contraception in inflammation independent of STIs. Importantly, soluble factors found in endocervical secretions during infection enhanced HIV infectivity while no difference in HIV infectivity was found with vaginal secretions or CVL during infection or at convalescence. Taken together, the profiles of immune mediators and in vitro HIV infectivity indicate that the endocervical and vaginal mucosa are immunologically distinct. Our results underscore the importance of considering anatomical site and local sampling methodology when measuring mucosal responses, particularly in the presence of C. trachomatis infection. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  12. Chimeric HCMV/HSV-1 and Δγ134.5 oncolytic herpes simplex virus elicit immune mediated antigliomal effect and antitumor memory

    Directory of Open Access Journals (Sweden)

    Mohammed G. Ghonime


    Full Text Available Malignant gliomas are the most common primary brain tumor and are characterized by rapid and highly invasive growth. Because of their poor prognosis, new therapeutic strategies are needed. Oncolytic virotherapy (OV is a promising strategy for treating cancer that incorporates both direct viral replication mediated and immune mediated mechanisms to kill tumor cells. C134 is a next generation Δγ134.5 oHSV-1 with improved intratumoral viral replication. It remains safe in the CNS environment by inducing early IFN signaling which restricts its replication in non-malignant cells. We sought to identify how C134 performed in an immunocompetent tumor model that restricts its replication advantage over first generation viruses. To achieve this we identified tumors that have intact IFN signaling responses that restrict C134 and first generation virus replication similarly. Our results show that both viruses elicit a T cell mediated anti-tumor effect and improved animal survival but that subtle difference exist between the viruses effect on median survival despite equivalent in vivo viral replication. To further investigate this we examined the anti-tumor activity in immunodeficient mice and in syngeneic models with re-challenge. These studies show that the T cell response is integral to C134 replication independent anti-tumor response and that OV therapy elicits a durable and circulating anti-tumor memory. The studies also show that repeated intratumoral administration can extend both OV anti-tumor effects and induce durable anti-tumor memory that is superior to tumor antigen exposure alone.

  13. mTOR signaling disruption from myeloid-derived suppressive cells protects against immune-mediated hepatic injury through the HIF1α-dependent glycolytic pathway. (United States)

    Chen, Xi; Zhang, Zhengguo; Bi, Yujing; Fu, Zan; Gong, Pingsheng; Li, Yan; Yu, Qing; Jia, Anna; Wang, Jian; Xue, Lixiang; Yang, Hui; Liu, Guangwei


    The mechanistic target of rapamycin (mTOR) pathway integrates diverse environmental inputs, including immune signals and metabolic cues, to direct innate and adaptive immune responses. Myeloid-derived suppressive cells (MDSCs) are a heterogeneous cell population that plays a crucial regulatory effect in immune-related diseases. However, whether mTOR signaling affects the functions of MDSCs remains largely unexplored. Here, we show that mTOR signaling is a pivotal, negative determinant of MDSC function in immune-mediated hepatic injury (IMH) diseases. In the context of IMH, the blocking of mTOR with rapamycin or mTOR-deficient CD11b+Gr1+ MDSCs mediates the protection against IMH; mTOR with rapamycin and mTOR-deficient CD11b+Gr1+ MDSCs are suppressive immune modulators that result in less IFN-γ-producing TH1 cells and more Foxp3+ Tregs Mechanistically, mTOR activity down-regulation in MDSCs induced iNOS expressions and NO productions. Pharmacologic inhibitions of iNOS completely eliminate MDSC-suppressive function and lose their inducible effects on T cell differentiation. Importantly, HIF1α-dependent glycolytic activity is responsible for mTOR-deficient, increased MDSC functional changes in IMH inflammation. Thus, these data demonstrate that mTOR acts as a fundamental "rheostat" in MDSCs to link immunologic signals to glycolytic pathways and functional fitness and highlights a central role of metabolic programming of MDSC-suppressive activity in protecting against immune hepatic injuries. © Society for Leukocyte Biology.

  14. Role of the Mitochondria in Immune-Mediated Apoptotic Death of the Human Pancreatic β Cell Line βLox5 (United States)

    Lightfoot, Yaíma L.; Chen, Jing; Mathews, Clayton E.


    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 ρ0 cells. βLox5 ρ0 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 ρ0 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. PMID:21738580

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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

  17. A Case Report of Drug-Induced Thrombocytopenia after Living Donor Liver Transplantation. (United States)

    Arai, Keisuke; Kuramitsu, Kaori; Fukumoto, Takumi; Kido, Masahiro; Takebe, Atsushi; Tanaka, Motofumi; Kinoshita, Hisoka; Ajiki, Tetsuo; Toyama, Hirochika; Asari, Sadaki; Goto, Tadahiro; Ku, Yonson


    There are few descriptions of severe thrombocytopenia during the early postoperative period after liver transplantation, and these have not been fully documented in the literature. Here, we report a case of drug-induced thrombocytopenia requiring transfusion of blood products after living donor liver transplantation. We determined that this was not caused by the interferon-free anti-viral therapy but by tacrolimus A 61-year-old woman with hepatitis C-related cirrhosis and hepatorenal syndrome underwent living donor liver transplantation using a left lobe graft from her son. After transplantation, immunosuppression consisted of tacrolimus and steroid. Seven weeks after transplantation, interferon-free therapy with daclatasvir and asunaprevir was started. Thirteen days thereafter, hepatitis C virus tested negative. However, the platelet count had begun to gradually decrease just before starting anti-viral therapy. Daclatasvir and asunaprevir were stopped because this was suspected to be a side-effect of these drugs, but the patient nonetheless went on to develop severe thrombocytopenia (platelet count 17,000/μL), which needed transfusions. Now suspecting tacrolimus as the inducer of this side effect, we changed to cyclosporin, after which the platelet count gradually recovered. Viral markers were still not detectable up to 2 months after discontinuation of the antiviral drugs. We conclude that when severe thrombocytopenia occurs, possible drug-induced thrombocytopenia as well as other disorders must be investigated.

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

    LENUS (Irish Health Repository)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  2. Glycoprotein IIb/IIIa inhibitor-associated thrombocytopenia: clinical predictors and effect on outcome. (United States)

    George, Benjamin J; Eckart, Robert E; Shry, Eric A; Simpson, Daniel E


    Glycoprotein IIb/IIIa inhibitors are used as an adjunct to antiplatelet therapy in percutaneous coronary intervention to reduce postprocedural enzyme elevations. Previous studies have shown a risk for thrombocytopenia that is associated with these agents. We sought to evaluate the incidence and outcomes of glycoprotein IIb/IIIa inhibitor-associated thrombocytopenia in an unselected series of patients undergoing percutaneous coronary intervention. We reviewed 984 interventions performed on 908 subjects over a specific time period. Glycoprotein IIb/IIIa inhibitors were used in 58.8% of cases. Their use increased from 38 to 82% during the study period (p 0.05). The occurrence of thrombocytopenia was not associated with increased in-hospital mortality, 1-year mortality, myocardial infarction or revascularization, but was associated with a hospital stay twice as long as in those patients without thrombocytopenia (5.6 +/- 11.3 vs. 2.1 +/- 2.2 days, p < 0.001). Of the 5.4% of patients who developed thrombocytopenia, only 2 patients (7.1%) required platelet or blood cell transfusion. Copyright (c) 2004 S. Karger AG, Basel.

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

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    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

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

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    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.

  5. Immune-mediated statin myopathy. (United States)

    Loganathan, Priyadarshini; Oddis, Chester V; Aggarwal, Rohit


    Statin-induced necrotizing autoimmune myopathy (SINAM) is associated with a unique clinical 5 phenotype of severe proximal muscle weakness during or after exposure to statins in patients with high creatine kinase (CK) levels. Electromyography (EMG) and muscle biopsy reveal features of a necrotizing myopathy and the anti-HMGCR autoantibody is frequently detected. Treatment requires a combination of statin discontinuation as well as immunomodulatory or immunosuppressive therapy. HLA typing (HLADRB1*1101) is strongly associated with anti-10 HMGCR autoantibody positivity in statin-exposed patients. It is well documented that statin triggers autoimmune disease in those with a genetic susceptibility. With the commercial availability of an accurate ELISA test, the natural history of the disease and its phenotypic features are becoming increasingly understood.

  6. A novel DNA repair disorder with thrombocytopenia, nephrosis and features overlapping Cockayne syndrome. (United States)

    Forsythe, Elizabeth; Wild, Ruth; Sellick, Gabrielle; Houlston, Richard S; Lehmann, Alan R; Wakeling, Emma


    We report on four siblings with Cockayne-like syndrome with thrombocytopenia and nephrotic syndrome. The parents were healthy and consanguineous, consistent with an autosomal recessive mode of disease inheritance. UV irradiation of fibroblasts revealed an intermediate sensitivity between normal and standard Cockayne syndrome (CS) control cells. A genome-wide linkage scan conducted using Affymetrix 10K arrays provided exclusion of the known CS genes in the family, and evidence that the disease gene maps to 1p33-p31.1. Thrombocytopenia has not previously been linked with CS, but two patients with CS in association with nephrotic syndrome have previously been documented and the phenotypes are compared with the patients described here. We suggest that this Cockayne-like phenotype with thrombocytopenia and nephrotic syndrome may be a novel DNA repair disorder, and propose that further investigation of other affected families may help identify the causative genetic defect.

  7. Refractor y thrombotic thrombocytopenic pur pura 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 ...

  8. Idiopathic Atypical Haemolytic Uraemic Syndrome presenting with acute dystonia

    LENUS (Irish Health Repository)

    Maduemem, Rizwan K E


    Hemolytic Uremic Syndrome (HUS), a triad of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. The atypical HUS (aHUS) results from over activation of complement system with formation of micro thrombi and damage to endothelial cells resulting in renal impairment in 50 % and death in 25 %, commonly in untreated patients. We report an intriguing case of aHUS presenting with acute onset of movement disorder and fluctuating delirium.

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

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    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.

  10. Unusual presentation of a severely ill patient having severe fever with thrombocytopenia syndrome: a case report. (United States)

    Kaneko, Masahiko; Maruta, Masaki; Shikata, Hisaharu; Asou, Kengo; Shinomiya, Hiroto; Suzuki, Tadaki; Hasegawa, Hideki; Shimojima, Masayuki; Saijo, Masayuki


    Severe fever with thrombocytopenia syndrome is an emerging infectious disease caused by a novel phlebovirus belonging to the family Bunyaviridate. Emergence of encephalitis/encephalopathy during severe fever with thrombocytopenia syndrome progression has been identified as a major risk factor associated with a poor prognosis. Here we report the case of a severely ill patient with severe fever with thrombocytopenia syndrome virus-associated encephalitis/encephalopathy characterized by a lesion of the splenium, which resolved later. A 56-year-old Japanese man presented with fever and diarrhea, followed by dysarthria. Diffusion-weighted magnetic resonance imaging demonstrated high signal intensity in the splenium of the corpus callosum. The severe fever with thrombocytopenia syndrome virus genome was detected in our patient's serum, and the clinical course was characterized by convulsion, stupor, and hemorrhagic manifestations, with disseminated intravascular coagulation and hemophagocytic lymphohistiocytosis. Supportive therapy not including administration of corticosteroids led to gradual improvement of the clinical and laboratory findings, and magnetic resonance imaging demonstrated resolution of the splenial lesion. The serum severe fever with thrombocytopenia syndrome viral copy number, which was determined with the quantitative reverse-transcription polymerase chain reaction, rapidly decreased despite the severe clinical course. Our patient's overall condition improved, allowing him to be eventually discharged. Patients with encephalitis/encephalopathy due to severe fever with thrombocytopenia syndrome virus infection may have a favorable outcome, even if they exhibit splenial lesions and a severe clinical course; monitoring the serum viral load may be of value for prediction of outcome and potentially enables the avoidance of corticosteroids to intentionally cause opportunistic infection.

  11. Immune thrombocytopenia in adults: a prospective cohort study of clinical features and predictors of outcome. (United States)

    Grimaldi-Bensouda, Lamiae; Nordon, Clémentine; Michel, Marc; Viallard, Jean-François; Adoue, Daniel; Magy-Bertrand, Nadine; Durand, Jean-Marc; Quittet, Philippe; Fain, Olivier; Bonnotte, Bernard; Morin, Anne-Sophie; Morel, Nathalie; Costedoat-Chalumeau, Nathalie; Pan-Petesch, Brigitte; Khellaf, Mehdi; Perlat, Antoinette; Sacre, Karim; Lefrere, François; Abenhaim, Lucien; Godeau, Bertrand


    This prospective observational cohort study aimed to explore the clinical features of incident immune thrombocytopenia in adults and predictors of outcome, while determining if a family history of autoimmune disorder is a risk factor for immune thrombocytopenia. All adults, 18 years of age or older, recently diagnosed with immune thrombocytopenia were consecutively recruited across 21 hospital centers in France. Data were collected at diagnosis and after 12 months. Predictors of chronicity at 12 months were explored using logistic regression models. The association between family history of autoimmune disorder and the risk of developing immune thrombocytopenia was explored using a conditional logistic regression model after matching each case to 10 controls. One hundred and forty-three patients were included: 63% female, mean age 48 years old (Standard Deviation=19), and 84% presented with bleeding symptoms. Median platelet count was 10×10(9)/L. Initial treatment was required in 82% of patients. After 12 months, only 37% of patients not subject to disease-modifying interventions achieved cure. The sole possible predictor of chronicity at 12 months was a higher platelet count at baseline [Odds Ratio 1.03; 95%CI: 1.00, 1.06]. No association was found between outcome and any of the following features: age, sex, presence of either bleeding symptoms or antinuclear antibodies at diagnosis. Likewise, family history of autoimmune disorder was not associated with incident immune thrombocytopenia. Immune thrombocytopenia in adults has been shown to progress to a chronic form in the majority of patients. A lower platelet count could be indicative of a more favorable outcome. Copyright© Ferrata Storti Foundation.

  12. Molecular typing of human platelet antigens in immune thrombocytopenia patients in northern Brazil. (United States)

    Carmo, Julia Cavalcante do; Klippel, Prissyla de Souza; Cordeiro, Sabrine da Costa; Fernandes, Ângela Maria Dos Santos; Pinto, Raquel Medeiros; Weber, Simone Schneider; Fantin, Cleiton

    Immune thrombocytopenia is an immune disease characterized by thrombocytopenia and bleeding due to platelet antibodies against platelet membrane glycoproteins. Human platelet antigens are derived from polymorphisms of these glycoproteins. The aim of this study was to investigate human platelet antigen frequencies in immune thrombocytopenia patients from the state of Amazonas, Brazil and investigate the potential association between specific antigens and risk for immune thrombocytopenia. Human platelet antigen typing was performed by BeadChip technology to determine allelic variants of 11 systems (HPA-1 to HPA-9, HPA-11 and HPA-15). Thirty-six patients (8 male and 28 female) with a median age of 34 years (range: 9-69 years) were evaluated and compared with data from Amazonas blood donors. Platelet counts varied from 3 to 98×109/L. The allele frequencies were 0.944 for HPA-1a, 0.056 for HPA-1b, 0.847 for HPA-2a, 0.153 for HPA-2b, 0.555 for HPA-3a, 0.444 for HPA-3b, 0.805 for HPA-5a, 0.222 for HPA-5b, 0.9975 for HPA-9a, 0.025 for HPA-9b, 0.486 for HPA-15a and 0.513 for HPA-15b. Among immune thrombocytopenia individuals, no b allele of the HPA-4, -6, -7, -8 and -11 were found. The results suggest HPA-1a, HPA-3b and HPA-5b are immune thrombocytopenia-specific autoepitopes. Copyright © 2017 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

  13. Prevalence of thrombocytopenia in HIV-infected and non-HIV infected drug users and homosexual men

    NARCIS (Netherlands)

    Mientjes, G. H.; van Ameijden, E. J.; Mulder, J. W.; van den Hoek, J. A.; Coutinho, R. A.; von dem Borne, A. E.


    We studied the prevalence and risk factors for thrombocytopenia among 299 drug users and 461 homosexual men. The prevalence of thrombocytopenia was 3.3% in HIV-negative homosexual men, 8.7% in HIV-negative drug users, 16.4% in HIV-positive homosexual men, and 36.9% in HIV-positive drug users. With

  14. Thrombocytopenia in hydropic fetuses with parvovirus B19 infection: incidence, treatment and correlation with fetal B19 viral load

    NARCIS (Netherlands)

    de Haan, T. R.; van den Akker, E. S. A.; Porcelijn, L.; Oepkes, D.; Kroes, A. C. M.; Walther, F. J.


    Objective To examine (1) the incidence of fetal thrombocytopenia in hydropic fetuses with congenital B19 virus infection, (2) the effect of intrauterine platelet transfusions and (3) the correlation between fetal B19 viral load and severity of thrombocytopenia. Design Retrospective analysis of data

  15. Incidence and risk factors of thrombocytopenia in patients receiving intermittent antiretroviral therapy: a substudy of the ANRS 106-window trial. (United States)

    Bouldouyre, Marie-Anne; Charreau, Isabelle; Marchou, Bruno; Tangre, Philippe; Katlama, Christine; Morlat, Philippe; Meiffredy, Vincent; Vittecoq, Daniel; Bierling, Philippe; Aboulker, Jean-Pierre; Molina, Jean-Michel


    Incidence and risk factors for thrombocytopenia in patients discontinuing highly active antiretroviral therapy (HAART) have not been fully investigated. Well-suppressed patients on HAART were randomized to continuous (CT) or intermittent therapy (IT) for 96 weeks. Incidence of thrombocytopenia (<150 x 10(3) platelets/mm(3)) was assessed and multivariate analysis performed to identify baseline predictors. Correlations were assessed between platelet, CD4, CD8 T-cell counts, and viral load after treatment interruption. Three hundred ninety-one patients were included, with a median baseline platelet count of 243,000/mm(3). The incidence of thrombocytopenia at week 96 was significantly higher in the IT versus the CT arm (25.4% versus 9.8%, respectively, P < 0.001) and median time to thrombocytopenia was 9 weeks. In multivariate analysis, the IT strategy: odds ratio (OR) = 4.1 (2.1-7.9; P < 0.0001), a history of thrombocytopenia: OR = 11.9 (2.4-57.9; P = 0.002), and a low baseline platelet count: OR = 3.4 (2.3-5.1; P < 0.0001) were associated with an increased risk of thrombocytopenia. Also, after treatment interruption, changes from baseline in platelet counts were correlated with changes in CD4 T-cell counts and plasma HIV RNA levels (P < 0.001 for both). Intermittent therapy is associated with a high incidence of thrombocytopenia, especially among patients with low platelet counts and a history of thrombocytopenia.

  16. Drug-Induced Thrombocytopenia following a Transvaginal Oocyte Retrieval for In Vitro Fertilization

    Directory of Open Access Journals (Sweden)

    Ioanna A. Comstock


    Full Text Available Drug-induced immune thrombocytopenia has been associated with hundreds of medications and can lead to devastating consequences for the patient. We present a case of a healthy 33-year-old female undergoing in vitro fertilization who developed a severe drug-induced thrombocytopenia, petechiae, and a large hemoperitoneum after receiving Cefazolin antibiotic prophylaxis for a transvaginal oocyte retrieval. The patient was admitted to the intensive care unit for resuscitation with blood products. The presence of drug-dependent platelet antibodies to Cefazolin was confirmed serologically.

  17. Drug-Induced Thrombocytopenia following a Transvaginal Oocyte Retrieval for In Vitro Fertilization. (United States)

    Comstock, Ioanna A; Longmire, Michelle; Aster, Richard H; Milki, Amin A


    Drug-induced immune thrombocytopenia has been associated with hundreds of medications and can lead to devastating consequences for the patient. We present a case of a healthy 33-year-old female undergoing in vitro fertilization who developed a severe drug-induced thrombocytopenia, petechiae, and a large hemoperitoneum after receiving Cefazolin antibiotic prophylaxis for a transvaginal oocyte retrieval. The patient was admitted to the intensive care unit for resuscitation with blood products. The presence of drug-dependent platelet antibodies to Cefazolin was confirmed serologically.

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

    Directory of Open Access Journals (Sweden)

    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

  19. Dapsone for primary immune thrombocytopenia in adults and children: an evidence-based review. (United States)

    Rodrigo, C; Gooneratne, L


    Primary immune thrombocytopenia is a potentially life-threatening condition. Approximately two-thirds of adult patients do not have a sustained response to steroids (first-line therapy). For these patients, a number of other treatment options exist, such as rituximab, splenectomy, immunosuppressants, and thrombopoietin receptor agonists, but they are costly and have side effects. Dapsone is an inexpensive drug with a well-established safety profile. Unfortunately, this treatment option has not been explored adequately. This review is aimed at analyzing the currently available evidence for the use of dapsone as second-line or third-line therapy in primary immune thrombocytopenia. © 2013 International Society on Thrombosis and Haemostasis.

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

    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

  1. Persistence with golimumab in immune-mediated rheumatic diseases: a systematic review of real-world evidence in rheumatoid arthritis, axial spondyloarthritis, and psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    Svedbom A


    Full Text Available Axel Svedbom,1 Chiara Storck,2 Sumesh Kachroo,3 Marinella Govoni,4 Ahmed Khalifa5 1Real World Strategy and Analytics, Mapi Group, Stockholm, Sweden; 2Real World Strategy and Analytics, Mapi Group, Munich, Germany; 3Center for Observational and Real-World Evidence (CORE, Merck & Co, Kenilworth, NJ, USA; 4MSD Italy, Rome, Italy; 5Medical Affairs Immunology, MSD Switzerland, Luzern, Switzerland Purpose: In immune-mediated rheumatic diseases (IMRDs, persistence to treatment may be used as a surrogate marker for long-term treatment success. In previous comparisons of persistence to tumor necrosis factor α inhibitors (TNFis, a paucity of data for subcutaneous (SC golimumab was identified. The aim of this study was to conduct a systematic review of persistence to SC golimumab in clinical practice and contextualize these data with five-year persistence estimates from long-term open-label extension (OLE trials of SC TNFis in IMRDs.Patients and methods: PubMed, Embase, MEDLINE, and conference proceedings from European League Against Rheumatism (EULAR, American College of Rheumatology (ACR, and International Society for Pharmacoeconomics and Outcomes Research (ISPOR were searched. All studies on patients treated with SC golimumab for IMRD were included if they reported data on the persistence to golimumab.Results: Of 376 available references identified through the searches, 12 studies with a total of 4,910 patients met the inclusion criteria. Furthermore, nine OLE trials were available. Among the included studies from clinical practice, at six months, one year, two years, and three years, the proportion of patients persistent to treatment ranged from 63% to 91%, 47% to 80%, 40% to 77%, and 32% to 67%, respectively. In the four studies that included comparisons to other biologics, golimumab was either statistically noninferior or statistically superior to other treatments, an observation that was supported by indirect comparisons of unadjusted point

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

    Directory of Open Access Journals (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.

  3. Use of serum concentrations of interleukin-18 and monocyte chemoattractant protein-1 as prognostic indicators in primary immune-mediated hemolytic anemia in dogs. (United States)

    Kjelgaard-Hansen, M; Goggs, R; Wiinberg, B; Chan, D L


    The cytokine response in immune-mediated hemolytic anemia (IMHA) is poorly characterized and correlation with outcome is unknown. To determine if cytokine activity is correlated with outcome in dogs with IMHA. Twenty dogs with primary IMHA and 6 control dogs. Prospective study on dogs with IMHA with blood sampling at admission. Serum activity of interleukin-2 (IL-2), IL-4, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-inducible protein-10, interferon-gamma, and keratinocyte chemoattractant (KC) was assessed. Thirty-day case fatality rate was 25% (5/20 dogs). Increased concentrations (median [range]) of IL-2 (45.5 ng/L [0;830] versus 0 ng/L [0;46.8]), IL-10 (8.2 ng/L [0;60.6] versus 0 ng/L [0;88.2]), KC (1.7 μg/L [0.3;4.7] versus 0.5 μg/L [0.2;1.1]), and MCP-1 (162 ng/L [97.6;438] versus 124 ng/L [90.2;168]) were observed in dogs with IMHA compared with controls. The cytokine profile was indicative of a mixture of pro- and anti-inflammatory cytokines of various cellular origins. Cytokines/chemokines strongly associated with macrophage/monocyte activation and recruitment were significantly increased in nonsurvivors compared with survivors; IL-15 (179 ng/L [48.0;570] versus 21.3 ng/L [0;193]), IL-18 (199 ng/L [58.7;915] versus 37.4 ng/L [0;128]), GM-CSF (134 ng/L [70.0;863] versus 57.6 ng/L [0;164]), and MCP-1 (219 ng/L [135;438] versus 159 ng/L [97.6;274]), respectively. Logistic regression suggested increased IL-18 and MCP-1 concentrations were independently associated with mortality in this population (Pdogs with IMHA and mediators of macrophage activation and recruitment might serve as prognostic indicators. Copyright © 2010 by the American College of Veterinary Internal Medicine.

  4. Transfusion-Related Acute Lung Injured (TRALI): Current Concepts (United States)

    Álvarez, P; Carrasco, R; Romero-Dapueto, C; Castillo, R.L


    Transfusion-related acute lung injury (TRALI) is a life-threatening intervention that develops within 6 hours of transfusion of one or more units of blood, and is an important cause of morbidity and mortality resulting from transfusion. It is necessary to dismiss other causes of acute lung injury (ALI), like sepsis, acute cardiogenic edema, acute respiratory distress syndrome (ARDS) or bacterial infection. There are two mechanisms that lead to the development of this syndrome: immune-mediated and no immune- mediated TRALI. A common theme among the experimental TRALI models is the central importance of neutrophils in mediating the early immune response, and lung vascular injury. Central clinical symptoms are dyspnea, tachypnea, tachycardia, cyanosis and pulmonary secretions, altogether with other hemodynamic alterations, such as hypotension and fever. Complementary to these clinical findings, long-term validated animal models for TRALI should allow the determination of the cellular targets for TRALI-inducing alloantibodies as well as delineation of the underlying pathogenic molecular mechanisms, and key molecular mediators of the pathology. Diagnostic criteria have been established and preventive measures have been implemented. These actions have contributed to the reduction in the overallnumber of fatalities. However, TRALI still remains a clinical problem. Any complication suspected of TRALI should immediately be reported. PMID:26312100

  5. Prevalence of thrombocytopenia among pregnant women attending antenatal care service at Gondar University Teaching Hospital in 2014, northwest Ethiopia. (United States)

    Asrie, Fikir; Enawgaw, Bamlaku; Getaneh, Zegeye


    Thrombocytopenia is a common hematologic abnormality during pregnancy. Pregnant women with thrombocytopenia have a higher risk of bleeding excessively during or after childbirth, particularly if they need to have a cesarean section or other surgical intervention during pregnancy, labor or in the puerperium. The main aim of this study was to determine the prevalence of thrombocytopenia among pregnant women attending antenatal care service at Gondar University Hospital, northwest Ethiopia. A cross-sectional study was used to assess the prevalence of thrombocytopenia among pregnant women attending antenatal care service at Gondar University Hospital from January to April 2015. A total of 217 pregnant women were included in the study and a structured pretested questionnaire was used to obtain sociodemographic information, nutritional factors, obstetrics and gynecological factors, history and clinical condition. Blood samples were collected for platelet count and other platelet parameters, which were determined by using SysmexKX 21 automation. The data were entered to Epi info version 6 software and analyzed using SPSS version 20 software. Bivariable and multivariable statistical analyses were used to evaluate the effect of independent variable over the dependent variable. A p-value of service at Gondar University Hospital participated in the study. Thrombocytopenia among 19 pregnant women showed a prevalence of 8.8%. The mean ± standard deviation platelet count was 238.85×10(9)/L (±74.57). Thrombocytopenia was significantly associated with patients who lived rurally (crude odds ratio =4.3, 95% confidence interval 1.48-12.76). The prevalence of thrombocytopenia was 8.8% predominantly with mild type of thrombocytopenia. Thrombocytopenia was higher among pregnant women who lived rurally. Therefore, health care providers should screen routinely for thrombocytopenia to avoid excessive bleeding during pregnancy, especially in women who live rurally.

  6. Idiopathic pulmonary embolism in a case of severe family ANKRD26 thrombocytopenia

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    Jérôme Guison


    Full Text Available Venous thrombosis affecting thrombocytopenic patients is challenging. We report the case of a thrombocytopenic woman affected by deep vein thrombosis and pulmonary embolism leading to the discovery of a heterozygous mutation in the gene encoding ankyrin repeat domain 26 (ANKRD26 associated with a heterozygous factor V (FV Leiden mutation. This woman was diagnosed with left lower-limb deep vein thrombosis complicated by pulmonary embolism. Severe thrombocytopenia was observed. The genetic study evidenced a heterozygous FV Leiden mutation. Molecular study sequencing was performed after learning that her family had a history of thrombocytopenia. Previously described heterozygous mutation c-127C>A in the 5′ untranslated region (5′UTR of the ANKRD26 gene was detected in the patient, her aunt, and her grandmother. ANKRD26-related thrombocytopenia and thrombosis are rare. This is, to our knowledge, the first case reported in the medical literature. This mutation should be screened in patients with a family history of thrombocytopenia.

  7. Fcγ receptor expression on splenic macrophages in adult immune thrombocytopenia

    NARCIS (Netherlands)

    Audia, S; Santegoets, K; Laarhoven, A G; Vidarsson, G; Facy, O; Ortega-Deballon, P; Samson, M; Janikashvili, N; Saas, P; Bonnotte, B; Radstake, T R


    Splenic macrophages play a key role in immune thrombocytopenia (ITP) pathogenesis by clearing opsonized platelets. Fcγ receptors (FcγR) participate in this phenomenon, but their expression on splenic macrophages and their modulation by treatment have scarcely been studied in human ITP. We aimed to

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

    DEFF Research Database (Denmark)

    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...

  9. Effect of thrombocytopenia on the efficacy of Photofrin-based photodynamic therapy in vivo (United States)

    de Vree, Wil J. A.; de Bruijn, Henriette S.; Kraak-Slee, Regina G.; Koster, Johan F.; Sluiter, Wim


    Neutrophils are indispensable for successful PDT. Recently it has been observed that the administration of anti-thrombocyte antiserum prevents the occlusion of the microvasculature that normally occurs upon Photofrin-based PDT. We hypothesized that this antiserium treatment would increase the therapeutic efficacy by facilitating the accumulation of neutrophils at the lesion. To study this we implanted the isologous rhabdomyosarcoma R-1 subcutaneously into the thigh of WAG/Raj rats, and treated the tumor by interstitial Photofrin-based PDT. We found that the increasing tumor doubling time after PDT under anti-thrombocyte antiserum-induced thrombocytopenia was significantly higher that in normal rats. Strikingly, the increase in tumor doubling time did not differ if thrombocytopenia was induced before or immediately after illumination. At least 1.5 times more neutrophils than normal accumulated into the PDT-treated tumors under thrombocytopenia. If the rats were rendered granulocytopenic by the administration of anti-granulocyte antiserum first followed by anti-thrombocyte antiserum post PDT, this lead to a considerable loss of the thrombocytopenia- dependent gain in the efficacy of PDT. These findings suggest that the increased accumulation of neutrophils into the tumor underlie the enhanced efficacy of PDT and may implicate that under normal clinical conditions the full granulocyte-dependent kill potential is not utilized due to the presence of activated thrombocytes that cause blood flow stasis.

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

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    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.

  11. Twenty-year mortality of adult patients with primary immune thrombocytopenia

    DEFF Research Database (Denmark)

    Frederiksen, Henrik; dybdal, Merete Lund; Nørgaard, Mette


    Studies have reported a 1·3- to 2·2-fold higher mortality rate among patients with primary immune thrombocytopenia (ITP) compared to the general population. However, long-term mortality estimates as well as cause-specific mortality data are sparse. In our population-based cohort of adult patients...

  12. Splenic arteriovenous malformation manifested by thrombocytopenia in hereditary hemorrhagic telangiectasia: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hee Jin; Choi, Jong Cheol; Oh, Jong Yeong; Cho, Jin Han; Kang, Myong Jin; Lee, Jin Hwa; Yoon, Seong Kuk; Nam, Kyeong Jin [College of Medicine, Dong-A University, Busan (Korea, Republic of)


    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease characterized by epistaxis, telangiectases and visceral arteriovenous malformations (AVMs). The involvement of the gastrointestinal tract, liver, lung and cerebrum for HHT has been described, whereas little is known about AVMs of the spleen. We report here the radiological findings of a case of a splenic AVM manifested by thrombocytopenia in HHT.

  13. Inherited thrombocytopenia: novel insights into megakaryocyte maturation, proplatelet formation and platelet lifespan. (United States)

    Johnson, Ben; Fletcher, Sarah J; Morgan, Neil V


    The study of patients with inherited bleeding problems is a powerful approach in determining the function and regulation of important proteins in human platelets and their precursor, the megakaryocyte. The normal range of platelet counts in the bloodstream ranges from 150 000 to 400 000 platelets per microliter and is normally maintained within a narrow range for each individual. This requires a constant balance between thrombopoiesis, which is primarily controlled by the cytokine thrombopoietin (TPO), and platelet senescence and consumption. Thrombocytopenia can be defined as a platelet count of less than 150 000 per microliter and can be acquired or inherited. Heritable forms of thrombocytopenia are caused by mutations in genes involved in megakaryocyte differentiation, platelet production and platelet removal. In this review, we will discuss the main causative genes known for inherited thrombocytopenia and highlight their diverse functions and whether these give clues on the processes of platelet production, platelet function and platelet lifespan. Additionally, we will highlight the recent advances in novel genes identified for inherited thrombocytopenia and their suggested function.

  14. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia

    DEFF Research Database (Denmark)

    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...

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

    African Journals Online (AJOL)

    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.

  16. Thrombocytopenia associated with olanzapine: A case report and review of literature

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    Swapnajeet Sahoo


    Full Text Available There is limited literature on olanzapine-associated thrombocytopenia. In this report, we present a case of a 32-year-old female, suffering from persistent delusional disorder who had thrombocytopenia (46,000/mm3 with the use of olanzapine 25 mg/day, 6 weeks after starting medication. Blood film did not reveal any evidence of any dysplastic cells, disturbance in the count of other cell lines, and autoimmune workup including antinuclear antibodies and anti-neutrophil cytoplasmic antibodies were found to be negative. Given no other etiology, olanzapine was gradually tapered, and platelet counts were monitored. Reduction in the dose of olanzapine led to an improvement in platelet counts which reached the normal range after complete stoppage of olanzapine. In view of continued psychotic symptoms, she was started on clozapine and which was gradually increased to 200 mg/day with biweekly monitoring of total platelet counts before each increment in the dose of clozapine. Thrombocytopenia did not recur with use of clozapine. With clozapine, her psychosis improved by nearly 60%. A review of literature revealed only eight case reports supporting the association of olanzapine and thrombocytopenia.

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


    Kuzmanović Miloš; Kunishima Shinji; Putnik Jovana; Stajić Nataša; Paripović Aleksandra; Bogdanović Radovan


    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 dia...

  18. A case of neonatal HPA-1b allo-immune thrombocytopenia

    NARCIS (Netherlands)

    van der Vlugt, AH; Hepkema, BG; Tamminga, RYJ


    We present a case of a newborn with neonatal alloimmune thrombocytopenia (NAIT) due to fete-maternal incompatibility for the thrombocyte allo-antigen HPA-1b. We discuss the policy of platelet transfusions and suggest to treat NAIT early on with thrombocytes transfusions from selected compatible

  19. Eptifibatide induced profound thrombocytopenia in a patient with pelvic malignancy: A case report


    Squires, Kathryn C.; Guntupalli, Saketh R.; Thaker, Premal H.


    ► Eptifibatide is associated with profound thrombocytopenia and thrombosis secondary to a HITT-like mechanism associated with drug-dependant antibodies. ► Caution with eptifibatide use is needed in those pre-disposed to hypercoaguability, particularly those with an underlying malignancy.

  20. Isolated thrombocytopenia; A report of a rare presentation of childhood systemic lupus erythematosus (SLE). (United States)

    Tamaddoni, Ahmad; Yousefghahari, Behnaz; Khani, Afshin; Esmaeilidooki, Mohammadreza; Barari Sawadkouhi, Rahim; Mohammadzadeh, Iraj


    Systemic lupus erythematosus (SLE) has various presentations in children. Hematologic abnormalities is common in childhood onset of SLE, however, isolated thrombocytopenia is relatively rare. Thus, we present a child with isolated thrombocytopenia as a rare presentation of SLE. A 12-year-old boy with chief complaints of loss of appetite, weight loss, decreased platelet count (8000/µL) and lymph node enlargement was referred to our hospital. Biopsy of lymph node showed reactive lymphadenopathy. Investigations regarding infectious disease was negative. Platelet count remained low after low dose steroidned therapy. Antinuclear antibody (ANA) and anti-double stranded DNA antibody screening tests were positive with titer of 1/62 and 1/54, respectively. Therefore, juvenile SLE was considered as the final diagnosis and raising the dose of prednisolone to 2mg/kg/day was associated with increasing platelet count to 40000/µL and a week later to 96000/µL. The findings of this study indicate that in cases with isolated thrombocytopenia refractory to conventional dose of steroids, SLE should be considered. This study justifies serum ANA and anti DNA assessment in children with thrombocytopenia.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Thrombocytopenia and craniotomy for tumor: A National Surgical Quality Improvement Program analysis. (United States)

    Dasenbrock, Hormuzdiyar H; Devine, Christopher A; Liu, Kevin X; Gormley, William B; Claus, Elizabeth B; Smith, Timothy R; Dunn, Ian F


    To the authors' knowledge, the current study is the first national analysis of the association between preoperative platelet count and outcomes after craniotomy. Patients who underwent craniotomy for tumor were extracted from the prospective National Surgical Quality Improvement Program registry (2007-2014) and stratified by preoperative thrombocytopenia, defined as mild (125,000-149,000/μL), moderate (100,000-124,000/μL), severe (75,000-99,000/μL), or very severe (thrombocytopenia and 30-day mortality, and multivariable logistic regression with complications and unplanned reoperation. Covariates included patient age, sex, tumor histology, American Society of Anesthesiologists class, functional status, comorbidities, and surgical time. A total of 14,852 patients were included in the current study and thrombocytopenia was classified as mild in 4.4% (646 patients), moderate in 2.0% (290 patients), severe in 0.7% (105 patients), or very severe in 0.4% (66 patients) of patients. The adjusted hazard of 30-day death was significantly higher for patients with moderate (6.6%; hazard ratio [HR], 2.13 [95% confidence interval (95% CI), 1.30-3.49; P =  0.003]), severe (10.5%; HR, 2.33 [95% CI, 1.18-4.60; P =  0.02]), and very severe (10.6%; HR, 3.65 [95% CI, 1.71-7.82; P =  0.001]) thrombocytopenia, compared with patients without thrombocytopenia (2.9%), with an increased effect size noted with greater thrombocytopenia. Likewise, when the platelet count was evaluated continuously, a higher platelet count was associated with a lower hazard of 30-day mortality (HR, 0.987 [95% CI, 0.981-0.993; Pthrombocytopenia. In this National Surgical Quality Improvement Program analysis, moderate and severe thrombocytopenia were associated with mortality and reoperation after craniotomy for tumor. Cancer 2016;122:1708-17. © 2016 American Cancer Society. © 2016 American Cancer Society.

  3. Prevalence of HIV-related thrombocytopenia among clients at Mbarara Regional Referral Hospital, Mbarara, southwestern Uganda

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    Taremwa IM


    Full Text Available Ivan M Taremwa,1 Winnie R Muyindike,2 Enoch Muwanguzi,1 Yap Boum II,1,3 Bernard Natukunda1 1Department of Medical Laboratory Sciences, Faculty of Medicine, Mbarara University of Science and Technology, 2Immune Suppression Syndrome Clinic, Mbarara Regional Referral Hospital, 3Epicentre Mbarara Research Centre, Mbarara, Uganda Aims/objectives: We aimed to determine the prevalence and correlates of thrombocytopenia among people living with human immunodeficiency virus (HIV/acquired immune deficiency syndrome (AIDS and to assess occurrence of antiplatelet antibodies, among thrombocytopenic HIV clients at Mbarara Regional Referral Hospital, southwestern Uganda.Materials and methods: This was a retrospective review of hematologic results at enrollment to HIV care from 2005 to 2013. The prevalence and correlates of thrombocytopenia were estimated based on the Immune Suppressed Syndrome (ISS Clinic electronic database. A cross-sectional study determined the occurrence of antiplatelet antibodies, using the monoclonal antibody-specific immobilization of platelet antigens (MAIPA technique.Results: We reviewed 15,030 client records. The median age was 35.0 (range 18–78; interquartile range [IQR] 28–42 years, and there were 63.2% (n=9,500 females. The overall prevalence of thrombocytopenia was 17.4% (95% confidence interval [CI]: 16.8%–18.0%. The prevalence of thrombocytopenia was 17.8% (95% CI: 17.1%–18.4% among antiretroviral therapy (ART-naïve clients (n=2,675 and was 13.0% (95% CI: 0.3%–21.9% for clients who were on ART (n=6. The study found a significant association between thrombocytopenia and other cytopenias, CD4 counts, ART, and deteriorating HIV stage (P<0.05. Two of the 40 participants (5.0% had antiplatelet antibodies.Conclusion: This study has showed a high prevalence of HIV-related thrombocytopenia. Antiplatelet antibodies were found in 5.0% of HIV-infected thrombocytopenic participants. Our study shows a significant association of

  4. Diabetes Mellitus Increases Severity of Thrombocytopenia in Dengue-Infected Patients

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    Chung-Yuan Chen


    Full Text Available Background: Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. Methods: We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. Results: Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54 ± 51.69 vs. 86.58 ± 63.4 (p ≤ 0.001, 43.98 ± 44.09 vs. 64.52 ± 45.06 (p = 0.002, 43.86 ± 35.75 vs. 62.72 ± 51.2 (p = 0.012. Diabetes mellitus, death, dengue shock syndrome (DSS and dengue hemorrhagic fever (DHF and increased glutamic-pyruvate transaminase (GPT levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression β of −13.981 (95% confidence interval (CI −27.587, −0.374, −26.847 (95% CI −37.562, −16.132, and 0.054 (95% CI 0.015, 0.094 respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of −2.947 (p = 0.004, 2.801 (p = 0.005, and −3.568 (p ≤ 0.001, respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF/dengue shock syndrome (DSS than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in

  5. Phylogenetic and Geographic Relationships of Severe Fever With Thrombocytopenia Syndrome Virus in China, South Korea, and Japan. (United States)

    Yoshikawa, Tomoki; Shimojima, Masayuki; Fukushi, Shuetsu; Tani, Hideki; Fukuma, Aiko; Taniguchi, Satoshi; Singh, Harpal; Suda, Yuto; Shirabe, Komei; Toda, Shoichi; Shimazu, Yukie; Nomachi, Taro; Gokuden, Mutsuyo; Morimitsu, Toshiharu; Ando, Katsuyuki; Yoshikawa, Akira; Kan, Miki; Uramoto, Marina; Osako, Hideo; Kida, Kouji; Takimoto, Hirokazu; Kitamoto, Hiroaki; Terasoma, Fumio; Honda, Akiko; Maeda, Ken; Takahashi, Toru; Yamagishi, Takuya; Oishi, Kazunori; Morikawa, Shigeru; Saijo, Masayuki


    Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne acute infectious disease caused by the SFTS virus (SFTSV). SFTS has been reported in China, South Korea, and Japan as a novel Bunyavirus. Although several molecular epidemiology and phylogenetic studies have been performed, the information obtained was limited, because the analyses included no or only a small number of SFTSV strains from Japan. The nucleotide sequences of 75 SFTSV samples in Japan were newly determined directly from the patients' serum samples. In addition, the sequences of 7 strains isolated in vitro were determined and compared with those in the patients' serum samples. More than 90 strains that were identified in China, 1 strain in South Korea, and 50 strains in Japan were phylogenetically analyzed. The viruses were clustered into 2 clades, which were consistent with the geographic distribution. Three strains identified in Japan were clustered in the Chinese clade, and 4 strains identified in China and 26 in South Korea were clustered in the Japanese clade. Two clades of SFTSV may have evolved separately over time. On rare occasions, the viruses were transmitted overseas to the region in which viruses of the other clade were prevalent. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail:

  6. Pentadecapeptide BPC 157 reduces bleeding time and thrombocytopenia after amputation in rats treated with heparin, warfarin or aspirin. (United States)

    Stupnisek, Mirjana; Franjic, Sandra; Drmic, Domagoj; Hrelec, Masa; Kolenc, Danijela; Radic, Bozo; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag


    Recently, in rat abdominal aorta terminoterminal-anastomosis the stable gastric pentadecapeptide BPC 157 prevents obstructive thrombus formation and rapidly destroys already formed obstructive thrombus. Also, BPC 157 wound healing may signify the clot as conductive matrix or "scaffold" to speed up wound healing process, and decrease bleeding. Here, in rats, BPC 157 (10 μg/kg, 10 ng/kg) improved always reduced bleeding time and amount of bleeding after (tail) amputation only, heparin (250 mg/kg, 25mg/kg, 10mg/kg i.v.), warfarin (1.5mg/kg i.g. once daily for 3 consecutive days), aspirin (0.1g/kg i.g. (once daily/3 consecutive days) or 1.0 g/kg i.p. once), and amputation associated with those agents application. BPC 157 counteracting regimens (i.v., i.p., i.g. (immediately after any challenge)) correspondingly follow the route of bleeding-agents application. All heparin-, warfarin-, and aspirin-rats and normal-rats that received BPC 157 exhibited lesser fall in platelets count. BPC 157 attenuated over-increased APTT-, TT-values in 10mg/kg heparin-rats, but did not influence heparin activity (anti-Xa test). Indicatively, unless counteracted in BPC 157 rats, excessive bleeding-acute thrombocytopenia (BPC 157 markedly prolongs the survival time (heparin-rats, 25mg/kg, right foot amputation). Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Acute disseminated encephalomyelitis and other inflammatory demyelinating variants. (United States)

    Scolding, Neil


    Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory central nervous system disorder characterized by acute or subacute onset of multifocal neurologic deficits with headache and impaired conscious level. Acute haemorrhagic leuoko-encephalitis (AHEM) is a more sever, often fatal variant. These disorders often follows a viral illness or vaccination, and are usually monophasic, though (probably more commonly in childhood) a multiphasic variant of ADEM is recognized. Because of the relative non-specificity of the clinical presentation (a sub-acute encephalopathy with focal signs), the differential diagnosis is wide; and distinction from the first episode of relapsing-remitting multiple sclerosis can occasionally be difficult. Here the clinical and investigational features of these disorders and their treatment are discussed. © 2014 Elsevier B.V. All rights reserved.

  8. Intraperitoneally administered IgG from patients with amyotrophic lateral sclerosis or from an immune-mediated goat model increase the levels of TNF-α, IL-6, and IL-10 in the spinal cord and serum of mice. (United States)

    Obál, Izabella; Klausz, Gergely; Mándi, Yvette; Deli, Mária; Siklós, László; Engelhardt, József I


    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that involves the selective loss of the upper and lower motor neurons (MNs). Neuroinflammation has been implicated in the pathogenesis of the sporadic form of the disease. We earlier developed immune-mediated animal models of ALS and demonstrated humoral and cellular immune reactions in the nervous system and in the sera of patients and animals. The accumulation of immunoglobulin G (IgG), an elevated intracellular level of calcium, ultrastructural alterations in the MNs, and activation of the microglia were noted in the spinal cord of ALS patients. Similar alterations developed in mice inoculated intraperitoneally with IgG from ALS patients or from an immune-mediated goat model. We have now examined whether the intraperitoneal injection of mice with IgG from sporadic ALS patients or from immunized goats with the homogenate of the anterior horn of the bovine spinal cord is associated with changes in the pro-inflammatory (TNF-α and IL-6) and anti-inflammatory (IL-10) cytokines in the spinal cord and serum of the mice. The levels of cytokines were measured by ELISA. Intraperitoneally administered IgG from the ALS patients induced subclinical signs of MN disease, while the injection of IgG from immunized goats resulted in a severe respiratory dysfunction and limb paralysis 24 h after the injections. Significantly increased levels of TNF-α and IL-10 were detected in the spinal cord of the mice injected with the human ALS IgG. The level of IL-6 increased primarily in the serum. The IgG from the immunized goats induced highly significant increases in the levels of all three cytokines in the serum and the spinal cord of mice. Our earlier experiments had proved that when ALS IgG or IgG from immune-mediated animal models was inoculated into mice, it was taken up in the MNs and had the ability to initiate damage in them. The pathological process was paralleled by microglia recruitment and activation in the

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

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    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.

  10. Epidemiology of primary and secondary thrombocytopenia: first analysis of an administrative database in a major Italian institution. (United States)

    Galdarossa, Michela; Vianello, Fabrizio; Tezza, Fabiana; Allemand, Emanuele; Treleani, Martina; Scarparo, Pamela; Fabris, Fabrizio


    Administrative databases can be a reliable source for estimating the epidemiology of blood disorders. No data are available estimating the epidemiology of thrombocytopenia from administrative data in Italian institutions. We analyzed the administrative database of the Padua University Hospital with the aim to study the epidemiology of thrombocytopenia in patients discharged with an International Classification of Disease, 9th Revision, Clinical Modification (ICD9-CM) code of thrombocytopenia. The database from year 2004 to 2008 was evaluated and all cases of thrombocytopenia (Code 287.1, 3, 4, 5) were identified and analyzed with regard to age, sex, associated diseases, therapeutics procedures and bleeding complications. The accuracy of electronic records was validated in all available medical records of patients discharged in 2009, by applying the ICD9-CM update 2007 version (Code 287.1, 4, 5; 287.30, 31, 32, 33, 39). We found 368 patients discharged from 2004 to 2008 with an ICD9-CM code of thrombocytopenia, correspondent to 0.1% of discharge rate and to a rate of 73.6 patients/year. The incidence of thrombocytopenia for this period was 14.8 cases per 100,000 per year. When considering patients with an ICD9-CM diagnosis of immune thrombocytopenia (ITP: Code 287.3), the incidence was of 6.8 cases per 100,000 per year. The clinical records of 40 patients with a discharge diagnosis of thrombocytopenia during year 2009 were reviewed for clinical consistency with ICD9-CM codes. A concordant diagnosis between clinical records and discharge code was found in 82.5% of cases. Following validation of ICD9-CM code, the incidence of ITP (Code 287.31) was 2.6 cases per 100,000 per year. When evaluated for sensitivity and specificity, we found the ICD-9-CM to be useful in studying thrombocytopenia using administrative data.

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

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    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

  12. Acute Myeloid Leukemia Presenting as Acute Appendicitis

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    Sherri Rauenzahn


    Full Text Available Appendicitis in leukemic patients is uncommon but associated with increased mortality. Additionally, leukemic cell infiltration of the appendix is extremely rare. While appendectomy is the treatment of choice for these patients, diagnosis and management of leukemia have a greater impact on remission and survival. A 59-year-old Caucasian female was admitted to the surgical service with acute right lower quadrant pain, nausea, and anorexia. She was noted to have leukocytosis, anemia, and thrombocytopenia. Abdominal imaging demonstrated appendicitis with retroperitoneal and mesenteric lymphadenopathy for which she underwent laparoscopic appendectomy. Peripheral smear, bone marrow biopsy, and surgical pathology of the appendix demonstrated acute myeloid leukemia (AML with nonsuppurative appendicitis. In the setting of AML, prior cases described the development of appendicitis with active chemotherapy. Of these cases, less than ten patients had leukemic infiltration of the appendix, leading to leukostasis and nonsuppurative appendicitis. Acute appendicitis with leukemic infiltration as the initial manifestation of AML has only been described in two other cases in the literature with an average associated morbidity of 32.6 days. The prompt management in this case of appendicitis and AML resulted in an overall survival of 185 days.

  13. [Acute disseminated encephalomyelitis is an important differential diagnosis in the acutely affected child]. (United States)

    Olofsson, Isa Amalie; Skov, Liselotte; Miranda, Maria Jose


    Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory paediatric disorder of the central nervous system (CNS). ADEM primarily affects the white matter of the brain and spinal cord. The aetiology of ADEM is unknown, but the illness is often precipitated by an infection, less often by vaccination. ADEM is characterized by acute polyfocal CNS deficit, including encephalopathy. This can be seen on MRI as simultaneously occurring multifocal lesions. Empirical treatment with steroids or immunoglobulins is often used. The prognosis of ADEM is usually favourable. This article describes two Danish cases both demonstrating trait characteristics of ADEM as well as the importance of an MRI considering an ADEM diagnosis early in the course of the illness.

  14. Malaria with Acute Renal Failure in a Middle Aged Man: A Case ...

    African Journals Online (AJOL)

    The case of a middle aged(39 years) man admitted with severe malaria in the male ward of the Federal Medical Centre, Owerri, Imo State, Nigeria is reported. The infecting species was Plasmodium falciparum and the patient was febrile, developed acute renal failure, severe thrombocytopenia and hepatic failure. Treatment ...

  15. Return to the Primary Acute Care Service Among Patients With Multiple Myeloma on an Acute Inpatient Rehabilitation Unit. (United States)

    Fu, Jack B; Lee, Jay; Shin, Ben C; Silver, Julie K; Smith, Dennis W; Shah, Jatin J; Bruera, Eduardo


    Pancytopenia, immunosuppression, and other factors may place patients with multiple myeloma at risk for medical complications. These patients often require inpatient rehabilitation. No previous studies have looked at risk factors for return to the primary acute care service of this patient population. To determine the percentage of and factors associated with return to the primary acute care service of multiple myeloma rehabilitation inpatients. Retrospective review. Acute inpatient rehabilitation unit within a National Cancer Institute Comprehensive Cancer Center. All patients with multiple myeloma admitted to the inpatient rehabilitation unit between March 1, 2004, and February 28, 2015. Return to the primary acute care service was analyzed with demographic information, multiple myeloma characteristics, medications, laboratory values, and hospital admission characteristics. One hundred forty-three inpatient rehabilitation admissions were found during the study period. After we removed multiple admissions of the same patients and planned transfers to the primary acute care service, 122 admissions were analyzed. Thirty-two (26%) patients transferred back to the primary acute care service for unplanned reasons. Multivariate analysis revealed male gender and thrombocytopenia as significantly associated with return to the primary acute care service. The median survival of patients who transferred back to the inpatient primary acute care service was 180 days versus 550 days for those who did not (P service. Factors associated with an increased risk of transfer back to the primary acute care service include male gender and thrombocytopenia. IV. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  16. Prevalence of thrombocytopenia among pregnant women attending antenatal care service at Gondar University Teaching Hospital in 2014, northwest Ethiopia

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    Asrie F


    Full Text Available Fikir Asrie, Bamlaku Enawgaw, Zegeye Getaneh Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia Introduction: Thrombocytopenia is a common hematologic abnormality during pregnancy. Pregnant women with thrombocytopenia have a higher risk of bleeding excessively during or after childbirth, particularly if they need to have a cesarean section or other surgical intervention during pregnancy, labor or in the puerperium. The main aim of this study was to determine the prevalence of thrombocytopenia among pregnant women attending antenatal care service at Gondar University Hospital, northwest Ethiopia.Materials and methods: A cross-sectional study was used to assess the prevalence of thrombocytopenia among pregnant women attending antenatal care service at Gondar University Hospital from January to April 2015. A total of 217 pregnant women were included in the study and a structured pretested questionnaire was used to obtain sociodemographic information, nutritional factors, obstetrics and gynecological factors, history and clinical condition. Blood samples were collected for platelet count and other platelet parameters, which were determined by using SysmexKX 21 automation. The data were entered to Epi info version 6 software and analyzed using SPSS version 20 software. Bivariable and multivariable statistical analyses were used to evaluate the effect of independent variable over the dependent variable. A p-value of <0.05 was considered as statistically significant.Result: A total of 217 women receiving antenatal care service at Gondar University Hospital participated in the study. Thrombocytopenia among 19 pregnant women showed a prevalence of 8.8%. The mean ± standard deviation platelet count was 238.85×109/L (±74.57. Thrombocytopenia was significantly associated with patients who lived rurally (crude odds ratio =4.3, 95

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

    DEFF Research Database (Denmark)

    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....

  18. Romiplostim in children with chronic immune thrombocytopenia (ITP): the French experience. (United States)

    Pasquet, Marlène; Aladjidi, Nathalie; Guiton, Corinne; Courcoux, Mary-France; Munzer, Martine; Auvrignon, Anne; Lutz, Patrick; Ducassou, Stéphane; Leroy, Gwennaelle; Munzer, Caroline; Leverger, Guy


    A minority of children with chronic immune thrombocytopenia (ITP) require therapeutic intervention to prevent haemorrhagic risk. This retrospective national study evaluated romiplostim in childhood non-responsive or refractory chronic ITP. Between 2009 and 2012, 10 patients whose Buchanan score was 3-4 were treated with romiplostim. The median duration of thrombocytopenia was 1·9 years (0·8-15). The median duration of romiplostim treatment was 9 months (3-36). A response was observed in 5/10 patients (one complete, four partial). No serious adverse effect was noticed. The long-term benefit/risk balance of this innovative treatment is currently recorded by Centre de Référence National des Cytopénies Auto-immunes de l'Enfant. © 2013 John Wiley & Sons Ltd.

  19. Safety and Efficacy of Argatroban in the Management of Heparin-Induced Thrombocytopenia

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    Bernd Saugel


    Full Text Available Heparin-induced thrombocytopenia (HIT is a life-threatening adverse reaction to heparin therapy that is characterized by thrombocytopenia and an increased risk of venous and arterial thrombosis. According to guidelines, in patients with strongly suspected or confirmed HIT all sources of heparin have to be discontinued and an alternative, nonheparin anticoagulant for HIT treatment must immediately be started. For both the prophylaxis of thrombembolic events in HIT and the treatment of HIT with thrombosis the direct thrombin inhibitor argatroban is approved in the United States. The objective of this review is to describe the mechanism of action and the pharmacokinetic profile of argatroban, to characterize argatroban regarding its safety and therapeutic efficacy and to discuss its place in therapy in HIT.

  20. Viruses, anti-viral therapy, and viral vaccines in children with immune thrombocytopenia. (United States)

    Elalfy, Mohsen S; Nugent, Diane


    Immune thrombocytopenia (ITP) might be preceded by silent or overt viral infections. Similarly, anti-viral drugs and viral vaccines could also trigger ITP and might play a central role in its pathogenesis. The seasonal nature of childhood ITP suggests that viral infections might initiate immune responses that increase the predisposition and occurrence of ITP. Active cytomegalovirus or Epstein-Barr virus should be considered in differential diagnosis when thrombocytopenia is associated with lymphadenopathy, especially with splenomegaly. This review will focus on the specific association of ITP in association with viral disease and vaccinations, and will discuss the effectiveness of current therapies in light of our current understanding of viral-associated ITP. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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    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.

  2. Are micromegakaryocytes specific for refractory cytopenia of childhood (RCC)? A study of 38 pediatric patients with thrombocytopenia unrelated to RCC. (United States)

    Aqil, Barina; Punia, Jyotinder N; Curry, Choladda V; Marcogliese, Andrea N; Elghetany, M Tarek


    Micromegakaryocytes (microMKs) are considered the most reliable dysplastic feature for myelodysplastic syndrome (MDS), particularly refractory cytopenia of childhood (RCC); there is no minimal threshold for the diagnosis of RCC. Since most RCC patients present with thrombocytopenia, the presence of microMKs should raise concern for MDS/RCC. This study attempted to investigate the prevalence of microMKs and associated marrow fibrosis in patients with thrombocytopenia unrelated to MDS/RCC and the need for establishing a threshold for microMKs for the diagnosis of MDS/RCC. Bone marrow biopsies of pediatric patients with thrombocytopenia unrelated to RCC were examined for microMKs and fibrosis by CD61 immunohistochemical and reticulin stains respectively. Thirty eight patients (1-18 years old) were included: 33 immune thrombocytopenia (ITP), 3 chronic thrombocytopenia, and 2 inherited macrothrombocytopenia. Fourteen cases (37%) had microMKs; four cases showed increased marrow fibrosis associated with microMKs (two had ITP and two had macrothrombocytopenia). All patients are alive and none developed MDS (follow up: 3months to 4 years). MicroMKs can be seen in pediatric patients with thrombocytopenia unrelated to RCC. Hence the mere presence of microMKs is insufficient for the diagnosis of RCC in the pediatric population, and a quantitative threshold needs to be established. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Oxidative Stress Is Predominant in Female but Not in Male Patients with Autoimmune Thrombocytopenia


    Julian Kamhieh-Milz; Abdulgabar Salama


    As the involvement of oxidative stress (OS) in autoimmune thrombocytopenia (AITP) has been reported, a fast and rapid test for the reliable measurement of OS and antioxidant capacities (AOCs) might be a useful tool in extending current diagnostic possibilities. The free oxygen radical test (FORT) and free oxygen radical defence (FORD) assay (Callegari, Italy) are easy to perform and reliable, with results available within 15 minutes. Thirty-seven AITP patients and 37 matched healthy individua...

  4. Management of menorrhagia associated with chemotherapy-induced thrombocytopenia in women with hematologic malignancy. (United States)

    Bates, Jill S; Buie, Larry W; Woodis, C Brock


    Abnormal uterine bleeding in women with a blood dyscrasia, such as leukemia, or who experience thrombocytopenia secondary to myelosuppressive chemotherapy is a clinical condition associated with significant morbidity. Consequently, effective management is necessary to prevent adverse outcomes. Prevention of menorrhagia, defined as heavy regular menstrual cycles with more than 80 ml of blood loss/cycle or a cycle duration longer than 7 days, in this patient population is the goal of therapy. Gonadotropin-releasing hormone analogs (e.g., leuprolide) are promising therapies that have been shown to decrease vaginal bleeding during periods of thrombocytopenia and to have minimal adverse effects other than those associated with gonadal inhibition. In patients who experience menorrhagia despite preventive therapies, or in patients who have thrombocytopenia and menorrhagia at diagnosis, treatment is indicated. For these women, treatment options may include platelet transfusions, antifibrinolytic therapy (e.g., tranexamic acid), continuous high-dose oral contraceptives, cyclic progestins, or other therapies for more refractory patients such as danazol, desmopressin, and recombinant factor VIIa. Hormonal therapies are often the mainstay of therapy in women with menorrhagia secondary to thrombocytopenia, but data for these agents are sparse. The most robust data for the treatment of menorrhagia are for tranexamic acid. Most women receiving tranexamic acid in randomized trials experienced meaningful reductions in menstrual bleeding, and this translated into improved quality of life; however, these trials were not performed in patients with cancer. Further clinical trials are warranted to evaluate both preventive and therapeutic agents for menorrhagia in premenopausal women with cancer who are receiving myelosuppressive chemotherapy.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Gestational Thrombocytopenia: Does It Cause Any Maternal and /or Perinatal Morbidity?

    Directory of Open Access Journals (Sweden)

    Carlo Pafumi


    Full Text Available Purpose: The iam of this study was retrospectively evaluate maternal platelet count fluctuation during pregnancy and puerperium and its correlation with the newborn’s platelet levels. Method: A group of 36 patients who have been referred to a haematology-clinic for gestational thrombocytopenia (GT and who delivered at the same hospital during a period of 4 years, from January 2006 to December2009 were included in the study. Mothers and their related foetuses- newborns were evaluated retrospectively for symptoms and/or signs of external and internal haemorrhage throughout pregnancy and early puerperium, even in relationship with mode of delivery (caesarean section versus spontaneous vaginal delivery. Results: All observed cases of GT have an uncomplicated course with no related perinatal and maternal morbidity even in patients with initial platelet count < 75.000/ml independently from the route of delivery. Conclusion: In case of gestational thrombocytopenia a complete normalization of maternal platelet count should be expected during the postpartum period, even if a diagnosis of a concomitant incidental neonatal thrombocytopenia cannot be excluded.No intervention, such as a foetal platelet count or caesarean section, is necessary. [Cukurova Med J 2013; 38(3.000: 349-357

  7. Nanoparticles camouflaged in platelet membrane coating as an antibody decoy for the treatment of immune thrombocytopenia. (United States)

    Wei, Xiaoli; Gao, Jie; Fang, Ronnie H; Luk, Brian T; Kroll, Ashley V; Dehaini, Diana; Zhou, Jiarong; Kim, Hyeon Woo; Gao, Weiwei; Lu, Weiyue; Zhang, Liangfang


    Immune thrombocytopenia purpura (ITP) is characterized by the production of pathological autoantibodies that cause reduction in platelet counts. The disease can have serious medical consequences, leading to uncontrolled bleeding that can be fatal. Current widely used therapies for the treatment of ITP are non-specific and can, at times, result in complications that are more burdensome than the disease itself. In the present study, the use of platelet membrane-coated nanoparticles (PNPs) as a platform for the specific clearance of anti-platelet antibodies is explored. The nanoparticles, whose outer layer displays the full complement of native platelet surface proteins, act as decoys that strongly bind pathological anti-platelet antibodies in order to minimize disease burden. Here, we study the antibody binding properties of PNPs and assess the ability of the nanoparticles to neutralize antibody activity both in vitro and in vivo. Ultimately, we leverage the neutralization capacity of PNPs to therapeutically treat a murine model of antibody-induced thrombocytopenia and demonstrate considerable efficacy as shown in a bleeding time assay. PNPs represent a promising platform for the specific treatment of antibody-mediated immune thrombocytopenia by acting as an alternative target for anti-platelet antibodies, thus preserving circulating platelets with the potential of leaving broader immune function intact. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Helicobacter pylori, anemia, iron deficiency and thrombocytopenia among pregnant women at Khartoum, Sudan. (United States)

    Mubarak, Nahla; Gasim, Gasim I; Khalafalla, Khalifa E; Ali, Naj I; Adam, Ishag


    Helicobacter pylori is a common gut pathogen that is linked to many complications of pregnancy such as iron deficiency anemia, pre-eclampsia and thrombocytopenia. There are no published data on H. pylori in Sudan. A cross-sectional study was conducted during the period May-June 2012 at the antenatal care unit of Khartoum Hospital, Sudan, to investigate prevalence of H. pylori and its association, if any, with anemia and thrombocytopenia. Obstetric and medical histories were gathered using questionnaires. Hemoglobin and serum ferritin were measured and H. pylori antibodies (IgA and IgG) investigated using ELISA. Among 179 women, rates of positivity for specific IgG formed against H. pylori were 69.8% (125/179), 94.0% (168/179) and 5.6% (10/179) for IgA, IgG and both IgG and IgA, respectively. There was no association between the expected risk factors (age, parity, education) and H. pylori seropositivity. Of these women, 42/179 (24.3%), 50/179 (28.9%) and 19/179 (11%), respectively, were anemic (hemoglobin Sudan, and it is not associated with anemia or thrombocytopenia. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail:

  9. Thrombocytopenia in malaria: can platelet counts differentiate malaria from other infections? (United States)

    Arshad, Abdul Rehman


    To determine the accuracy of thrombocytopenia as a diagnostic marker for malaria. Cross-sectional study. Department of Medicine, 1 Mountain Medical Battalion (Bagh, Azad Kashmir) from July to September 2013. Adult patients presenting with a short history of fever without any localizing symptoms or signs were included. Exclusion criteria included patients with fever of > 7 days duration, those in whom an underlying diagnosis could be easily confirmed on the basis of history and physical examination, those on antibiotics/ antimalarials or antiplatelet agents and patients with Dengue fever. Platelet counts in venous whole blood samples were analysed with Sysmex KX-21 Haematology analyzer. Thick and thin peripheral blood smears were then prepared and examined for malarial parasites. Diagnosis of malaria was established on the basis of smear findings. There were 245 patients in total. Out of the 109 patients with thrombocytopenia, 61 had vivax malaria. Platelets count was normal in 136 patients, including 4 with vivax malaria. Falciparum malaria was not seen in any patient. All cases with malaria were uncomplicated. Various measures of accuracy thus calculated were sensitivity 93.85%, specificity 73.33%, positive predictive value 55.96%, negative predictive value 97.06%, positive likelihood ratio of 3.52, negative likelihood ratio of 0.08, diagnostic odds ratio 41.94 and diagnostic accuracy of 78.78%. Thrombocytopenia has an excellent sensitivity and a very good specificity for vivax malaria. Normal platelet counts provide very strong evidence against malaria as the etiology of fever without a focus.

  10. Comparison of different platelet transfusion thresholds prior to insertion of central lines in patients with thrombocytopenia. (United States)

    Estcourt, Lise J; Desborough, Michael; Hopewell, Sally; Doree, Carolyn; Stanworth, Simon J


    Patients with a low platelet count (thrombocytopenia) often require the insertion of central lines (central venous catheters (CVCs)). CVCs have a number of uses; these include: administration of chemotherapy; intensive monitoring and treatment of critically-ill patients; administration of total parenteral nutrition; and long-term intermittent intravenous access for patients requiring repeated treatments. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to CVC insertion, in order to mitigate the risk of serious procedure-related bleeding. However, the platelet count threshold recommended prior to CVC insertion varies significantly from country to country. This indicates significant uncertainty among clinicians of the correct management of these patients. The risk of bleeding after a central line insertion appears to be low if an ultrasound-guided technique is used. Patients may therefore be exposed to the risks of a platelet transfusion without any obvious clinical benefit. To assess the effects of different platelet transfusion thresholds prior to the insertion of a central line in patients with thrombocytopenia (low platelet count). We searched for randomised controlled trials (RCTs) in CENTRAL (The Cochrane Library 2015, Issue 2), MEDLINE (from 1946), EMBASE (from 1974), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 23 February 2015. We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in patients of any age with thrombocytopenia requiring insertion of a CVC. We used standard methodological procedures expected by The Cochrane Collaboration. One RCT was identified that compared different platelet transfusion thresholds prior to insertion of a CVC in people with chronic liver disease. This study is still recruiting participants (expected recruitment: up to 165 participants

  11. Thrombotic Thrombocytopenic Purpura: A Case Presenting with Acute Ischemic Colitis

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    Joseph R. H. See


    Full Text Available Thrombotic thrombocytopenic purpura (TTP consists of the pentad of thrombocytopenia, hemolytic anemia, fever, neurologic abnormalities, and renal disease. We present a case report of acute TTP following a bout of ischemic colitis. This report reminds the clinician that ischemic colitis can be an atypical presentation of TTP. The prompt recognition and treatment of this disease process resulted in a good prognosis for our patient.

  12. Recipient-derived HPA-1a antibodies: a cause of prolonged thrombocytopenia after unrelated donor stem cell transplantation. (United States)

    Lucas, Geoff; Culliford, Steven; Green, Frances; Sidra, Gamal; Calvert, Anthony; Green, Ann; Harrison, Penny; Harvey, John; Allen, Dave; Smillie, David; Masurekar, Ashish; Marks, David; Russell, Nigel; Massey, Edwin


    Patients with human platelet antigen (HPA) specific antibodies in cases of neonatal alloimmune thrombocytopenia and platelet (PLT) refractoriness derive clinical benefit from the use of HPA-selected PLTs. This study describes three patients with underlying diagnoses of acute myeloid leukemia, chronic lymphocytic leukemia, and myelodysplasia, respectively, who underwent allogeneic bone marrow transplantation (BMT) with unrelated donors matched at the HLA-A, B, C, Dr, and DQ loci but who failed to achieve an adequate PLT count. Investigation using PLT immunofluorescence test, monoclonal antibody immobilization of PLT antigens assay, and genotyping revealed the presence of recipient-derived HPA-1a antibodies. In two patients, anti-HPA-1a was detected post-BMT and in the third patient, anti-HPA-1a was detected during pre-BMT chemotherapy. Despite apparent 100% engraftment of donor cells, the patients' PLT counts failed to recover 9-10 months posttransplant. The patients remained PLT-transfusion dependent and failed to achieve satisfactory increments following random donor or HLA-matched PLT transfusions. After the identification of HPA-1a antibodies, the patients were supported by HPA-1a(-) PLTs and satisfactory posttransfusion PLT increments were obtained. These cases illustrate that HPA-1a antibodies may remain detectable for 10 months following apparently successful donor engraftment and the disappearance of recipient-derived HLA antibodies. The prolonged persistence of recipient-derived PLT-specific antibodies following BMT has to our knowledge not been described previously. HPA-1a antibodies were associated with protracted PLT-transfusion dependence and significant hemorrhagic complications. Appropriate and timely laboratory investigation for HPA-specific antibodies followed by transfusion support with HPA-selected PLTs provided the cornerstone of the hemostatic management in these cases.

  13. Acute Disseminated Encephalomyelitis: A Gray Distinction. (United States)

    Abu Libdeh, Amal; Goodkin, Howard P; Ramirez-Montealegre, Denia; Brenton, J Nicholas


    Acute disseminated encephalomyelitis (ADEM) is an immune-mediated, inflammatory acquired demyelinating syndrome predominantly affecting the white matter of the central nervous system. We describe a three-year-old boy whose clinical presentation was suspicious for ADEM but whose initial imaging abnormalities were confined to the deep gray matter (without evidence of white matter involvement). His clinical course was fluctuating and repeat imaging one week after presentation demonstrated interval development of characteristic white matter lesions. Treatment with adjunctive intravenous immunoglobulin and high-dose corticosteroids resulted in significant clinical improvement. Isolated deep gray matter involvement can precede the appearance of white matter abnormalities of ADEM, suggesting that repeat imaging is indicated in individuals whose findings are clinically suspicious for ADEM but who lack characteristic imaging findings. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Vang, Sophia Ingeborg; Schmiegelow, Kjeld; Frandsen, Thomas


    High-dose methotrexate (HD-MTX) courses with concurrent oral low-dose MTX/6-mercaptopurine (6MP) for childhood acute lymphoblastic leukaemia (ALL) are often followed by neutro- and thrombocytopenia necessitating treatment interruptions. Plasma MTX during HD-MTX therapy guides folinic acid rescue ...

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

    DEFF Research Database (Denmark)

    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......, higher age, endothelial cell activation and damage, and leukocytosis. We suggest that platelet dysfunction and leukocytosis in AML causes endothelial perturbation....

  16. Frank hematuria as the presentation feature of acute leukemia

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    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.

  17. Effect of Carica papaya Leaf Extract Capsule on Platelet Count in Patients of Dengue Fever with Thrombocytopenia. (United States)

    Gadhwal, Ajeet Kumar; Ankit, B S; Chahar, Chitresh; Tantia, Pankaj; Sirohi, P; Agrawal, R P


    Thrombocytopenia in dengue fever is a common and serious complication. However, no specific treatment is available for dengue fever induced thrombocytopenia. In few countries (Pakistan, Malaysia, Sri Lanka and other Asian countries) the leaf extract of Carica papaya has been effectively used for thrombocytopenia. So, the study is planned to access effect of Carica papaya leaf extract on platelet count in dengue fever patients. All participants were randomised into two groups, study group and control group; the study group was given papaya leaf extract capsule of 500 mg once daily and routine supportive treatment for consecutive five days. The controls were given only routine supportive treatment. Daily complete blood counts, platelet counts and haematocrit level, liver function test, renal function test of both groups were observed. On the first day platelet count of study group and control group was (59.82±18.63, 61.06±20.03 thousands, p value 0.36). On the 2nd day platelet count of both study and control groups was not significantly different (61.67±19.46 and 59.93±19.52 thousands, p value 0.20) but on 3rd day platelet count of study group was significantly higher than control group (82.96±16.72, 66.45±17.36 thousands, p value dengue fever without any side effect and prevents the complication of thrombocytopenia. So, it can be used in dengue fever with thrombocytopenia patients.

  18. Thrombocytopenia from combination treatment with oseltamivir and probenecid: case report, MedWatch data summary, and review of the literature. (United States)

    Raisch, Dennis W; Straight, Timothy M; Holodniy, Mark


    The possibility of an avian flu pandemic has spurred interest in preventive treatments with antivirals such as oseltamivir. Combining treatment with probenecid to delay excretion may extend limited supplies of oseltamivir. We previously conducted a pharmacokinetic study of oseltamivir plus probenecid among healthy volunteers. In this article, we describe a 68-year-old woman who, during the pharmacokinetic study, developed severe thrombocytopenia 2 weeks after starting oseltamivir plus probenecid. She was receiving no other drug therapy at the time. Her platelet count decreased from 200 to 15 x 10(3)/mm(3), although no clinically evident bleeding abnormalities were noted. The two drugs were discontinued. One week later, without any therapeutic intervention, her platelet count returned to normal. By using the Naranjo adverse drug reaction probability scale to assess the strength of the association between the drugs and the adverse event, a score of 7 was derived for both drugs, indicating that the association was probable. We found no previous literature reports of thrombocytopenia associated with either drug. However, a review of the United States Food and Drug Administration's Adverse Event Reporting System database found 93 cases of thrombocytopenia and/or decreased platelet counts associated with oseltamivir and 24 cases associated with probenecid administration. Signal detection analyses were significant for oseltamivir (p=0.001), but not probenecid. The underlying mechanism of thrombocytopenia with these drugs is unknown. Clinicians should be aware that the use of oseltamivir and probenecid has been reported to be associated with thrombocytopenia.

  19. Combination therapy with pegylated interferon plus ribavirin in the treatment of hepatitis C virus-related thrombocytopenia (United States)

    Karakan, Tarkan; Cindoruk, Mehmet; Degertekin, Bulent; Dogan, Ibrahim; Sancak, Alper; Dumlu, Sukru; Gorgul, Ahmet; Unal, Selahattin


    Background: Isolated thrombocytopenia is a common manifestation of hepatitis C virus (HCV) infection. There is no established treatment modality for this condition. The efficacy of standard interferon (IFN) monotherapy has been reported in some studies. The major disadvantage of this treatment is the high rate of recurrence due to viral breakthrough during the first 12 weeks of treatment. Pegylated IFNs are now the standard regimen for chronic hepatic disease due to HCV infection. However, due to a lack of evidence, pegylated IFNs are not widely used for HCV-related isolated thrombocytopenia. Objective: The aim of this report was to present the case of a male patientwith severe symptomatic thrombocytopenia due to HCV infection. Methods: Thrombocytopenia was treated with pegylated IFN plus ribavirin. Results: Although standard IFN monotherapy failed to achieve virologic and hematologic improvement, therapy with pegylated IFN alfa-2a plus ribavirin was associated with both virologic and hematologic improvement without any significant adverse effects. Conclusions: Pegylated IFN plus ribavirin was effective in this patient for thetreatment of HCV-related thrombocytopenia. However, further research is needed to define the response rate in different patient populations. PMID:24764593

  20. Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia (United States)

    Arnold, Donald M.; Nazi, Ishac; Warkentin, Theodore E.; Smith, James W.; Toltl, Lisa J.; George, James N.; Kelton, John G.


    Drug-induced immune thrombocytopenia (DITP) is a challenging clinical problem that is under-recognized, difficult to diagnose and associated with severe bleeding complications. DITP may be caused by classic drug-dependent platelet antibodies (eg, quinine); haptens (eg, penicillin); fiban-dependent antibodies (eg, tirofiban); monoclonal antibodies (eg, abciximab); autoantibody formation (eg, gold); and immune complex formation (eg, heparin). A thorough clinical history is essential in establishing the diagnosis of DITP and should include exposures to prescription medications, herbal preparations and even certain foods and beverages. Clinical and laboratory criteria have been established to determine the likelihood of a drug being the cause of thrombocytopenia, but these criteria can only be applied retrospectively. The most commonly implicated drugs include quinine, quinidine, trimethoprim/sulfamethoxazole and vancomycin. We propose a practical approach to the diagnosis of the patient with suspected DITP. Key features are: the presence of severe thrombocytopenia (platelet nadir <20 × 109/L); bleeding complications; onset 5 to 10 days after first drug exposure, or within hours of subsequent exposures or after first exposure to fibans or abciximab; and exposure to drugs that have been previously implicated in DITP reactions. Treatment involves stopping the drug(s), administering platelet transfusions or other therapies if bleeding is present and counselling on future drug avoidance. The diagnosis can be confirmed by a positive drug re-challenge, which is often impractical, or by demonstrating drug-dependent platelet reactive antibodies in vitro. Current test methods, which are mostly flow cytometry-based, must show drug-dependence, immunoglobulin binding, platelet specificity and ideally should be reproducible across laboratories. Improved standardization and accessibility of laboratory testing should be a focus of future research. PMID:23845922

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

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    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.

  2. Interleukin-11-induced capillary leak syndrome in primary hepatic carcinoma patients with thrombocytopenia

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    Li-Rong Shen


    Full Text Available Abstract Background Capillary leak syndrome (CLS is a rare condition characterized by recurrent episodes of generalized edema and severe hypotension associated with hypoproteinemia. Interleukin-11 (IL-11 is a promising therapeutic agent for thrombocytopenia. A direct correlation between IL-11 and CLS has never been reported previously, particularly in patients with hepatic carcinoma. Case presentation We describe two cases of CLS after IL-11 administration in two males with thrombocytopenia. Case 1 was a 46-year-old man with recurrence of hepatic carcinoma who was treated with IL-11 (3 mg per day. After four days of therapy, hypotension and hypoproteinemia were detected. The chest X-ray and B ultrasound of the abdomen showed pleural effusion and ascites. IL-11 was then discontinued, fluid resuscitation was performed, and fresh frozen plasma and packed red blood cells were transfused into this patient. The patient had recovered after 19 days of treatment. Case 2 was a 66-year-old man who had undergone radiofrequency ablation (RFA for hepatic carcinoma. He was treated with IL-11 (3 mg per day for thrombocytopenia. After two days of therapy, this patient complained of dyspnea with bilateral edema of the hands. Laboratory values showed hypoproteinemia. IL-11 was stopped and human albumin was transfused at a rate of 10 g per day. On the 4th day, fluid resuscitation was performed. The patient had recovered after treatment for two weeks. Conclusions The detection of IL-11-induced CLS supports the hypothesis that CLS could be a severe side effect of IL-11 treatment in some patients. These two case reports also demonstrate that patients with hepatic carcinoma who experience this rare form of CLS after treatment with IL-11 seem to respond to a therapeutic regimen that involves hydroxyethyl starch, albumin, and diuretic therapy. Liver cancer patients might be more susceptible to CLS because of poor liver function and hypersplenia. In addition, bleeding

  3. Jacobsen syndrome without thrombocytopenia: a case report and review of the literature. (United States)

    Nalbantoğlu, Burçin; Donma, M Metin; Nişli, Kemal; Paketçi, Cem; Karasu, Erkut; Ozdilek, Burcu; Mintaş, Nuriye Ece


    Jacobsen syndrome (JS), a rare disorder with multiple dysmorphic features, is caused by the terminal deletion of chromosome 11q. Typical features include mild to moderate psychomotor retardation, trigonocephaly, facial dysmorphism, cardiac defects, and thrombocytopenia, though none of these features are invariably present. The estimated occurrence of JS is about 1/100,000 births. The female/male ratio is 2:1. The patient admitted to our clinic at 3.5 years of age with a cardiac murmur and facial anomalies. Facial anomalies included trigonocephaly with bulging forehead, hypertelorism, telecanthus, downward slanting palpebral fissures, and a carp-shaped mouth. The patient also had strabismus. An echocardiogram demonstrated perimembranous aneurysmatic ventricular septal defect and a secundum atrial defect. The patient was deletion of chromosome 11. The karyotype was designated 46, XX, del(11) (q24.1). A review of published reports shows that the severity of the observed clinical abnormalities in patients with JS is not clearly correlated with the extent of the deletion. Most of the patients with JS had short stature, and some of them had documented growth hormone deficiency, or central or primary hypothyroidism. In patients with the classical phenotype, the diagnosis is suspected on the basis of clinical findings: intellectual disability, facial dysmorphic features and thrombocytopenia. The diagnosis must be confirmed by cytogenetic analysis. For patients who survive the neonatal period and infancy, the life expectancy remains unknown. In this report, we describe a patient with the clinical features of JS without thrombocytopenia. To our knowledge, this is the first case reported from Turkey.

  4. Association of Primary Biliary Cirrhosis-autoimmune Hepatitis Overlap Syndrome with Immune Thrombocytopenia and Graves' Disease. (United States)

    Koyamada, Ryosuke; Higuchi, Takakazu; Kitada, Ayako; Nakagawa, Tomoko; Ikeya, Takashi; Okada, Sadamu; Fujita, Yoshiyuki


    A 54-year-old woman suffering from pruritus for five years was diagnosed to have Graves' disease and immune thrombocytopenia (ITP) associated with primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome, which was confirmed histologically after a prompt recovery in the platelet count number following steroid therapy. The association between PBC-AIH overlap syndrome and ITP has been rarely reported and the additional association with Graves' disease has not yet been reported. An underlying global derangement of autoimmunity or shared genetic susceptibility was suspected.

  5. Intracranial hemorrhage (ICH) in children with immune thrombocytopenia (ITP): study of 40 cases


    Psaila, Bethan; Petrovic, Aleksandra; Page, Lemke K.; Menell, Jill; Schonholz, Matthew; Bussel, James B.


    Intracranial hemorrhage (ICH) is a rare but devastating complication of childhood immune thrombocytopenia purpura (ITP). A survey of ICH from 1987 to 2000 identified cases of ICH in childhood ITP in the United States. Forty patients with ICH and 80 matched ITP control subjects were accrued. The estimated incidence of ICH was 0.19% to 0.78%. Platelet counts were less than 20 × 109/L in 90% and less than 10 × 109/L in 75% of children with ICH. Eighteen (45%) children developed ICH within 7 days...

  6. Sitaxsentan-Induced Acute Severe Hepatitis Treated with Glucocorticoid Therapy

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    Marcus W Chin


    Full Text Available Endothelin receptor antagonists are commonly used in the treatment of pulmonary hypertension. Sitaxsentan, a selective endothelin A receptor blocker, induces a mild transaminitis in approximately 3% to 5% of patients, but rarely an acute severe hepatitis. A case involving a 61-year-old female with sitaxsentan-induced acute severe liver failure is presented. Depite withdrawal of therapy, her liver tests failed to improve. After six weeks of monitoring, the patient was administered high-dose corticosteroids, with a good clinical and biochemical response. While endothelin receptor antagonists are postulated to cause hepatitis by inhibition of a bile salt transporter pump, an immune-mediated or idiosyncratic mechanism should be considered.

  7. Acute disseminated encephalomyelitis associated with influenza A H1N1 infection. (United States)

    Ozkale, Yasemin; Erol, Ilknur; Ozkale, Murat; Demir, Senay; Alehan, Füsun


    Acute disseminated encephalomyelitis is an immune-mediated inflammatory disorder of the central nervous system, characterized by demyelination. Acute disseminated encephalomyelitis predominantly involves the white matter of the brain and spinal cord, and often follows upper respiratory tract infection. We describe a case of acute disseminated encephalomyelitis associated with the influenza A (H1N1) virus. The H1N1 virus usually causes febrile respiratory signs, e.g., fever, cough, and sore throat. Although these signs exhibit a self-limited course, the frequencies of severe complications and death are increasing. To date, only a few reports of acute disseminated encephalomyelitis secondary to the H1N1 virus have been published. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Successful eltrombopag treatment of severe refractory thrombocytopenia in chronic myelomonocytic leukemia: Two cases reports: A CARE-compliant article. (United States)

    Gao, Yayue; Gong, Ming; Zhang, Chunxia; Kong, Xudong; Ma, Yigai


    Thrombocytopenia in chronic myelomonocytic leukemia (CMML) is usually attributed to impaired marrow production resulting from cytotoxic drug use or CMML itself ("CMML-induced thrombocytopenia"). In very rare cases, immune thrombocytopenia (ITP) can be a complication of CMML ("CMML-associated ITP"). However, treatment of severe thrombocytopenia in patients with CMML is still a challenge. Case 1 was a 61-year-old female patient admitted to our hospital because of skin petechiae and purpura for 6 days. She had increased monocyte cell count (1.82 × 10/L), markedly decreased platelet count (2 × 10/L), hypercellularity of the megakaryocyte lineage with many immature megakaryocytes, and ZRSR2(zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2) mutation. She failed to the treatment of corticosteroids, intravenous immunoglobulin (IVIg), TPO (thrombopoietin), and cyclosporin A (CsA). Case 2 was a 72-year-old female patient with thrombocytosis and monocytosis for 4 years, and thrombocytopenia for 6 months. After 10 courses of decitabine therapy, she had a persistent severe thrombocytopenia and decreased number of megakaryocytes, TET2 (tet methylcytosine dioxygenase 2) and SRSF2 (serine and arginine rich splicing factor 2) mutations were detected. She was dependent on platelet transfusion. Case 1 was diagnosed as CMML-associated ITP, and case 2 as CMML with decitabine therapy-induced thrombocytopenia. Both patients were treated with eltrombopag. In both patients, the platelet counts returned to the normal within 1 week after eltrombopag therapy. The platelet count in case 1 patient remained stable at 141-200 × 10/L for 20 months with stopping therapy for 3 months. In case 2 patient, eltrombopag was stopped 1 month later. Her platelet count decreased to 41 × 10/L, but was stable at ∼30 × 10/L for 3 months with platelet transfusion independency for 12 months. Both patients had no adverse effects with eltrombopag. CMML-associated ITP is

  9. The Potential of Antimicrobials to Induce Thrombocytopenia in Critically Ill Patients: Data from a Randomized Controlled Trial (United States)

    Johansen, Maria Egede; Jensen, Jens-Ulrik; Bestle, Morten Heiberg; Hein, Lars; Lauritsen, Anne Øberg; Tousi, Hamid; Larsen, Kim Michael; Løken, Jesper; Mohr, Thomas; Thormar, Katrin; Johansson, Pär I.; Cozzi-Lepri, Alessandro; Lundgren, Jens D.


    Background Antimicrobial-induced thrombocytopenia is frequently described in the literature among critically ill patients. Several antimicrobials have been implicated, although experimental evidence to demonstrate causality is limited. We report, using a randomized trial, the potential of antimicrobials to induce thrombocytopenia. Methods Randomized trial allocated patients to antimicrobial treatment according to standard- of-care (SOC group) or drug-escalation in case of procalcitonin increases (high-exposure group). Patients were followed until death or day 28. Thrombocytopenia defined as absolute (platelet count ≤100x109/L) or relative (≥20% decrease in platelet count). Analyses were performed in the two randomized groups and as a merged cohort. Results Of the 1147 patients with platelet data available, 18% had absolute thrombocytopenia within the first 24 hours after admission to intensive care unit and additional 17% developed this complication during follow-up; 57% developed relative thrombocytopenia during follow-up. Absolute and relative thrombocytopenia day 1-4 was associated with increased mortality (HR: 1.67 [95% CI: 1.30 to 2.14]; 1.71 [95% CI: 1.30 to 2.30], Pthrombocytopenia (RR: 0.9 [0.7-1.3], p=0.7439; 1.2 [1.0-1.4], p=0.06; respectively), as well as absolute platelet count (daily difference, high-exposure vs. SOC -1.7 [-3.8-0.5], p=0.14) was comparable between groups. In observational analyses, use of ciprofloxacin and piperacillin/tazobactam predicted risk of relative thrombocytopenia (vs. cefuroxime, RR: 2.08 [1.48-2.92]; 1.44 [1.10-1.89], respectively), however only ciprofloxacin were associated with a reduction in absolute platelet count (p=0.0005). Conclusion High exposure to broad-spectrum antimicrobials does not result in a reduction in thrombocytopenia in critically ill patients. However, single use of ciprofloxacin, and less so piperacillin/tazobactam, may contribute to a lower platelet count. Trial Registration NCT

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

    Directory of Open Access Journals (Sweden)

    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

  11. Congenital amegakaryocytic thrombocytopenia in three siblings: molecular analysis of atypical clinical presentation. (United States)

    Gandhi, Manish J; Pendergrass, Thomas W; Cummings, Carrie C; Ihara, Kenji; Blau, C Anthony; Drachman, Jonathan G


    An 11-year-old girl, presenting with fatigue and bruising, was found to be profoundly pancytopenic. Bone marrow exam and clinical evaluation were consistent with aplastic anemia. Family members were studied as potential stem cell donors, revealing that both younger siblings displayed significant thrombocytopenia, whereas both parents had normal blood counts. We evaluated this pedigree to understand the unusually late presentation of congenital amegakaryocytic thrombocytopenia (CAMT). The coding region and the intron/exon junctions of MPL were sequenced from each family member. Vectors representing each of the mutations were constructed and tested for the ability to support growth of Baf3/Mpl(mutant) cells. All three siblings had elevated thrombopoietin levels. Analysis of genomic DNA demonstrated that each parent had mutations/polymorphisms in a single MPL allele and that each child was a compound heterozygote, having inherited both abnormal alleles. The maternal allele encoded a mutation of the donor splice-junction at the exon-3/intron-3 boundary. A mini-gene construct encoding normal vs mutant versions of the intron-3 donor-site demonstrated that physiologic splicing was significantly reduced in the mutant construct. Mutations that incompletely eliminate Mpl expression/function may result in delayed diagnosis of CAMT and confusion with aplastic anemia.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Blalock-taussig shunt thrombosis prophylaxis in a patient with jacobsen syndrome and thrombocytopenia. (United States)

    Casadonte, Joseph R; Kim, Jennifer M; Dadlani, Gul H; Jacobs, Jeffrey P; Cooper, David S; Stapleton, Gary E


    Jacobsen syndrome (JS) is a rare chromosomal anomaly caused by deletions in the distal long arm of chromosome 11. Features of the syndrome include growth and developmental delays, a distinctive facial appearance, and a variety of physical problems including heart defects and bleeding disorders. Congenital heart defects occur in approximately 50% of children with JS. Hypoplastic left heart syndrome (HLHS) has been occasionally reported in association with JS. In such cases, the hematological abnormalities may influence the outcome from single-ventricle palliation through staged surgical reconstruction. Thrombotic obstruction or occlusion of the modified Blalock-Taussig (BT) shunt is a well-documented cause of interstage mortality following the Norwood operation. Although there is no consensus regarding the therapeutic value of antiplatelet therapy during the interstage period following the first stage of palliation, maintenance of shunt patency is critically important. For patients with JS undergoing single-ventricle palliation, decisions regarding antiplatelet therapy during the interstage period may be further complicated by the presence of thrombocytopenia and platelet dysfunction related to JS. We report the case of a patient with HLHS, JS, and thrombocytopenia who underwent the Norwood procedure, and we describe our strategy for prophylaxis against thrombosis of the BT shunt.

  14. [Development of acquired hemophilia A during maintenance therapy for immune thrombocytopenia]. (United States)

    Ogawa, Yoshiyuki; Yanagisawa, Kunio; Ishizaki, Takuma; Naito, Chiaki; Mihara, Masahiro; Handa, Hiroshi; Shizuka, Reiko; Inoue, Madoka; Naito, Sumiyoshi; Ieko, Masahiro; Ichinose, Akitada; Nojima, Yoshihisa


    Acquired hemophilia A (AHA) is a rare coagulation disorder caused by autoantibodies against coagulation factor VIII (FVIII). We report herein a very rare case of AHA complicated by immune thrombocytopenia (ITP). A 30-year-old woman was hospitalized with severe thrombocytopenia. Her platelet count was 5,000/μl on admission, at which time APTT was normal. ITP was diagnosed and she was treated with γ-globulin, platelet transfusion, and prednisolone at 1 mg/kg/day. She was discharged after platelet count normalization and prednisolone was tapered to 5 mg/day. During the prednisolone tapering, purpura appeared on both thighs and in the left inguinal region, and APTT was found to be prolonged. She was referred to our hospital for examination of APTT prolongation. FVIII activity was markedly decreased to 7.7% and the FVIII inhibitor was positive (1.5 BU/ml), based on which AHA was diagnosed. We carefully followed this patient without intensification of immunosuppressive therapy for 7 weeks, but her platelet count decreased from 150,000/μl to 70,000/μl and the FVIII inhibitor increased to 4 BU/ml. We therefore increased prednisolone to 30 mg/day, after which her platelet count increased and complete remission of AHA was achieved by day 42. In addition, we examined the relationship of the FVIII inhibitor and FVIII binding antibody in this case.

  15. Serum thrombopoietin and cMpl expression in thrombocytopenia of different etiologies

    Directory of Open Access Journals (Sweden)

    Fabrizio Vianello


    Full Text Available The relationship between thrombopoietin (TPO and its receptor cMpl in thrombocytopenic conditions has not been entirely clarified. To elucidate this interplay may expand the spectrum of indications of TPO mimetics. In this study we have explored the relationship between TPO and cMpl in platelets and megakaryocytes of 43 patients with thrombocytopenia due to idiopathic thrombocytopenic purpura (ITP, bone marrow hypoplasia, myelodysplastic syndromes (MDS, and familial thrombocytopenia. Data were compared to cMpl and TPO in patients with a normal platelet count and in patients with thrombocytosis due to essential thrombocythemia (ET. All but familial patients showed higher TPO compared to controls. All thrombocytopenic states were invariably associated with increased expression of platelet cMPL compared to healthy controls. ET patients showed normal TPO and a trend toward a reduced cMpl expression. Immunofluorescence of bone marrow sections from patients with ITP and MDS failed to show a peculiar pattern compared to controls. Multiple mechanisms regulate TPO and cMpl in thrombocytopenic conditions.

  16. Significance of periodontal health in primary immune thrombocytopenia- a case report and review of literature. (United States)

    Sangwan, Aditi; Tewari, Shikha; Narula, Satish C; Sharma, Rajinder K; Sangwan, Pankaj


    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.

  17. Heparin-induced thrombocytopenia: a review of concepts regarding a dangerous adverse drug reaction. (United States)

    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. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  18. Thrombocytopenia in the first 24 hours after birth and incidence of patent ductus arteriosus. (United States)

    Sallmon, Hannes; Weber, Sven C; Hüning, Britta; Stein, Anja; Horn, Peter A; Metze, Boris C; Dame, Christof; Bührer, Christoph; Felderhoff-Müser, Ursula; Hansmann, Georg; Koehne, Petra


    Experimental studies suggest that platelet-triggered ductal sealing is critically involved in definite ductus arteriosus closure. Whether thrombocytopenia contributes to persistently patent ductus arteriosus (PDA) in humans is controversial. This was a retrospective study of 1350 very low birth weight (VLBW; gender, and sepsis on PDA was determined by receiver operating characteristic curve, odds ratio, and regression analyses. Platelet numbers within the first 24 hours after birth did not differ between VLBW/ELBW infants with and without spontaneous ductal closure. Platelet numbers were not associated with subsequent PDA treatment. Low platelet counts were not related to failure of pharma-cologic PDA treatment and the need for subsequent surgical ligation. Lower gestational age or birth weight, male gender, and sepsis were linked to the presence of PDA in VLBW infants on day of life 4 to 5. Thrombocytopenia in the first 24 hours after birth was not associated with PDA in this largest VLBW/ELBW infant cohort studied to date. Impaired platelet function, due to immaturity and critical illness, rather than platelet number, might play a role in ductus arteriosus patency.

  19. Oral surgery in a patient with cirrhosis and thrombocytopenia: a case report. (United States)

    Patel, Seena; Perry, Maureen Munnelly; Spolarich, Ann Eshenaur


    While most oral surgical procedures can be safely performed in an outpatient setting, certain medical conditions may present a higher chance of postoperative complications. In particular, those predisposing the patient to bleeding abnormalities pose a potential risk when performing such treatments. The authors report a case involving full-mouth extractions in a patient with cirrhosis and thrombocytopenia after obtaining a platelet transfusion. A 62-year-old Caucasian female presented to a university special care dental clinic requiring extractions. Her pertinent medical history was remarkable for cirrhosis and thrombocytopenia, with a platelet count of 32,000/uL. Upon medical consultation, the patient was appointed for a prophylactic platelet transfusion. The surgery was rendered uneventfully, and the patient achieved adequate hemostasis without hospitalization. Patients with cirrhosis pose a potential bleeding risk with dental surgical procedures. Pre-operative medical consultation, review of pertinent laboratory values, and prophylactic platelet transfusion allow these patients to be managed safely in an outpatient setting. © 2015 Special Care Dentistry Association and Wiley Periodicals, Inc.

  20. Assessing risk of liver enzyme elevation in patients with immune-mediated diseases and different hepatitis B virus serostatus receiving anti-TNF agents: a nested case-control study. (United States)

    Chiu, Ying-Ming; Lai, Mei-Shu; Chan, K Arnold


    Liver enzyme elevation is an important and common adverse effect among patients with immune-mediated diseases who receive tumour necrosis factor inhibitors (anti-TNF), and has various causes. Hence, we evaluated the relative risks of developing liver enzyme elevation in anti-TNF users with differing hepatitis B virus (HBV) infection status. At a hospital in central Taiwan, 407 patients with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis received anti-TNF therapy between 1 January 2004 and 30 June 2012. We performed a nested case-control study (n = 368) of cases with serum alanine aminotransferase (ALT) > 40 international units/L ≤ 12 months after starting anti-TNF therapy, and corresponding controls without liver enzyme elevation. Conditional logistic regression was used to evaluate associations between liver enzyme elevation and HBV serostatus, as well as other risk factors. Thirty cases were compared to 338 controls. After adjustment for potential confounders, HBV surface antigen-positive (HBsAg(+)) serostatus was associated with substantially higher likelihood of developing elevated ALT (adjusted odds ratio 7.91, 95% confidence interval (CI) 2.16-31.31) relative to those with an uninfected HBV status; no such association was observed among HBsAg-negative/HBV core antibody-positive (HBsAg(-)/HBcAb(+)) patients (adjusted odds ratio 1.00, 95% CI 0.33-3.25). Increased risk of ALT elevation was associated with methotrexate used alone, without folic acid (adjusted odds ratio 11.60, 95% CI 2.52-56.46), and history of ALT elevation (adjusted odds ratio 13.71, 95% CI 4.32-45.75). HBsAg(+) patients with immune-mediated diseases who received anti-TNF therapy had an approximately eight-fold higher likelihood of liver enzyme elevation than those without HBV infection, whereas patients with HBsAg(-)/HBcAb(+) serostatus had a risk similar to that of uninfected patients.

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

    DEFF Research Database (Denmark)

    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....

  2. A pilot study to assess the hemostatic function of pathogen-reduced platelets in patients with thrombocytopenia

    DEFF Research Database (Denmark)

    Johansson, Pär I; Simonsen, Anne Catrine; Brown, Peter de Nully


    Platelet (PLT) support is critical to the care of patients with thrombocytopenia, but allogeneic transfusions carry risk. Pathogen reduction mitigates some transfusion risks, but effects on PLT function remain a concern. This clinical pilot study assessed the effect of pathogen reduction technology...

  3. Effect of thrombopoietin-receptor agonists on circulating cytokine and chemokine levels in patients with primary immune thrombocytopenia (ITP)

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Ghanima, Waleed; Nielsen, Claus H


    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...

  4. Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia

    NARCIS (Netherlands)

    Sonneveld, Myrthe E.; Natunen, Suvi; Sainio, Susanna; Koeleman, Carolien A. M.; Holst, Stephanie; Dekkers, Gillian; Koelewijn, Joke; Partanen, Jukka; van der Schoot, C. Ellen; Wuhrer, Manfred; Vidarsson, Gestur


    Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Pathophysiology and management of thrombocytopenia in bone marrow failure: possible clinical applications of TPO receptor agonists in aplastic anemia and myelodysplastic syndromes. (United States)

    Townsley, Danielle M; Desmond, Ronan; Dunbar, Cynthia E; Young, Neal S


    Aplastic anemia is a bone marrow failure syndrome that causes pancytopenia and can lead to life-threatening complications. Bone marrow transplantation remains the standard of care for younger patients and those with a good performance status but many patients may not have a suitable donor. Immunosuppressive therapy is able to resolve cytopenias in a majority of patients with aplastic anemia but relapses are not uncommon and some patients remain refractory to this approach. Patients may require frequent blood and platelet transfusion support which is expensive and inconvenient. Life-threatening bleeding complications still occur despite prophylactic platelet transfusion. Thrombopoietin (TPO) mimetics, such as romiplostim and eltrombopag, were developed to treat patients with refractory immune thrombocytopenia but are now being investigated for the treatment of bone marrow failure syndromes. TPO is the main regulator for platelet production and its receptor (c-Mpl) is present on megakaryocytes and hematopoietic stem cells. Trilineage hematopoietic responses were observed in a recent clinical trial using eltrombopag in patients with severe aplastic anemia refractory to immunosuppression suggesting that these agents can provide a new therapeutic option for enhancing blood production. In this review, we discuss these recent results and ongoing investigation of TPO mimetics for aplastic anemia and other bone marrow failure states like myelodysplastic syndromes. Clonal evolution or progression to acute myeloid leukemia remains a concern when using these drugs in bone marrow failure and patients should only be treated in the setting of a clinical trial.

  7. Nye behandlingsmuligheder ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    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...

  8. Patofysiologien ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    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...

  9. Nye behandlingsmuligheder ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    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...

  10. Absolute lymphocyte count and risk of short-term infection in patients with immune thrombocytopenia. (United States)

    Hu, Ming-Hung; Yu, Yuan-Bin; Huang, Yu-Chung; Gau, Jyh-Pyng; Hsiao, Liang-Tsai; Liu, Jin-Hwang; Chen, Ming-Huang; Chiou, Tzeon-Jye; Chen, Po-Min; Tzeng, Cheng-Hwai; Liu, Chun-Yu


    Patients with immune thrombocytopenia (ITP) may be at increased risk of infection because of the steroids and other immunosuppressive agents used in its treatment. This study aimed to identify events that are associated with infection within 6 months of diagnosis and the impact that infection has on survival. We retrospectively evaluated 239 patients (107 men, 132 women; median age 61 years) diagnosed between January 1997 and August 2011. Every patient received steroid treatment according to the platelet count and the extent of bleeding. Logistic regression analysis was used to identify risk factors associated with the development of infection within 6 months of ITP being diagnosed. Sixty-two patients (25.9 %) developed an infection within 6 months of diagnosis. Multivariate analysis revealed that a lower absolute lymphocyte count (ALC) at diagnosis (lymphocyte count at diagnosis have an increased risk of infection, and those who develop infections have lower 1-year survival.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  12. Effects of maternal thrombocytopenia on platelet counts of pre- and postnatal mice

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, T.P.; Clift, R.; Dunn, C.D.R.


    The effects of maternal thrombocytopenia on platelet counts of pre- and postnatal mice were determined. Platelet counts of gravid mice were reduced at 2 to 3 days before parturition by injection of rabbit anti-mouse platelet serum (RAMPS). Marked rebound-thrombocytosis was observed after 4 to 6 days. Platelet counts of pre- and postnatal mice whose mothers were injected with RAMPS 3 days before parturition were unaltered except at 1 day before and at the time of birth when they were significantly (P less than 0.005) reduced. The results of immunodiffusion techniques showed that RAMPS crossed the placental barrier resulting in reduced platelet counts of the fetuses, but significant fetal rebound-thrombocytosis was not observed.

  13. Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults. (United States)

    Gómez-Almaguer, David; Herrera-Rojas, Miguel A; Jaime-Pérez, José C; Gómez-De León, Andrés; Cantú-Rodríguez, Olga G; Gutiérrez-Aguirre, César H; Tarín-Arzaga, Luz; Hernández-Reyes, Jesús; Ruiz-Arguelles, Guillermo J


    Immune thrombocytopenia (ITP) results from platelet destruction and production suppression. Eltrombopag belongs to a new class of thrombopoietin-mimetic drugs that raise platelet counts in ITP patients. We performed a single-arm study to assess the response to a single course of dexamethasone (40 mg by mouth, days 1-4) in combination with eltrombopag (50 mg, days 5-32) in 12 adults with newly diagnosed ITP in an outpatient setting. Median follow-up was 12.5 months. After therapy (day 33), 100% of patients achieved at least ≥30 × 10(9)/L platelets. Four patients relapsed. Complete response at 6 months (platelets ≥100 × 10(9)/L) was achieved in 50% of patients and response at 6 months (platelets ≥30 dexamethasone is a feasible frontline therapy for ITP. This trial is registered at as NCT01652599. © 2014 by The American Society of Hematology.

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

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    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.

  15. Case report of an SGA infant with jaundice, direct hyperbilirubinemia, hepatosplenomegaly, thrombocytopenia, and a negative VDRL. (United States)

    Dalgleish, Stacey; Premji, Shahirose; Young, Sandra; Kamaluddeen, Majeeda


    This case report highlights the presentation of syphilis in a small-for-gestational age (SGA) female infant who was born to a mother with no prenatal care. In the first 2 days of life, the infant developed hepatosplenomegaly, conjugated hyperbilirubinemia, thrombocytopenia, and hemolysis. After extensive diagnostic investigation, the case was solved on the infant's day of life (DOL) 12. In retrospect, the health care team had obtained a diagnostic result that could potentially have solved the case on DOL 2. Although this infant suffered no long-term sequelae secondary to the delayed diagnosis, the review of this case presentation may assist other clinicians in an early identification of a potentially lethal diagnosis.

  16. Anastrozole-related acute hepatitis with autoimmune features: a case report

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    D'Argento Ettore


    Full Text Available Abstract Background Two cases of acute hepatitis occurring during treatment with anastrozole have previously been reported, but the underlying mechanisms of liver injury are still uncertain. We report the case of anastrozole-related acute hepatitis with some autoimmune features. Case presentation A 70-year-old woman developed acute hepatitis associated with serum antinuclear antibodies during anastrozole treatment; after drug withdrawal, liver function parameters rapidly improved and serum auto-antibodies were no longer detectable. Conclusions Anastrozole-induced hepatotoxicity is a very rare event. Drug-drug interactions or metabolically-mediated damage might be involved, with a possible role of individual susceptibility. Our report suggests that an immune-mediated mechanism may also be considered in anastrozole-related liver injury.

  17. Mutations in MECOM, Encoding Oncoprotein EVI1, Cause Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia (United States)

    Niihori, Tetsuya; Ouchi-Uchiyama, Meri; Sasahara, Yoji; Kaneko, Takashi; Hashii, Yoshiko; Irie, Masahiro; Sato, Atsushi; Saito-Nanjo, Yuka; Funayama, Ryo; Nagashima, Takeshi; Inoue, Shin-ichi; Nakayama, Keiko; Ozono, Keiichi; Kure, Shigeo; Matsubara, Yoichi; Imaizumi, Masue; Aoki, Yoko


    Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is an inherited bone marrow failure syndrome, characterized by thrombocytopenia and congenital fusion of the radius and ulna. A heterozygous HOXA11 mutation has been identified in two unrelated families as a cause of RUSAT. However, HOXA11 mutations are absent in a number of individuals with RUSAT, which suggests that other genetic loci contribute to RUSAT. In the current study, we performed whole exome sequencing in an individual with RUSAT and her healthy parents and identified a de novo missense mutation in MECOM, encoding EVI1, in the individual with RUSAT. Subsequent analysis of MECOM in two other individuals with RUSAT revealed two additional missense mutations. These three mutations were clustered within the 8th zinc finger motif of the C-terminal zinc finger domain of EVI1. Chromatin immunoprecipitation and qPCR assays of the regions harboring the ETS-like motif that is known as an EVI1 binding site showed a reduction in immunoprecipitated DNA for two EVI1 mutants compared with wild-type EVI1. Furthermore, reporter assays showed that MECOM mutations led to alterations in both AP-1- and TGF-β-mediated transcriptional responses. These functional assays suggest that transcriptional dysregulation by mutant EVI1 could be associated with the development of RUSAT. We report missense mutations in MECOM resulting in a Mendelian disorder that provide compelling evidence for the critical role of EVI1 in normal hematopoiesis and in the development of forelimbs and fingers in humans. PMID:26581901

  18. Establishment of an antiviral assay system and identification of severe fever with thrombocytopenia syndrome virus inhibitors. (United States)

    Baba, Masanori; Toyama, Masaaki; Sakakibara, Norikazu; Okamoto, Mika; Arima, Naomichi; Saijo, Masayuki


    Aims Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease. SFTS is epidemic in Asia, and its fatality rate is around 30% in Japan. The causative virus severe fever with thrombocytopenia syndrome virus (SFTSV) is a phlebovirus of the family Phenuiviridae (the order Bunyavirales). Although effective treatments are required, there are no antiviral agents currently approved for clinical use. Ribavirin and favipiravir were examined for their anti-SFTSV activity and found to be selective inhibitors of SFTSV replication in vitro. However, their activity was not sufficient. Therefore, it is mandatory to identify novel compounds active against SFTSV. To this end, we have established a safe and rapid assay system for screening selective inhibitors of SFTSV. Methods The virus was isolated from SFTS patients treated in Kagoshima University Hospital. Vero cells were infected with SFTSV and incubated in the presence of various concentrations of test compounds. After three days, the cells were examined for their intracellular viral RNA levels by real-time reverse transcription-PCR without extracting viral RNA. The cytotoxicity of test compounds was determined by a tetrazolium dye method. Results Among the test compounds, the antimalarial agent amodiaquine was identified as a selective inhibitor of SFTSV replication. Its 50% effective concentration (EC50) and cytotoxic concentration (CC50) were 19.1 ± 5.1 and >100 µM, respectively. The EC50 value of amodiaquine was comparable to those of ribavirin and favipiravir. Conclusion Amodiaquine is considered to be a promising lead of novel anti-SFTSV agents, and evaluating the anti-SFTSV activity of its derivatives is in progress.

  19. Exanthema and acute anuric renal failure. (United States)

    Resch, M; Banas, B; Endemann, D; Mack, M; Riegger, G A J; Gröne, H J; Krämer, B K


    A 15-year-old girl with a history of Kawasaki disease was admitted to our nephrological department due to acute renal failure. Despite antibiotic therapy because of fever and the symptoms of a pharyngitis in the last few days, the girl showed persisting fever and developed arthralgias, an exanthema and a rising serum creatinine as well as anuria. A wide variety of differential diagnoses has to be thought of because of the history of the Kawasaki disease (symptoms like fever, pharyngitis, exanthema and arthralgia), i.e. hemolytic-uremic syndrome, vasculitis, ascending infection, postinfection glomerulonephritis. In consideration of etiologically unclear "rapidly progressive renal failure" with anuria and thrombocytopenia an immediate renal biopsy was done and revealed a severe drug induced acute interstitial nephritis. Due to this diagnosis we treated the patient with corticosteroids. Within 4 weeks serum creatinine declined to 1.8 mg/dl but did not normalize.

  20. Acute ciprofloxacin-induced crystal nephropathy with granulomatous interstitial nephritis

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    R Goli


    Full Text Available Crystal-induced acute kidney injury (AKI is caused by the intratubular precipitation of crystals, which results in obstruction and kidney injury. Ciprofloxacin, a commonly used antibiotic, causes AKI secondary to immune-mediated interstitial injury. Rare mechanisms of ciprofloxacin-induced renal injury include crystalluria, rhabdomyolysis, and granulomatous interstitial nephritis. Clinical and experimental studies have suggested that crystalluria and crystal nephropathy due to ciprofloxacin occur in alkaline urine. Preexisting kidney function impairment, high dose of the medication, and advanced age predispose to this complication. We report a case of ciprofloxacin-induced crystal nephropathy and granulomatous interstitial nephritis in a young patient with no other predisposing factors. The patient responded to conservative treatment without the need for glucocorticoids.