Tsuyama, Nobuaki; Ichiba, Toshihisa; Naito, Hiroshi
We herein present a case of acquired hemophilia A with a normal activated partial thromboplastin (aPTT), intramuscular hematoma and cerebral hemorrhage occurring in a 73-year-old man. The patient visited our emergency department with gait disturbance, pain and swelling in his right leg. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed intramuscular hematoma and intracranial hemorrhage. The results of initial coagulation studies were normal, but repeated coagulation studies revealed an isolated prolongation of the aPTT. Additional laboratory tests confirmed the diagnosis of acquired hemophilia A. If the initial aPTT is normal, we should therefore repeat the aPTT and also perform other coagulation studies including a mixing study, factor VIII level and inhibitor, to investigate the underlying diseases in elderly patients with spontaneous hemorrhaging of unknown etiology.
Full Text Available An 80-year-old man was admitted for acute subdural hematoma caused by a mild brain injury. His coagulation test showed an isolated prolongation of activated partial thromboplastin time (aPTT. Though the subdural hematoma did not progress, oozing bleed from the wound of tracheostomy continued. Failure of correction on aPTT mixing test supported the presence of an inhibitor to a coagulation factor. Once the diagnosis of acquired hemophilia A (AHA was made, steroid therapy was performed, which leads him to complete remission of AHA. Isolated prolongation of aPTT can be the key to diagnose a rare coagulopathy, such as AHA.
Burish, Mark J; Aysenne, Aimee; Singh, Vineeta
Acquired hemophilia A (AHA) is a rare coagulopathy linked to a variety of etiologies including autoimmune diseases, neoplasms, diabetes, respiratory diseases, and the post-partum state. While bleeding in AHA is often seen in mucocutaneous or intramuscular locations, intracranial and intraspinal bleeds are exceedingly rare. We report an unusual case of spontaneous multifocal subdural hematomas in a 25 year old Asian woman with lupus who presented with headache and backache, and was found to have an elevated partial thromboplastin time (PTT) level and new diagnosis of AHA. Subdural hematomas as the initial sign of AHA are all but unknown in the medical literature. We bring this entity to the attention of the neurology community because lumbar puncture and/or conventional angiogram are often indicated in the work-up of idiopathic multifocal subdural hematomas, but may be dangerous in patients with AHA.
Hemophilia is a rare disorder in which the blood does not clot normally. It is usually inherited. Hemophilia usually occurs in males. If you have hemophilia, you have little or no clotting factor. Clotting ...
Fernando Campos Gomes Pinto
Full Text Available INTRODUCTION: Head trauma is an important consequence of child abuse. Specific pathophysiological mechanisms in child abuse are responsible for the ''whiplash shaken-baby syndrome'', which would favour the occurrence of intracranial hemorrhages. CASE REPORT: We report the case of a child who developed epidural hematoma following minor-intensity head trauma. Initial diagnosis of child abuse was made, but subsequent investigation led to the diagnosis of hemophilia A. CONCLUSION: Even though epidural hematoma is not closely associated with child abuse, this aethiology must always be considered when the reported trauma mechanism is out of proportion to the magnitude of the encountered lesions.INTRODUÇÃO: Traumatismo crânio-encefálico é importante conseqüência de abuso infantil. Mecanismos fisiopatológicos específicos do abuso infantil são responsáveis pela ''whiplash shaken-baby syndrome'', o que favoreceria o aparecimento de hemorragias intracranianas. RELATO DE CASO: Relatamos o caso de uma criança que desenvolveu hematoma extradural após trauma de pequena intensidade. Foi feito diagnóstico inicial de abuso infantil, mas investigações subseqüentes levaram ao diagnóstico de hemofilia A. CONCLUSÃO: Embora o hematoma extradural não esteja intimamente relacionado com abuso infantil, esta etiologia deve ser sempre considerada quando o mecanismo de trauma relatado estiver fora de proporção com as lesões encontradas.
... and the severity. Families With a History of Hemophilia Any family history of bleeding, such as following ... for hemophilia . Families With No Previous History of Hemophilia About one-third of babies who are diagnosed ...
Resources - hemophilia ... The following organizations provide further information on hemophilia : Centers for Disease Control and Prevention -- www.cdc.gov/ncbddd/hemophilia/index.html National Heart, Lung, and Blood Institute -- www.nhlbi.nih.gov/ ...
Shimizu, Tomoki; Tsunoda, Yuya; Ito, Tsuyoshi; Imamura, Satoshi; Nagakubo, Shuichi; Morohoshi, Yuichi; Koike, Yuji; Fujita, Yuriko; Komatsu, Hirokazu
Acquired hemophilia A leads to severe bleeding and is known to be related to many underlying diseases; however, it has not been reported to occur as a complication of pancreatitis. We present a case of acquired hemophilia A secondary to severe acute pancreatitis. A 76-year-old female developed a hematoma in the lower leg muscle while being treated for severe acute pancreatitis. Blood tests revealed prolonged activated partial thromboplastin time (APTT) and the presence of an autoantibody to factor VIII. The bleeding diathesis was successfully controlled by immunosuppressive therapy. This case highlights the need for careful differential diagnosis for successful management of bleeding disorders as complications of pancreatitis.
Concepción Guardo B.; José Sequeda M.
Neonatal asymptomatic suprarrenal hemorrhage is relatively frequent; sometimes it is detected only after resolution when a calcification is found; symptomatic forms are rare; most times hemorrhage and hematoma are due to an obstetric trauma and are related to macrosomia, breech presentation, maternal diabetes and neonatal hypoxia. Clinical picture is characterized by abdominal mass and anemia; diagnosis is confirmed by imagenology. Two patients with suprarrenal hematoma from the University Ho...
... hemophilia may be treated with desmopressin (DDAVP). This medicine helps the body release factor VIII that is stored within the lining of blood vessels. To prevent a bleeding crisis, people with hemophilia and their families can be ...
Lamy, Olivier; Elmiger, Hubert; Fiche, Maryse; Bauer, Jean; Livio, FranCoise
A 69-year-old man under long-term spironolactone therapy (16 years) was hospitalized with spontaneous hematoma on the trunk and extremities. Coagulation studies disclosed an acquired hemophilia that was successfully treated with human factor VIII for a few days and immunosuppressive agents for several months. Physical examination revealed bilateral gynecomastia and an upper left quadrant breast nodule. Complete staging was unremarkable. Complete left mastectomy was performed. Histopathology showed invasive ductal carcinoma, expressing positivity for estrogen and progesterone receptors. The acquired hemophilia was considered to be a paraneoplasic syndrome. The question of a linkage between long-term spironolactone therapy and breast carcinoma is discussed.
Concepción Guardo B.
Full Text Available Neonatal asymptomatic suprarrenal hemorrhage is relatively frequent; sometimes it is detected only after resolution when a calcification is found; symptomatic forms are rare; most times hemorrhage and hematoma are due to an obstetric trauma and are related to macrosomia, breech presentation, maternal diabetes and neonatal hypoxia. Clinical picture is characterized by abdominal mass and anemia; diagnosis is confirmed by imagenology. Two patients with suprarrenal hematoma from the University Hospital at Cartagena, Colombia, are presented. Both were related with traumatic delivery and cephalohematoma; one of them had oral and gastric bleeding and the othersuffered hematoma infection; diagnosis was done with abdominal ecography and CAT. Both patients recovered with medical treatment. La hemorragia suprarrenal asintomática del neonato es relativamente frecuente y muchas veces se detecta como una calcificación local después de que se resuelve el hematoma. La forma sintomática es rara y, a menudo, se debe a un trauma obstétrico relacionado con la macrosomía fetal, la presentación podálica, la diabetes materna o la hipoxia perinatal. Las manifestaciones clínicas son, principalmente, una masa abdominal y anemia importante; el diagnóstico se confirma con la imaginología. Se presentan dos casos de hematoma suprarrenal derecho tratados en el Hospital Universitario de Cartagena, ambos relacionados con un parto traumático y acompañados de cefalohematomas; uno de ellos presentó sangrado gastrointestinal alto y el otro infección del hematoma suprarrenal. El diagnóstico se comprobó con la ecografía abdominal y se verificó con la tomografía. El tratamiento fue médico y no se requirió cirugía a pesar de la anemia severa que presentó uno de los pacientes.
Azza A.G. Tantawy
Deep-muscle hematomas. Intracranial bleeding in the absence of major trauma .... major trauma or surgery. Often later in life. Clinical severity does not always correlate with the in vitro assay result. Molecular genetics of hemophilia A: Clinical perspectives. 107 .... treatment . The cumulative risk of inhibitor development.
... Personal Plan Hot Topics Flu Facts Arrhythmias Abuse Hemophilia KidsHealth > For Teens > Hemophilia Print A A A ... bruises can be a big deal. What Is Hemophilia? Hemophilia is a disease that prevents blood from ...
... Your Teeth Bad Breath How to Deal With Hemophilia KidsHealth > For Kids > How to Deal With Hemophilia ... mild case of hemophilia. Why Do Kids Get Hemophilia? Hemophilia almost always affects boys. Why? Because the ...
... belts). Follow safety precautions at work and in sports and recreation. For example, do not dive into water if the water depth is unknown or if rocks may be present. Alternative Names Extradural hematoma; Extradural hemorrhage; Epidural hemorrhage; EDH ...
Full Text Available Hemophilia A is a sex-linked recessive coagulation disorder almost exclusively occurring in male subjects and caused by a deficiency of factor VIII. It is a rare disorder characterized by spontaneous hemorrhages. Spontaneous bleeding in the pleural space is very rare in hemophilia both in children and adults. Here in, we present the case of a 56-year-old hemophilia A patient with hemorrhagic pleural effusion and intracranial hematoma.
Nishiura, Nobuko; Ujimoto, Daisuke; Fujita, Jiro; Maeda, Tetsuo; Nakagawa, Yukinobu; Kashiwagi, Hirokazu; Oritani, Kenji; Tomiyama, Yoshiaki; Kanakura, Yuzuru
A 67-year-old man was admitted with a 1-month history of spontaneous hematoma in his right back and severe anemia. He had suffered from rashes with blisters involving both legs for 10 years, which had shown worsening and extended to his entire body concurrently with the hematoma. APTT was markedly prolonged to 119 seconds, and Factor VIII:C and FVIII inhibitor levels were less than 1% and 153.1 BU/ml, respectively, confirming the diagnosis of acquired hemophilia A (AHA). Skin biopsy revealed his rashes to be caused by autoimmune bullous disease (ABD), and laboratory and physical findings showed that he also had autoimmune hypothyroidism (Hashimoto's disease). Recombinant FVIIa was effective for management of his bleeding; in addition, FVIII inhibitor reduction and FVIII:C recovery, in parallel with improvement of the skin lesions, were achieved by administering prednisolone and cyclophosphamide. To our knowledge, this is the first report of AHA associated with ABD and Hashimoto's disease.
... such as from falls Very young or very old age In infants and young children, a subdural hematoma ... the brain severe enough to cause coma and death) Persistent symptoms such as memory loss, dizziness , headache , anxiety , and difficulty concentrating Seizures Short-term or permanent ...
Impact of mild to severe hemophilia on education and work by US men, women, and caregivers of children with hemophilia B: The Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study.
Cutter, Susan; Molter, Don; Dunn, Spencer; Hunter, Susan; Peltier, Skye; Haugstad, Kimberly; Frick, Neil; Holot, Natalia; Cooper, David L
The psychosocial impact of hemophilia on work was recently investigated in the Hemophilia Experiences, Results and Opportunities (HERO) study. The findings revealed that hemophilia had an impact for adults with moderate/severe hemophilia and caregivers of children with hemophilia. HERO did not specifically evaluate impact on education in adults/children with mild/moderate hemophilia or the impact on employment of spouses/partners of caregivers of affected children. The Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study evaluated the impact of hemophilia on the lives of adult men/women with mild-severe hemophilia B and caregivers of boys/girls with hemophilia B and their spouses/partners. Many adults with hemophilia B (94%) reported that hemophilia had a negative effect on their ability to complete a formal education, often attributed to the inability to attend or concentrate in school as a result of hemophilia-related bleeding or pain. Most adults with hemophilia B (95%) and caregivers/partners (89%/84%) indicated that hemophilia had a negative impact on employment. Most adults with hemophilia were employed (81%), with construction/manufacturing (35%) as the most frequently reported industry; many worked in jobs requiring manual labor (39%). Of those unemployed, 62% never worked, and those who stopped working reported that they left the workforce due to financial issues (59%), including insurance coverage/co-pays, or hemophilia-related issues (55%). Nearly one-third of caregivers voluntarily left the workforce to care for children with hemophilia. These results suggest a need to focus more effort on career counseling for adults with hemophilia B and caregivers of affected children, especially around mild/moderate hemophilia, as this population may not be as well informed regarding potential impact in school and the workplace. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Full Text Available Deep vein thrombosis (DVT is a rare disease in patients with hemophilia A. We report a case of 22-year-old male with severe hemophilia A who presented to the emergency room with 5-day history of right arm pain that was attributed initially to bleeding event. In the absence of external signs of bleeding or hematoma and normal hemoglobin level, we suspected an underlying DVT. Doppler ultrasonography of the right upper limb revealed thrombosis of the subclavian vein and this was confirmed by CT venography. The d-dimer level was normal and investigations for prothrombotic state revealed heterozygosity for prothrombin G20210A mutation. Treatment with factor VIII and low molecular weight heparin led to successful resolution and marked improvement of his clinical condition.
Full Text Available Sébastien Lobet,1,2 Cedric Hermans,1 Catherine Lambert1 1Hemostasis-Thrombosis Unit, Division of Hematology, 2Division of Physical Medicine and Rehabilitation, Cliniques Universitaires Saint-Luc, Brussels, Belgium Abstract: Hemophilia is a hematological disorder characterized by a partial or complete deficiency of clotting factor VIII or IX. Its bleeding complications primarily affect the musculoskeletal system. Hemarthrosis is a major hemophilia-related complication, responsible for a particularly debilitating chronic arthropathy, in the long term. In addition to clotting factor concentrates, usually prescribed by the hematologist, managing acute hemarthrosis and chronic arthropathy requires a close collaboration between the orthopedic surgeon and physiotherapist. This collaboration, comprising a coagulation and musculoskeletal specialist, is key to effectively preventing hemarthrosis, managing acute joint bleeding episodes, assessing joint function, and actively treating chronic arthropathy. This paper reviews, from a practical point of view, the pathophysiology, clinical manifestations, and treatment of hemarthrosis and chronic hemophilia-induced arthropathy for hematologists, orthopedic surgeons, and physiotherapists. Keywords: hemophilia, arthropathy, hemarthrosis, hematoma, physiotherapy, target joint
María Antonia Cabezas Poblet
Full Text Available Periparturient hemorrhages are the leading cause of extremely serious maternal morbidity and maternal death in Cuba and the world. Acquired Hemophilia A is a rare bleeding disorder characterized by the presence of antibodies against circulating factor VIII (FVIII. We present the case of a 36 years old pregnant woman with term pregnancy and vaginal delivery that suffers from hemorrhagic manifestations in the immediate postpartum secondary to raffia hematoma, requiring blood transfusion. Then she presents a bruise in the right upper limb secondary to stroke that requires surgical repair. The postpartum torpid evolution characterized by sustained bleeding raffia and the surgically treated arm, makes us suspect of the presence of a blood disorder. We observed a decrease in the FVIII factor, which involves the diagnosis of acquired hemophilia and requires treatment with recombinant VIIa factor (FVIIar concentrate and cyclophosphamide. Posterior evolution was favorable. The patient was discharged without sequelae.
Rogers, Geoffrey L.; Herzog, Roland W.
Hemophilia is an X-linked inherited bleeding disorder consisting of two classifications, hemophilia A and hemophilia B, depending on the underlying mutation. Although the disease is currently treatable with intravenous delivery of replacement recombinant clotting factor, this approach represents a significant cost both monetarily and in terms of quality of life. Gene therapy is an attractive alternative approach to the treatment of hemophilia that would ideally provide life-long correction of clotting activity with a single injection. In this review, we will discuss the multitude of approaches that have been explored for the treatment of both hemophilia A and B, including both in vivo and ex vivo approaches with viral and nonviral delivery vectors. PMID:25553466
Sabatino, Denise E.; Nichols, Timothy C.; Merricks, Elizabeth; Bellinger, Dwight A.; Herzog, Roland W.; Monahan, Paul E.
The X-linked bleeding disorder hemophilia is caused by mutations in coagulation factor VIII (hemophilia A) or factor IX (hemophilia B). Unless prophylactic treatment is provided, patients with severe disease (less than 1% clotting activity) typically experience frequent spontaneous bleeds. Current treatment is largely based on intravenous infusion of recombinant or plasma-derived coagulation factor concentrate. More effective factor products are being developed. Moreover, gene therapies for sustained correction of hemophilia are showing much promise in pre-clinical studies and in clinical trials. These advances in molecular medicine heavily depend on availability of well-characterized small and large animal models of hemophilia, primarily hemophilia mice and dogs. Experiments in these animals represent important early and intermediate steps of translational research aimed at development of better and safer treatments for hemophilia, such a protein and gene therapies or immune tolerance protocols. While murine models are excellent for studies of large groups of animals using genetically defined strains, canine models are important for testing scale-up and for longer-term follow-up as well as for studies that require larger blood volumes. PMID:22137432
Tranholm, M.; Kristensen, Annemarie Thuri; Broberg, M. L.
INTRODUCTION: Muscle hematomas are the second most common complication of hemophilia and insufficient treatment may result in serious and even life-threatening complications. Hemophilic dogs and rats do experience spontaneous muscle bleeding, but currently, no experimental animal model is available...... specifically investigating spontaneous muscle bleeds in a hemophilic setting. AIM: The objective of this study was to develop a model of spontaneous muscle bleeds in hemophilia B mice. We hypothesized that treadmill exercise would induce muscle bleeds in hemophilia B mice but not in normal non-hemophilic mice...... and that treatment with recombinant factor IX (rFIX) before treadmill exercise could prevent the occurrence of pathology. METHODS: A total of 203 mice (123 F9-KO and 80 C57BL/6NTac) were included in three separate studies: (i) the model implementation study investigating the bleeding pattern in hemophilia B mice...
Lee, Ji Hyun; Kim, Dong-Hwan; Yoo, Kiyoung; Choi, Yongmook; Kim, Sun-Hee; Kim, Hee-Jin
Acquired hemophilia A (AHA) is a rare coagulopathy caused by autoantibodies to coagulation factor VIII (FVIII). Most patients with AHA have been previously healthy; however, a variety of morbidities have been associated with the condition including pregnancy. A 40-yr-old woman visited our institution with extensive hematoma on the right hip area. Her medical history revealed no personal or familial history of bleeding diathesis. Her coagulation tests showed markedly prolonged aPTT (117 sec), markedly decreased level of FVIII activity (0.4%) and high-titer FVIII inhibitor (77 BU). Collectively, she was diagnosed as having postpartum AHA and was treated with bypassing agents and corticosteroids. Her aPTT was normalized on the 174 th postpartum day and FVIII inhibitor showed negative conversion on the 224 th postpartum day. This is the first case of postpartum AHA with high-titer FVIII inhibitor in Korea. Timely diagnosis and management can reduce morbidity and mortality of this potentially life-threatening condition.
Sleightholm, Richard; Wahlmeier, Steven; Carson, Jeffrey S; Drincic, Andjela; Lazenby, Audrey; Foster, Jason M
Visceral venous aneurysms are exceedingly rare, and until now, there have been no reports of this phenomenon in the adrenal vasculature. This report details the first adrenal venous aneurysm reported in the literature. The aneurysm presented as an 18-cm mass that was initially suspected to be a hematoma or tumor on the basis of the complex medical history of the patient, which included hemophilia A and testicular cancer. After surgical excision, pathologic examination confirmed this mass to be a 15.9-cm adrenal vein aneurysm, the largest aneurysm of any type or location recorded in the medical literature. A 58-year-old caucasian male with hemophilia A presented to the emergency room of another institution with abdominal pain, blood in the stool, and a history of diverticulosis and symptomatic hemorrhoids. A large, left-sided adrenal mass was detected by computed tomography, and because of the patient's hemophilia A and imaging consistent with a hemorrhagic mass, a hematoma was initially suspected. The patient was transferred to our institution, monitored for further bleeding with a stable hospital course, and discharged from the hospital under close monitoring. After 7-8 weeks with no change in the size of the mass, concerns grew regarding increasing symptoms of both satiety and mass effects from the large anomaly, as well as about the patient's complicated medical history, which also included cancer. Surgical excision was recommended because of the concerns about increasing symptoms and the possibility of a malignancy. Correction and maintenance of factor VIII levels were incorporated pre-, intra-, and postoperatively, and en bloc surgical resection was performed to minimize bleeding and provide oncologic extirpation of the mass. A bowling ball-sized mass was removed, and careful pathologic examination revealed the mass to be a venous adrenal aneurysm. After a brief hospital stay, the patient made a full recovery. Extensive review of the literature revealed 11
Full Text Available Abstract Background Visceral venous aneurysms are exceedingly rare, and until now, there have been no reports of this phenomenon in the adrenal vasculature. This report details the first adrenal venous aneurysm reported in the literature. The aneurysm presented as an 18-cm mass that was initially suspected to be a hematoma or tumor on the basis of the complex medical history of the patient, which included hemophilia A and testicular cancer. After surgical excision, pathologic examination confirmed this mass to be a 15.9-cm adrenal vein aneurysm, the largest aneurysm of any type or location recorded in the medical literature. Case presentation A 58-year-old caucasian male with hemophilia A presented to the emergency room of another institution with abdominal pain, blood in the stool, and a history of diverticulosis and symptomatic hemorrhoids. A large, left-sided adrenal mass was detected by computed tomography, and because of the patient’s hemophilia A and imaging consistent with a hemorrhagic mass, a hematoma was initially suspected. The patient was transferred to our institution, monitored for further bleeding with a stable hospital course, and discharged from the hospital under close monitoring. After 7–8 weeks with no change in the size of the mass, concerns grew regarding increasing symptoms of both satiety and mass effects from the large anomaly, as well as about the patient’s complicated medical history, which also included cancer. Surgical excision was recommended because of the concerns about increasing symptoms and the possibility of a malignancy. Correction and maintenance of factor VIII levels were incorporated pre-, intra-, and postoperatively, and en bloc surgical resection was performed to minimize bleeding and provide oncologic extirpation of the mass. A bowling ball-sized mass was removed, and careful pathologic examination revealed the mass to be a venous adrenal aneurysm. After a brief hospital stay, the patient made a
... safe for most people with hemophilia, while American football, rugby, and boxing are usually not recommended. What ... issues in inhibitors Resources Prophylaxis Types of Prophylaxis Administration & Dosing Schedules Monitoring outcomes When to Start & Stop ...
Skip to main content Learning About Hemophilia Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research News Features Funding Divisions Funding ...
Buckner, Tyler W; Witkop, Michelle; Guelcher, Christine; Frey, Mary Jane; Hunter, Susan; Peltier, Skye; Recht, Michael; Walsh, Christopher; Kessler, Craig M; Owens, Wendy; Clark, David B; Frick, Neil; Rice, Michelle; Iyer, Neeraj N; Holot, Natalia; Cooper, David L; Sidonio, Robert
The Bridging Hemophilia B Experiences, Results and Opportunities Into Solutions (B-HERO-S) initiative was launched in an effort to address specific gaps in the understanding of the psychosocial impact of mild-moderate-severe hemophilia B. The original Hemophilia Experiences, Results and Opportunities (HERO) qualitative study evaluated the needs of people with hemophilia A or B in multiple countries; however, a majority of participants had the more common moderate-severe hemophilia A. The B-HERO-S study was designed in collaboration with the hemophilia community to evaluate the needs of adults with hemophilia B and caregivers of children with hemophilia B, including affected women and caregivers of girls with hemophilia. The report presented here describes participant demographics and comorbidities, as well as treatment regimens and access to treatment. Bleeding symptoms were reported by 27% of mothers of children with hemophilia B who participated. Women were more likely than men to self-report arthritis and depression/anxiety as comorbidities associated with hemophilia B. More adults and children with hemophilia B were on routine treatment than on on-demand treatment, and a high percentage of adults with moderate hemophilia B received routine treatment (86%). Many adults with hemophilia B (78%) and caregivers (69%) expressed concern about access to factor in the next 5 years, and of adults with hemophilia B, women more commonly experienced issues with access to factor in the past than did men (72% vs 44%). The findings of the B-HERO-S study reveal potential unmet needs of some patients with mild-moderate hemophilia B, and the results may be leveraged to inform patient outreach by hemophilia treatment centers and education initiatives. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Webert, Kathryn E
Acquired hemophilia A is a rare, autoimmune disorder that is caused by autoantibodies that act as inhibitors to factor VIII. It is characterized by severe, unexpected bleeding that may be life-threatening. The incidence of acquired hemophilia A is ~ 0.2 to 1.48 cases per 1 million individuals per year. Acquired hemophilia A has been associated with several clinical conditions including pregnancy, autoimmune or collagen vascular disorders, malignancies, drugs, respiratory disorders, and infections. However, in ~ 50% of cases, no disease association is determined. Acquired hemophilia A should be suspected when a patient with no previous personal or family history of bleeding, presents with bleeding and an unexplained prolonged activated partial thromboplastin time (APTT) and other common causes of a prolonged APTT are ruled out. The treatment of acquired hemophilia A has two main goals: (1) to treat and/or prevent bleeding complications and (2) to eradicate the inhibitor. The recommended agents to be used for the treatment or prevention of bleeding in patients with acquired hemophilia A are the bypassing agents. Patients should be treated initially with corticosteroids, either alone or in combination with cyclophosphamide, to eradicate the inhibitor. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Fijnvandraat, Karin; Bril, Wendy S.; Voorberg, Jan
After treatment with factor (F) VIII concentrate a significant number of patients with hemophilia A develop inhibitory antibodies that neutralize FVIII. Epitope mapping revealed that antibodies bind to selected regions within the A2, A3, and C2 domains of FVIII. Anti-A2 and anti-A3 antibodies
Sidonio, Robert; Holot, Natalia; Cooper, David L
The needs of individuals living with hemophilia B, especially those with mild or moderate hemophilia and affected females, are not well understood. The Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) initiative was developed in an effort to obtain greater insights into the unique issues and challenges faced by those with hemophilia B. This study explored the impact of hemophilia B on education, employment, engagement in physical activities and other psychosocial aspects of the lives of affected individuals and their families. The B-HERO-S findings reveal a number of unmet needs in the hemophilia B population, and these results may be leveraged to inform patient outreach and education initiatives. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Coelho, Jeffrey D.
Describes hemophilia and ways to provide appropriate physical education experiences to children with hemophilia. The article focuses on what hemophilia is, how to treat hemophilia, benefits of physical activity, how to teach children with hemophilia, choosing and modifying sports and activities, and safety and emergency situations. (SM)
Brummel-Ziedins, Kathleen E.; Whelihan, Matthew F.; Gissel, Matthew; Mann, Kenneth G.; Rivard, Georges E.
Introduction Hemophilia A displays phenotypic heterogeneity with respect to clinical severity. Aim To determine if tissue factor (TF)-initiated thrombin generation profiles in whole blood in the presence of corn trypsin inhibitor (CTI) are predictive of bleeding risk in hemophilia A. Methods We studied factor(F) VIII deficient individuals (11 mild, 4 moderate and 12 severe) with a well-characterized five-year bleeding history that included hemarthrosis, soft tissue hematoma and annual FVIII concentrate usage. This clinical information was used to generate a bleeding score. The bleeding scores (range 0–32) were separated into three groups (bleeding score groupings: 0, 0 and ≤9.6, >9.6), with the higher bleeding tendency having a higher score. Whole blood collected by phlebotomy and contact pathway suppressed by 100μg/mL CTI was stimulated to react by the addition of 5pM TF. Reactions were quenched at 20min by inhibitors. Thrombin generation, determined by ELISA for thrombin – antithrombin was evaluated in terms of clot time (CT), maximum level (MaxL) and maximum rate (MaxR) and compared to the bleeding score. Results Data are shown as the mean±SD. MaxL was significantly different (phemophilia A. PMID:19563500
Full Text Available Hemophilia — an hereditary coagulopathy, in which the process of anticoagulation is due to genetic deficiency and decreased procoagulant activity of FVIII (IX. The most difficult manifestation of hemophilia is the development of chronic hemophilic arthropathy, the severity of which is directly dependent on the level of the scarce factor and the adequacy of replacement therapy. The clinical course of hemophilic arthropathy begins with acute hemarthrosis, is at the stage of chronic villous synovitis and ultimately leads to osteoarthritis deformans, fibrous ankylosis, and the development of secondary periarticular osteoporosis. The aim of our study was to identify risk factors for osteopenia and osteoporosis in metaepiphysis bones forming the joint, as well as trace the dependence of reduction in bone mineral density from the level of deficient FVIII (IX in patients with hemophilia.
Full Text Available Abstract Background Intraseptal hematoma and subsequent myocardial infarction due to accidental contrast agent deposition complicating diagnostic cineventriculography is a previously undescribed complication of angiography. Case presentation A 61 year old man was admitted at intensive care unit because of unstable angina pectoris 1 hour after coronary angiography. Transthoracic contrast echocardiography showed a non-perfused area in the middle of interventricular septum with an increase of thickening up to 26 mm. Review of cineventriculography revealed contrast enhancement in the interventricular septum after contrast medium injection and a dislocation of the pigtail catheter tip. Follow up by echocardiography and MRI showed, that intramural hematoma has resolved after 6 weeks. After 8 weeks successful stent implantation in LAD was performed and after 6 month the patient had a normal LV-function without ischemic signs or septal thickening demonstrated by stressechocardiography. Conclusion A safe and mobile position of the pigtail catheter during ventriculography in the middle of the LV cavity should be ensured to avoid this potentially life-threatening complication. For assessment and absolute measurement of intramural hematoma contrast-enhanced echocardiography is more feasible than MRI and makes interchangeable results.
Full Text Available A 34-year-old female presented with sudden onset of severe abdominal pain in a flank distribution. A large mass was palpable in the right upper quadrant on physical examination. Abdominal contrast-enhanced computed tomography showed a well-defined, right-sided, retroperitoneal cystic lesion located between the abdominal aorta and the inferior vena cava (IVC. The tumor size was 55 × 58 mm, and it compressed the gallbladder and the duodenum. Upper gastrointestinal radiography revealed a stricture of the second portion of the duodenum by the tumor. T2-weighted magnetic resonance imaging showed that the whole part was hyperintense with hypointense rims, but the inner was partially hypointense. Based on the radiological findings, the preoperative differential diagnosis included retroperitoneal teratoma, Schwannoma, abscess, and primary retroperitoneal tumor. On laparotomy, the tumor was located in the right retroperitoneal cavity. Kocher maneuver and medial visceral rotation, which consists of medial reflection of the upper part of right colon and duodenum by incising their lateral peritoneal attachments, were performed. Although a slight adhesion to the IVC was detected, the tumor was removed safely. Thin-section histopathology examination detected neither tumor tissues nor any tissues such as adrenal gland, ovarian tissue, or endometrial implants. The final pathological diagnosis was idiopathic retroperitoneal hematoma; the origin of the bleeding was unclear. The patient was discharged without any complication 5 days after the operation.
Kashiwakura, Yuji; Mimuro, Jun; Onishi, Akira; Iwamoto, Masaki; Madoiwa, Seiji; Fuchimoto, Daiichiro; Suzuki, Shunichi; Suzuki, Misae; Sembon, Shoichiro; Ishiwata, Akira; Yasumoto, Atsushi; Sakata, Asuka; Ohmori, Tsukasa; Hashimoto, Michiko; Yazaki, Satoko; Sakata, Yoichi
Hemophilia A is a common X chromosome-linked genetic bleeding disorder caused by abnormalities in the coagulation factor VIII gene (F8). Hemophilia A patients suffer from a bleeding diathesis, such as life-threatening bleeding in the brain and harmful bleeding in joints and muscles. Because it could potentially be cured by gene therapy, subhuman animal models have been sought. Current mouse hemophilia A models generated by gene targeting of the F8 have difficulties to extrapolate human disease due to differences in the coagulation and immune systems between mice and humans. Here, we generated a porcine model of hemophilia A by nuclear transfer cloning from F8-targeted fibroblasts. The hemophilia A pigs showed a severe bleeding tendency upon birth, similar to human severe hemophiliacs, but in contrast to hemophilia A mice which rarely bleed under standard breed conditions. Infusion of human factor VIII was effective in stopping bleeding and reducing the bleeding frequency of a hemophilia A piglet but was blocked by the inhibitor against human factor VIII. These data suggest that the hemophilia A pig is a severe hemophilia A animal model for studying not only hemophilia A gene therapy but also the next generation recombinant coagulation factors, such as recombinant factor VIII variants with a slower clearance rate.
Full Text Available Hemophilia A is a common X chromosome-linked genetic bleeding disorder caused by abnormalities in the coagulation factor VIII gene (F8. Hemophilia A patients suffer from a bleeding diathesis, such as life-threatening bleeding in the brain and harmful bleeding in joints and muscles. Because it could potentially be cured by gene therapy, subhuman animal models have been sought. Current mouse hemophilia A models generated by gene targeting of the F8 have difficulties to extrapolate human disease due to differences in the coagulation and immune systems between mice and humans. Here, we generated a porcine model of hemophilia A by nuclear transfer cloning from F8-targeted fibroblasts. The hemophilia A pigs showed a severe bleeding tendency upon birth, similar to human severe hemophiliacs, but in contrast to hemophilia A mice which rarely bleed under standard breed conditions. Infusion of human factor VIII was effective in stopping bleeding and reducing the bleeding frequency of a hemophilia A piglet but was blocked by the inhibitor against human factor VIII. These data suggest that the hemophilia A pig is a severe hemophilia A animal model for studying not only hemophilia A gene therapy but also the next generation recombinant coagulation factors, such as recombinant factor VIII variants with a slower clearance rate.
Full Text Available Background. Traumatic delayed epidural hematoma (DEH can be defined as insignificant or not seen on the initial CT scan performed after a trauma but seen on the subsequent CT scan as a “massive” epidural bleeding. Case report. We presented two cases of traumatic DEH after mild head injury. Both patients were conscious and without neurological deficit on the admission. Initial CT scan did not reveal intracranial hematoma. Repeated CT scan, that was performed after neurological deterioration, revealed epidural hematoma in both cases. The patients were operated with a favorable surgical outcome. Conclusion. Traumatic DEH could occur in the patients with head injuries who were conscious on the admission with a normal initial CT scan finding. Early detection of DEH and an urgent surgical evacuation were essential for a good outcome.
Yano, Hiroyuki; Tsunoda, Misako; Onishi, Tetsuro; Mizuno, Shigeyoshi; Koibuchi, Hitoshi; Kigawa, Yoshiaki; Suzuki, Tastuya; Nakano, Hiroshi; Oba, Kenzo
We report a case of an 82-year-old woman with senile dementia who was hospitalized at a specialist dementia hospital for 10 months. She had swelling of the left shoulder joint, subcutaneous hematoma in the left upper arm, and anemia was noted on blood examination. Her serum hemoglobin level was lower than normal at 4.6 g/dL, but there was no sign of gastrointestinal disease or gastrointestinal bleeding, and her stool specimens were negative for occult blood. Hematoma subsequently appeared on her chest and back. She had a low activation level of factor VIII (<1%), a high concentration of acquired inhibitors of factor VIII (18.5 BU/mL), and prolonged activated partial thromboplastin time (83.1 seconds). The possibility of drug-induced anemia or hematoma were ruled out. We diagnosed acquired hemophilia A (AHA), and suspected that this was the cause of her hematomas. We began treatment of her AHA with oral prednisolone and intravenous infusion of factor VIII. The bleeding improved, but she later died due to bacterial pneumonia. AHA is very rare, with a reported annual incidence of 0.1/100,000 in Japan. However, it is necessary to consider such a rare disease when we encounter bleeding in elderly patients.
Aljasser, Mohammed I; Sladden, Chris; Crawford, Richard I; Au, Sheila
Acquired hemophilia (AH) is a rare autoimmune disease with an annual incidence of one per million and has a mortality rate of up to 22%. It is caused by the development of autoantibodies against factor VIII. Approximately half of the reported cases are associated with autoimmune disorders, pregnancy, malignancies, and adverse drug reactions. Autoimmune diseases are the most frequently associated disorders and include rheumatoid arthritis, systemic lupus erythematosus, cryoglobulinemia, pemphigus vulgaris, and bullous pemphigoid. There are a few reports of acquired hemophilia and bullous pemphigoid in the literature. We report a 73-year-old male who presented with cutaneous blistering, upper gastrointestinal bleeding, and hemoptysis. He later developed right flank pain secondary to a retroperitoneal hematoma. He had a prolonged partial thromboplastin time, a low factor VIII level, and a high factor VIII inhibitor level, all consistent with acquired hemophilia. Skin biopsies were diagnostic for bullous pemphigoid. He was treated successfully with prednisone, cyclophosphamide, rituximab, and intravenous immunoglobulin.
Drake, M E
No commemoration of the bicentennial of Mozart's death would be complete without some consideration of that premature yet predictable demise. Mozart's premonitions of death are well known and apparently played a role in the composition of the K.626 Requiem and perhaps other works. His death has traditionally been ascribed to infectious causes, chiefly rheumatic fever or post-streptococcal glomerulonephritis, exacerbated by intemperance and chronic penury. Pathology has been difficult because of his supposed burial in a pauper's grave, the location and contents of which were later supposedly lost. Mozart's burial place in St. Mark's Cemetery in Vienna was known and, in the parlance of the day, "reorganized" a decade later, as the occupants of plots were disinterred to make room for the more recently decreased. A skull believed to the Mozart's was saved by the successor of the gravedigger who had supervised Mozart's burial, and then passed into the collections of the anatomist Josef Hyrtl, the municipality of Salzburg, and the Mozarteum museum (Salzburg). Forensic reconstruction of soft tissues related to this skull reveals substantial concordance with Mozart's portraits. The skull suggests premature closure of the metopic suture, which has been suggested on the basis of his physiognomy. A left temporal fracture and concomitant erosions raise the question of chronic subdural hematoma, which would be consistent with several falls in 1789 and 1790 and could have caused the weakness, headaches, and fainting he experienced in 1790 and 1791. Aggressive bloodletting to treat suspected rheumatic fever could have decompensated such a lesion to produce his death on December 5, 1791.
Full Text Available Background. Fracture of the penis is a direct blunt trauma of the erect or semi-erect penis. It can be treated by conservative or surgical means. Retrospective analyses of conservative penile fracture treatment reveal frequent immediate and later complications. Case report. We presented a 41- year-old patient with pulsative hematoma caused by an unusual fracture of the penis. Fracture had appeared 40 days before the admittance during a sexual intercourse. The patient was treated surgically. Conclusion. Pulsative hematoma (pulsative diverticulum is a very rare, early complication of a conservatively treated penile fracture. Surgical treatment has an advantage over surgical one, which was confirmed by our case report.
Antonsen, Lisbeth; Thayssen, Per; Jensen, Lisette Okkels
. Intravascular ultrasound (IVUS) is an important diagnostic tool in establishing the correct diagnosis, as it provides a complete vessel wall assessment, and enables morphometric information regarding the magnitude and severity of the underlying hematoma. Due to the rarity of this clinical scenario...
Andersen-Ranberg, Nina Christine; Rom Poulsen, Frantz; Bergholt, Bo
OBJECTIVE Bilateral chronic subdural hematoma (bCSDH) is a common neurosurgical condition frequently associated with the need for retreatment. The reason for the high rate of retreatment has not been thoroughly investigated. Thus, the authors focused on determining which independent predictors ar...
In the early stages it typically presents as generalized abdominal pain, nausea, anorexia. The symptoms and signs of hypovolemic shock normally present late. As management of idiopathic retroperitoneal hematoma is usually conservative, early diagnosis can save the patient an unnecessary exploration. This will improve.
Nathwani, Amit C; Davidoff, Andrew M; Tuddenham, Edward G D
The best currently available treatments for hemophilia A and B (factor VIII or factor IX deficiency, respectively) require frequent intravenous infusion of highly expensive proteins that have short half-lives. Factor levels follow a saw-tooth pattern that is seldom in the normal range and falls so low that breakthrough bleeding occurs. Most hemophiliacs worldwide do not have access to even this level of care. In stark contrast, gene therapy holds out the hope of a cure by inducing continuous endogenous expression of factor VIII or factor IX following transfer of a functional gene to replace the hemophilic patient's own defective gene. Copyright © 2017 Elsevier Inc. All rights reserved.
Yanagisawa, Kunio; Ogawa, Yoshiyuki; Mitsui, Takeki; Noguchi, Hiroyuki; Shimizu, Hiroaki; Ishizaki, Takuma; Handa, Hiroshi; Ieko, Masahiro; Ichinose, Akitada; Nojima, Yoshihisa
Although acquired hemophilia A (AHA) often develops in patients with neoplasms, there are few reports on the efficacy of radiation therapy during the bleeding phase of AHA in the prior literature. We herein present a case of AHA experiencing remission soon after radiation therapy for esophageal cancer. A man in his seventies, who had a history of radical nephrectomy for left renal cell carcinoma, received a diagnosis of esophageal cancer. Three months later, he noticed a right thigh hematoma, and was transferred to our hospital. Laboratory data revealed a marked reduction of coagulation factor VIII (FVIII) activity at 0.9% and the inhibitor to FVIII was detected in his serum at 21.8 BU/ml. Under a diagnosis of AHA, the patient received high-dose oral prednisolone, which failed to achieve disease remission. He then underwent radiation therapy to eradicate the underlying esophageal cancer. Despite tapering of the prednisolone dosage, FVIII inhibitor declined to undetectable levels. In this case, radiation therapy for the underlying cancer was associated with achieving complete remission of AHA.
MORALES G,JUAN L; ARRIAGADA H,RENATO; SALAS G,LUIS; MORALES A,CARLOS; FUENTES A,FELIPE; Santana, Roberto
Presentamos el caso de una paciente de sexo femenino de 60 años de edad, ingresada en nuestro centro hospitalario por cuadro agudo de dolor abdominal en hipocondrio derecho asociado a vómitos y fiebre. Destaca la presencia de leucocitosis con eosinofilia de 56%. La tomografía computanzada abdominal muestra una colección subcapsular hepática. Durante su evolución presenta abdomen agudo, realizándose una laparoscopía exploratoria que confirma un hematoma subcapsular con presencia de hemopentone...
left parietal trephine craniotomy was performed (to decompress dominant cerebral hemisphere and no fracture) and without disturbing the blood clot, left trephine craniotomy was performed and both hematomas were exposed. Hematomas were evacuated left followed by right and the bleeding from meningeal arteries was.
... Consumers Home For Consumers Consumer Updates Hemophilia Treatments Have Come a Long Way Share Tweet Linkedin Pin ... Research and Review. Hemophilia A occurs when people have low levels, or missing, clotting factor VIII (8). ...
Gouw, Samantha C.; Fijnvandraat, Karin
In this issue of Blood, Astermark et al have identified novel genetic markers of inhibitory antibody formation in hemophilia patients that may ultimately lead to prediction and even prevention of this severe complication of hemophilia treatment.(1)
Full Text Available Intracranial bleeding in hemophilia patients is a rare but a mortal complication. Diagnosis of hemophilia in adulthood is an uncommon occurrence. In this case report an adult patient with intracranial hemorrhage is presented.
Amodio, John; Fefferman, Nancy; Rivera, Rafael; Pinkney, Lynne; Strubel, Naomi [Division of Pediatric Radiology, Department of Radiology, New York University Medical Center, 560 1st Avenue, New York, NY 10016 (United States)
Hepatic hematomas in newborn infants are not frequently detected clinically, but are often found at perinatal autopsies. These hematomas of the liver are usually subcapsular in location. A variety of etiologies for such hematomas has been implicated, such as trauma, sepsis, and coagulopathies. We present a neonate who presented with jaundice and abdominal distention. Initial imaging studies revealed a large intraparenchymal lesion of the liver, which was at first thought to be suspicious for neoplasm; however, MRI showed the lesion to be hemorrhagic and follow-up sonographic studies showed total resolution of this lesion, compatible with hematoma. The intraparenchymal location and the idiopathic nature of this lesion distinguish this case from others previously reported. (orig.)
Sugino, Keishi; Gocho, Kyoko; Ishida, Fumiaki; Kikuchi, Naoshi; Hirota, Nao; Sato, Keita; Sano, Go; Isobe, Kazutoshi; Sakamoto, Susumu; Takai, Yujiro; Hata, Yoshinobu; Shibuya, Kazutoshi; Uekusa, Toshimasa; Kurosaki, Atsuko; Homma, Sakae
Immunoglobulin G4 (IgG4)-related lung diseases can occur in patients with autoimmune pancreatitis (AIP). However, the causal relationship between AIP and acquired hemophilia A (AH) is unknown. We herein report the first case of AH associated with IgG4-related lung disease that developed in a patient with AIP. A 65-year-old asymptomatic man with a history of AIP and sclerosing cholangitis diagnosed at the age of 57 was admitted to our hospital due to an abnormal reticulonodular shadow on chest X-ray. An examination of lung biopsy specimens revealed IgG4-positive plasma cell infiltration in the interstitium. The serum IgG4 level was elevated. One year later, the patient developed a progressive severe hematoma in the left femoral muscle. On admission, laboratory examinations revealed severe anemia with a markedly prolonged activated partial prothrombin time, a decreased level of factor VIII (FVIII) activity, and the existence of anti-FVIII antibodies. These findings were consistent with a diagnosis of AH. No relapse has been observed over the past 25 months, during which time, corticosteroid therapy has been continuously administered.
Full Text Available Hemophilia A is a X-linked hereditary condition that lead to decreased factor VIII activity, occurs mainly in males. Decreased factor VIII activity leads to increased risk of bleeding events. During neonatal period, diagnosis is made after post-partum bleeding complication or unexpected bleeding after medical procedures. Subgaleal hemorrhage during neonatal period is a rare, severe extracranial bleeding with high mortality and usually related to traumatic labor or coagulation disorders. Subgaleal hemorrhage complications result from massive bleeding. We present a neonate with unremarkable family history and uneventful pregnancy with a vaginal delivery with no instrumentation, presenting with severe subgaleal bleeding at 52 hours of life. Aggressive support measures were implemented and bleeding managed. The unexpected bleeding lead to a coagulation study and the diagnosis of severe hemophilia A. There were no known sequelae. This case shows a rare hemophilia presentation reflecting the importance of coagulation studies when faced with unexplained severe bleeding.
Kiessling, J Willis; Hertzler, Dean A; Drucker, David E M; Spader, Heather S
This case report illustrates the need to evaluate the possibility of multiple arterial sources when presented with a frontal epidural hematoma associated with facial trauma. The patient presented after being struck in the face by a baseball. Computed tomography of the brain revealed a large frontal epidural hematoma. Intraoperatively, bleeding from a frontal branch of the middle meningeal artery was encountered and cauterized, and the hematoma was removed. Routine follow-up imaging performed the next day showed a residual frontal hematoma; however, the epidural hematoma was in a more medial location than the initial hematoma. The patient was taken back to the operating room; after frontal lobe retraction and extensive exploration, a different source of bleeding from posterior ethmoidal artery feeders was encountered. After the second operation, the patient's hematoma did not recur, and he was discharged home with no neurologic deficits 3 days later. We report a case of an epidural hematoma caused by 2 distinct arterial feeders. We discuss radiologic review and operative management of anterior fossa epidural hematomas and stress the importance of considering arterial bleeding from sources other than the middle meningeal artery in anterior fossa epidural hematomas. We discuss the utility of preoperative angiography for these patients and reinforce the need for acute postoperative imaging to ensure successful operative and patient outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.
Full Text Available Vinodan Paramanathan, Ardalan ZolnourianQueen's Hospital NHS Foundation Trust, Burton on Trent, Staffordshire DE13 0RB, UKAbstract: Spontaneous intraorbital hematoma is an uncommon clinical entity seen in ophthalmology practice. It is poorly represented in the literature. Current evidence attributes it to orbital trauma, neoplasm, vascular malformations, acute sinusitis, and systemic abnormalities. A 65-year-old female presented with spontaneous intraorbital hematoma manifesting as severe ocular pains, eyelid edema, proptosis, and diplopia, without a history of trauma. Computer tomography demonstrated a fairly well defined extraconal lesion with opacification of the paranasal sinuses. The principal differential based on all findings was that of a spreading sinus infection and an extraconal tumor. An unprecedented finding of a spontaneous orbital hematoma was discovered when the patient was taken to theater. We discuss the rarity of this condition and its management.Keywords: hemorrhage, ophthalmology, spontaneous, intra-orbital, hematoma
Hagen, T.; Lensch, T. [Radiologengemeinschaft, Augsburg (Germany)
Compared with spinal epidural hematomas, spinal subdural hematomas are rare; chronic forms are even more uncommon. These hematomas are associated not only with lumbar puncture and spinal trauma, but also with coagulopathies, vascular malformations and tumors. Compression of the spinal cord and the cauda equina means that the patients develop increasing back or radicular pain, followed by paraparesis and bladder and bowel paralysis, so that in most cases surgical decompression is carried out. On magnetic resonance imaging these hematomas present as thoracic or lumbar subdural masses, their signal intensity varying with the age of the hematoma. We report the clinical course and the findings revealed by imaging that led to the diagnosis in three cases of chronic spinal subdural hematoma. (orig.) [German] Spinale subdurale Haematome sind im Vergleich zu epiduralen Haematomen selten, chronische Verlaufsformen noch seltener. Ursaechlich sind neben Lumbalpunktionen und traumatischen Verletzungen auch Blutgerinnungsstoerungen, Gefaessmalformationen und Tumoren. Aufgrund der Kompression von Myelon und Cauda equina kommt es zu zunehmenden Ruecken- oder radikulaeren Schmerzen mit anschliessender Paraparese sowie einer Darm- und Blasenstoerung, weshalb in den meisten Faellen eine operative Entlastung durchgefuehrt wird. Magnetresonanztomographisch stellen sich die Haematome meist als thorakale bzw. lumbale subdurale Raumforderungen dar, die Signalintensitaet variiert mit dem Blutungsalter. Wir berichten ueber den klinischen Verlauf und die bildgebende Diagnostik von 3 Patienten mit spinalen chronischen subduralen Haematomen. (orig.)
Full Text Available Spontaneous liver bleeding is often reported in preeclampsia. It is otherwise rare and has been linked to gross anatomical lesions and coagulopathy. We report a case of subcapsular hematoma of the liver without any apparent lesion and in the absence of coagulopathy. A 41-year-old male, paraplegic for 16 years, presented to the emergency department 3 days after sudden onset of right upper quadrant and shoulder pain. He had been on vitamins and 5,000 units subcutaneous heparin 12-hourly at the nursing home for the last month. He was in no distress, afebrile, with stable vitals. Physical examination showed a diverting colostomy, tender hepatomegaly and sacral decubiti. A fecal occult blood test was negative. There was spastic paraplegia below the level of T12. Two days after admission, the patient was afebrile and hemodynamically stable. PTT, PT, liver profile, BUN and creatinine were all normal, however his hemoglobin had dropped from 11.3 to 7.6 g/dl. An abdominal CT scan revealed an isolated 9.0 × 1.8 cm subcapsular hematoma. The patient received blood transfusion in the intensive care unit and was discharged 7 days later. In conclusion, spontaneous liver hemorrhage occurs in the nonobstetrical population in the setting of gross anatomical lesions or coagulopathy. This is the first report of an isolated subcapsular liver hematoma.
Lee, Jun-Hwan; Lee, Hyangsook; Jo, Dae-Jean
A retrospective case report. The objective of this article is to report an unusual complication of dry needling. Epidural hematomas after dry needling are quite unusual and only a few cases of epidural hematoma after acupuncture have been reported in the literature. We are presenting the first report of acute cervical epidural hematoma after dry needling. A 58-year-old woman presented with quadriparesis and neck pain. Magnetic resonance imaging of the spine revealed a hyperintense mass in the T2-weighted magnetic resonance image at the C2-T2 level, which proved to be an epidural hematoma. Symptoms related to the epidural hematoma resolved after decompression. Though rare, epidural hematomas are a possible complication when applying needling therapies. Therapists need to have precise knowledge of human anatomy, especially in the region where he or she will puncture. Continuous attention must be paid throughout the whole procedure.
Vazquez-Barquero, A.; Pinto, J.I. [Univ. Hospital ' ' Marques de Valdecilla' ' , Santander (Spain). Dept. of Neurosurgery; Abascal, F.; Garcia-Valtuille, R.; Cerezal, L. [Hospital Mompia, Cantabria, (Spain). Dept. of Radiology; Figols, F.J. [Univ. Hospital Marques de Valdecilla, Santander (Spain). Dept. of Pathology
An uncommon case of chronic nontraumatic spinal epidural hematoma of the lumbar spine in a 75-year-old woman is reported. The patient presented with a 7-month history of low back pain and bilateral sciatica. Magnetic resonance imaging enabled a correct preoperative diagnosis revealing a nodular, well-circumscribed epidural mass with peripheral enhancement and signal intensities consistent with chronic hematoma, which extended from L2 to L3. Laminectomy of L2-L3 was performed and the hematoma was totally resected. Histological examination of the surgical specimen demonstrated a chronic encapsulated hematoma. No evidence of vascular malformation was found. The patient recovered fully after surgical treatment. (orig.)
Full Text Available Background. Bleeding in acquired hemophilia A patients with FVIII autoantibodies is often severe. The authors describe a successfuly acquired hemophilia A treatment with Feiba, glucocorticoids and cyclophosphamide in three patients.Results. In a 66-year patient with chest hematoma and m. iliopsoas hematoma, APTT 50.1 s, FVIII 0.05 IU/mL and inhibitors FVIII (anti-FVIII 22 BU/ml were found. After treatment of hemorrhages with Feiba, dexamethasone and cyclophosphamide, FVIII increased to 0.54 IU/mL and no inhibitors were found on day seventeen. In a 46-year patient with advanced AIDS, multiple hematomas and liver cirrhosis after HCV infection, the platelet count was 92 × 109/L, APTT 48.2 s, FVIII 0.05 IU/mL and anti-FVIII 1.7 BU/mL. The hemorrhages were treated with FEIBA and methylprednisolone therapy was started after 14 months. After 42 days FVIII increased to 0.56 IU/mL and no inhibitors were found. In a 69-year patient suffering from thyroiditis and idiopathic thrombocytopenic purpura, extensive gluteal and chest hematomas were detected during the maintenance therapy with methylprednisolone 16 mg/day. The thrombocyte count was normal but APTT 48.8 s, FVIII 0.01 IU/mL and anti-FVIII 7.0 BU/mL was found. FVIII activity were 1.72 IU/mL and no inhibitors was noted after 330-days of treatment with cyclophosphamide.Conclusions. The treatment with FEIBA was effective in stopping the hemorrhages. The glucocorticoids were efficient in prompt decreasing of the inhibitor titer whereas the effect of cyclophosphamide was retarded.
Melchiorre, Daniela; Linari, Silvia; Manetti, Mirko; Romano, Eloisa; Sofi, Francesco; Matucci-Cerinic, Marco; Carulli, Christian; Innocenti, Massimo; Ibba-Manneschi, Lidia; Castaman, Giancarlo
Recent evidence suggests that patients with severe hemophilia B may have a less severe disease compared to severe hemophilia A. To investigate clinical, radiological, laboratory and histological differences in the arthropathy of severe hemophilia A and hemophilia B, 70 patients with hemophilia A and 35 with hemophilia B with at least one joint bleeding were consecutively enrolled. Joint bleedings (50), regimen of treatment (prophylaxis/on demand), World Federation of Hemophilia, Pettersson and ultrasound scores, serum soluble RANK ligand and osteoprotegerin were assessed in all patients. RANK, RANK ligand and osteoprotegerin expression was evaluated in synovial tissue from 18 hemophilia A and 4 hemophilia B patients. The percentage of patients with either 10-50 or more than 50 hemarthrosis was greater in hemophilia A than in hemophilia B (Phemophilia B (PHemophilia (36.6 vs. 20.2; Phemophilia A patients. Serum osteoprotegerin and soluble RANK ligand were decreased in hemophilia A versus hemophilia B (Phemophilia A patients. In conclusion, the reduced number of hemarthrosis, the lower World Federation of Hemophilia and ultrasound scores, and higher osteoprotegerin expression in serum and synovial tissue in hemophilia B suggest that hemophilia B is a less severe disease than hemophilia A. Osteoprotegerin reduction seems to play a pivotal role in the progression of arthropathy in hemophilia A. Copyright© Ferrata Storti Foundation.
Full Text Available History of present illness: A 21-year-old female with no past medical history presented to the ED after multiple tonic-clonic seizures over the previous 12 hours, the longest lasting 20 seconds. She returned to baseline after each seizure, had no obvious signs of trauma, and did not exhibit any focal neurologic deficits. She denied illicit drugs or new medications. A family member noted that she had fallen from her bed (approximately 3 feet high 2 days ago. Significant findings: Non-contrast Computed Tomography (CT of the Head showed a dense extra-axial collection along the left frontal and parietal regions, extending superior to the vertex with mild mass effect, but no midline shift. Discussion: Intracranial hemorrhage (ICH is a term to describe any abnormal bleeding within the bony confines of the skull. Most commonly, subdural hemorrhages (SDH result from injury to the bridging veins that lead to bleeding between the dura and arachnoid maters. However, in 20%-30% of cases an arterial source of bleeding can be found.1 For adults, motor vehicle collisions and other unintentional head trauma are typically the provoking factors in developing SDH. Falls in the elderly are a common cause of SDH since diffuse cerebral atrophy leads to increased shear forces upon vasculature structures during the fall. The risk of SDH increases with the use of anti-thrombotic agents.2 Clinical presentation varies from asymptomatic to coma (in 50 percent of acute SDH. Chronic SDH may present with headaches, light-headedness, cognitive impairment, and seizures.1 The risk of posttraumatic epileptic seizures (PTS is higher in acute SDH. Risk factors for acute SDH PTS include low Glasgow Coma Score and craniotomy, whereas risk factors for PTS in chronic SDH include alcohol abuse, change in mental status, previous stroke, and hematoma density on CT.3 CT is the most widely used imaging modality for identifying ICH. Acute SDH (within 1-2 days are visualized as hyperdense
Sokal, Etienne M; Lombard, Catherine Anne; Roelants, Véronique; Najimi, Mustapha; Varma, Sharat; Sargiacomo, Camillo; Ravau, Joachim; Mazza, Giuseppe; Jamar, François; Versavau, Julia; Jacobs, Vanessa; Jacquemin, Marc; Eeckhoudt, Stéphane; Lambert, Catherine; Stéphenne, Xavier; Smets, Françoise; Hermans, Cédric
With the exception of liver transplantation, there is no cure for hemophilia, which is currently managed by preemptive replacement therapy. Liver-derived stem cells are in clinical development for inborn and acquired liver diseases and could represent a curative treatment for hemophilia A. The liver is a major factor VIII (FVIII) synthesis site, and mesenchymal stem cells have been shown to control joint bleeding in animal models of hemophilia. Adult-derived human liver stem cells (ADHLSCs) have mesenchymal characteristics and have been shown able to engraft in and repopulate both animal and human livers. Thus, the objectives were to evaluate the potency of ADHLSCs to control bleeding in a hemophilia A patient and assess the biodistribution of the cells after intravenous injection. A patient suffering from hemophilia A was injected with repeated doses of ADHLSCs via a peripheral vein (35 million In-oxine-labeled cells, followed by 125 million cells the next day, and 3 infusions of 250 million cells every 2 weeks thereafter; total infusion period, 50 days). After cell therapy, we found a temporary (15 weeks) decrease in the patient's FVIII requirements and severe bleeding complications, despite a lack of increase in circulating FVIII. The cells were safely administered to the patient via a peripheral vein. Biodistribution analysis revealed an initial temporary entrapment of the cells in the lungs, followed by homing to the liver and to a joint afflicted with hemarthrosis. These results suggest the potential use of ADHLSCs in the treatment of hemophilia A.
Paroskie, Allison; Oso, Olatunde; DeBaun, Michael R.; Sidonio, Robert F
Introduction Hemophilia A, the result of reduced factor VIII (FVIII) activity, is an X-linked recessive bleeding disorder. Previous reports of Hemophilia A carriers suggest an increased bleeding tendency. Our objective was to determine the attitudes and understanding of the Hemophilia A carrier bleeding phenotype, and opinions regarding timing of carrier testing from the perspective of both medical providers and affected patients. Data from this survey was used as preliminary data for an ongoing prospective study. Material and Methods An electronic survey was distributed to physicians and nurses employed at Hemophilia Treatment Centers (HTC), and Hemophilia A carriers who were members of Hemophilia Federation of America. Questions focused on the clinical understanding of bleeding symptoms and management of Hemophilia A carriers, and the timing and intensity of carrier testing. Results Our survey indicates that 51% (36/51) of providers compared to 78% (36/46) of carriers believe that Hemophilia A carriers with normal FVIII activity have an increased bleeding tendency (pHemophilia A carriers report a high frequency of bleeding symptoms. Regarding carrier testing, 72% (50/69) of medical providers recommend testing after 14 years of age, conversely 65% (29/45) of Hemophilia A carriers prefer testing to be done prior to this age (pHemophilia A carriers self-report a higher frequency of bleeding than previously acknowledged, and have a preference for earlier testing to confirm carrier status. PMID:24309601
Siddiqi, F; Hammond, R; Lee, D; Duggal, N
Spontaneous chronic spinal subdural hematoma is rare. We describe a case of spontaneous chronic spinal subdural hematoma associated with arachnoiditis and syringomyelia in a 76-year old woman who presented with a 14-year history of progressive myelopathy. MRI scan revealed a thoraco-lumbar subdural cystic lesion and a thoracic syrinx. The patient underwent thoracic laminectomy and decompression of the lesion, which was a subdural hematoma. A myelotomy was performed to drain the syrinx. Pathological examination revealed features consistent with chronic subdural membrane. This report attempts to elucidate the pathogenesis of chronic spinal subdural hematoma. We discuss possible etiological factors in light of the current literature and pathogenesis of both spinal subdural hematoma and syrinx formation.
Park, Sihyung; Lee, Ga Hee; Jin, Kyubok; Park, Kang Min; Kim, Yang Wook; Park, Bong Soo
Acute renal infarction is an uncommon condition resulting from an obstruction or a decrease in renal arterial blood flow. Isolated spontaneous renal artery intramural hematoma is a rare cause of renal infarction. A 46-year-old healthy man presented to our emergency room because of sudden onset of severe right flank pain. An enhanced abdominal computed tomography scan showed a low-attenuated lesion in the lateral portion of the right kidney but no visible thromboembolisms in the main vessels. Computed tomography angiography revealed acute infarction resulting from intramural hematoma of the anterior segmental artery of the right kidney, with distal occlusion. The rarity and non-specific clinical presentation of renal infarction often lead to a delayed diagnosis that may result in impaired renal function. Clinical suspicion is important in the early diagnosis, and intramural hematoma of the renal artery should be considered the cause of renal infarction even in healthy patients without predisposing factors.
Full Text Available Acquired factor VIII deficiency (acquired hemophilia A is a rare condition characterized by the acquisition of autoantibodies that affect the clotting activity of factor VIII (fVIII. The most common manifestation in affected patients is a hemorrhagic diathesis. This disorder is associated with autoimmune diseases, pregnancy, postpartum period, drugs, and malignancy. Management of this condition begins with attempts to arrest an acute bleed based on the site and severity of bleeding and inhibitor titer. The next priority is eradication of the fVIII antibodies using immunosuppressive therapies. We report the case of a 66-year-old male who presented with spontaneous right thigh hematoma with prolonged activated partial prothrombin time and normal prothrombin time. Mixing studies confirmed the presence of an inhibitor. Further investigation for the underlying etiology of acquired hemophilia A leads to diagnosis of prostate cancer. Treatment consisted of bypassing agents including activated factor VII and activated prothrombin plasma concentrate to arrest the bleeding. Steroids and cyclophosphamide were added to suppress the fVIII inhibitors. Concomitant treatment of locally advanced prostate cancer with chemotherapy confirmed the eradication of the inhibitors. To our knowledge, this is the first reported case of prostate cancer diagnosed and treated simultaneously with acquired hemophilia A resulting in favorable patient outcome.
Sheth, Chirag; Gill, Amandeep; Sekhon, Sumeet
Acquired factor VIII deficiency (acquired hemophilia A) is a rare condition characterized by the acquisition of autoantibodies that affect the clotting activity of factor VIII (fVIII). The most common manifestation in affected patients is a hemorrhagic diathesis. This disorder is associated with autoimmune diseases, pregnancy, postpartum period, drugs, and malignancy. Management of this condition begins with attempts to arrest an acute bleed based on the site and severity of bleeding and inhibitor titer. The next priority is eradication of the fVIII antibodies using immunosuppressive therapies. We report the case of a 66-year-old male who presented with spontaneous right thigh hematoma with prolonged activated partial prothrombin time and normal prothrombin time. Mixing studies confirmed the presence of an inhibitor. Further investigation for the underlying etiology of acquired hemophilia A leads to diagnosis of prostate cancer. Treatment consisted of bypassing agents including activated factor VII and activated prothrombin plasma concentrate to arrest the bleeding. Steroids and cyclophosphamide were added to suppress the fVIII inhibitors. Concomitant treatment of locally advanced prostate cancer with chemotherapy confirmed the eradication of the inhibitors. To our knowledge, this is the first reported case of prostate cancer diagnosed and treated simultaneously with acquired hemophilia A resulting in favorable patient outcome.
Urgent cranial ultrasound showed epidural hematoma with mass effect on the underlying parietal lobe and the right lateral ventricle with mid-line shift (A). It also revealed hydropcephaly sequelae of prenatal intraventricular hemorrhage; with periventricular cysts and thalamic arteritis, signs of fetopathy (B). Congenital rubella ...
Jensen, Kristian Kiim; Hangaard, Stine
An otherwise healthy 28-year old male presented to his general practitioner with dyspnoea in the morning and abdominal discomfort through months. Four months earlier, he had experienced a blunt trauma to the left side of his abdomen. Abdominal ultrasonography revealed a splenic hematoma...
Dabdoub, Carlos B; Adorno, Juan Oscar; Urbano, Jair; Silveira, Elisabeth N; Orlandi, Bianca Maria M
Infection of a subdural hematoma is an unusual cause of subdural empyema, with fewer than 50 cases reported in the literature. The appropriate surgical option for this entity has not been determined because of its rarity. We present a case report of a post-traumatic subdural hematoma infected with Escherichia coli that was successfully treated with craniotomy. In addition, we performed a PubMed search to comprehensively illustrate the causative organism, source of infection, clinical picture, surgical treatment, and outcome for this condition. This article presents an update on the condition. A 55-year-old man was admitted to our hospital complaining of headache, seizure, and urinary incontinence. He had a history of alcoholism and several hospitalizations for mild head trauma. Neuroimaging studies revealed a chronic hematic collection in the left frontal-parietal region. Laboratory tests showed increased C-reactive protein levels. In addition, surgical results revealed an infected subdural hematoma. A bacterial culture of the purulent specimen identified E. coli. In view of the urinary complaint and leukocyturia, the cause of the infected subdural hematoma was postulated as a urinary tract infection. Infected subdural hematoma is an unusual disorder. We must keep in mind the possibility of this complication when seeing a patient who presents with any of the 3 most common symptoms in this review. In these patients, craniotomy should be the method of surgical drainage, especially in adults. It ensures maximal drainage of the loculated pus and allows the total removal of the infected hematoma capsule. Copyright © 2016 Elsevier Inc. All rights reserved.
Kamphuisen, Pieter W.; ten Cate, Hugo
Patients with hemophilia, who have a life-long hypocoagulability, seem to have a lower cardiovascular mortality than the general population. Nevertheless, the prevalence of cardiovascular risk factors in patients with hemophilia is as prevalent as in the general population, and hypertension is even
Azza A.G. Tantawy
cian about progress in hemophilia treatment. Prenatal testing is generally indicated in families with severe or moderate forms of hemophilia. In families with the mild disease such indication is rare [27,80]. 10.1. Molecular genetic testing. Prenatal testing can be done for carrier women if the mutation is identified in a family ...
Yan, H J; Lin, K E; Lee, S T; Tzaan, W C
Calcified or ossified chronic subdural hematoma is a rare entity that usually presents as a space-occupying lesion over the cerebral convexity. We report a case of calcified and ossified chronic subdural hematoma in an unusual location that has not been previously reported. A 24-year-old man with a history of tonic-clonic convulsions since 7 months of age was admitted because of increasing frequency and duration of seizures. Computed tomography and magnetic resonance imaging demonstrated a fusiform extra-axial lesion just above the tentorium and adjacent to the cerebral falx. A calcified and ossified chronic subdural hematoma was noted and was almost completely removed by craniotomy. Better seizure control was achieved by removal of the calcified chronic subdural hematoma. Calcified subdural hematoma, calcified epidural hematoma, calcified empyema, meningioma, calcified arachnoid cyst, and calcified convexity of the dura mater with acute epidural hematoma should be considered for the differential diagnosis of an extra-axial calcified lesion.
Chouhan, Varun; Mandliya, Alok; Chouhan, Kiran
Obturator internus hematoma(OIH) is a very rare entity. In past it has been reported in hemophilics, we firstly report obturator internus hematoma in a patient of stroke on antiplatelet drugs. Obturator internus hematoma can cause severe hip pain with normal X-rays, so it should kept in differential diagnosis of hip pain with normal radiographs. 74 year old male with history of recent onset stroke presented to us with left side weakness and left hip pain. Radiographs were normal. MRI revealed left obturator internus hematoma. Patient was treated conservatively by stopping antiplatelet medications. Obturator internus hematoma is very rare but very important entity to recognise as it may mimic myositis or abscess around hip joint. Failing to recognize it and treating patient surgically may lead to untoward consequences.
Osama Shukir Muhammed Amin
Full Text Available Acute posterior fossa subdural hematomas are rare and most of them are trauma-related. Non-traumatic ones have been reported in patients who had idiopathic thrombocytopenic purpura or those who had been receiving anticoagulant therapy. We report on the case of 57-year-old Iranian man who developed sudden severe occipital headache, drowsiness, repeated vomiting, and instability of stance and gait. He was neither hypertensive nor diabetic. No history of head trauma was obtained and he denied illicit drug or alcohol ingestion. A preliminary diagnosis of acute intra-cerebellar hemorrhage was made. His CT brain scan revealed an acute right-sided, extra-axial, crescent-shaped hyperdense area at the posterior fossa. His routine blood tests, platelets count, bleeding time, and coagulation profile were unremarkable. The patient had spontaneous acute infratentorial subdural hematoma. He was treated conservatively and discharged home well after 5 days. Since then, we could not follow-up him, clinically and radiologically because he went back to Iran. Our patients presentation, clinical course, and imaging study have called for conservative management, as the overall presentation was relatively benign. Unless the diagnosis is entertained and the CT brain scan is well-interpreted, the diagnosis may easily escape detection.
This study attempts to explain the cellular events characterizing the changes seen in the medullary callus adjacent to the interfragmentary hematoma during the early stages of fracture healing. It also shows that human fracture hematoma contains the angiogenic cytokine vascular endothelial growth factor and has the inherent capability to induce angiogenesis and thus promote revascularization during bone repair. Patients undergoing emergency surgery for isolated bony injury were studied. Raised circulating levels of vascular endothelial growth factor were seen in all injured patients, whereas the fracture hematoma contained significantly higher levels of vascular endothelial growth factor than did plasma from these injured patients. However, incubation of endothelial cells in fracture hematoma supernatant significantly inhibited the in vitro angiogenic parameters of endothelial cell proliferation and microtubule formation. These phenomena are dependent on a local biochemical milieu that does not support cytokinesis. The hematoma potassium concentration is cytotoxic to endothelial cells and osteoblasts. Subcutaneous transplantation of the fracture hematoma into a murine wound model resulted in new blood vessel formation after hematoma resorption. This angiogenic effect is mediated by the significant concentrations of vascular endothelial growth factor found in the hematoma. This study identifies an angiogenic cytokine involved in human fracture healing and shows that fracture hematoma is inherently angiogenic. The differences between the in vitro and in vivo findings may explain the phenomenon of interfragmentary hematoma organization and resorption that precedes fracture revascularization.
Olivares, P; Tovar, J A; Díez-Pardo, J A; Corbatón, J; Monereo, J
Two cases of duodenal hematoma secondary to abdominal trauma in children are reported. The latent periods between trauma and the onset of symptoms were two and fifteen days. X-ray studies were conclusive for diagnosis. Pancreatic signs were mild in one case. Both cases were treated surgically, draining the fluid collection extramucosally. The authors advise surgical treatment whenever associated lesions need to be ruled out and when obstruction persists after the first days.
Full Text Available We report three cases of spontaneous spinal epidural hematoma (SSEH with hemiparesis. The first patient was a 73-year-old woman who presented with left hemiparesis, neck pain, and left shoulder pain. A cervical MRI scan revealed a left posterolateral epidural hematoma at the C3–C6 level. The condition of the patient improved after laminectomy and evacuation of the epidural hematoma. The second patient was a 62-year-old man who presented with right hemiparesis and neck pain. A cervical MRI scan revealed a right posterolateral dominant epidural hematoma at the C6-T1 level. The condition of the patient improved after laminectomy and evacuation of the epidural hematoma. The third patient was a 60-year-old woman who presented with left hemiparesis and neck pain. A cervical MRI scan revealed a left posterolateral epidural hematoma at the C2–C4 level. The condition of the patient improved with conservative treatment. The classical clinical presentation of SSEH is acute onset of severe irradiating back pain followed by progression to paralysis, whereas SSEH with hemiparesis is less common. Our cases suggest that acute cervical spinal epidural hematoma should be considered as a differential diagnosis in patients presenting with clinical symptoms of sudden neck pain and radicular pain with progression to hemiparesis.
Full Text Available Massimo Franchini1, Annarita Tagliaferri2, Pier Mannuccio Mannucci31Transfusion and Hemophilia Center, City Hospital of Verona, Italy; 2Regional Reference Center for Inherited Bleeding Disorders, University Hospital of Parma, Italy; 3Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Department of Medicine and Medical Specialties, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, University of Milan, ItalyAbstract: After the increasing rate of deaths observed during the 1980s due to human immunodeficiency virus (HIV infection, the health-related quality of life and life expectancy of persons with hemophilia have improved, mainly due to the progresses of replacement therapy and antiviral drugs and to the improvement of the global comprehensive care provided by specialized centers. As a consequence, an increasing number of hemophiliacs have reached an older age and nowadays physicians in hemophilia centers find that they must handle age-related clinical problems never previously observed in this population. The management of elderly persons with congenital hemophilia is discussed in the first part of this review. The second part describes the general aspects of acquired hemophilia due to anti-factor VIII autoantibodies, focusing on the clinical management of elderly patients, one of the groups most frequently affected by this acquired bleeding disorder.Keywords: hemophilia, factor VIII, elderly, aging, inhibitors, bleeding
Song, Jun H.; Abbott, Daniel; Gewirtz, Eric; Hauck, Ellen; Eun, Daniel D.
Abstract Obturator nerve injury is a known injury after robot-assisted laparoscopic radical prostatectomy (RALP) and patients often present with motor and sensory deficits in the immediate postoperative period. We describe a 65-year-old male who presented with motor deficits, indicative of obturator neurapraxia after RALP upon waking from anesthesia. Work-up revealed an expansile hematoma possibly compressing the obturator nerve. After evacuation of the hematoma, the patient had immediate improvement of his neurologic deficits. Our patient's clinical vignette illustrates the importance of considering postsurgical hematoma in the differential diagnosis when patients present with signs and symptoms of obturator neurapraxia after RALP. PMID:27579444
Castillo-Cañadas, Ana María; Serrano-Diana, Carolina; López-Del Cerro, Esther; Gómez-García, María Teresa; González De Merlo, Gaspar
Acquired hemophilia A is a truly exceptional hemorrhagic diathesis, that consists of the emergence of polyclonal autoantibodies (inhibitor) IgG-type (subclasses 1 and 4, in most cases) against the coagulant function of the circulating factor VIII, which acts in the domains C2, A2 and A3 of the molecule, thus interfering their interaction with the factor IXa, the phospholipids and the Von Willebrand factor. Its morbidity and mortality are high, but nevertheless its low incidence (1-1.5 cases per million population per year) is the most frequent autoimmune disorder. This paper reports the clinical case of two patients; the first one, 36 years old, who the tenth day of postpartum required re-entry due to a diagnosis of hematoma of the abdominal wall that was surgically drained twice. The patient of case 2 was 39 years old and at six days of postpartum went to the emergency room due to bleeding, she was underwent to curettage and therapeutic transfusion of 3 UCH. Because of the persistence of bleeding, which was not possible to control with medical treatment and conservative measures, therapeutic hysterectomy was performed, with blood transfusion later. Due to the hemorrhagic complications of this condition and the serious clinical consequences derived from them, it is important to establish an early diagnosis; it is therefore critical to know the existence of this very rare disease to be able to avoid its consequences.
Franchini, Massimo; Tagliaferri, Annarita; Mannucci, Pier Mannuccio
After the increasing rate of deaths observed during the 1980s due to human immunodeficiency virus (HIV) infection, the health-related quality of life and life expectancy of persons with hemophilia have improved, mainly due to the progresses of replacement therapy and antiviral drugs and to the improvement of the global comprehensive care provided by specialized centers. As a consequence, an increasing number of hemophiliacs have reached an older age and nowadays physicians in hemophilia centers find that they must handle age-related clinical problems never previously observed in this population. The management of elderly persons with congenital hemophilia is discussed in the first part of this review. The second part describes the general aspects of acquired hemophilia due to anti-factor VIII autoantibodies, focusing on the clinical management of elderly patients, one of the groups most frequently affected by this acquired bleeding disorder. PMID:18044186
Chuah, Marinee K; Nair, Nisha; VandenDriessche, Thierry
Hemophilia A and B are X-linked monogenic disorders caused by deficiencies in coagulation factor VIII (FVIII) and factor IX (FIX), respectively. Current treatment for hemophilia involves intravenous infusion of clotting factor concentrates. However, this does not constitute a cure, and the development of gene-based therapies for hemophilia to achieve prolonged high level expression of clotting factors to correct the bleeding diathesis are warranted. Different types of viral and nonviral gene delivery systems and a wide range of different target cells, including hepatocytes, skeletal muscle cells, hematopoietic stem cells (HSCs), and endothelial cells, have been explored for hemophilia gene therapy. Adeno-associated virus (AAV)-based and lentiviral vectors are among the most promising vectors for hemophilia gene therapy. Stable correction of the bleeding phenotypes in hemophilia A and B was achieved in murine and canine models, and these promising preclinical studies prompted clinical trials in patients suffering from severe hemophilia. These studies recently resulted in the first demonstration that long-term expression of therapeutic FIX levels could be achieved in patients undergoing gene therapy. Despite this progress, there are still a number of hurdles that need to be overcome. In particular, the FIX levels obtained were insufficient to prevent bleeding induced by trauma or injury. Moreover, the gene-modified cells in these patients can become potential targets for immune destruction by effector T cells, specific for the AAV vector antigens. Consequently, more efficacious approaches are needed to achieve full hemostatic correction and to ultimately establish a cure for hemophilia A and B.
Rattanathammethee, Thanawat; Norasetthada, Lalita; Tantiworawit, Adisak; Rattarittamrong, Ekarat; Hantrakool, Sasinee; Chai-Adisaksopha, Chatree
Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies against factor VIII (FVIII). Spontaneous bleeding in the various sites and severity is the most common clinical presentation. Here, we report a 74-year-old Thai woman with HIV infection who presented with spontaneous ecchymoses. The laboratory revealed isolated activated partial thromboplastin time prolongation with low FVIII activity and a presence of FVIII inhibitor. She was diagnosed with acquired hemophilia A. Corticosteroid monotherapy was the treatment regimen for inhibitor eradication. We demonstrate the clinical course of the rare condition and review the relevant literature.
Nathwani, Amit C; Davidoff, Andrew M; Tuddenham, Edward G D
Gene therapy provides hope for a cure for patients with hemophilia by establishing continuous endogenous expression of factor VIII or factor IX following transfer of a functional gene copy to replace the hemophilic patient's own defective gene. Hemophilia may be considered a "low-hanging fruit" for gene therapy because a small increment in blood factor levels (≥2% of normal) significantly improves the bleeding tendency from severe to moderate, eliminating most spontaneous bleeds. After decades of research, the first trial to provide clear evidence of efficiency after gene transfer in patients with hemophilia B using adeno-associated virus vectors was reported by the authors' group in 2011. This has been followed by unprecedented activity in this area, with the commencement of seven new early-phase trials involving >55 patients with hemophilia A or hemophilia B. These studies have, in large part, generated promising clinical data that lay a strong foundation for gene therapy to move forward rapidly to market authorization. This review discusses the data from the authors' studies and emerging results from other gene therapy trials in both hemophilia A and B.
Glavind, K; Nøhr, S; Nielsen, P H
In 60 patients with a live fetus and an intra-uterine hematoma (IUH) proven by ultrasonic scanning the outcome of pregnancy was spontaneous abortion in 12% and premature delivery in 10%. No correlation between the outcome of the pregnancy and the maximum size of the hematoma or the week...
Song, Jun H.; Joshua R. Kaplan; Abbott, Daniel; Gewirtz, Eric; Hauck, Ellen; Eun, Daniel D.
Abstract Obturator nerve injury is a known injury after robot-assisted laparoscopic radical prostatectomy (RALP) and patients often present with motor and sensory deficits in the immediate postoperative period. We describe a 65-year-old male who presented with motor deficits, indicative of obturator neurapraxia after RALP upon waking from anesthesia. Work-up revealed an expansile hematoma possibly compressing the obturator nerve. After evacuation of the hematoma, the patient had immediate imp...
Al-Sarraj, S; Mohamed, S; Kibble, M; Rezaie, P
Macrophages are an inherent component of the dura mater, and can be characterised in cases of subdural hematoma (SDH) by their progressive and varying accumulation within areas of damage. Gross and histological methods used to determine the age of SDH are inexact. These are in part due to the active nature of such lesions and the diverse manner in which trauma victims respond to injury. Correct diagnosis has obvious medico-legal implications. However, there is as yet no specific diagnostic method that allows the age of SDH to be reliably determined. This study investigated the progressive and orderly pattern of reactivity of resident and infiltrating dural macrophages that occurs in response to injury associated with SDH. 26 postmortem cases of traumatic SDH were examined with survival times (onset of trauma to death) ranging from a few hours and up to 31 days. Macrophage reactivity associated with the dura mater and the underlying hematoma was determined using CD68 and MHC class II immunohistochemistry and the qualitative and quantitative findings compared with the presence of iron detected using conventional Perl's Prussian blue method. The results show that CD68 and MHC class II are differentially expressed within the dura mater and hematoma in SDH, and that the expression of MHC class II is markedly upregulated in the inner aspect of the dura mater within the initial 24 hours following injury. CD68 expression can be detected quantitatively in the hematoma, 24-48 hours after SDH, and within the dura following this period. Linear regression analysis further revealed a significant and positive association between the expression of MHC class II or CD68 antigens and the progressive survival of SDH up to 31 days post-injury, which was not seen with Perl's histochemical method. The expression of MHC class II antigen was a distinguishing, and quantifiable feature particularly localized within the inner aspect of the dura from a very early stage in the progression of
National Heart and Lung Inst. (DHEW/PHS), Bethesda, MD.
The Hemophilia Health Education Planning Project was designed to (1) create a set of tools useful in hemophilia planning and education, and (2) create a planning model for other diseases with similar factors. The project used the game-simulations technique which was felt to be particularly applicable to hemophilia health problems, since as a…
Hall, Christopher S.
Children with hemophilia and Human Immunodeficiency Virus (HIV) infection are not a transmission risk to other children, and they can help enact best practices for school attendance by other such children. The article examines the National Hemophilia Foundation's work to promote appropriate inclusion of students with hemophilia and HIV in all…
Md Rafiqul Alam
Full Text Available We report a 25 years old man developed Haemarthrosis of left hip joint with a history of recurrent swelling and pain in multiple joints and prolonged bleeding following minor trauma since childhood. Subsequent investigations revealed Christmas disease (Haemophilia B. Hemophilia B is an X-linked bleeding disorder. This case emphasises the importance of considering a diagnosis of haemophilia in a man with unexplained bleeding, even in the absence of a positive family history. DOI: 10.3329/bsmmuj.v2i2.4766 BSMMU J 2009; 2(2: 90-91
Bitting, Rhonda L; Bent, Stephen; Li, Yongmei; Kohlwes, Jeffrey
The inhibition of factor VIII by autoantibody development, or acquired hemophilia, occurs in approximately one person per million each year and can cause life-threatening bleeding. Due to the disease rarity, there are no randomized studies addressing prognostic features and treatment. The goal of this study is to identify prognostic indictors in acquired hemophilia to guide treatment choices. MEDLINE and EMBASE search from 1985-2008 retrieved 32 studies with detailed clinical information on five or more patients with acquired hemophilia. Univariate and multivariate analysis of the effects of age, sex, underlying condition, inhibitor titer, and treatment regimen were evaluated with regards to complete remission and death. A total of 32 studies containing 359 patients with acquired hemophilia were included in the analysis. The all-cause mortality rate in this cohort was 21%. Multivariate analyses revealed that patients more likely to die are the elderly [odds ratio (OR) 2.4, 95% confidence interval (CI) 1.32-4.36] and those with underlying malignancy (OR 2.76, CI 1.38-5.50). Early achievement of complete remission resulted in improved survival. Complete remission occurred in 94% of patients receiving combination chemotherapy, 82% receiving dual therapy, and 68% receiving steroids alone. Patients receiving immunosuppression had reduced odds of persistent hemophilia, with combination chemotherapy being the most efficacious (OR 0.04, CI 0.01-0.23) and steroid therapy alone being the least (OR 0.38, CI 0.14-0.94). In acquired hemophilia, increased age, underlying malignancy, and lack of complete remission are risk factors for death. Although the included studies were not randomized, patients treated with combination chemotherapy had the greatest odds of remission and the lowest odds of death.
Pinto, Fernando Campos Gomes; Porro, Fabrizio Frutos; Suganuma, Liliana; Fontes, Ricardo Bragança de Vasconcellos; de Andrade, Almir Ferreira; Marino Jr, Raul
Head trauma is an important consequence of child abuse. Specific pathophysiological mechanisms in child abuse are responsible for the "whiplash shaken-baby syndrome", which would favour the occurrence of intracranial hemorrhages...
Gül Pamukçu Günaydın
Full Text Available Introduction. We present a case of concurrent spontaneous sublingual and intramural small bowel hematoma due to warfarin anticoagulation. Case. A 71-year-old man presented to the emergency department complaining of a swollen, painful tongue. He was on warfarin therapy. Physical examination revealed sublingual hematoma. His international normalized ratio was 11.9. The computed tomography scan of the neck demonstrated sublingual hematoma. He was admitted to emergency department observation unit, monitored closely; anticoagulation was reversed with fresh frozen plasma and vitamin K. 26 hours after his arrival to the emergency department, his abdominal pain and melena started. His abdomen tomography demonstrated intestinal submucosal hemorrhage in the ileum. He was admitted to surgical floor, monitored closely, and discharged on day 4. Conclusion. Since the patient did not have airway compromise holding anticoagulant, reversing anticoagulation, close monitoring and observation were enough for management of both sublingual and spontaneous intramural small bowel hematoma.
Abdulhamid, Mohamed M; Li, Yan Michael; Hall, Walter A
Spontaneous acute subdural hematoma is rare and limited to sporadic case reports, associated with neoplasm, aneurysm, arteriovenous malformation and cocaine use. Subdural hematoma has also been reported in association with leukemic malignancies, either during therapy or after diagnosis. However, there are no reports of spontaneous acute subdural hematoma as the primary initial presenting manifestation of a chronic myeloid leukemia. Here we describe one case of a 53-year-old male that presented with severe right-sided headache and intermittent left-sided paresthesias. CT scan showed non-traumatic right-sided acute subdural hematoma. Further evaluation revealed that the patient had chronic myeloid leukemia. His peripheral white blood count normalized after Gleevec and hydroxyurea chemotherapy. Furthermore, he had no neurological deficits after his subdural collection was adequately evacuated.
Schwartz, Carolyn E; Powell, Victoria E; Eldar-Lissai, Adi
The purpose of this article is to describe the psychometric development of the Hemophilia Caregiver Impact measure. Qualitative interviews (n = 22) and a cross-sectional web-based study (n = 458) were implemented with caregivers of people with hemophilia. Classical test theory and item response theory analyses were implemented to evaluate the psychometric characteristics of the measure. The study sample had a mean age of 39 and a median level of college education. It was predominantly female (88%), and had an average of two children. 85% of this study sample had at least one child with hemophilia. The final 36-item Hemophilia Caregiver Impact measure is composed of seven subscales assessing relevant negative aspects of caregiver impact (Burden Summary) as well as one subscale reflecting a positive aspect of caregiver impact (Positive Emotions). These two summary scores are orthogonal and can be used together in analyses examining negative and positive aspects of caregiver impact. The items included within each subscale reflect a unidimensional construct, demonstrate good item information and trace lines, and lack of local dependence. The resulting subscales demonstrate high reliability, and good construct validity. They show moderate incremental and discriminant validity. The Hemophilia Caregiver Impact measure is a useful new tool for clinical research on hemophilia. In addition to having eight relevant subscales, the measure can also be summarized with two scores. This versatility can be useful in analyzing studies with very small samples, which is to be expected when dealing with a rare condition like hemophilia.
Komai, Takanori; Nakashima, Kazuya; Tominaga, Takashi; Nogaki, Hidekazu
We report a rare case of a patient with spinal epidural hematoma who presented with transient hemiplegia. A 90-year-old man awakened from sleep due to sudden neck pain. Fifteen minutes later, the man experienced progressively worsening weakness in his left hand, and was transported in an ambulance to our hospital. At the hospital, he presented with hemiplegia, and we suspected intracranial disease. Therefore, we performed magnetic resonance imaging (MRI), which revealed no intracranial lesions. Shortly after the MRI, the patient showed no signs of hemiplegia. However, since the severe neck pain persisted, we performed cervical MRI, which showed a high-intensity area at the C2-C5 level, predominantly on the left side. Despite recovery from hemiplegia, we performed a laminectomy of C3-C5 with evacuation of a hematoma at the C2-C6 level. After the surgery, the patient had no neck pain.
Burenchev, D V; Skvortsova, V I; Tvorogova, T V; Guseva, O I; Gubskiĭ, L V; Kupriianov, D A; Pirogov, Iu A
The aim of this study was to assess the possibility of revealing intracerebral hematomas (ICH), using MRI, within the first hours after onset and to determine their MRI semiotics features. Thirty animals with experimental ICH were studied. A method of two-stage introduction of autologous blood was used to develop ICH as human spontaneous intracranial hematomas. Within 3-5h after blood introduction to the rat brain. The control MRI was performed in the 3rd and 7th days after blood injections. ICH were definitely identified in the first MRI scans. The MRI semiotics features of acute ICH and their transformations were assessed. The high sensitivity of MRI to ICH as well as the uniform manifestations in all animals were shown. In conclusion, the method has high specificity for acute ICH detection.
Banse, Christopher; Benhamou, Ygal; Lequerré, Thierry; Le Cam-Duchez, Véronique; Lévesque, Hervé; Vittecoq, Olivier
A 47-year-old woman with rheumatoid arthritis (RA) treated successively with infliximab, abatacept, and etanercept spontaneously developed subcutaneous bruises and a noncompressive hematoma 11 months after starting etanercept therapy (50mg/week). Her prothrombin time was normal but her activated partial thromboplastin time was increased to 2.48 (normal range, 0.85-1.17). She had a circulating anticoagulant (Rosner index, 45; normal,etanercept and leflunomide were stopped and prednisone was given in a daily dosage of 1mg/kg, in combination with rituximab, two 1-g doses at an interval of 2 weeks. After 5 months, persistence of the anti-factor VIII antibody prompted the initiation of azathioprine therapy, 2mg/kg/d. A remission was achieved 9 months after the diagnosis of acquired hemophilia and was sustained at last follow-up after 3 years. This new case of acquired hemophilia in a patient with RA may reflect a simple association or an inducing role of etanercept. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.
Full Text Available Blunt traumatic injuries to the superior gluteal artery are rare in clinic. A majority of injuries present as aneurysms following penetrating trauma, fracture pelvis or posterior dislocation of the hip joint. We reported a rare case of superior gluteal artery pseudoaneurysm following blunt trauma presenting as large expanding right gluteal hematoma without any bony injury. The gluteal hematoma was suspected clinically, confirmed by ultrasound and the arterial injury was diagnosed by CT angiography that revealed a large right gluteal hematoma with a focal contrast leakage forming a pseudoaneurysm within the hematoma. Pseudoaneurysm arose from the superior gluteal branch of right internal iliac artery, which was successfully angioembolized. The patient was discharged on day 4 of hospitalization with resolving gluteal hematoma. This report highlighted the importance of considering an arterial injury following blunt trauma to the buttocks with subsequent painful swelling. Acknowledgment of this rare injury pattern was necessary to facilitate rapid diagnosis and appropriate treatment.
Abstract. We present two middle aged Nigerian patients who developed significant chronic subdural hematomas weeks after going on vibrating Chinese massage chairs. This complication of using the chairs has not been previously reported.
Wajid Nazir Wani
Full Text Available Secondary parkinsonism is attributable to a wide variety of causes including supratentorial mass lesions. While tumors are known to present with parkinsonism, chronic subdural hematoma is rarely seen presenting as rapidly deteriorating parkinsonian features with complete disappearance following evacuation of hematoma. The authors present two such patients-70- and 78-year-old males who presented with sudden onset of parkinsonism features. Both failed to recollect any significant head injury. Imaging diagnosed the presence of chronic subdural hematomas, being unilateral in one and bilateral in other. Surgical evacuation resulted in complete resolution of parkinsonian symptoms. These cases reinforce earlier studies for chronic subdural hematoma to be one of the causes of reversible parkinsonism apparently from distortion of basal ganglia mechanically and bringing changes in dopaminergic function, harming the susceptible aging brain.
Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jeronimo Buzetti; Jung, Gustavo Simiano; Silva Junior, Luis Fernando; Ramina, Ricardo, E-mail: email@example.com [Instituto de Neurologia de Curitiba (INC), Curitiba, PR (Brazil)
According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xarelto®. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban. (author)
Quesnel, Carlos; Weber, Alejandro; Mendoza, Dalila; Garteiz, Denzil
The hepatic hematoma or rupture appear in 1 of every 100,000 pregnancies. The most common causes of hepatic hematoma in pregnancy are severe preeclampsia and HELLP syndrome; some predisposing factors are seizures, vomiting, labor, preexistent hepatic disease and trauma. A 33 year old primigravid with a normal 33 week twin pregnancy presented abdominal pain and hypovolemic shock due to spontaneous subcapsular hepatic hematoma; laparoscopy was performed to evaluate the possibility of rupture, which was not found, later emergency cesarean section was carried out followed by hepatic hematoma drainage and abdominal packaging by laparoscopy. After surgery the flow through drainage was too high additionally hemodynamic instability and consumption coagulopathy. Abdominal panangiography was performed without identifying bleeding areas. Intesive care was given to the patient evolving satisfactorily, was discharged 19 days after the event. Seven months later she had laparoscopic cholecystectomy due to acute litiasic colecistitis. We found 5 cases in literatura about hepatic hematoma during pregnancy no related to hypertensive disorders of pregnancy; these were related to hepatoma, amebian hepatic abscess, falciform cell anemia, cocaine consumption and molar pregnancy. Hepatics hematomas have high morbidity and mortality so is significant early diagnosis and multidisciplinary approach.
de Koning, M L Y; Fischer, K; de Laat, B; Huisman, A; Ninivaggi, M; Schutgens, R E G
Essentials: It is unknown if hemophilia patients with atrial fibrillation need anticoagulation. Endogenous thrombin potentials (ETP) in hemophilia patients and patients on coumarins were compared. Severe hemophilia patients had comparable ETP to therapeutic international normalized ratio (INR). In
Full Text Available A 74 year-old patient with a nocturnal onset of neck and chest pain was brought to an emergency clinic. Physical examination and cardiac assessment were normal. Three hours after the addmittance, a flaccid paralysis of the four limbs supervened. Suspecting of an unusual onset of central nervous system infection, a lumbar puncture was performed, yielding 20 ml of normal cerebrospinal fluid. Thirty oinutes after the puncture, the patient completely regained neurological funcion. He was then referred to a General Hospital where a computed tomography (CT scan was done showing a large cervical epidural bleeding in the posterolateral region of C4/C5 extending to C7/Th1, along with a C6 vertebral body hemangioma. A magnetic resonance imaging revealed the same CT findings. A normal selective angiography of vertebral arteries, carotid arteries and thyreocervical trunk was carried out. Spontaneous spinal epidural hematoma (ASSEH is a rare but dramatic cause of neurological impairment. In this article we report a fortunate case of complete recovery after an unusual spine cord decompression. We also review the current literature concerning diagnosis and treatment of ASSEH.
Eckhoff, Kerstin; Wedel, Thilo; Both, Marcus; Bas, Kayhan; Maass, Nicolai; Alkatout, Ibrahim
Rectus sheath hematoma is a rare clinical diagnosis, particularly in pregnancy. Due to unspecific symptoms, misdiagnosis is likely and could potentially endanger a patient as well as her fetus. A 26-year-old white woman presented with mild right-sided abdominal pain, which increased during palpation and movement, at 26 + 3 weeks' gestational age. Ultrasound imaging initially showed a round and well-demarcated structure, which appeared to be in contact with her uterine wall, leading to a suspected diagnosis of an infarcted leiomyoma. However, she reported increasing levels of pain and laboratory tests showed a significant drop in her initially normal hemoglobin level. A magnetic resonance imaging scan finally revealed a large type III rectus sheath hematoma on the right side. Because of progressive blood loss into her rectus sheath under conservative therapy, with a significant further decrease in her hemoglobin levels, surgical treatment via right-sided paramedian laparotomy was initiated. During the operation the arterial bleed could be ligated. She eventually achieved complete convalescence and delivered a healthy newborn spontaneously after 40 weeks of gestation. This case report highlights the clinical and diagnostic features of rectus sheath hematoma and shows the anatomical aspects of the rectus sheath, simplifying early and correct diagnosis.
Micic, Dejan; Williams, Eliot C; Medow, Joshua E
Acquired hemophilia A (AHA) is an uncommon coagulation disorder caused by the development of autoantibodies against coagulation factor VIII (FVIII). While intracranial hemorrhage is a known complication of AHA, intracranial hemorrhage as the presenting manifestation of AHA has only been described in three previous case reports. We report a case of an 86-year-old woman with no previously reported history of coagulopathy presenting with an acute intraparenchymal cerebellar hemorrhage and laboratory studies demonstrating an isolated prolonged activated partial thromboplastin time (aPTT). We discuss an approach to the prolonged aPTT, and review the literature concerning the diagnosis and treatment of AHA. Occipital decompressive craniectomy with evacuation of the hemorrhage was performed. Eight hours following the procedure, the patient's status acutely declined with demonstration of a reoccurrence of the cerebellar hemorrhage and new right frontal lobe hemorrhage. After discussion with the patient's family, life-sustaining support measures were withdrawn. Postmortem analysis revealed a low FVIII activity level and the presence of FVIII inhibitor. The presentation of intracranial hemorrhage with an isolated prolonged aPTT is concerning for an acquired hemophilia with FVIII deficiency. Other causes of isolated prolonged aPTT such as a lupus anticoagulant must also be considered. Preoperative identification and work-up of the coagulation abnormality is essential to guide initial treatment.
Akpinar, Aykut; Ucler, Necati; Erdogan, Uzay; Yucetas, Cem Seyho
Patient: Male, 41 Final Diagnosis: Healty Symptoms: Headache Medication: — Clinical Procedure: Chronic subdural hematoma Specialty: Neurosurgery Objective: Diagnostic/therapeutic accidents Background: Chronic subdural hematoma generally occurs in the elderly. After chronic subdural hematoma evacuation surgery, the development of epidural hematoma is a very rare entity. Case Report: We report the case of a 41-year-old man with an epidural hematoma complication after chronic subdural hematoma evacuation. Under general anesthesia, the patient underwent a large craniotomy with closed system drainage performed to treat the chronic subdural hematoma. After chronic subdural hematoma evacuation, there was epidural leakage on the following day. Conclusions: Although trauma is the most common risk factor in young CSDH patients, some other predisposing factors may exist. Intracranial hypotension can cause EDH. Craniotomy and drainage surgery can usually resolve the problem. Because of rapid dynamic intracranial changes, epidural leakages can occur. A large craniotomy flap and silicone drainage in the operation area are key safety points for neurosurgeons and hydration is essential. PMID:26147957
Damiano, Mary Lou; And Others
Care of the school student with hemophilia requires a cooperative effort by the health care team. A multidisciplinary approach is suggested for the team, whose members include a hematologist, orthopedist, oral surgeon, geneticist, physical therapist, social worker, and school nurse. (JD)
Hemophilia A is an X-linked inherited bleeding disorder that affects approximately 1 in 5000 male live births. It is caused by a deficient plasma level of clotting factor VIII and can be treated by the intravenous administration of factor VIII concentrates. A severe complication of the treatment
Willinsky, R.A. (Dept. of Radiology, Toronto Hospital, Western Div., Toronto, ON (Canada) Univ. of Toronto, Brain Vascular Malformation Study Group, ON (Canada)); Fitzgerald, M. (Dept. of Radiology, Toronto Hospital, Western Div., Toronto, ON (Canada)); TerBrugge, K. (Dept. of Radiology, Toronto Hospital, Western Div., Toronto, ON (Canada) Univ. of Toronto, Brain Vascular Malformation Study Group, ON (Canada)); Montanera, W. (Dept. of Radiology, Toronto Hospital, Western Div., Toronto, ON (Canada)); Wallace, M. (Div. of Neurosurgery, Dept. of Surgery, Toronto Hospital, Western Div., ON (Canada) Univ. of Toronto, Brain Vascular Malformation Study Group, ON (Canada))
We reviewed the clinical and radiological features of ten patients with small arteriovenous malformations that caused intracerebral hematomas. In six patients, angiography showed a small nidus (less than 1 cm in diameter) with a shunt at the site of the hematoma, and in four only an early-filling vein was evident. Six patients had only delayed angiography (4 weeks or more after the ictus). In three, angiography within 2 days of the ictus failed to reveal the cause of the bleed, but repeat angiography showed an early-filling vein in two, and a nidus with shunting in one. In only one patient did early angiography reveal the malformation. MRI was obtained in eight patients, and in two prominent vessels were evident in the wall of the hematoma cavity. In investigation of an unexplained intracerebral hematoma, MRI may be useful to exclude a neoplasm or cavernoma, although the latter may be not be evident in the presence of a recent hematoma. We suggest early MRI and angiography for investigation of an unexplained, nonhypertensive intracerebral bleed, with follow-up MRI and dealyed angiography if the initial studies fail to reveal the cause. (orig.)
Lozier, Jay N.; Nichols, Timothy C.
Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study PMID:23956467
Full Text Available Abstract Abdominal wall hematoma is a rare and life-threatening complication after carotid artery stenting (CAS, but it can occur when activated clotting time is prolonged. We report a right lateral abdominal wall hematoma caused by rupture of the superficial circumflex iliac artery after CAS in a 72-year-old man with severe stenosis of the origin of the right internal carotid artery. We performed CAS for the targeted lesion while activated clotting time exceeded 300 seconds. After 2 hours, he complained of right lateral abdominal pain. Abdominal computed tomography revealed an extensive hematoma in the right lateral abdominal wall. Activated clotting time was 180 seconds at this point. Seven hours later, he developed hypotension and hemoglobin level dropped to 11.3 g/dl. Subsequent computed tomography showed enlargement of the hematoma. Emergent selective angiography of the external iliac artery revealed active bleeding from the right superficial circumflex iliac artery. Transcatheter arterial embolization with Gelfoam and microcoils was performed successfully. With more CAS procedures being performed, it is important for endovascular surgeons and radiologists to consider the possibility of abdominal wall hematoma in this situation.
Tokmak, Mehmet; Ozek, Erdinc; Iplikçioğlu, Celal
Chronic intradiploic hematoma was first described by Chorbski and Davis in 1934. To date, only twelve cases have been reported in the literature. Chronic intradiploic hematomas have also been described as non-neoplastic cysts of the diploe, traumatic cysts, and giant cell repetitive granulomas. The term chronic intradiploic hematoma was coined by Sato et al. in 1994. Case 1: a 16-year-old male presented with a non-tender scalp swelling on the right fronto-orbital region. Computed tomography (CT) scans showed an intraosseous isodense lesion with surrounding sclerosis. Magnetic resonance imaging (MRI) results revealed an intradiploic mass with homogeneous cystic and abnormal signal intensities. Case 2: a 64-year-old male presented with a 6-month history of headaches and visual disturbances. CT scans showed an isodense lesion with surrounding sclerosis in the posterolateral left orbit. MRI results revealed a hypointense lesion on both the T1weighted and T2-weighted images of the posterolateral left orbit. Although rarely seen, the presence of a benign chronic hematoma should be considered as part of the differential diagnosis for each intradiploic mass lesion. When taking the medical history, all patients with such mass lesions should be asked about previous minor or major head traumas. Due to the possibility of progressive growth, surgical excision of an intradiploic hematoma is recommended after radiological diagnosis of the condition. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.
El-Asrar, Mohamed Abo; Hamed, Ahmed El-Saeed; Darwish, Yasser Wagih; Ismail, Eman Abdel Rahman; Ismail, Noha Ali
A rapidly growing evidence showed that regulatory T cells (Tregs) play a crucial role in tolerance to coagulation factors and may be involved in the pathogenesis of inhibitor formation in patients with hemophilia. We determined the percentage of Tregs (CD4CD25CD127) in 45 children with hemophilia A compared with 45 healthy controls, and assessed their relation to the clinical characteristics of patients and factor VIII (FVIII) inhibitors. Patients were studied stressing on frequency of bleeding attacks, joint pain, history of viral hepatitis, and the received therapy (FVIII precipitate/cryotherapy). FVIII activity and FVIII inhibitors were assessed with flow cytometric analysis of CD4CD25CD127 Tregs. According to residual FVIII activity levels, 30 patients (66.7%) had mild/moderate hemophilia A, whereas 15 (33.3%) patients had severe hemophilia A. The frequency of Tregs was significantly lower among all patients with hemophilia A compared with controls (2.59 ± 1.1 versus 3.73 ± 1.12%; P = 0.002). Tregs were significantly decreased among patients with FVIII inhibitors compared with the inhibitor-negative group (P hemophilia A had lower Tregs levels than those without (P = 0.34 and P = 0.011, respectively). A significant positive correlation was found between the percentage of Tregs and FVIII among hemophilia A patients. ROC curve analysis revealed that the cut-off value of Tregs at 1.91% could differentiate patients with and without FVIII inhibitors, with a sensitivity of 100% and a specificity of 91.3%. We suggest that alteration in the frequency of Tregs in young patients with hemophilia A may contribute to inhibitor formation and disease severity.
Full Text Available ABSTRACT A 34 year-old woman was admitted to our hospital with left flank pain. A non-contrast enhanced computerized tomography (NCCT revealed a 1.5x2cm left proximal ureter stone. Patient was scheduled for ureterorenoscopy (URS and stone removal. She was submitted to retrograde intrarenal surgery (RIRS. At the postoperative 1st day, the patient began to suffer from left flank pain. A NCCT was taken, which revealed a subcapsular hematoma and perirenal fluid. The patient was managed conservatively with intravenous fluid, antibiotic and non-steroidal anti-inflammatory drug therapy and was discharged at the postoperative 6th day. Two weeks after the discharge the patient was admitted to emergency department with severe left flank pain, palpitation and malaise. KUB (kidney-ureter-bladder radiography showed double-J stent (DJS to be repositioned to the proximal ureter. Patient was evaluated with contrast enhanced CT which revealed an 8cm intraparenchymal hematoma/abscess in the middle part of the kidney. A percutaneous drainage catheter was inserted into the collection. The percutaneous drainage catheter and the DJS were removed at the 10th day of second hospitalization. RIRS surgery is an effective and feasible choice for renal stones with high success and acceptable complication rates. However, clinician should be alert to possible complications.
Yang, Seoung Ho [Donga University College of Medicine, Pusan (Korea, Republic of); Kang, Hung Sik; Chang, Kee Hyun; Lee, Myung Chul; Koo, Kyung Hoi; Seung, Sang Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)
It has been reported that hematoma is one of the most crucial factors in fracture healing since callus formation is disturbed by washing out the hematoma near a fracture site. However, it is not clear why the hematoma is important and how it plays a role during the fracture healing. In order to investigate the role of hematoma in the process of fracture healing, the osteogenic potential by subperiosteal transplantation have been studied. Experimental fractures by operation were made at the mid-shaft of the tibia in New Zealand white rabbits. Removal of hematoma at the fracture site was done after 2 and 3 days from experimental fracture, and the removed hematoma was transplanted into the subperiosteal area at the mid-shaft of the ulna of each rabbit. As control groups, we have performed 3 different procedures 1) the hematoma was transplanted into the muscular layers at the thigh and forearm; 2) autologous blood clots were transplanted into the subperiosteal area of the ulna; and 3) sham operation without a transplantation into the subperiosteal area. After transplantation, serial bone scintigraphy and simple radiography were performed at 4 days, 1 week, and 2 weeks to detect an abnormality. The results of bone scintigraphy were positive in 5 of 6 experimental group. However, all in three control groups were negative. Histological observation of the positive bone revealed new bone formation with trabeculation. These results suggest the hematoma in fracture site has osteogenic potential in the subperiosteal area which can be demonstrable by bone scintigraphy and histologic findings. Therefore, it is considered that hematoma of the fracture site plays an important role in the process of fracture healing. Further biochemical investigation using various experimental models is mandatory to apply this preliminary result to the treatment of clinical delayed union or nonunion.
Shimizu, Satoshi; Fukuda, Atsuhiro; Sato, Masaharu; Kohama, Akitsugu (Kawasaki Medical School, Kurashiki, Okayama (Japan))
The authors report a case of a bilateral chronic subdural hematoma with niveau formation and another rare case of an acute subdural hematoma with niveau formation on plain CT. The different mechanisms of the niveau formation in these cases are speculated about. The first case was a 75-year-old male who showed a drowsy state, urinary incontinence, and muscle weakness of the bilateral lower limbs. No definite history of head trauma could be found. A plain CT scan showed a bilateral-crescent type fluid collection with niveau formation, consisting of a low-density area in the upper part and a high-density area in the lower part. An operation showed bilateral, moderately encapsulated subdural hematomas; they were evacuated. The second case was a 61-year-old male with head trauma due to a fall from a ladder. On admission, neurological examination revealed a decerebrate posture, a deep coma, and anisocoria. A plain CT scan twenty hours after the onset showed a crescent-type fluid collection with niveau formation in the left fronto-parietal region. The operation showed an acute subdural hematoma containing xanthochromic fluid and coagulated blood. No capsule of hematoma could be seen. The incidence of niveau formation in chronic subdural hematomas is not low (5 - 20%); such niveau formation is thought to be caused by rebleeding into the hematoma and the spending of considerable time in the supine position. On the other hand, no case of an acute subdural hematoma with niveau formation has previously been reported. With regard to this mechanism of niveau formation, we speculate that the hematoma is mixed with cerebrospinal fluid from the arachnoidal tear caused by the head trauma; also, a considerable time in the supine position is necessary.
Full Text Available Subdural hematoma is a rare cause of secondary Parkinsonism. In this study, we presented a case of Parkinsonian syndrome caused by a bilateral subdural hematoma. The patient’s Parkinsonism completely healed following successful surgical removal of the hematomas without any anti-parkinson drug.
Enatsu, Rei; Asahi, Minoru; Matsumoto, Masato; Hirai, Osamu
Spontaneous intracerebral hemorrhage represents 20 to 30% of all stroke patients in Japan. However, the treatment strategy of intracerebral hematoma remains controversial. Stereotactic hematoma evacuation is minimally invasive surgery and is beneficial for clot removal with limited tissue damage. The purpose of this study was to investigate the factors affecting motor recovery after stereotactic hematoma evacuation. This retrospective analysis included 30 patients with spontaneous thalamic or putaminal hemorrhage who underwent stereotactic hematoma evacuation. We compared age, presurgical muscle strength, hematoma volume and removal rate between the patients who showed improvement of motor function (improved group) and the patients associated with no motor improvement (unchanged group). Twenty-one patients were classified into the improved group and nine patients into the unchanged group. Statistical analysis revealed that age in the improved group was significantly younger than in the unchanged group (p post-surgical rehabilitation. In addition, this procedure could provide functional improvement in severely disabled patients. Proper patient selection to receive this therapy would be beneficial for further advances of this technique. The present result might be useful in elucidating the mechanism of motor recovery and proper patient selection for this technique.
Tamura, Tatsuya; Sakai, Toshinori; Sairyo, Koichi; Katoh, Shinsuke; Yasui, Natsuo [The University of Tokushima Graduate School, Department of Orthopedics, Institute of Health Biosciences, Tokushima (Japan); Takao, Shoichiro [The University of Tokushima Graduate School, Department of Radiology, Institute of Health Biosciences, Tokushima (Japan); Kagawa, Seiko [The University of Tokushima Graduate School, Department of Human Pathology, Institute of Health Biosciences, Tokushima (Japan)
Hematoma of the cervical ligamentum flavum is very rare, and its pathogenesis is unknown. We describe a case of ligamentum flavum hematoma in the cervical spine causing severe myelopathy. Postoperative histological examination suggested it was the result of the rupture of a hemangioma or of an arteriovenous malformation in the ligamentum flavum. After removal of the lesion, the patient's condition immediately improved. Review of all three reported cases, including this one, showed that complete resection of the mass resulted in immediate relief of symptoms of incomplete paraplegia. The findings of magnetic resonance imaging (MRI) of the hematoma may vary with time, and they may show no characteristic intensity. However, MRI of this case revealed that the tissues surrounding the mass were enhanced with gadolinium diethylene triamine penta-acetic acid, and an area of homogeneous iso-intensity was clearly surrounded by a low-intensity area (flavum) on T2-weighed short-tau inversion recovery images. These findings could be characteristic of the ligamentum flavum hematoma and might help in the differentiation from a cervical epidural hematoma. (orig.)
Carr, Marcus E; Tortella, Bartholomew J
Marcus E Carr,1,2 Bartholomew J Tortella3,4 1Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, 2Worldwide Research and Development, Pfizer, Inc., Cambridge, MA, 3Drexel University College of Medicine, Philadelphia, PA, 4Global Innovative Pharma, Pfizer, Inc., Collegeville, PA, USA Abstract: The evolution of care in hemophilia is a remarkable story. Over the last 60 years, advances in protein purification, protein chemistry, donor screening, viral inactivation, gene s...
Impact of mild to severe hemophilia on engagement in recreational activities by US men, women, and children with hemophilia B: The Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study.
Baumann, Kimberly; Hernandez, Grace; Witkop, Michelle; Peltier, Skye; Dunn, Spencer; Cutter, Susan; Frick, Neil; Haugstad, Kimberly; Guelcher, Christine; Frey, Mary Jane; Rotellini, Dawn; Clark, David B; Iyer, Neeraj N; Cooper, David L
The psychosocial impact of hemophilia on activities was recently investigated in the Hemophilia Experiences, Results and Opportunities (HERO) study (675 people with hemophilia and 561 caregivers of children with hemophilia in 10 countries). The impact of hemophilia B may not be accurately reflected in the HERO results, as ~75% of respondents described issues affecting males with hemophilia A. To address the needs of this population, the Bridging Hemophilia B Experiences, Results and Opportunities Into Solutions (B-HERO-S) was developed as a pilot study in the United States in collaboration with the hemophilia community. The analysis reported here assessed engagement in recreational activities and changes to treatment regimens around activities as reported by 299 adults with hemophilia B and 150 caregivers of children with hemophilia B. Nearly all adults with hemophilia B (98%) experienced a negative impact on their participation in recreational activities due to hemophilia-related issues, and most caregivers (90%) reported that hemophilia B had a negative impact on their child's engagement in recreational activities. One of the main reasons identified for discontinuing past activities was the risk of bruising or bleeding (adults/children with hemophilia B, 49%/41%). In particular, adults with hemophilia B reported a history of activity-related bleeding, and most adults decreased their participation in high-risk activities as they aged. Substantial percentages of adults and children with hemophilia B (including mild/moderate severity) altered their treatment regimens to accommodate planned activities. These findings may help inform guidelines for individualizing treatment regimens around participation in recreational activities based on hemophilia severity, baseline factor level, and activity risk and intensity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Robert D Herbert
Full Text Available Prophylactic injections of factor VIII reduce the incidence of bleeds and slow the development of joint damage in people with hemophilia. The aim of this study was to identify optimal person-specific prophylaxis regimens for children with hemophilia A.Analytic and numerical methods were used to identify prophylaxis regimens which maximize the time for which plasma factor VIII concentrations exceed a threshold, maximize the lowest plasma factor VIII concentrations, and minimize risk of bleeds.It was demonstrated analytically that, for any injection schedule, the regimen that maximizes the lowest factor VIII concentration involves sharing doses between injections so that all of the trough concentrations in a prophylaxis cycle are equal. Numerical methods were used to identify optimal prophylaxis schedules and explore the trade-offs between efficacy and acceptability of different prophylaxis regimens. The prophylaxis regimen which minimizes risk of bleeds depends on the person's pattern of physical activity and may differ greatly from prophylaxis regimens that optimize pharmacokinetic parameters. Prophylaxis regimens which minimize risk of bleeds also differ from prophylaxis regimens that are typically prescribed. Predictions about which regimen is optimal are sensitive to estimates of the effects on risk of bleeds of factor VIII concentration and physical activity.The methods described here can be used to identify optimal, person-specific prophylaxis regimens for children with hemophilia A.
Herbert, Robert D; Broderick, Carolyn R; Barnes, Chris; Billot, Laurent; Zhou, Albert; Latimer, Jane
Prophylactic injections of factor VIII reduce the incidence of bleeds and slow the development of joint damage in people with hemophilia. The aim of this study was to identify optimal person-specific prophylaxis regimens for children with hemophilia A. Analytic and numerical methods were used to identify prophylaxis regimens which maximize the time for which plasma factor VIII concentrations exceed a threshold, maximize the lowest plasma factor VIII concentrations, and minimize risk of bleeds. It was demonstrated analytically that, for any injection schedule, the regimen that maximizes the lowest factor VIII concentration involves sharing doses between injections so that all of the trough concentrations in a prophylaxis cycle are equal. Numerical methods were used to identify optimal prophylaxis schedules and explore the trade-offs between efficacy and acceptability of different prophylaxis regimens. The prophylaxis regimen which minimizes risk of bleeds depends on the person's pattern of physical activity and may differ greatly from prophylaxis regimens that optimize pharmacokinetic parameters. Prophylaxis regimens which minimize risk of bleeds also differ from prophylaxis regimens that are typically prescribed. Predictions about which regimen is optimal are sensitive to estimates of the effects on risk of bleeds of factor VIII concentration and physical activity. The methods described here can be used to identify optimal, person-specific prophylaxis regimens for children with hemophilia A.
Oldenburg, Johannes; Mahlangu, Johnny N; Kim, Benjamin; Schmitt, Christophe; Callaghan, Michael U; Young, Guy; Santagostino, Elena; Kruse-Jarres, Rebecca; Negrier, Claude; Kessler, Craig; Valente, Nancy; Asikanius, Elina; Levy, Gallia G; Windyga, Jerzy; Shima, Midori
Emicizumab (ACE910) bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A. This phase 3, multicenter trial assessed once-weekly subcutaneous emicizumab prophylaxis in persons with hemophilia A with factor VIII inhibitors. We enrolled participants who were 12 years of age or older. Those who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B). The primary end point was the difference in bleeding rates between group A and group B. Participants who had previously received prophylactic treatment with bypassing agents received emicizumab prophylaxis in group C. A total of 109 male participants with hemophilia A with inhibitors were enrolled. The annualized bleeding rate was 2.9 events (95% confidence interval [CI], 1.7 to 5.0) among participants who were randomly assigned to emicizumab prophylaxis (group A, 35 participants) versus 23.3 events (95% CI, 12.3 to 43.9) among those assigned to no prophylaxis (group B, 18 participants), representing a significant difference of 87% in favor of emicizumab prophylaxis (Phemophilia A with inhibitors. (Funded by F. Hoffmann-La Roche and Chugai Pharmaceutical; HAVEN 1 ClinicalTrials.gov number, NCT02622321 .).
Full Text Available Intraventricular septum-hematoma is a rare complication following percutaneous coronary intervention (PCI. This complication may represent a challenge for accurate diagnosis and treatment. This case report is about a 60-year-old male patient being admitted with an acute coronary syndrome. Despite successful PCI with drug eluting stent implantation into the right coronary artery (RCA the patient complained about recurrent angina pectoris according to Canadian Cardiovascular Society (CCS class IV. Cardiac magnetic resonance imaging and transthoracic echocardiography revealed a massive 4.9×9.2 cm sized end-diastolic septum-hematoma, which compromised right ventricular cavity. Emergent recoronary angiography ruled out further contrast extravasation from the RCA. Conservative treatment was intended after discussion in the “heart-team.” The patient completely recovered with nearly complete resolution of the hematoma after 6 months.
Full Text Available Colonic angiodysplasia (AD with bleeding as a comorbidity in the aging population is being increasingly reported. However, to our knowledge, there is no report on colonic AD accompanied by a huge hematoma. Herein, we report a case of colonic AD with a huge submucosal hematoma. A 75-year-old man with sudden melena was referred to our hospital. Helical computed tomographic angiography (CTA revealed bleeding from the sigmoid colon. Additionally, colonoscopy showed a huge submucosal hematoma with bleeding in the sigmoid colon. As endoscopic hemostasis was difficult, sigmoidectomy was performed. The pathological diagnosis was colonic AD. The present case indicates that colonic AD should be considered in the differential diagnosis for melena. In addition, the case shows that helical CTA, which is a noninvasive imaging modality, is useful for the diagnosis of colonic AD and is as effective as colonoscopy and angiography for diagnosis.
Acute extradural (epidural) hematoma (EDH) is a neurosurgical emergency and timely surgical intervention for significant EDH is the accepted standard for treatment. Acute (EDH) occurs in approximately 1-3% of patients with head injuries and in 5 to. 15% of patients with severe head injuries. It is rare before the age of 2 ...
involving left upper and lower limb with exaggerated ipsilateral deep tendon reflexes and extensor plantar. ... as a result of indirect signs of a space-occupying lesion are easily recognizable on CT, bilateral CSDH may ... diagnosis and for the management of such lesions. Key words: Chronic subdural hematoma, extradural.
O'Sullivan, Robert; Baltes, Emily C; Reid, Duncan; Shi, Veronica; Marcus, Peter
Cornual ectopic pregnancies are rarely encountered in clinical practice. A diagnostic and therapeutic challenge, complications include hemorrhage and the presence of persistently elevated serum beta-hCG requiring administration of methotrexate. In this case, we present a patient whose postoperative course was complicated by an infected hematoma that responded to conservative management.
Bartek, J; Sjåvik, K; Ståhl, F
OBJECTIVE: Chronic subdural hematoma (cSDH) is a prevalent condition often seen in the elderly, with surgery being the treatment of choice when symptomatic. So far, few have explored the surgical outcomes in patients 90 years or older. The aim of this study was to investigate outcome after cSDH s...
Annals of Medical and Health Sciences Research | Jul-Sep 2013 | Vol 3 | Issue 3 |. 447. Address for correspondence: ... and D had recurrence of hematoma, the patient treated with improvised plastic material had pressure necrosis of areas of the pinna which ... DOI: 10.4103/2141-9248.117930. Methods and Devices ...
Ivankiv, Taras; Ogurtsov, Oleksii; Pokhylevych, Galina
Isolated retroperitoneal cysts are uncommon with an estimated incidence of 1/5750-1/250,000. In women they occur about 1.5-2 times more often than in men. The largest numbers of patients are young or middle aged (20-50 years). Lack of knowledge about the causes of these rare entities and asymptomatic clinical picture often leads to diagnostic and tactical mistakes. The medical history of 54-year old male patient B., who has been hospitalized at Surgical Department №1 of Danylo Halytsky Lviv National Medical University (Surgical Department of Lviv Regional Clinical Hospital), was processed retrospectively. Diagnosing of retroperitoneal organized hematoma in the early stages is not always possible, because exploration of retroperitoneal space can be difficult. General tests and tumor markers are usually normal range and not prognostically informative in this case. Decisively important were imaging diagnostic methods-USG and CT. As clinical cases of organized hematoma are quite rare, finding out retroperitoneal formation with irregular contours and infiltrative component indicates for retroperitoneal tumors. Thus, this formation accumulated contrast that says for increased vascularization. Intraoperative: formation with thick walls and heterogeneous structure. Histological diagnosis: hematoma in a phase of deep organization. On our opinion, taking into account location and structure of tumors, laparoscopic intervention was not appropriate, open surgery was reasonable approach. Preoperative biopsy has a crucial role to set preliminary diagnosis. Despite the fact that organized retroperitoneal hematomas are quite rare, their diagnosis requires detailed examination and histological verification. Copyright © 2016. Published by Elsevier Ltd.
Spontaneous Retroperitoneal Hematoma: A Rare Devastating. Clinical Entity of a Pleiada of Less Common Origins. Definition of Wunderlich syndrome, also known as spontaneous retroperitoneal hemorrhage. (SRH), was first given in 1700 by ... of SRH as a complication of tumors, however, is low. In renal cell carcinoma, ...
van Vulpen, Lize F D|info:eu-repo/dai/nl/413986330; Saccullo, Giorgia; Iorio, Alfonso; Makris, Michael
INTRODUCTION: Replacement of the missing clotting factor is the mainstay of hemophilia treatment. Whilst historically many hemophilia patients were infected with blood-borne viruses transmitted via plasma-derived products, nowadays the formation of alloantibodies against the missing clotting factor
von der Lippe, Charlotte; Frich, Jan C; Harris, Anna; Solbraekke, Kari Nyheim
In Norway, boys with hemophilia usually begin treatment after their first bleeding episode. Boys with severe hemophilia usually start prophylactic treatment around 18-24 months. Health professionals administer factor concentrate initially, but when boys are around 4 years old most parents start treating their children at home. There is a lack of research on how parents, and especially how carrier mothers, experience the medical treatment for their sons' hemophilia. Our aim was to investigate how carrier mothers experience this treatment in the hospital setting and at home. In this qualitative study, we interviewed 16 mothers of boys or men with hemophilia A or B. Data were collected via semistructured interviews and analyzed using an inductive thematic analytical approach. Mothers experienced both practical and emotional challenges in relation to their sons' treatment, and repeated venipuncture was especially difficult emotionally. Parents preferred home treatment to hospital treatment because it was less time-consuming, less disruptive to family life, and provided a greater sense of control. Encountering healthcare professionals who were unfamiliar with hemophilia was a second major stress factor, especially when parents felt that health professionals lacked competence and were unwilling to seek advice. While home treatment for hemophilia enables freedom, flexibility, and autonomy for the boys as well as for the family, mothers may experience treatment of hemophilia as a burden. Health professionals should provide tailored practical and emotional support to parents by probing into their experiences with treating their sons' hemophilia. © 2016 Wiley Periodicals, Inc.
McLain, Larry G.; Heldrich, Fred T.
Presents a case report of a 15-year-old boy with severe hemophilia who played soccer 1 school year but was denied continued participation following another screening examination. Before deciding about participation, physicians must assess the type and severity of hemophilia and risk factors for injury. Appropriate sports for hemophiliacs are…
Whitney, Christopher K.
The hemophilia community has been deeply affected by the catastrophe of AIDS (Acquired Immune Deficiency Syndrome). The use of blood products that had first restored the potential for normal survival now bring the threat of AIDS infection and fear and discrimination from others. Strong leadership has come from the National Hemophilia Foundation.…
Ohmori, T; Mizukami, H; Ozawa, K; Sakata, Y; Nishimura, S
Hemophilia is considered suitable for gene therapy because it is caused by a single gene abnormality, and therapeutic coagulation factor levels may vary across a broad range. Recent success of hemophilia B gene therapy with an adeno-associated virus (AAV) vector in a clinical trial showed the real prospect that, through gene therapy, a cure for hemophilia may become a reality. However, AAV-mediated gene therapy is not applicable to patients with hemophilia A at present, and neutralizing antibodies against AAV reduce the efficacy of AAV-mediated strategies. Because patients that benefit from AAV treatment (hemophilia B without neutralizing antibodies) are estimated to represent only 15% of total patients with hemophilia, the development of basic technologies for hemophilia A and those that result in higher therapeutic effects are critical. In this review, we present an outline of gene therapy methods for hemophilia, including the transition of technical developments thus far and our novel techniques. © 2015 International Society on Thrombosis and Haemostasis.
Prince, Raja; Bologna, Luca; Manetti, Mirko; Melchiorre, Daniela; Rosa, Irene; Dewarrat, Natacha; Suardi, Silvia; Amini, Poorya; Fernández, José A; Burnier, Laurent; Quarroz, Claudia; Reina Caro, Maria Desiré; Matsumura, Yasuhiro; Kremer Hovinga, Johanna A; Griffin, John H; Simon, Hans-Uwe; Ibba-Manneschi, Lidia; Saller, François; Calzavarini, Sara; Angelillo-Scherrer, Anne
Improved treatments are needed for hemophilia A and B, bleeding disorders affecting 400,000 people worldwide. We investigated whether targeting protein S could promote hemostasis in hemophilia by re-balancing coagulation. Protein S is an anticoagulant acting as cofactor for activated protein C and tissue factor pathway inhibitor (TFPI). This dual role makes PS a key regulator of thrombin generation. Here, we report that targeting protein S rebalances coagulation in hemophilia. Protein S gene targeting in hemophilic mice protected them against bleeding, especially when intra-articular. Mechanistically, these mice displayed increased thrombin generation, resistance to activated protein C and TFPI, and improved fibrin network. Blocking protein S in plasma of hemophilia patients normalized in vitro thrombin generation. Both protein S and TFPIα were detected in hemophilic mice joints. Protein S and TFPI expression was stronger in joints of hemophilia A than hemophilia B patients when receiving on demand therapy, e.g., during a bleeding episode. In contrast, protein S and TFPI expression was decreased in hemophilia A patients receiving prophylaxis with coagulation factor concentrates, and comparable to osteoarthritis patients. These results establish protein S inhibition as both controller of coagulation and potential therapeutic target in hemophilia. The murine protein S silencing RNA approach that we successfully used in hemophilic mice might constitute a new therapeutic concept for hemophilic patients. Copyright © 2018 American Society of Hematology.
Ueda, Hitoshi; Baba, Hiromitsu; Ondo, Kaoru
We report a rare case of chronic expanding hematoma of thorax extended to the neck. An 83-year-old man with a history of Lucite ball plombage and thoracoplasty of bilateral thorax was admitted with numbness of left upper extremity. In 6 months, left supraclavicular fossa was gradually bulged like tumor. The lesion was diagnosed as chronic expanding hematoma. Surgically, Lucite balls were removed with surrounding hematoma debris and fluid, and neck hematoma, which was slightly communicated to the thorax, was extirpated. We discussed the genesis of this hematoma and its extension to the neck.
Full Text Available Subgaleal hematoma is defined as blood collection within the loose areolar tissue of the scalp. The major cause of subgaleal hematoma in children is minor head trauma. It is characterized by diffuse scalp swelling crossing the suture lines which usually results in spontaneous recovery. Underlying coagulopathy should be evaluated in case of subgaleal hematoma after a trivial trauma. Another consideration for physicians, who face with a case of subgaleal hematoma, is complications such as proptosis, keratitis, and even airway compromise as a life-threatening event. Here, we present a case of uneventfully resolved subgaleal hematoma related with hair pulling.
Okamura, Takuma; Komatsu, Michiharu; Ito, Akihiro; Ito, Tetsuya; Suga, Tomoaki; Arakura, Norikazu; Sakai, Hitoshi; Tanaka, Eiji
A 65-year-old male with no personal or familial history of bleeding disorders underwent percutaneous endoscopic gastrostomy (PEG) for neurogenic dysphagia due to subarachnoid hemorrhage. On postoperative day 6, continuous oozing of venous blood was observed at the stoma. Prothrombin time was within normal range, but activated partial thromboplastin time was prolonged. Cross-mixing test results indicated the existence of an inhibitor, and laboratory findings revealed decreased factor VIII activity and high levels of factor VIII inhibitor. The patient was diagnosed as having acquired hemophilia A, for which steroid monotherapy was effective. Acquired hemophilia A is a rare but potentially fatal disease. Clinicians should be aware of this condition in patients presenting with sudden hemorrhage after PEG or other endoscopic treatments, even in those with no apparent history of bleeding.
Wrobel, Marie; Comio, Emilie; Gay, Valerie; Baroudi, Noureddine; Meyer, Pascal; Chuniaud-Louche, Christine; Hacini, Maya; Pica, Gian Matteo
Myelofibrosis and acquired hemophilia A is a rare association. To the best of our knowledge only one case of myelofibrosis and acquired hemophilia A has been previously described. A 66-year-old Caucasian man diagnosed with myelofibrosis evolving in acute myeloid leukemia was referred to us for postoperative bleeding. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer; these findings led to a diagnosis of acquired hemophilia A for which he was treated with methylprednisolone and recombinant activated factor VII on admission. Due to a lack of response he was subsequently treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he received azacytidine to treat the underlying hematological malignancies. Immunosuppressive rituximab therapy resolved acquired hemophilia A with marked efficacy. Rapid and accurate diagnosis, effective hemostatic therapy, and timely treatment for underlying disease are important in the management of acquired hemophilia A secondary to hematological malignancy.
Full Text Available Maria I Cancio,1 Ulrike M Reiss,2 Amit C Nathwani,3 Andrew M Davidoff,4 John T Gray2 1Department of Hematology-Oncology, 2Department of Hematology, St Jude Children’s Research Hospital, Memphis, TN, USA; 3Department of Haematology, University College London Cancer Institute, London, UK; 4Department of Surgery, St Jude Children’s Research Hospital, Memphis, TN, USA Abstract: Hemophilia B is a genetic disorder that is characterized by a deficiency of clotting factor IX (FIX and excessive bleeding. Advanced understanding of the pathophysiology of the disease has led to the development of improved treatment strategies that aim to minimize the acute and long-term complications of the disease. Patients with hemophilia B are ideal candidates for gene therapy, mostly because a small increase in protein production can lead to significantly decreased bleeding diathesis. Although human clotting FIX was cloned and sequenced over 30 years ago, progress toward achieving real success in human clinical trials has been slow, with long-term, therapeutically relevant gene expression only achieved in one trial published in 2011. The history of this extensive research effort has revealed the importance of the interactions between gene therapy vectors and multiple arms of the host immune system at multiple stages of the transduction process. Different viral vector systems each have unique properties that influence their ability to deliver genes to different tissues, and the data generated in several clinical trials testing different vectors for hemophilia have guided our understanding toward development of optimal configurations for treating hemophilia B. The recent clinical success implementing a novel adeno-associated virus vector demonstrated sufficient FIX expression in patients to convert a severe hemophilia phenotype to mild, an achievement which has the potential to profoundly alter the impact of this disease on human society. Continued research should
Rivera Cora, Nalyssa I; Irizarry Delgado, Freddie; Merle Ramírez, Santa M; Vera Quiñones, Jorge
Acquired Hemophilia A (AHA) is a rare hematological disorder that exhibits an incidence of approximately 1.5 cases per million patients a year. It is characterized by the development of autoantibodies against circulating Factor VIII coagulation proteins which, in turn, which in turn lead to potentially life-threatening hemorrhagic episodes. The incidence of AHA increases with age; with 80% of the affected patient population encompassing men and women that are 65 years or older. Some of the challenges that are highlighted in managing this disorder relate to the delayed diagnosis of this condition due to the rarity of the latter, the difficulty in establishing reliable hemostasis, and the secondary complications that are found when using immunosuppressive and hemostatic treatments in tandem with the elderly population afflicted with this disease. A 90-year-old female of Hispanic origin presented with a 2-week history of generalized weakness, dizziness, shortness of breath and extensive purpuric formations that involved the left arm towards the lateral aspect of the thorax with the inclusion of a small right lateral neck hematoma formation. Upon initial laboratory screening, a hemoglobin level of 7.9, a hematocrit level of 21.9 and a PTT value of 70.9 were discovered. Despite conventional hemostatic treatment approaches, the patient did not show marked improvement of the laboratory values. Ongoing specialized laboratory reports, combined with the clinical presentation of the patient, led to the diagnosis of Acquired Hemophilia A. Treatment with recombinant porcine Factor VIII was initiated, which led to rapid improvement of clinical symptoms and laboratory values. The patient was discharged with current treatment plan and emergent follow/up with a hematologist was scheduled. Acquired Hemophilia A is an elusive bleeding disorder that has been seldom encountered in the demographics of Puerto Rico. The prompt detection of this diagnosis based on the clinical
Lozier, Jay N; Kloos, Mark T; Merricks, Elizabeth P; Lemoine, Nathaly; Whitford, Margaret H; Raymer, Robin A; Bellinger, Dwight A; Nichols, Timothy C
Animals with hemophilia are models for gene therapy, factor replacement, and inhibitor development in humans. We have actively sought dogs with severe hemophilia A that have novel factor VIII mutations unlike the previously described factor VIII intron 22 inversion. A male Old English Sheepdog with recurrent soft-tissue hemorrhage and hemarthrosis was diagnosed with severe hemophilia A (factor VIII activity less than 1% of normal). We purified genomic DNA from this dog and ruled out the common intron 22 inversion; we then sequenced all 26 exons. Comparing the results with the normal canine factor VIII sequence revealed a C→T transition in exon 12 of the factor VIII gene that created a premature stop codon at amino acid 577 in the A2 domain of the protein. In addition, 2 previously described polymorphisms that do not cause hemophilia were present at amino acids 909 and 1184. The hemophilia mutation creates a new TaqI site that facilitates rapid genotyping of affected offspring by PCR and restriction endonuclease analyses. This mutation is analogous to the previously described human factor VIII mutation at Arg583, which likewise is a CpG dinucleotide transition causing a premature stop codon in exon 12. Thus far, despite extensive treatment with factor VIII, this dog has not developed neutralizing antibodies (‘inhibitors’) to the protein. This novel mutation in a dog gives rise to severe hemophilia A analogous to a mutation seen in humans. This model will be useful for studies of the treatment of hemophilia. PMID:27780008
Gu, Ruo-lan; Liu, Liang; Xie, Liang-zhi; Gai, Wen-lin; Cao, Si-shuo; Meng, Zhi-yun; Gan, Hui; Wu, Zhuo-na; Li, Jian; Zheng, Ying; Zhu, Xiao-xia; Dou, Gui-fang
Aim: SCT800 is a new third-generation recombinant FVIII agent that is undergoing promising preclinical study. This study aimed to investigate the pharmacokinetic and pharmacodynamic profiles of SCT800 in hemophilia A mice. Methods: After hemophilia A mice were intravenously injected with single dose of SCT800 (80, 180, and 280 IU/kg) or the commercially available product Xyntha (280 IU/kg), pharmacokinetics profiles were evaluated based on measuring plasma FVIII: C. For pharmacodynamics study, dose-response curves of SCT800 and Xyntha (1–200 IU/kg) were constructed using a tail bleeding model monitoring both bleeding time and blood loss. Results: Pharmacokinetics profile analysis showed a dose independency of SCT800 ranging from 80 to 280 IU/kg and comparable pharmacokinetic profiles between SCT800 and Xyntha at the doses tested. Pharmacodynamics study revealed comparable ED50 values of SCT800 and Xyntha in the tail bleeding model: 14.78 and 15.81 IU/kg for bleeding time, respectively; 13.50 and 13.58 IU/kg for blood loss, respectively. Moreover, at the doses tested, the accompanying dose-related safety evaluation in the tail bleeding model showed lower hypercoagulable tendency and wider dosage range potential for SCT800 than Xyntha. Conclusion: In hemophilia A mice, SCT800 shows comparable pharmacokinetics and pharmacodynamics to Xyntha at the doses tested, and possibly with better safety properties. PMID:26806305
George, Lindsey A; Fogarty, Patrick F
After numerous preclinical studies demonstrated consistent success in large and small animal models, gene therapy has finally seen initial signs of clinically meaningful success. In a landmark study, Nathwani and colleagues reported sustained factor (F)IX expression in individuals with severe hemophilia B following adeno-associated virus (AAV)-mediated in vivo FIX gene transfer. As the next possible treatment-changing paradigm in hemophilia care, gene therapy may provide patients with sufficient hemostatic improvement to achieve the World Federation of Hemophilia's aspirational goal of "integration of opportunities in all aspects of life… equivalent to someone without a bleeding disorder." Although promising momentum supports the potential of gene therapy to replace protein-based therapeutics for hemophilia, several obstacles remain. The largest challenges appear to be overcoming the cellular immune responses to the AAV capsid; preexisting AAV neutralizing antibodies, which immediately exclude approximately 50% of the target population; and the ability to scale-up vector manufacturing for widespread applicability. Additional obstacles specific to hemophilia A (HA) include designing a vector cassette to accommodate a larger cDNA; avoiding development of inhibitory antibodies; and, perhaps the greatest difficulty to overcome, ensuring adequate expression efficiency. This review discusses the relevance of gene therapy to the hemophilia disease state, previous research progress, the current landscape of clinical trials, and considerations for promoting the future availability of gene therapy for hemophilia. Copyright © 2016 Elsevier Inc. All rights reserved.
Cuesta-Barriuso, Ruben; Torres-Ortuño, Ana; Pérez-Alenda, Sofía; José Carrasco, Juan; Querol, Felipe; Nieto-Munuera, Joaquín
Sports activities are part of multidisciplinary treatments in people with hemophilia. The objective of this study was to assess the incidence of sports activities in the quality of life as perceived by children with hemophilia. A total of 53 children with hemophilia aged 7 to 13 years and 51 children without hemophilia were evaluated. The perception of quality of life, clinical variables, and the frequency of sports activities were registered. The joint condition of patients with hemophilia was measured with the Spanish version of the Haemophilia Joint Health Score. There were no significant differences in the perception of quality of life between children with hemophilia and children without hemophilia. Sports activities in people with hemophilia promoted a greater health satisfaction. Sports activity in children with hemophilia is associated with an improved quality of life and joint health. It is also associated with improved psychosocial wellness.
Monahan, P. E.
Summary Factor IX deficiency (hemophilia B) is less common than factor VIII deficiency (hemophilia A) and innovations in therapy for hemophilia B have generally lagged behind those for hemophilia A. Recently the first sustained correction of the hemophilia bleeding phenotype by clotting factor gene therapy has been described using recombinant adeno-associated virus (AAV) to deliver factor IX. Despite this success, many individuals with hemophilia B, including children, men with active hepatitis, and individuals who have pre-existing natural immunity to AAV are not eligible for the current iteration of hemophilia B gene therapy. In addition, recent advances in recombinant factor IX protein engineering have led some hemophilia treaters to reconsider the urgency of genetic cure. Current clinical and preclinical approaches to advancing AAV-based and alternative approaches to factor IX gene therapy are considered in the context of current demographics and treatment of the hemophilia B population. PMID:26149016
Solimeno, Luigi Piero; Pasta, Gianluigi
Today, major surgical procedures can be safely performed in hemophilic patients with chronic arthropathy, using available factor concentrates. In this setting, total knee replacement is considered the "gold standard", while the use of total ankle replacement is still debated. Indeed, the unsatisfactory results obtained with the previous available design of implants did not raise enthusiasm as knee or hip replacement. Recently, the introduction of new implant designs and better reported outcomes have renewed the interest in total ankle replacement in people with hemophilia. In this review, the role of replacement surgery in the treatment of chronic hemophilic arthropathy will be described.
Luigi Piero Solimeno
Full Text Available Today, major surgical procedures can be safely performed in hemophilic patients with chronic arthropathy, using available factor concentrates. In this setting, total knee replacement is considered the “gold standard”, while the use of total ankle replacement is still debated. Indeed, the unsatisfactory results obtained with the previous available design of implants did not raise enthusiasm as knee or hip replacement. Recently, the introduction of new implant designs and better reported outcomes have renewed the interest in total ankle replacement in people with hemophilia. In this review, the role of replacement surgery in the treatment of chronic hemophilic arthropathy will be described.
Feldman, Brian M.; Funk, Sharon M.; Bergstrom, Britt-Marie; Zourikian, Nichan; Hilliard, Pamela; van der Net, Janjaap; Engelbert, Raoul; Petrini, Pia; van den Berg, H. Marijke; Manco-Johnson, Marilyn J.; Rivard, Georges E.; Abad, Audrey; Blanchette, Victor S.
Repeated hemarthrosis in hemophilia causes arthropathy with pain and dysfunction. The Hemophilia Joint Health Score (HJHS) was developed to be more sensitive for detecting arthropathy than the World Federation of Hemophilia (WFH) physical examination scale, especially for children and those using
Zdziarska, Joanna; Musiał, Jacek
Acquired hemophilia is a rare bleeding disorder caused by autoantibodies that inhibit coagulation factor VIII. In most cases, it manifests with severe, often life‑threatening bleeds. Acquired hemophilia may be idiopathic or secondary to another condition, most commonly other autoimmune disease or cancer. Treatment is directed to stop bleeding and eradicate inhibitory autoantibodies. Like in most life‑threatening conditions, early diagnosis and treatment are essential for good prognosis. Prompt diagnosis and treatment of acquired hemophilia are constantly improving owing to the increasing availability of laboratory diagnostic tests and growing awareness of physicians of various specialties.
Full Text Available Hemophilia is a genetically mediated disease caused by recessive transmission of the gene. At present etiological orientation in treatment of the given pathology has just begun to develop. Replacement therapy by the concentrate of blood factors is the principal method of treatment. With great success in the sphere of medicine life quality of children suffering from hemophilia has improved significantly. However, the given category of patients refers to the high risk group to render surgical care as before. The example of the surgical intervention is an intertrochanteric osteotomy of the femur in a child with hemophilia
Aledort, Louis; Ljung, Rolf; Mann, Kenneth; Pipe, Steven
Hemophilia A is a congenital, recessive, X-linked bleeding disorder that is managed with infusions of plasma-derived or recombinant factor (F) VIII. The primary considerations in FVIII replacement therapy today are the: 1) immunogenicity of FVIII concentrates, 2) role of longer-acting FVIII products, 3) prophylactic use of FVIII in children and adults with severe hemophilia A, and 4) affordability and availability of FVIII products. Improving patient outcomes by increasing the use of FVIII prophylaxis, preventing or eliminating FVIII inhibitors, and expanding access to FVIII concentrates in developing countries are the major challenges confronting clinicians who care for patients with hemophilia A.
Gaist, David; Rodríguez, Luis Alberto García; Hellfritzsch, Maja
Importance: Incidence of subdural hematoma has been reported to be increasing. To what extent this is related to increasing use of antithrombotic drugs is unknown. Objectives: To estimate the association between use of antithrombotic drugs and subdural hematoma risk and determine trends in subdural...... with antithrombotic drug use, subdural hematoma incidence rate, and annual prevalence of treatment with antithrombotic drugs. Results: Among 10 010 patients with subdural hematoma (mean age, 69.2 years; 3462 women [34.6%]), 47.3% were taking antithrombotic medications. Current use of low-dose aspirin (cases: 26...... hematoma incidence and antithrombotic drug use in the general population. Design, Setting, and Participants: Case-control study of 10 010 patients aged 20 to 89 years with a first-ever subdural hematoma principal discharge diagnosis from 2000 to 2015 matched by age, sex, and calendar year to 400...
Full Text Available To investigate the performance of hematoma shape, hematoma size, Glasgow coma scale (GCS score, and intracerebral hematoma (ICH score in predicting the 30-day mortality for ICH patients. To examine the influence of the estimation error of hematoma size on the prediction of 30-day mortality.This retrospective study, approved by a local institutional review board with written informed consent waived, recruited 106 patients diagnosed as ICH by non-enhanced computed tomography study. The hemorrhagic shape, hematoma size measured by computer-assisted volumetric analysis (CAVA and estimated by ABC/2 formula, ICH score and GCS score was examined. The predicting performance of 30-day mortality of the aforementioned variables was evaluated. Statistical analysis was performed using Kolmogorov-Smirnov tests, paired t test, nonparametric test, linear regression analysis, and binary logistic regression. The receiver operating characteristics curves were plotted and areas under curve (AUC were calculated for 30-day mortality. A P value less than 0.05 was considered as statistically significant.The overall 30-day mortality rate was 15.1% of ICH patients. The hematoma shape, hematoma size, ICH score, and GCS score all significantly predict the 30-day mortality for ICH patients, with an AUC of 0.692 (P = 0.0018, 0.715 (P = 0.0008 (by ABC/2 to 0.738 (P = 0.0002 (by CAVA, 0.877 (P<0.0001 (by ABC/2 to 0.882 (P<0.0001 (by CAVA, and 0.912 (P<0.0001, respectively.Our study shows that hematoma shape, hematoma size, ICH scores and GCS score all significantly predict the 30-day mortality in an increasing order of AUC. The effect of overestimation of hematoma size by ABC/2 formula in predicting the 30-day mortality could be remedied by using ICH score.
Yenisey Quintero Méndez
Full Text Available Las hemorragias del periparto son la principal causa de morbilidad materna extremadamente grave y de muerte materna en Cuba y en el mundo. La hemofilia A adquirida es un trastorno hemorrágico poco frecuente, caracterizado por la presencia de anticuerpos contra el factor VIII (FVIII circulante. Se presenta el caso de una gestante de 36 años de edad, con embarazo a término, que tiene parto eutócico y presenta manifestaciones hemorrágicas en el postparto inmediato, secundarias a hematoma de la rafia que requiere de hemoterapia. Luego presenta hematoma del miembro superior derecho secundario a accidente vascular que requiere de reparo quirúrgico. La evolución tórpida del puerperio, caracterizada por hemorragia mantenida por la rafia y por el brazo intervenido, hace sospechar la presencia de un trastorno hematológico. Se constata una disminución del factor FVIII, que implica el diagnóstico de hemofilia A adquirida, se impone tratamiento con concentrado de factor VIIa recombinante (FVIIar y ciclofosfamida. La evolución posterior fue favorable, la paciente se egresa sin secuelas.Periparturient hemorrhages are the leading cause of extremely serious maternal morbidity and maternal death in Cuba and the world. Acquired Hemophilia A is a rare bleeding disorder characterized by the presence of antibodies against circulating factor VIII (FVIII. We present the case of a 36 years old pregnant woman with term pregnancy and vaginal delivery that suffers from hemorrhagic manifestations in the immediate postpartum secondary to raffia hematoma, requiring blood transfusion. Then she presents a bruise in the right upper limb secondary to stroke that requires surgical repair. The postpartum torpid evolution characterized by sustained bleeding raffia and the surgically treated arm, makes us suspect of the presence of a blood disorder. We observed a decrease in the FVIII factor, which involves the diagnosis of acquired hemophilia and requires treatment with
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.
Full Text Available Marcus E Carr,1,2 Bartholomew J Tortella3,4 1Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, 2Worldwide Research and Development, Pfizer, Inc., Cambridge, MA, 3Drexel University College of Medicine, Philadelphia, PA, 4Global Innovative Pharma, Pfizer, Inc., Collegeville, PA, USA Abstract: The evolution of care in hemophilia is a remarkable story. Over the last 60 years, advances in protein purification, protein chemistry, donor screening, viral inactivation, gene sequencing, gene cloning, and recombinant protein production have dramatically enhanced the treatment and lives of patients with hemophilia. Recent efforts have produced enhanced half-life (EHL clotting factors to better support prophylaxis and decrease the frequency of infusions. Medical needs remain in the areas of alternate modes of administration to decrease the need for venous access, better treatment, and prophylaxis for patients who form antibodies to clotting factors, and ultimately a cure of the underlying genetic defect. In this brief review, the authors summarize data on EHL clotting factors, introduce agents whose mode of action is not clotting factor replacement, and list current gene therapy efforts. Keywords: extended half-life clotting factors, gene therapy, anti-tissue factor pathway inhibitor antibodies, clotting factor analogs, nonfactor replacement therapy
Rubén Sabogal Barrios
Full Text Available Treatment of subdural cronic hematoma in all ages is a therapeutic challenge. Chronic subdural hematoma is a disease that can be fatal without surgical treatment. A variety of treatment options like subdural tapping, endoscopic washout, shunting and craniotomy have been discussed. In chronic subdural hematoma, spontaneous resolution with conservative treatment is not an common therapeutic method because it has causes high mortality, requires long periods of time, and finally, many patients need surgical treatment. The etiology, physiopathology and surgical alternatives in the treatment of subdural chronic hematoma is discussed.
Full Text Available Intramural hematoma of the gastrointestinal tract is an uncommon occurrence, with the majority being localized to the esophagus or duodenum. Hematoma of the gastric wall is very rare, and has been described most commonly in association with coagulopathy, peptic ulcer disease, trauma, and amyloid-associated microaneurysms. A case of massive gastric intramural hematoma, secondary to anticoagulation therapy, and a gastric ulcer that was successfully managed with conservative therapy, is presented. A literature review of previously reported cases of gastric hematoma is also provided.
–30%, moderate if 1–5% and severe if <1% of normal.
The severe presentation represents the majority in 76.7% followed by moderate severity in 17.2%.The commonest IBDs was hemophilia A affecting 44 patients, followed by Hemophilia B affecting 15 patients. The rare types were Factor XI deficiency, Factor V deficiency, Factor VII deficiency and combined FVIII, FIX and FX deficiency. The commonest orthopedic manifestation needing therapy was found among hemophilia A representing 8.3%. Hepatitis C viremia detected by PCR was found in 11.1% of patients. The bleeding complications as hematoma or hemarthrosis were the common complications. Nevertheless, 44.4% of patients had no complications,
From this study we can conclude that the most common IBDs in our locality is hemophilia A followed by hemophilia B. The common presenting symptom was bleeding following male circumcision. Hepatitis C infection and arthropathy represented the main complications. The discovery of IBDs in young age children with proper supportive therapy could prevent arthropathy. Proper screening of blood and blood products reduce the risk of viral hepatitis and HIV acquisition.
Morimoto, Tadatsugu; Yoshihara, Tomohito; Yakushiji, Yusuke; Eriguchi, Makoto; Hara, Hideo; Sonohata, Motoki; Mawatari, Masaaki
Case report. To report an extremely rare case of stroke-mimicking, cervical spontaneous epidural hematoma (SEH) treated with tissue plasminogen activator (tPA) for hemiparesis followed by emergency cervical decompression. Although hemiparesis caused by cervical SEH is a relatively uncommon symptom compared with tetraparesis, such cases were often misdiagnosed as cerebral infarction and worsened by antithrombic therapy. A case report and literature review are presented. A 71-year-old male presented with sudden neck pain followed by left-sided hemiparesis, and was believed to have had a stroke. He was administered tPA as intracranial computed tomography showed no signs of hemorrhage. However, his neurological condition continued to decline, and MRI of the cervical spine revealed a large spontaneous epidural hematoma. He subsequently underwent evacuation of the epidural hematoma and C3-6 laminoplasty, and his clinical status improved after the surgery. To our knowledge, only three cases of cervical SEH with hemiparesis erroneously treated with tPA resulting in neurological decline because of the enlargement of an existing hematoma, including the current case, have been reported in the English literature. It is important for physicians, especially those who administer tPA treatment, to include cervical SEH in the differential diagnosis of stroke in patients presenting with sudden back pain followed by the onset of neurological deficits including hemiparesis. 5.
Juan, Yu-Hsiang; Saboo, Sachin S; Desai, Naman S; Khandelwal, Kanika; Khandelwal, Ashish
We present a case of a 71-year-old woman with an unusual complication of aortic intramural hematoma and hepatic artery pseudoaneurysm following cardiopulmonary resuscitation and thrombolysis done for sudden cardiopulmonary arrest and pulmonary embolism. Patient was on Warfarin treatment for a prior history of pulmonary embolism and experienced recurrent cardiac arrests, which finally resolved after intravenous administration of thrombolytic agents. However, follow-up computed tomographic angiography revealed descending aortic intramural hematoma with intramural blood pool and concomitant liver laceration with hepatic artery pseudoaneurysm. The patient received transcatheter embolization for the hepatic injury with careful follow-up for the aortic injury and was later discharged in a stable condition. Follow-up with subsequent computed tomographic angiography at a regular interval over 1 month shows near complete resolution of the intramural hematoma. The purpose of this report is to describe the rare complication of cardiopulmonary resuscitation and thrombolysis in the form of concomitant injuries of the aorta and liver. Although the use of thrombolytic agents in patients with pulmonary embolism and cardiac arrest is still a matter of debate, this case report supports the concept that thrombolysis has a role in restoring cardiopulmonary circulation, especially in recurrent cardiac arrests resulting from pulmonary embolism. On the other hand, this case also highlights the increased association of the bleeding-related complication as a result of vigorous efforts of cardiopulmonary resuscitation. Aggressive management with interventional radiology for hepatic pseudoaneurysm and conservative management of the aortic intramural hematoma resulted in favorable outcome for our patient.
Kahle, Joerg; Orlowski, Aleksander; Stichel, Diana; Healey, John F; Parker, Ernest T; Jacquemin, Marc; Krause, Manuela; Tiede, Andreas; Schwabe, Dirk; Lollar, Pete; Königs, Christoph
Several studies showed that neutralizing anti-factor VIII (anti-fVIII) antibodies (inhibitors) in patients with acquired hemophilia A (AHA) and congenital hemophilia A (HA) are primarily directed to the A2 and C2 domains. In this study, the frequency and epitope specificity of anti-C1 antibodies were analyzed in acquired and congenital hemophilia inhibitor patients (n = 178). The domain specificity of antibodies was studied by homolog-scanning mutagenesis (HSM) with single human domain human/porcine fVIII proteins and antibody binding to human A2, C1, and C2 domains presented as human serum albumin (HSA) fusion proteins. The analysis with HSA-fVIII domain proteins confirmed the results of the HSM approach but resulted in higher detection levels. The higher detection levels with HSA-fVIII domain proteins are a result of antibody cross-reactivity with human and porcine fVIII leading to false-negative HSM results. Overall, A2-, C1-, and C2-specific antibodies were detected in 23%, 78%, and 68% of patients with AHA (n = 115) and in 52%, 57%, and 81% of HA inhibitor patients (n = 63). Competitive binding of the human monoclonal antibody (mAb) LE2E9 revealed overlapping epitopes with murine C1-specific group A mAbs including 2A9. Mutational analyses identified distinct crucial binding residues for LE2E9 (E2066) and 2A9 (F2068) that are also recognized by anti-C1 antibodies present in patients with hemophilia. A strong contribution of LE2E9- and 2A9-like antibodies was particularly observed in patients with AHA. Overall, our study demonstrates that the C1 domain, in addition to the A2 and C2 domains, contributes significantly to the humoral anti-fVIII immune response in acquired and congenital hemophilia inhibitor patients. © 2017 by The American Society of Hematology.
Luiz Fernando Haikel Jr.
Full Text Available Relatamos caso incomum de um paciente de 37 anos com hematoma extradural traumático do vértex com sintomas de hipertensão intracraniana. O diagnóstico foi feito através da tomografia do crânio em cortes coronais e o paciente foi submetido a craniotomia com drenagem do hematoma.We report the unusual case of a 37 years old man with an epidural traumatic hematoma at the vertex with intracranial hypertension symptoms. The diagnostic was achieved with coronal cranial tomographic scans and a craniotomy was performed for hematoma removal.
Full Text Available Hemorrhage of a previously normal thyroid gland as a result of blunt trauma is a very rare condition. We report a case of blunt trauma that caused acute hemorrhage into the thyroid gland and presented with hoarseness. The diagnosis of thyroid gland hematoma was made with a combination of fiberoptic laryngoscopy, cervical computed tomography, and carotid angiography. The patient was treated conservatively, had a favorable course without further complications, and was discharged four days after admission.[West J Emerg Med. 2009;10(4:247-249.
Jairo Martínez Rozo
Full Text Available Se estudiaron 169 pacientes con diagnóstico de Hematoma Subdural Crónico (H.S.C. admitidos en el Servicio Neurocirugía del Hospital San Juan de Dios desde 1959 a 1980. Los datos clínicos y paraclínicos fueron recopilados en un formato precodificado y luego perforados en tarjetas de computador. Usando el Computador 360/40 disponible en el Centro de Cálculo de la Universidad Nacional y el Computador Intel de el DANE y utilizando el programa SPSS se clasificó, ordenó y depuró.la información. Se analizaron en cuadro y gráficas los resultados que son los siguientes: el 75% de los pacientes hospitalizados por T.C.E. tenían Hematomas Subdurales Crónicos. El mayor número de casos estaba entre 50 y 60 años. La incidencia de H.S.C. era más elevada en el grupo de los hombres. La cefalea ocurrió en el 75% de los casos, el antecedente traumático estaba presente en 83% de casos y la alteración de la conciencia en el 71%. El 90% de los pacientes consultó dentro de los primeros 4 meses. La angiografía continúa siendo el examen de elección con el 100% de positividad. En la T.A.C.la isodensidad en diferentes etapas de evolución del H.S.C. dificulta el diagnóstico. El E.E.G. tiene una positividad del 93% . La frecuencia de H.S.C. bilateral fue de 20%. La anisocoria fue un índice poco confiable para indicar el sitio del Hematoma porque hubo 11 casos de anisocoria por midriasis derecha que tenían el hematoma contralateral. El predominio parietal en la localización del H.S,C. creemos que se deba a su mecanismo de producción. Se analiza la mortalidad que fue en el estudio de 8% , las secuelas aumentaron con la edad de los pacientes. El estudio de seguimiento se hizo en el 40% de los pacientes que sobrevivieron y demostró la baja morbilidad del H.S.C.
William Alves Martins, MD
Full Text Available Subdural hematoma (SH is a neurosurgical emergency, usually caused by head trauma. Non-traumatic causes include aneurysm or arterial–venous malformation rupture, coagulopathy and others. We report the case of a 66 year-old man who developed apparently unprovoked signs of increased intracranial pressure. Brain computed tomography scan showed an acute spontaneous SH, surgically treated. Throughout surgery, a ruptured cortical artery with intensive bleeding appeared and was cauterized. After surgery, patient remained comatose and a new CT demonstrated Duret hemorrhage at the brainstem. Acute spontaneous SH of arterial origin is rare and highly lethal, in which a good prognosis relies on early diagnosis and treatment.
Full Text Available A 60-year-old female who has a history significant for diabetes, depression, and rheumatoid arthritis presented with a progressively enlarging hematoma of the left upper extremity. She was found to have an enlarging hematoma and an isolated elevation of activated partial thromboplastin time (aPTT. Lab work-up revealed low factor VIII activity levels and inhibitor titers at 13.38 Bethesda units (BU. Dilute Russell’s viper venom time (dRVVT revealed a lupus anticoagulant. Hemostasis was achieved with factor VIII inhibitor bypassing activity (FEIBA and inhibitor eradication with-rituxan after the failure of first-line treatment with cyclophosphamide and prednisone.
Li, C; Narkbunnam, N; Samulski, R J; Asokan, A; Hu, G; Jacobson, L J; Manco-Johnson, M J; Monahan, P E
.... We investigated the development of NAbs in early childhood by examining sera gathered prospectively from 62 children with hemophilia A, participating in a multi-institutional hemophilia clinical trial...
Full Text Available Introduction: To date, suction drainage has been routinely used after hip joint replacement. Currently, the validity of this practice is questioned in the literature. Hematoma is a risk factor of periprosthetic infection. Post-operative ultrasonography enables precise assessment of hip joint hematoma. Aim: The aim of the study was to evaluate the usefulness of hip joint ultrasonography with respect to the validity of using suction drainage after primary hip arthroplasty. Material: Inclusion criteria: coxarthrosis. Exclusion criteria: primary and secondary coagulopathy, renal or hepatic failure and history of venous or arterial thrombosis. In total, 90 patients were enrolled. Methods: The study was prospective. The patients were assigned into groups in accordance with simple randomization. On the third day postsurgery, an ultrasound examination was conducted in all patients. Results: Deep infection was found in two patients with suction drainage. Hematoma was almost twice bigger in the drainage group. There were no statistically significant differences in the Harris Hip Score between the groups. No statistically significant differences were found between the groups in: complete blood count parameters and C-reactive protein values in the first and third day after surgery, the amount of transfused packed red blood cells, duration of hospital stay, cost of hospital stay and the relationship between osteophyte removal and hematoma size. Conclusions: Ultrasonography performed after hip replacement surgeries is useful in the assessment of hematoma. The randomized study did not reveal statistically significant differences between the group with and without drainage, thus suggesting that this practice can be abandoned, except for selected cases. Due to a short hospital stay, it is recommended to conduct an ultrasound scan in addition to routine radiography and laboratory tests in order to reduce the risk of complications.
Ankay Yilbas, Aysun; Kanburoglu, Cigdem; Uzumcugil, Filiz; Cifci, Coskun; Saralp, Ozge Ozen; Karagoz, Heves; Akinci, Seda Banu; Arat, Anil
Cervical hematomas can lead to airway compromise, a life threatening condition, regardless of the cause. The following case is the first presentation of cervical hematoma as a complication of endovascular treatment of middle cerebral artery aneurysm. A 49 year-old woman was scheduled for stent placement under general anesthesia for middle cerebral artery aneurysm. Few days before intervention, acetyl salicylic acid and clopidogrel treatment was started. Following standard monitoring and anesthesia induction, the patient's trachea was intubated with a 7.5mm endotracheal tube and the procedure was completed without any complications. Three hours later, dyspnea developed and physical examination revealed progressive swelling and stiffness in the neck. Endotracheal intubation was performed with a 6mm diameter uncuffed tube with the aid of sedation. The vocal cords were completely closed due to compression. There was no leak around the endotracheal tube. The rapidly performed computerized tomography scans showed an enormous hematoma around the neck and extravasation of contrast medium through superior thyroid artery. After coil embolization of superior thyroid artery, she was taken to the intensive care unit as intubated and sedated. Surgical exploration of the hematoma was not recommended by the surgeons, because she was on clopidogrel. After two days, the patient's trachea was extubated safely ensuring that the swelling was sufficiently ceased and leak detected around the endotracheal tube. Securing the airway rapidly by endotracheal intubation is the most crucial point in the management of cervical hematomas. Diagnostic and therapeutic procedures should be performed only afterwards. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.
Kanika Sharma, MBBS
Full Text Available Submucosal esophageal hematoma is an uncommon clinical entity. It can occur spontaneously or secondary to trauma, toxins, medical intervention, and in this case, coagulopathy. Management of SEH is supportive and aimed at its underlying cause. This article reports an 81-year-old male patient with chronic idiopathic thrombocytopenic purpura and hypertension that develops a submucosal esophageal hematoma.
Satyarthee Guru Dutta
Full Text Available Extradural hematoma with air bubbles has been described in literature. However the significance of it needs special attention with respect to prognosis. We report five case of extradural hematoma with air bubble and its management along with pertinent literature is reviewed briefly.
Syuto, Takahiro; Hatori, Motoaki; Masashi, Nomura; Sekine, Yoshitaka; Suzuki, Kazuhiro
Chronic expanding hematoma is a rare condition that develops after surgery, trauma, or injury. It can also develop at any location in the body in the absence of trauma. Clinical findings and various diagnostic imaging modalities can aid in the differential diagnosis of this condition. In general, hematomas are naturally reabsorbed and rarely cause serious problems. However, hematomas that develop slowly without a history of trauma, surgery, or bleeding disorders could be difficult to differentiate from soft tissue neoplasms. In the present case, we describe a patient, without any history or physical evidence of trauma, who exhibited a large chronic expanding hematoma in the retroperitoneal space that resulted in hydronephrosis because of the pressure exerted on the left ureter. A 69-year-old man presented to our hospital with a swollen lesion in the left flank. A mass, 19 cm in diameter, was detected in the retroperitoneal space by computed tomography. We suspected the presence of a chronic expanding hematoma, soft tissue tumor, or left renal artery aneurysm. Surgical treatment was performed. However, postoperative histopathological examination indicated that the mass was a nonmalignant chronic expanding hematoma. No recurrence was observed during a 2-year follow-up period. In patients without a history of trauma who present slowly growing masses, the differential diagnosis should include chronic expanding hematoma in addition to cysts and soft tissue tumors. Moreover, the use of magnetic resonance imaging and computed tomography is essential to differentiate between chronic expanding hematoma and soft tissue tumors.
Armstrong, Edward P; Malone, Daniel C; Krishnan, Sangeeta; Wessler, Maj Jacob
To evaluate the health system costs among patients with hemophilia A and B with and without inhibitors over 5 years. This was a retrospective, observational study utilizing medical and pharmacy electronic medical records and administrative encounters/claims data tracking US patients between 2006-2011. Patients with diagnosis codes for hemophilia A and B were identified. Patients with inhibitors were characterized by utilization of bypassing agents activated prothrombin complex concentrate or factor VIIa on two or more distinct dates. Severity was classified as mild, moderate, or severe based on laboratory tests of clotting factor. There were 160 hemophilia A patients and 54 hemophilia B patients identified. From this group, seven were designated as patients with inhibitors (five with hemophilia A and two with hemophilia B). Hemophilia A patients without inhibitors reported 65 (41.9%) as being severe, 19 (12.3%) as moderate, and 71 (45.8%) as mild. Hemophilia B patients without inhibitors reported nine (17.3%) had severe, 13 (25.0%) had moderate, and 30 (57.7%) had mild hemophilia. All patients with inhibitors had been hospitalized in the previous 5 years compared to 64 (41.3%) with hemophilia A without inhibitors and 22 (42.3%) with hemophilia B without inhibitors. The median aggregate cost per year (including factor and health resource use) was $325,780 for patients with inhibitors compared to $98,334 for hemophilia A patients without inhibitors and $23,265 for hemophilia B patients without inhibitors. The results suggest that, while the frequency of inhibitors within the hemophilia cohort was low, there was a higher frequency of hospitalizations, and the associated median aggregate costs per year were 3-fold higher than those patients without inhibitors. In contrast, hemophilia B patients experience less severe disease and account for lower aggregate yearly costs compared to either patients with hemophilia A or patients with inhibitors.
Full Text Available Purpose. Research objective — studying of consequences of the operated traumatic intracranial hematomas in the remote period. Material. The nearest and remote results of the operated traumatic intracranial hematomas at 105 patients in terms from 6 months till 3 years are analyzed. During research the anamnesis was studied, neurologic investigation, and also research cognitive functions by means of scale MMSE, the test of drawing of hours, a scale of studying of alarm/depression HADS, learning of 5 words, scale quality of life SF-36. Results. It is established, that in the remote period the condition of the majority of patients gradually improves, at the same time, frequent enough and expressed consequences which are necessary for analyzing with the purpose of optimization of outcomes and the forecast at the given disease are observed. The special attention should be given again developing complications to which it is possible to carry epileptic seizures and behavioral-memorable infringements. Conclusion. Studying of the remote consequences of this heavy kind of craniocereberal trauma allows to optimize results of treatment and to provide complex medical, labor, social and family adaptation
Full Text Available Maissaa Janbain,1 Cindy A Leissinger,1 Rebecca Kruse-Jarres2 1Louisiana Center for Bleeding and Clotting Disorders, Tulane University Medical Center, New Orleans, LA, USA; 2Washington Center for Bleeding Disorders, Blood Works NW, Seattle, WA, USA Abstract: Acquired hemophilia A is a rare autoimmune disorder caused by an autoantibody (inhibitor to factor VIII (FVIII that interferes with its coagulant function and predisposes to severe, potentially life-threatening hemorrhage. Disease management focuses on controlling bleeding, primarily with the use of bypassing therapy and recombinant porcine FVIII, and permanently eradicating the autoantibody using various immunosuppressants. Treatment challenges include delayed diagnosis, difficulty achieving hemostasis and durable remissions, and complications associated with the use of hemostatic and immunosuppressive therapy in a primarily older patient population. Keywords: autoantibodies, factor VIII, hemostasis, inhibitors, inhibitor eradication
Full Text Available We present a case of a 59-year-old man who was found to have clusters of hyperchromatic, small, round nucleated cells within a subdural hematoma removed after a skull fracture. Immunohistochemistry study confirmed that the cells were hematopoietic components predominantly composed of normoblasts. In this paper, we describe the clinical and pathological findings. A brief review of published information on extramedullary hematopoiesis in subdural hematoma and the mechanisms of pathogenesis are also discussed. While extramedullary hematopoiesis is seen anecdotally by neuropathologists in chronic subdural hematomas, only a few cases are documented in the literature. Furthermore, extramedullary hematopoiesis in subdural hematoma can pose a diagnostic challenge for general pathologists who encounter subdural hematoma evacuations seldom in their surgical pathology practices.
Full Text Available We describe an interesting case of intramural duodenal hematoma in an otherwise healthy male who presented to emergency room with gradually progressive abdominal pain, nausea, and vomiting. This condition was missed on initial evaluation and patient was discharged from emergency room with diagnosis of acute gastritis. After 3 days, patient came back to emergency room and abdominal imaging studies were conducted which showed that patient had intramural duodenal hematoma associated with gastric outlet obstruction and pancreatitis. Hematoma was the cause of acute pancreatitis as pancreatic enzymes levels were normal at the time of first presentation, but later as the hematoma grew in size, it caused compression of pancreas and subsequent elevation of pancreatic enzymes. We experienced a case of pancreatitis which was caused by intramural duodenal hematoma. This case was missed on initial evaluation. We suggest that physicians should be more vigilant about this condition.
Nitta, Naoki; Jito, Junya; Nozaki, Kazuhiko
"Headbanging" is the slang term used to denote violent shaking of one's head in time with the music. This abrupt flexion-extension movement of the head to rock music extremely rarely causes a subdural hematoma. A 24-year-old female was admitted to our department because of right sided partial seizure and acute or subacute subdural hematoma over the left cerebral convexity. She had no history of recent head trauma but performed headbanging at a punk rock concert at 3 days before admission. Since, she had a previous acute subdural hematoma on the same side after an accidental fall from a baby buggy when she was 11 months old, the present was recurrent subdural hematoma probably due to headbanging. Headbanging has the hazardous potential to cause a subdural hematoma.
Anegawa, S; Hayashi, T; Furukawa, Y; Nagashima, T; Kumate, M
Acute epidural hematoma not associated with head injury is rarely encountered and is known as spontaneous epidural hematoma. To our knowledge, only five cases with epidural hematoma after open-heart surgery have been published. Pathogenesis and preventive measures have not yet been determined. We report a case of such spontaneous epidural hematoma and consider the possible pathogenesis. A 12-year-old female received a radical operation for severe subaortic stenosis. The intraoperative course was uneventful except for massive hemorrhage which was adequately controlled. Postoperatively, she was moved to the CCU still not having aroused from anesthesia. Eleven hours later, it was found that her pupils were fixed and dilated. CT scan demonstrated a huge bifrontal epidural hematoma with disappearance of the basal cistern. Even though immediate emergency evacuation was performed, the patient died of acute brain swelling four days after the operation.
... Treatment of Hemophilia AGENCY: National Institutes of Health, HHS. ACTION: Notice. SUMMARY: This is notice..., ``Oral Treatment of Hemophilia'' and ``Induction of Tolerance by Oral administration of Factor VIII and Treatment of Hemophilia''. The patent rights in these inventions have been assigned to or exclusively...
Loomans, Janneke I.; Eckhardt, Corien L.; Reitter-Pfoertner, Sylvia E.; Holmstrom, Mats; Van Gorkom, B. Laros; Leebeek, F. W. G.; Santoro, C.; Haya, Saturnino; Meijer, K.; Nijziel, M. R.; Van Der Bom, J. G.; Fijnvandraat, K.
Background: Non-severe hemophilia (factor VIII concentration [FVIII: C] of 2-40 IU dL(-1)) is characterized by a milder bleeding phenotype than severe hemophilia A. However, some patients with non-severe hemophilia A suffer from severe bleeding complications that may result in death. Data on
Loomans, J. I.; Eckhardt, C. L.; Reitter-Pfoertner, S. E.; Holmström, M.; van Gorkom, B. Laros; Leebeek, F. W. G.; Santoro, C.; Haya, S.; Meijer, K.; Nijziel, M. R.; van der Bom, J. G.; Fijnvandraat, K.
Background: Non-severe hemophilia (factor VIII concentration [FVIII: C] of 2-40 IU dL(-1)) is characterized by a milder bleeding phenotype than severe hemophilia A. However, some patients with non-severe hemophilia A suffer from severe bleeding complications that may result in death. Data on
Nussberger, Fabio; Roth, Beat; Metzger, Tobias; Kiss, Bernhard; Thalmann, George N; Seiler, Roland
The purpose of this study was to evaluate risk factors for renal hematoma after extracorporeal shock wave lithotripsy (SWL) for kidney stones in a matched case-control analysis of a subgroup of patients recruited from a prospective randomized cohort. Between 06/2010 and 03/2013, 418 patients underwent SWL with the MODULITH®-SLX-F2-lithotripter for kidney stones. In 39/418 patients (9 %), ultrasound at post-treatment day 1 revealed renal hematomas. For 37 of these patients, a matched group without hematoma could be selected according to the following matching criteria: age, gender, number and energy of shock waves, stone burden and localization. Risk factors for renal hematoma after SWL were compared between the two groups. The rates of diabetes, stopped anticoagulant/antiplatelet medications and arterial hypertension were not different between the two groups (p > 0.2). The skin-kidney distance was virtually the same in both groups (p = 0.5). In the hematoma group, significantly more patients had a high (>30: n = 16) as well as a low (30) or low (<21.5) BMI had a higher risk for renal damage after SWL. Therefore, alternative endoscopic treatment options should be considered in these patients.
He, Jin Peng; Feng, Jie Xiong
The main complication of patients with severe hemophilia is recurrent bleeding events that usually affected musculoskeletal contractures. And replacement therapy methods were continuously improved to minimize adverse impacts brought by those complications. However, only several cases reported about the appendectomy for hemophilia A. We report a case of acute appendicitis treated by two-incision laparoscopy in a boy with hemophilia A and coagulation factor VII deficiency for the first time. An 8y7m-old Chinese boy presented with half a day of right sided abdominal pain, fever, nausea, and vomiting. He received a computed tomography (CT) scan which revealed an enlarged appendix, thickened wall and appendiceal fecalith, and had received a conservative anti-bacterial treatment for his acute appendicitis but failed. He was diagnosed with hemophilia A and coagulation factor VII deficiency. Two-incision laparoscopic appendectomy was made in success with a careful management of perioperative period. We monitored the clotting factor FVIII level and gave him a replacement therapy. The patient had an uneventful recovery. It is important to exclude intraabdominal or retroperitoneal hemorrhage in patients suffering from hemophilia and acute abdominal pain. Pre-operative evaluation of validity of the FVIII replacement therapy is another effective strategy to assess the safety and feasibility of applying an operation procedure. The two-incision laparoscopic appendectomy is an effective treatment for this kind of patients for its minimal trauma and fast recovery characteristics. Our report shows that laparoscopic appendectomy is feasible in a child suffering from hemophilia after adequate blood clotting factor replacement treatment.
Full Text Available Sciatica is defined as pain in the sciatic nerve distribution. The most common reason of sciatica is radiculopathy due to lumbar disc hernia. Other causes can be congenital, acquired, infectious, neoplastic, or inflammatory. The piriformis syndrome is another cause. The pain starts in an insidious manner when the cause of sciatica is an extraspinal tumor. It is intermittent at first but a constant and progressive pain that does not decrease with position or rest gradually develops in all patients. The possibility of an intraabdominal or pelvic mass should always be considered and the relevant tests requested when the cause of the sciatica cannot be explained. We present an 83-year-old male who presented with non-traumatic and non-vascular lumbosacral plexopathy due to a large hematoma in the left adductor muscle following the use of warfarin sodium.
Hayashi, Tomoe; Morishita, Eriko; Asakura, Hidesaku; Nakao, Shinji
Acquired hemophilia A is a rare bleeding diathesis caused by autoantibodies against clotting factor VIII. The incidence of acquired hemophilia A increases with age. We report two cases of acquired hemophilia A in elderly patients and their clinical characteristics. Case 1: A 66-year-old man was referred to our hospital with massive subcutaneous and intramuscular hemorrhage. Prolonged APTT, low factor VIII activity and factor VIII inhibitor with high titer (42 BU/ml ) were observed, confirming the diagnosis of acquired hemophilia A. His hemorrhages disappeared soon after 50 mg/day oral prednisolone was administered. Although early steroid withdrawal lead to repeated prolongation of APTT, the addition of 20 mg/day oral prednisolone successfully decreased the inhibitor titer. The underlying disease was not identified. Case 2: An 85-year-old man with advanced gastric cancer was referred to our division because of severe bleeding. His factor VIII inhibitor titer was 64 BU/ml . Activated prothrombin complex concentrates were used to control the bleeding. Initially, he did not seem to respond to 20 mg/day oral prednisolone, but a further 12 weeks of 20 mg/day prednisolone finally achieved normalization of his hemostatic parameters. Subsequently, he successfully underwent surgery for cancer. The responses to immunosuppressive therapy were very different in the two cases, probably because of the difference in the underlying diseases. The immunosuppressive therapy of acquired hemophilia A should be strictly tailored to the patient's characteristics to minimize treatment-related adverse effects.
Franchini, Massimo; Mannucci, Pier Mannuccio
Over the past forty years the availability of coagulation factor replacement therapy has greatly contributed to the improved care of people with hemophilia. Following the blood-borne viral infections in the late 1970s and early 1980, caused by coagulation factor concentrates manufactured using non-virally inactivated pooled plasma, the need for safer treatment became crucial to the hemophilia community. The introduction of virus inactivated plasma-derived coagulation factors and then of recombinant products has revolutionized the care of these people. These therapeutic weapons have improved their quality of life and that of their families and permitted home treatment, i.e., factor replacement therapy at regular intervals in order to prevent both bleeding and the resultant joint damage (i.e. primary prophylaxis). Accordingly, a near normal lifestyle and life-expectancy have been achieved. The main current problem in hemophilia is the onset of alloantibodies inactivating the infused coagulation factor, even though immune tolerance regimens based on long-term daily injections of large dosages of coagulation factors are able to eradicate inhibitors in approximately two-thirds of affected patients. In addition availability of products that bypass the intrinsic coagulation defects have dramatically improved the management of this complication. The major challenges of current treatment regimens, such the short half life of hemophilia therapeutics with need for frequent intravenous injections, encourage the current efforts to produce coagulation factors with more prolonged bioavailability. Finally, intensive research is devoted to gene transfer therapy, the only way to ultimately obtain cure in hemophilia.
Tseng, Guo-Shiang; Liau, Guo-Shiou; Shyu, Hann-Yeh; Chu, Shi-Jye; Ko, Fu-Chang; Wu, Kuo-An
Rectus sheath hematoma is an uncommon but well-described complication of a tussive paroxysm. It is an accumulation of blood within the sheath of the rectus abdominis secondary to disruption of the epigastric vessels or the rectus muscle and is often misdiagnosed as acute abdomen. Increases in the number of elderly patients and the use of therapeutic anticoagulation may increase the prevalence and severity of rectus sheath hematomas encountered in clinical practice. Expanding rectus sheath hematomas are occasionally refractory to conservative treatment and may require hemostatic intervention. Here, we describe the case of an 87-year-old woman who presented with two separate rectus sheath hematomas that were precipitated by a paroxysm of coughing. Repeated computed tomography showed two separate expanding rectus sheath hematomas, which were not accompanied by obvious contrast extravasation on angiography. Empiric left inferior epigastric artery embolization resulted in rapid hemodynamic stabilization, and the hematomas shrank gradually. Early empiric transcatheter arterial embolization may be appropriate for patients who are poor surgical candidates and have enlarging hematomas that are refractory to conservative treatment.
Full Text Available Abstract Introduction Hypereosinophilic syndrome is defined as a prolonged state (more than six months of eosinophilia (greater than 1500 cells/μL, without an apparent etiology and with end-organ damage. Hypereosinophilic syndrome can cause coagulation abnormalities. Among hypereosinophilic syndrome types, the lymphocytic variant (lymphocytic hypereosinophilic syndrome is derived from a monoclonal proliferation of T lymphocytes. Here, we describe the case of a patient with lymphocytic hypereosinophilic syndrome who presented with a coagulation abnormality. To the best of our knowledge, this is the first such report including a detailed clinical picture and temporal cytokine profile. Case presentation A 77-year-old Japanese man presented to our facility with massive hematuria and hypereosinophilia (greater than 2600 cells/μl. His eosinophilia first appeared five years earlier when he developed femoral artery occlusion. He manifested with multiple hematomas and prolonged activated partial thromboplastin time. His IgG4 level was remarkably elevated (greater than 2000 mg/dL. Polymerase chain reaction tests of peripheral blood and bone marrow identified lymphocytic hypereosinophilic syndrome. His prolonged activated partial thromboplastin time was found to be due to acquired hemophilia. Glucocorticoids suppressed both the hypereosinophilia and coagulation abnormality. However, tapering of glucocorticoids led to a relapse of the coagulation abnormality alone, without eosinophilia. Tumor necrosis factor α, interleukin-5, and/or eotaxin-3 may have caused the hypereosinophilia, and interleukin-10 was correlated with the coagulation abnormality. Conclusions To the best of our knowledge, this is the first case in which lymphocytic hypereosinophilic syndrome and IgG4-related disease have overlapped. In addition, our patient is only the second case of hypereosinophilic disease that manifested with acquired hemophilia. Our patient relapsed with the
Full Text Available Spontaneous rectus sheath hematoma (SRSH is an uncommon medical emergency in the elderly. We present a case of SRSH with an atypical clinical presentation and discuss literature regarding diagnosis and proper management. A 75-year-old female patient was transferred to the emergency department due to acute dyspnoea and confusion. Her medical history revealed a viral infection of the upper respiratory tract, and no coughing or use of anticoagulants. The clinical examination showed tenderness of the left lower abdomen, although palpation was misleading due to patient’s obesity. Laboratory investigations showed light anaemia. Ultrasonography and computed tomography revealed a large rectus sheath hematoma of the left abdominal wall. Despite further deterioration of the patient, conservative management including bed rest, fluid replacement, blood products transfusion, and proper analgesia was successful. No surgical intervention was needed. Prompt diagnosis and management of SRSH plays significant role in the prognosis, especially in elder patients. Independently of size and severity, conservative management remains the first therapeutic choice. Only by failure of supportive management, progressive and large hematoma or uncontrollable hemodynamic patients, interventional management including surgery or less invasive newer techniques is indicated.
Lee, Yeon Soo; Park, Kuhn; Kim, Jong Ok; Choi, Eun Seok; Kang, Si Won [Daejeon St. Mary' s Hospital, The Catholic University of Korea, Daejeon (Korea, Republic of)
Hematoma on the thoracic wall is very rare. We describe here a 63-year-old man with a huge chest wall hematoma and the man had no history of trauma. The patient was found to have a large mass located subjacent to the inferior angle of the right scapula area and the CT and MRI findings were similar to those of an elastofibroma dorsi. We describe the CT and MRI findings of this hematoma and how to make the differential diagnosis from elastofibroma dorsi
Esophagic Intramural Hematoma is an uncommon clinical condition, with a prognosis which is essentially benign. On most cases, a predisposing or precipitating factor may be seen, with the most common ones being the history of esophagic instrumentation, food impactations and thrombocytopenia. In the following manuscript, the authors present the case of a 54-years-old male with history of valve replacement surgery, who was treated at the Clinica Cardiovascular (Medellin, Colombia), with a clinical case of Intramural Esophagic Hematoma that was later confirmed to be due to a Coumarinic overanticoagulation. On this case, it is evidenced that Intramural Esophagic Hematoma is an unrecognized complication of Courmarinic anticoagulation therapy. PMID:20069068
Pathak, Ranjan; Supplee, Suzanne; Aryal, Madan Raj; Karmacharya, Paras
Sublingual hematoma is a rare but life-threatening complication of oral anticoagulants. It is important to differentiate this from infectious processes like Ludwig's angina. Securing the airway should be a priority and immediate reversal of anticoagulation with close monitoring is required. We present a case of sublingual hematoma secondary to warfarin therapy without airway compromise which was managed conservatively with reversal of INR with oral vitamin K. Although rare, it is crucial to differentiate sublingual hematomas from infectious processes. Reversal of anticoagulation with low threshold for artificial airway placement in the event of airway compromise is the treatment of choice. Copyright © 2015 Elsevier Inc. All rights reserved.
Fernanda Cristina Cunha
Full Text Available ABSTRACTIn Latin America, Bothrops envenomation is responsible for the majority of accidents caused by venomous snakes. Patients usually present local edema, bleeding and coagulopathy. Visceral hemorrhage is extremely rare and considered a challenge for diagnosis and management. We report the first case of hepatic hematoma owing to the bothropic envenomation in a 66-year-old man who was bitten in the left leg. He presented local edema, coagulopathy, and acute kidney injury. Radiological findings suggested hepatic hematoma, with a volume of almost 3 liters. The hepatic hematoma was gradually absorbed without the need for surgical intervention with complete resolution in 8 months.
Lin, Shu-Wha; Lin, Shu-Rung; Shen, Ming-Ching (National Taiwan Univ., Taipei (Taiwan, Province of China))
The molecular characterization of hemophilia A of Chinese origin was carried out by the polymerase chain reaction (PCR) and direct sequencing of patient's factor VIII genes. Single-strand conformation polymorphism (SSCP) and dideoxy fingerprinting (ddF) were used as screening methods to detect mutated DNAs. A total of 102 individuals from 87 different families, including 10 patients (10 families) with mild-to-moderate and 92 patients (77 families) with severe hemophilia A, were analyzed by PCR-SSCP and PCR-ddF. Of the 87 independent cases, 40 revealed a single mutation in the coding regions of their factor VIII genes. These mutations include 21 with single base changes resulting in 8 nonsense and 13 missense codons, 16 with deletion or insertion of 1-11 nucleotides, and 3 with deletion of large DNA fragments. The frequency of 8 of the identified factor VIII polymorphisms or silent mutations was also determined among Chinese. The frequencies for codons 1241, 1269, and 2223 (the numbering system follows J. Gitschier et al., 1984, Nature 312: 326-330) were found to be different from those reported for other populations. As for the 47 severe cases whose mutational events were not readily detected by PCR-SSCP and PCR-ddF, the reverse transcriptase PCR method was applied. In 24 such cases analyzed, 17 were found to be of the [open quotes]intron 22 mutations[close quotes] as described by Naylor et al. (1992, The Lancet, 342: 1066-1067), accounting for 39% of Chinese patients with hemophilia A. 31 refs., 2 figs., 6 tabs.
Full Text Available It comes to consulting the Faculty of Dentistry at the University of Nuevo León pediatric male patient of 9 years 10 months, who was admitted with a presumptive diagnosis of hemophilia due to a subsequent persistent bleeding to treatment with steel crowns made in an earlier appointment. Interconsultation is performed with the hematologist who by laboratory examinations notice decreased coagulation factor VIII confirming the diagnosis of hemophilia A. It plans and conducts comprehensive treatment dental team with the hematologist who said that patients in hospitals with the replacement of missing clotting factor is prepared by cryo precipitates or with concentrated factor VIII intravenously before and after his dental intervention. The aim of the article is to highlight that hemophilia can be a disease detected during dental surgery in some patients and for it to be successfully treated with multidisciplinary management protocol is required between hematologists and dentists.
Serious issues in current hemostatic treatment of hemophilia A are the requirement for frequent intravenous administrations of factor (F) VIII, FVIII inhibitor development, and hemostatic treatment for patients with this inhibitor. For the purpose of overcoming these challenges, the FVIIIa-substituting bispecific antibody against FIXa/FX (ACE910, INN emicizumab) was produced. Emicizumab demonstrated marked hemostatic effects on both ongoing and spontaneous joint bleeding in the acquired hemophilia A primate model. The clinical phase 1 study designed to assess the pharmacokinetics, pharmacodynamics and safety of emicizumab has been initiated. Severe emicizumab-related adverse events were minimal. The t1/2 was approximately 30 days, and bleeding events were significantly decreased by weekly subcutaneous administration in severe hemophilia A patients, independently of the presence of the inhibitor. Currently, the phase 1/2 extension study is ongoing. We anticipate that emicizumab will show the benefits of prophylactic efficacy with subcutaneous administration at a much lower frequency.
Zhou, Zheng-Yi; Koerper, Marion A; Johnson, Kathleen A; Riske, Brenda; Baker, Judith R; Ullman, Megan; Curtis, Randall G; Poon, Jiat-Ling; Lou, Mimi; Nichol, Michael B
To examine the direct and indirect costs of hemophilia care among persons with hemophilia A in the US. Observational data were obtained from HUGS-Va, a multi-center study from six federally supported hemophilia treatment centers (HTCs). Eligible individuals completed a standardized initial questionnaire and were followed regularly for 2 years to obtain information on work or school absenteeism, time spent arranging hemophilia care, and unpaid hemophilia-related support from caregivers. Data from 1-year healthcare utilization records and 2-year clotting factor dispensing records measured direct medical costs. Indirect costs were imputed using the human capital approach, which uses wages as a proxy measure of work time output. A total of 222 patients with complete data were included in the analysis. Two-thirds had severe hemophilia and the mean age was 21.1 years. The use of prophylaxis in severe hemophilia patients is associated with statistically significant reduction in the numbers of emergency department (ED) visits and bleeding episodes compared with those who were treated episodically. From the societal perspective, mild hemophilia costs $59,101 (median: $7519) annually per person, $84,363 (median: $61,837) for moderate hemophilia, $201,471 (median: $143,431) for severe hemophilia using episodic treatment, and $301,392 (median: $286,198) for severe hemophilia receiving prophylaxis. Clotting factor contributed from 54% of total costs in mild hemophilia to a maximum of 94% for patients with severe hemophilia receiving prophylaxis. Hemophilia is a costly disorder not only because of its high medical expenses, but also due to the high indirect costs incurred.
Eckhardt, C L; Loomans, J I; van Velzen, A S; Peters, M; Mauser-Bunschoten, E P; Schwaab, R; Mazzucconi, M G; Tagliaferri, A; Siegmund, B; Reitter-Pfoertner, S E; van der Bom, J G; Fijnvandraat, K
The life expectancy of non-severe hemophilia A (HA) patients equals the life expectancy of the non-hemophilic population. However, data on the effect of inhibitor development on mortality and on hemophilia-related causes of death are scarce. The development of neutralizing factor VIII antibodies in non-severe HA patients may dramatically change their clinical outcome due to severe bleeding complications. We assessed the association between the occurrence of inhibitors and mortality in patients with non-severe HA. In this retrospective cohort study, clinical data and vital status were collected for 2709 non-severe HA patients (107 with inhibitors) who were treated between 1980 and 2011 in 34 European and Australian centers. Mortality rates for patients with and without inhibitors were compared. During 64,200 patient-years of follow-up, 148 patients died (mortality rate, 2.30 per 1000 person-years; 95% confidence interval (CI), 1.96-2.70) at a median age of 64 years (interquartile range [IQR], 49-76). In 62 patients (42%) the cause of death was hemophilia related. Sixteen inhibitor patients died at a median age of 71 years (IQR, 60-81). In ten patients the inhibitor was present at time of death; seven of them died of severe bleeding complications. The all-cause mortality rate in inhibitor patients was > 5 times increased compared with that for those without inhibitors (age-adjusted mortality rate ratio, 5.6). Inhibitor development in non-severe hemophilia is associated with increased mortality. High rates of hemophilia-related mortality in this study indicate that non-severe hemophilia is not mild at all and stress the importance of close follow-up for these patients. © 2015 International Society on Thrombosis and Haemostasis.
Rodriguez-Merchan, E Carlos
Several methods have been investigated to effectively and safely transmit genes that stimulate cells to release therapeutic factor VIII (FVIII) and factor IX (FIX) into the circulation of people with hemophilia (PWH). To review the role of gene therapy (GT) in PWH. A Cochrane Library and PubMed (MEDLINE) search related to the role of GT in hemophilia was analyzed. The most promising vectors for hemophilia GT are adeno-associated virus (AAV) and lentivirus. Several gene methods are available to lessen risks related to random vector integration and insertional mutagenesis, based on designer nucleases or CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated system). However, off-target issues need to be more meticulously and widely evaluated. Some clinical studies on hemophilia B based on AAV have obtained transitory or subtherapeutic levels of FIX expression. Another problem is possible transitory liver toxicity. Therefore, to reduce unintentional immune responses, transitory immunosuppression must be used, particularly when administering high-vector doses. Codon-optimized FVIII or FIX transgenes are able to promote clotting factor expression levels. The inclusion of a hyper-active gain-of-function R338L mutation in the FIX gene (FIX-R338L [FIX Padua]) makes the procedure more effective. Achieving a safe and efficient remedy for hemophilia A and B by means of GT vector engineering needs further improvement. No randomized or quasi-randomized clinical trials of GT for hemophilia have been found. Given it is in its incipient period, there is need for well-designed clinical trials to evaluate the long-term practicability, efficacy and risks of GT for PWH. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Kasuda, Shogo; Tatsumi, Kohei; Sakurai, Yoshihiko; Shima, Midori; Hatake, Katsuhiko
Hemophilia A is an X-linked rescessive bleeding disorder that results from F8 gene aberrations. Previously, we established embryonic stem (ES) cells (tet-226aa/N6-Ainv18) that secrete human factor VIII (hFVIII) by introducing the human F8 gene in mouse Ainv18 ES cells. Here, we explored the potential of cell transplantation therapy for hemophilia A using the ES cells. Transplant tet-226aa/N6-Ainv18 ES cells were injected into the spleens of severe combined immunodeficiency (SCID) mice, carbon tetrachloride (CCl4)-pretreated wild-type mice, and CCl4-pretreated hemophilia A mice. F8 expression was induced by doxycycline in drinking water, and hFVIII-antigen production was assessed in all cell transplantation experiments. Injecting the ES cells into SCID mice resulted in an enhanced expression of the hFVIII antigen; however, teratoma generation was confirmed in the spleen. Transplantation of ES cells into wild-type mice after CCl4-induced liver injury facilitated survival and engraftment of transplanted cells without teratoma formation, resulting in hFVIII production in the plasma. Although CCl4 was lethal to most hemophilia A mice, therapeutic levels of FVIII activity, as well as the hFVIII antigen, were detected in surviving hemophilia A mice after cell transplantation. Immunolocalization results for hFVIII suggested that transplanted ES cells might be engrafted at the periportal area in the liver. Although the development of a safer induction method for liver regeneration is required, our results suggested the potential for developing an effective ES-cell transplantation therapeutic model for treating hemophilia A in the future. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.
Galant, J.; Poyatos, C.; Marti-Bonmarti, L.; Martinez, J.; Ferrer, D.; Dualde, D.; Talens, A. (Universidad de Valencia (Spain). Facultad de Ciencias Quimicas)
Magnetic resonance is highly sensitive for the detection of intraparenchymatous hemorrhage. The evolution of hematoma over time translates into changes in signal intensity. This means that we can determine when the hematoma presented and, in addition. follow its course. On the other hand, many intracranial processes developing association with hemorrhage, the recognition of which is, in some cases, of importance. We have studied 60 cerebral hematomas and have described the changes that will take place in their signal and the reasons for them. (author)
E. C. Rodriguez-Merchan
Full Text Available Hemophilia is an inherited disorder of clotting factor deficiencies resulting in musculoskeletal bleeding, including hemarthroses, leading to musculoskeletal complications. The articular problems of hemophiliac patients begin in infancy. These include: recurrent hemarthroses, chronic synovitis, flexion deformities, hypertrophy of the growth epiphyses, damage to the articular cartilage, and hemophilic arthropathy. The most commonly affected joints are the ankle, the knee, and the elbow. Hematologic prophylactic treatment from ages 2 to 18 years could avoid the development of hemophilic arthropathy if the concentration of the patient's deficient factor is prevented from falling below 1% of normal. Hemarthroses can be prevented by the administration of clotting factor concentrates (prophylaxis. However, high costs and the need for venous access devices in younger children continue to complicate recommendations for universal prophylaxis. Prevention of joint arthropathy needs to focus on prevention of hemarthroses through prophylaxis, identifying early joint disease through the optimal use of cost-effective imaging modalities and the validation of serological markers of joint arthropathy. Screening for effects on bone health and optimal management of pain to improve quality of life are, likewise, important issues. Major hemarthrosis and chronic hemophilic synovitis should be treated aggressively to prevent hemophilic arthropathy.
Full Text Available Acquired hemophilia A (AHA is a rare bleeding disorder due to the development of specific autoantibodies against factor VIII. The anti-CD20 monoclonal antibody Rituximab has been proven to be effective in obtaining a long-term suppression of inhibitors of AHA, besides other immunosuppressive standard treatments. Here we describe a case of idiopathic AHA in a 60-year old man successfully treated with rituximab. He showed a complete clinical response with a normalization of clotting parameters after 5 weekly courses of rituximab given at a dose of 375 mg/sqm. , but after stopping rituximab, an initial worsening of coagulation parameters induced the addition of 3 further courses. At present, the patient is in complete clinical and hematological remission after 200 days. This case confirms that Rituximab may be a safe and useful tool to treat AHA and, a prolonged administration can overcome the initial resistance. However, the precise position of this drug in the therapeutic strategy (first or second-line, alone or in combination with other drugs remains to be established and warrants further investigation.
Full Text Available Intramural hematoma of the esophagus is a rare injury causing esophageal mucosal dissection. Forceful vomiting and coagulopathy are common underlying causes in the elderly population taking antiplatelets or anticoagulation agents. Acute retrosternal pain followed by hematemesis and dysphagia differentiates the hematoma from other cardiac or thoracic emergencies, including acute myocardial infarction or aortic dissection. Direct inspection by endoscopy is useful, but chest computed tomography best assesses the degree of obliteration of the lumen and excludes other differential diagnoses. Intramural hematoma of the esophagus is generally benign and most patients recover fully with conservative treatment. Bleeding can be managed medically unless in hemodynamically unstable patients, for whom surgical or angiographic treatment may be attempted; only rarely esophageal obstruction requires endoscopic decompression. We report an unusual case of esophageal hematoma, presenting in a young preeclamptic woman after surgical delivery of a preterm twin pregnancy, with a favorable outcome following medical management.
Carazo H,Belén; Romero C,Manuel Ángel; Puebla M,Cristina; Sanz M,Amelia; Rojas P,Beatriz
El hematoma hepático subcapsular es una complicación infrecuente y grave durante la gestación o el período puerperal. Esta patología generalmente se relaciona con preeclampsia o síndrome de HELLP. Su diagnóstico debe confirmarse por tomografía axial computarizada. La precocidad del diagnóstico y tratamiento es importante para evitar la ruptura del hematoma.
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.
Verma, Sumit; Sivanandan, Sindhu; Seth, Rachna; Kabra, Shushil [All India Institute of Medical Sciences (AIIMS), Department of Pediatrics, New Delhi (India); Aneesh, Mangalasseril K.; Gupta, Vaibhav [All India Institute of Medical Sciences (AIIMS), Department of Radiodiagnosis, New Delhi (India)
We report a 3-year-old boy with unilateral proptosis, painful swelling of the right thigh and aphasia. He had radiographic evidence of scurvy in the limbs and bilateral frontal extradural hematomas with a mass lesion in the left orbit on MRI. He was treated with vitamin C and on follow-up 8 weeks later had recovered with no evidence of the orbital mass on clinical or radiological study. Scurvy manifesting as proptosis and extradural hematoma is rare. (orig.)
Full Text Available Gene- or cell-based therapies aimed at creating delivery systems for coagulation factor VIII (FVIII protein have emerged as promising options for hemophilia A treatment. However, several issues remain to be addressed regarding the efficacies and adverse events of these new classes of therapies. To improve an existing cell-based therapy involving the subcutaneous transplantation of FVIII-transduced blood outgrowth endothelial cells (BOECs, we employed a novel cell-sheet technology that allows individual dispersed cells to form a thin and contiguous monolayer without traditional bioabsorbable scaffold matrices. Compared to the traditional methodology, our cell-sheet approach resulted in longer-term and 3-5-fold higher expression of FVIII (up to 11% of normal in recipient hemophilia A mice that lacked a FVIII humoral immune response due to transient immunosuppression with cyclophosphamide. Histological studies revealed that the transplanted BOEC sheets were structured as flat clusters, supporting the long-term expression of therapeutic FVIII in plasma from an ectopic subcutaneous space. Our novel tissue-engineering approach using genetically modified BOEC sheets could aid in development of cell-based therapy that will allow safe and effective in vivo delivery of functional FVIII protein in patients with hemophilia A.
Tatsumi, Kohei; Sugimoto, Mitsuhiko; Lillicrap, David; Shima, Midori; Ohashi, Kazuo; Okano, Teruo; Matsui, Hideto
Gene- or cell-based therapies aimed at creating delivery systems for coagulation factor VIII (FVIII) protein have emerged as promising options for hemophilia A treatment. However, several issues remain to be addressed regarding the efficacies and adverse events of these new classes of therapies. To improve an existing cell-based therapy involving the subcutaneous transplantation of FVIII-transduced blood outgrowth endothelial cells (BOECs), we employed a novel cell-sheet technology that allows individual dispersed cells to form a thin and contiguous monolayer without traditional bioabsorbable scaffold matrices. Compared to the traditional methodology, our cell-sheet approach resulted in longer-term and 3-5-fold higher expression of FVIII (up to 11% of normal) in recipient hemophilia A mice that lacked a FVIII humoral immune response due to transient immunosuppression with cyclophosphamide. Histological studies revealed that the transplanted BOEC sheets were structured as flat clusters, supporting the long-term expression of therapeutic FVIII in plasma from an ectopic subcutaneous space. Our novel tissue-engineering approach using genetically modified BOEC sheets could aid in development of cell-based therapy that will allow safe and effective in vivo delivery of functional FVIII protein in patients with hemophilia A.
O'Brien, Kevin J; Lozier, Jay; Cullinane, Andrew R; Osorio, Brigitte; Nghiem, Khanh; Speransky, Vladislav; Zein, Wadih M; Mullikin, James C; Neff, Anne T; Simon, Karen L; Malicdan, May Christine V; Gahl, William A; Young, Lisa R; Gochuico, Bernadette R
Hemophilia B, an X-linked disease, manifests with recurrent soft tissue bleeding episodes. Hermansky-Pudlak syndrome, a rare autosomal recessive disorder, is characterized by oculocutaneous albinism and an increased tendency to bleed due to a platelet storage pool defect. We report a novel mutation in HPS6 in a Caucasian man with hemophilia B and oculocutaneous albinism. The patient was diagnosed with hemophilia B at age 4months due to recurrent soft tissue bleeding episodes, and he was also diagnosed with Hermansky-Pudlak syndrome at 32years of age due to unexplained oculocutaneous albinism. His factor IX level was markedly reduced at 13%; whole exome and Sanger sequencing showed the Durham mutation in F9 (NM_000133.3). The diagnosis of Hermansky-Pudlak syndrome subtype 6 was established by demonstrating absence of platelet delta granules on whole mount electron microscopy, an abnormal secondary wave in platelet aggregation studies, and a novel homozygous c.1114 C>T (p.Arg372*) mutation in HPS6 (NM_024747.5) on exome analysis and Sanger sequencing. Clinical phenotyping revealed no evidence of recurrent or unusual infections, interstitial lung disease or pulmonary fibrosis, or neurological disorders. The patient was treated with fresh frozen plasma, recombinant factor IX, and aminocaproic acid. Treatment with desmopressin was added to his regimen after he was diagnosed with Hermansky-Pudlak syndrome. Treatment of bleeding episodes results in effective hemostasis, and the patient has not required platelet or blood product transfusions. This report highlights the need to consider Hermansky-Pudlak syndrome as an etiology of oculocutaneous albinism even in patients with known hematologic disorders associated with bleeding. Identification of a novel mutation in HPS6 in an individual with hemophilia B shows that, although quite rare, patients may be diagnosed with two independent inherited bleeding disorders. No evidence of lung disease was found in this adult patient
Braun, Petra [Department of Radiology, Hospital La Plana, Ctra. De Vila-real a Borriana km. 0.5, 12540 Vila-real (Castello) (Spain)], E-mail: PetraBraun@gmx.de; Kazmi, Khuram [Department of Radiology, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033 (United States); Nogues-Melendez, Pablo; Mas-Estelles, Fernando; Aparici-Robles, Fernando [Department of Radiology, La Fe Hospital, Avenida Campanar, 21, 46009 Valencia (Spain)
Background: Spinal hematomas are rare entities that can be the cause of an acute spinal cord compression syndrome. Therefore, an early diagnosis is of great importance. Patients and Methods: From 2001 to 2005 seven patients with intense back pain and/or acute progressive neurological deficit were studied via 1.5 T MRI (in axial and sagittal T1- and T2-weighted sequences). Follow-up MRI was obtained in six patients. Results: Four patients showed the MRI features of a hyperacute spinal hematoma (two spinal subdural hematoma [SSH] and two spinal epidural hematoma [SEH]), isointense to the spinal cord on T1- and hyperintense on T2-weighted sequences. One patient had an early subacute SEH manifest as heterogeneous signal intensity with areas of high signal intensity on T1- and T2-weighted images. Another patient had a late subacute SSH with high signal intensity on T1- and T2-weighted sequences. The final patient had a SEH in the late chronic phase being hypointense on T1- and T2-weighted sequences. Discussion: MRI is valuable in diagnosing the presence, location and extent of spinal hematomas. Hyperacute spinal hematoma and the differentiation between SSH and SEH are particular diagnostic challenges. In addition, MRI is an important tool in the follow-up in patients with conservative treatment.
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.
Kimmoun, Antoine; Abboud, Georges; Steinbach, Gérard; Tellaroli, Jean-Claude; Bemer, Michel
Dissecting intramural hematoma of the esophagus is a rare cause of chest pain that can be misinterpreted as a myocardial infarction. The use of anticoagulants in this case may lead to hemorrhagic complications. A 51-year-old patient, with coronary artery disease, diabetes, hypertension and dependent on both alcohol and tobacco, was admitted for chest pain and an elevated troponin T plasma level. He was treated with anticoagulants. He developed hematemesis on the third day and was transferred to intensive care. Esophageal endoscopy revealed a hematoma with active bleeding, covered by esophageal mucosa from the middle to the lower third of the esophagus (for 13 cm). Computed tomography allowed us to rule out an aortoesophageal fistula. Symptomatic treatment consisted of withdrawing the anticoagulant, mechanical ventilation, intravenous sedation, and blood transfusion. The patient recovered, after a long stay in ICU. Intramural dissecting hematoma of the esophagus is not always easy to diagnose. Administration of anticoagulant treatment after a misdiagnosis of acute coronary syndrome can have serious hemorrhagic consequences. Prognosis is excellent with conservative treatment.
Are Hugo Pripp
, but lasso regression revealed an association with inflammatory and angiogenic biomarkers in hematoma fluid. We thus suggest that lasso regression should be a recommended statistical method in research on biological processes in CSDH patients.
Full Text Available As hemophilia is a chronic bleeding disease and can interfere with daily performance of children, these children require continuous training to prevent bleeding and take timely action (1. Since children nurses play an important role in the education of involved children and their Selfefficacy and also due to today’s approach which is using educational computer games, the use of educational games in respect to teach hemophilia children how to have self-efficacy can be effective (2. Hemoaction game is a computerized educational game designed by the World Federation of Hemophilia to educate hemophilia disease and related procedures to the care of children with hemophilia. By the use of this game children with hemophilia (aged 8-12 and also nursing experts were educated how to increase self efficacy. Nursing School of Shiraz University of Medical Sciences has used this game for the first time after its publishing, in the world (3. The results of the mentioned study demonstrates that after the Hemophilia disease and its related procedures were instructed to children with hemophilia and nursing experts in order to know how to increase patients’ self efficacy by modern approaches, self efficacy of hemophilia children and nurses were both improved. This educational method is a novel way to enhance both Hemophilia children and nursing staff, as major participants in routine and lifelong education process, self-efficacy. Due to nurses’ important role in improving children with hemophilia self-efficacy by different instructions and world leading educational approaches towards use of modern technology in education, using Hemoaction educational game, published by World Federation of Hemophilia and used by Nursing and Midwifery College of Shiraz University of Medical Sciences for the first time, can fulfill hemophilia children needs of care.
Gissel, Matthew; Whelihan, Matthew F; Ferris, Lauren A; Mann, Kenneth G; Rivard, Georges E; Brummel-Ziedins, Kathleen E
Introduction Hemophilia A individuals displaying a similar genetic defect have heterogeneous clinical phenotypes. Aim To evaluate the underlying effect of exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in severe hemophilia utilizing both empirical and computational models. Methods We investigated twenty-five clinically severe hemophilia A patients. All individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4 days prior to phlebotomy. Coagulation was initiated by the addition of Tf to contact-pathway inhibited whole blood ± an anti-fVIII antibody. Aliquots were quenched over 20 min and analyzed for thrombin generation and fibrin formation. Coagulation factor levels were obtained and used to computationally predict thrombin generation with fVIII set to either zero or its value at the time of the draw. Results Due to prophylactic fVIII, at the time of the blood draw, the individuals had fVIII levels that ranged from hemophilia A. The combination of each individual's coagulation factors (outside of fVIII) determine each individual's baseline thrombin potential and may affect bleeding risk. PMID:21899664
Morfini, Massimo; Zanon, Ezio
Replacement therapy with clotting factor concentrates is the most appropriate and effective way to treat bleedings of Hemophilia A&B to prevent chronic arthropathy. Unfortunately, the short half-life (HL) of FVIII/IX concentrates obliges the patients to receive frequent infusions, a big concern for children. The development of inhibitors in about 30-45% of hemophilia A and in 3-5% of hemophilia B patient is the major adverse event of replacement therapy. In the last few years, new rFIX have been developed with HL. New rFVIII concentrates are displaying small increase of PK characteristics. The new bio-engineering methods allowed the production of molecules fused with Fc fragment of IgG or Albumin or linked to PEG. A new approach to improve hemostasis is represented by Mab against TFPI and small RNA interfering with Antithrombin synthesis. Another innovative drug seems to be the new bi-specific antibody which mimics FVIII function in linking FXa and FX to tenase production. The emerging drugs for hemophilia treatment seem to be very promising. The extended half-life will improve the adherence of patients to therapy. Accurate post-marketing surveillance studies will be necessary to check the efficacy, safety and immunogenicity of these new molecules.
Objectives: The main objective is to determine the screening, vaccination, seroconversion of hepatitis B, C and HIV among Sudanese hemophilic patients registered in Hemophilia Center Khartoum Teaching Hospital. Methods: During the period from July to November 2008, sixty two hemophilic male patients were randomly ...
Since the publication of the sequence of the factor VIII (F8) gene in 1984, a large number of mutations that cause hemophilia A have been identified and a significant progress has been made in translating this knowledge for clinical diagnostic and therapeutic purposes. Molecular genetic testing is used to determine the ...
Carrai, Edward B.; Handford, H. Allen
Because of the multiple problems associated with hemophilia, optimal treatment is usually provided in a comprehensive care setting by a team of medical and nonmedical professionals. The rehabilitation counselor contributes expertise to that of other team members in development and implementation of an individual rehabilitation plan for…
High, Katherine A.; Anguela, Xavier M.
Gene transfer studies for the treatment of hemophilia began more than two decades ago. A large body of pre-clinical work evaluated a variety of vectors and target tissues, but by the start of the new millennium it became evident that adeno-associated viral (AAV)-mediated gene transfer to the liver held great promise as a therapeutic tool. The transition to the clinical arena uncovered a number of unforeseen challenges, mainly in the form of a human-specific immune response against the vector that poses a significant limitation in the application of this technology. While the full nature of this response has not been elucidated, long-term expression of therapeutic levels of factor IX is already a reality for a small number of patients. Extending this success to a greater number of hemophilia B patients remains a major goal of the field, as well as translating this strategy to clinical therapy for hemophilia A. This review summarizes the progress of AAV-mediated gene therapy for the hemophilias, along with its upcoming prospects and challenges. PMID:26614390
Dec 21, 2016 ... described with this disease in 1952. It is characterized by spontaneous or prolonged hemorrages due to factor IX deficiency. Factor IX mutations have not been previously reported in Algerian patients. To understand the molecular basis of hemophilia B in Algeria, polymerase chain reaction (PCR) and direct.
Full Text Available Abstract Over the past forty years the availability of coagulation factor replacement therapy has greatly contributed to the improved care of people with hemophilia. Following the blood-borne viral infections in the late 1970s and early 1980, caused by coagulation factor concentrates manufactured using non-virally inactivated pooled plasma, the need for safer treatment became crucial to the hemophilia community. The introduction of virus inactivated plasma-derived coagulation factors and then of recombinant products has revolutionized the care of these people. These therapeutic weapons have improved their quality of life and that of their families and permitted home treatment, i.e., factor replacement therapy at regular intervals in order to prevent both bleeding and the resultant joint damage (i.e. primary prophylaxis. Accordingly, a near normal lifestyle and life-expectancy have been achieved. The main current problem in hemophilia is the onset of alloantibodies inactivating the infused coagulation factor, even though immune tolerance regimens based on long-term daily injections of large dosages of coagulation factors are able to eradicate inhibitors in approximately two-thirds of affected patients. In addition availability of products that bypass the intrinsic coagulation defects have dramatically improved the management of this complication. The major challenges of current treatment regimens, such the short half life of hemophilia therapeutics with need for frequent intravenous injections, encourage the current efforts to produce coagulation factors with more prolonged bioavailability. Finally, intensive research is devoted to gene transfer therapy, the only way to ultimately obtain cure in hemophilia.
Full Text Available Background: Pain, as a crucial subsequence of joint hemorrhages in hemophilia patients, is chronic, debilitating, and distracting. This study aimed to describe and interpret pain experiences of hemophilia patients in their lives. Methods: This qualitative study with hermeneutic phenomenological approach was conducted on fourteen hemophilia patients who had been referred to a hemophiliacenter affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. The study question was “what is the meaning of pain in hemophilia patients’ lives? The data were collected through semi-structured interviews and field notes through purposeful sampling. Then, thematic analysis with van Manen’s six-step methodological framework was used. MAX.QDA qualitative software package, 2010, was used to analyze the data. Results: The three main themes that emerged in this study were “alteration in physical health”, “engagement in psychological problems”, and “impairment in social relationships”. Alteration in physical health consisted of three subthemes, namely “impairment of physical function”, “change in body physics”, and “disturbance in sleep quality”. In addition, two subthemes including “nostalgia of pain in adults with hemophilia” and “psychological distress” emerged from engagement in psychological problems. Finally, “loss of social activity” and “change in relationships” were related to impairment in social relationships. Conclusion: The present study highlighted alteration in physical health, engagement in psychological problems, and impairment in social relationship as a result of pain in hemophilia patients. Thus, healthcare providers and family members have to pay special attention to these problems. Besides, providing complementary therapy interventions is suggested for reducing these issues.
Lee, Yul; Lee, Kwan Seop; Hwang, Dae Hyun; Lee, In Jae; Kim, Hyun Beom; Lee, Jae Young [Hallym University College of Medicine, Anyang (Korea, Republic of)
Shaken baby syndrome (SBS) is a form of child abuse that can cause significant head injuries, of which subdural hematoma (SDH) is the most common manifestation. We report the MRI findings of chronic SDH in three cases of SBS, involving two-, three- and eight-month-old babies. The SDH signal was mostly low on T1-weighted images and high on T2-weighted images, suggesting chronic SDH. In chronic SDH, a focal high signal on T1-weighted images was also noted, suggesting rebleeding. Contrast-enhanced MRI revealed diffuse dural enhancement.
Full Text Available We report successful outcome of a huge post- trabeculectomy intra-bleb hematoma and hyphema that occurred following digital ocular compression. The patient was a 64-year-old lady suffering from bilateral primary angle closure glaucoma and cataract. She was on anti-platelet therapy. She underwent single-site phacoemulsification, intra-ocular lens implantation and trabeculectomy with mitomycin C in the right eye. The trabeculectomy was under-filtering. She was asked to perform digital ocular compression thrice daily. On 15 th post-operative day, she presented with a huge intra-bleb hematoma and hyphema. The hematoma did not respond to conservative measures and was drained to prevent bleb failure. We recommend caution in the consideration of digital ocular compression in patients on prophylactic anti-coagulation.
Full Text Available Shraddha S Chaugule,1 Joel W Hay,1 Guy Young2 1Department of Clinical Pharmacy, Pharmaceutical Economics and Policy, University of Southern California, 2Hemostasis and Thrombosis Center, Children’s Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA Background: Despite clearly improved clinical outcomes for prophylaxis compared to on-demand therapy, on average only 56% of patients diagnosed with severe hemophilia receive prophylactic factor replacement therapy in the US. Prophylaxis rates generally drop as patients transition from childhood to adulthood, partly due to patients becoming less adherent when they reach adulthood. Assessment of patient preferences is important because these are likely to translate into increased treatment satisfaction and adherence. In this study, we assessed preferences and willingness to pay (WTP for on-demand, prophylaxis, and longer acting prophylaxis therapies in a sample of US hemophilia patients.Methods: Adult US hemophilia patients and caregivers (N=79 completed a discrete-choice survey that presented a series of trade-off questions, each including a pair of hypothetical treatment profiles. Using a mixed logit model for analysis, we compared the relative importance of five treatment characteristics: 1 out-of-pocket treatment costs (paid by patients, 2 factor dose adjustment, 3 treatment side effects, 4 availability of premixed factor, and 5 treatment effectiveness and dosing frequency. Based on these attribute estimates, we calculated patients’ WTP.Results: Out-of-pocket treatment costs (P<0.001, side effects (P<0.001, and treatment effectiveness and dosing frequency (P<0.001 were found to be statistically significant in the model. Patients were willing to pay US $410 (95% confidence interval: $164–$656 out of pocket per month for thrice-weekly prophylaxis therapy compared to on-demand therapy and $360 (95% confidence interval: $145–$575 for a switch
Full Text Available Duodenal intramural hematoma (DIH usually occurs in childhood and young adults following blunt abdominal trauma. It may also develop in the presence of coagulation disorders and may rarely be an iatrogenic outcome of endoscopic procedures. Management of DIH is usually a conservative approach. A case of intramural duodenal hematoma that developed following endoscopic epinephrine sclerotherapy and/or argon plasma coagulation and that was nonresponsive to conservative therapy in a patient with chronic renal failure who died from sepsis is being discussed in this report. Clinicians should be aware of such possible complications after endoscopic hemostasis in patients with coagulation disorders.
Naran, A.D.; Fontana, L. [Dept. of Diagnostic Radiology, New York Methodist Hospital, Brooklyn, NY (United States)
Although bone infarction is a common feature in sickle cell disease, the involvement of the orbit is an unusual complication. Intracranial bleeding is another uncommon and serious complication. Few cases of orbital infarction alone have been reported. We report imaging findings (CT, bone scan, MRI) in a 16-year-old boy with sickle cell disease with orbital infarction and epidural hematoma. The precise cause of epidural hematoma is not well known, but it is probably related to vaso-occlusive episodes and the tearing of small vessels. (orig.)
Rashid Saeed Khokhar
Full Text Available Hemophilia A is a hemorrhagic trend almost exclusively affecting males (X-related recessive disease. In 85% of cases, it is caused by factor VIII deficiency, called hemophilia A or classic hemophilia. Successful anesthetic management depends on the special care and a multidisciplinary team of health professionals informed about the disease, including qualified hematologist, surgeon, and anesthesiologist.
Lee, Kyung Mi; Kim, Eui Jong [Dept. of Radiology, Kyung Hee University Hospital, Kyung Hee University Graduate School of Medicine, Seoul (Korea, Republic of); Park, Bong Jin [Dept. of Neurosurgery, Kyung Hee University Hospital, Kyung Hee University Graduate School of Medicine, Seoul (Korea, Republic of); Kim, Keon Ha [Dept. of Radiology, Samsug Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)
We present a case of scalp arteriovenous malformation (AVM) in a patient with severe hemophilia A. The 22-year-old man presented with a pulsatile right parietal scalp mass. Digital subtraction angiography revealed an AVM in the right parietal scalp, supplied by superficial temporal and occipital arteries that drained into multiple venous structures. We successfully performed direct puncture embolization followed by surgical resection of the scalp AVM in conjunction with supplemental infusion of coagulation factor VIII before, during and after the embolization and the operation.
Gabrovsky, Vanessa; Calos, Michele P
Gene therapy for hemophilia A has fallen short of success despite several clinical trials conducted over the past decade. Challenges to its success include vector immunogenicity, insufficient transgene expression levels of Factor VIII, and inhibitor antibody formation. Gene therapy has been dominated by the use of viral vectors, as well as the immunogenic and oncogenic concerns that accompany these strategies. Because of the complexity of viral vectors, the development of nonviral DNA delivery methods may provide an efficient and safe alternative for the treatment of hemophilia A. New types of nonviral strategies, such as DNA integrating vectors, and the success of several nonviral animal studies, suggest that nonviral gene therapy has curative potential and justifies its clinical development.
Gruen, D.R. [Dept. of Radiology, The New York Hospital-Cornell Medical Center, New York, NY (United States); Winchester, P.H. [Dept. of Radiology, The New York Hospital-Cornell Medical Center, New York, NY (United States); Brill, P.W. [Dept. of Radiology, The New York Hospital-Cornell Medical Center, New York, NY (United States); Ramirez, E. [Dept. of Radiology, The New York Hospital-Cornell Medical Center, New York, NY (United States)
In patients with hemophilia, prothrombin complex concentrates (PCCs) have been successfully used to bypass inhibitors to fctor VIII during bleeding episodes. The use of PCCS, including FEIBA (factor eight inhibitor bypassing activity), has been associated with thromboembolic complications. Myocardial infarction (MI) is a rare but serious complication, reported in 13 previous cases, six in the pediatric age group. In all four patients who died during the acute MI, autopsy revealed extensive myocardial hemorrhage. The hearts of three other patients examined at least 5 months after the acute MI showed no evidence of prior hemorrhage. Magnetic resonance (MR) imaging has been shown to be able to evaluate the sequelae of myocardial infarction in adults with coronary artery disease and in children with Kawasaki syndrome. We report the first case of the used of MR imaging in the evaluation of myocardial damage during the acute stage of a FEIBA-associated MI in a 10-year-old boy. (orig.)
Monogenic diseases are ideal candidates for treatment by the emerging advanced therapies, which are capable of correcting alterations in protein expression that result from genetic mutation. In hemophilia A and B such alterations affect the activity of coagulation factors VIII and IX, respectively, and are responsible for the development of the disease. Advanced therapies may involve the replacement of a deficient gene by a healthy gene so that it generates a certain functional, structural or transport protein (gene therapy); the incorporation of a full array of healthy genes and proteins through perfusion or transplantation of healthy cells (cell therapy); or tissue transplantation and formation of healthy organs (tissue engineering). For their part, induced pluripotent stem cells have recently been shown to also play a significant role in the fields of cell therapy and tissue engineering. Hemophilia is optimally suited for advanced therapies owing to the fact that, as a monogenic condition, it does not require very high expression levels of a coagulation factor to reach moderate disease status. As a result, significant progress has been possible with respect to these kinds of strategies, especially in the fields of gene therapy (by using viral and non-viral vectors) and cell therapy (by means of several types of target cells). Thus, although still considered a rare disorder, hemophilia is now recognized as a condition amenable to gene therapy, which can be administered in the form of lentiviral and adeno-associated vectors applied to adult stem cells, autologous fibroblasts, platelets and hematopoietic stem cells; by means of non-viral vectors; or through the repair of mutations by chimeric oligonucleotides. In hemophilia, cell therapy approaches have been based mainly on transplantation of healthy cells (adult stem cells or induced pluripotent cell-derived progenitor cells) in order to restore alterations in coagulation factor expression. PMID:23237078
Full Text Available A 36-year-old female started having postpartum vaginal bleeding after normal vaginal delivery. She underwent hysterectomy for persistent bleeding and was referred to our institution. An elevation of PTT and normal PT made us suspect postpartum acquired hemophilia (PAH, and it was confirmed by low factor VIII activity levels and an elevated factor VIII inhibitor. Hemostasis was achieved with recombinant factor VII concentrates and desmopressin, and factor eradication was achieved with cytoxan, methylprednisolone, and plasmapheresis.
Full Text Available Abstract Monogenic diseases are ideal candidates for treatment by the emerging advanced therapies, which are capable of correcting alterations in protein expression that result from genetic mutation. In hemophilia A and B such alterations affect the activity of coagulation factors VIII and IX, respectively, and are responsible for the development of the disease. Advanced therapies may involve the replacement of a deficient gene by a healthy gene so that it generates a certain functional, structural or transport protein (gene therapy; the incorporation of a full array of healthy genes and proteins through perfusion or transplantation of healthy cells (cell therapy; or tissue transplantation and formation of healthy organs (tissue engineering. For their part, induced pluripotent stem cells have recently been shown to also play a significant role in the fields of cell therapy and tissue engineering. Hemophilia is optimally suited for advanced therapies owing to the fact that, as a monogenic condition, it does not require very high expression levels of a coagulation factor to reach moderate disease status. As a result, significant progress has been possible with respect to these kinds of strategies, especially in the fields of gene therapy (by using viral and non-viral vectors and cell therapy (by means of several types of target cells. Thus, although still considered a rare disorder, hemophilia is now recognized as a condition amenable to gene therapy, which can be administered in the form of lentiviral and adeno-associated vectors applied to adult stem cells, autologous fibroblasts, platelets and hematopoietic stem cells; by means of non-viral vectors; or through the repair of mutations by chimeric oligonucleotides. In hemophilia, cell therapy approaches have been based mainly on transplantation of healthy cells (adult stem cells or induced pluripotent cell-derived progenitor cells in order to restore alterations in coagulation factor expression.
Barg, Assaf A; Livnat, Tami; Kenet, Gili
Acquired hemophilia A (AHA) is a severe bleeding disorder caused by autoantibodies against clotting factor VIII (FVIII). With an estimated annual incidence of 1.3 to 1.5 per million, AHA is a rare disease. An extremely rare form of AHA has been described among women in the peripartum period, and may present with peripartum hemorrhage. Notably, although hemorrhagic symptoms commonly present 1-4 months around delivery, they may occur up to 1 year after parturition. When caring for a mother with AHA it is important to note that Factor VIII inhibitor may be transferred via the placenta from the mother to the fetus. Hence the newborn may also be affected. It is important to increase the awareness of Gynecologists for clinical symptoms and laboratory signs of AHA in order to avoid delayed diagnosis. Treatment may involve use of bypass agents to control hemorrhage, despite the risk of thrombosis, while immunomodulation (with increasing role for Rituximab) may be required to eradicate the inhibiting antibodies. Our review will evaluate the epidemiology, diagnosis, clinical course and treatment of peripartum AHA, focusing upon mother and infant care. © 2017 Elsevier Ltd. All rights reserved.
Yang, Yanhui; Xue, Feng; Shi, Hao; Wang, Hongmei; Zhang, Lei; Ji, Linxiang; Yang, Renchi
Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the autoantibody directed against factor VIII in patients without previous history of a bleeding disorder. We retrospectively analyzed the characteristics and outcomes of 49 patients with AHA diagnosed in our center from February 1994 to October 2012. Twenty-four patients with acute bleeding episodes were treated with prothrombin complex concentrate (PCC) at a relative low dose of 30 to -50 U/kg/d and achieved good outcomes without any adverse reaction. Corticosteroids alone or in combination with cyclophosphamide were used as the first-line therapy to eradicate the inhibitors. In 39 evaluable patients, 35 (89.7%) achieved complete remission (CR). This study demonstrates that when bypassing agents such as recombinant activated factor VII and activated PCCs are not affordable or available, low dose PCC is effective and safe to control acute bleeding in patients with AHA. First-line therapy achieved good outcomes with a CR rate of 89.7%. © The Author(s) 2013.
Arruda, V R; Samelson-Jones, B J
The development of inhibitors, i.e. neutralizing alloantibodies against factor (F) VIII or FIX, is the most significant complication of protein replacement therapy for patients with hemophilia, and is associated with both increased mortality and substantial physical, psychosocial and financial morbidity. Current management, including bypassing agents to treat and prevent bleeding, and immune tolerance induction for inhibitor eradication, is suboptimal for many patients. Fortunately, there are several emerging gene therapy approaches aimed at addressing these unmet clinical needs of patients with hemophilia and inhibitors. Herein, we review the mounting evidence from preclinical hemophilia models that the continuous uninterrupted expression of FVIII or FIX delivered as gene therapy can bias the immune system towards tolerance induction, and even promote the eradication of pre-existing inhibitors. We also discuss several gene transfer approaches that directly target immune cells in order to promote immune tolerance. These preclinical findings also shed light on the immunologic mechanisms that underlie tolerance induction. © 2016 International Society on Thrombosis and Haemostasis.
Saito, Makoto; Wakasa, Kentaro; Mori, Akio; Irie, Tatsuro; Tanaka, Masanori; Morioka, Masanobu; Ieko, Masahiro
In this paper we report our clinical investigation of three cases with acquired hemophilia A treated in our department. These patients were all elderly males (79, 77, and 68 years old), and presented with subcutaneous bleeding, a prolonged activated partial thromboplastin time (APTT), and anemia. On the basis of these findings as well as decreased factor VIII activities (0.9~3.1%) and the presence of factor VIII inhibitors (57.1~173 BU/ml), we made a diagnosis of acquired hemophilia A. In cases 1 and 2, a recombinant activated factor VII was used to achieve hemostasis. The factor VIII inhibitor disappeared with prednisolone (PSL) alone in case 1 and a combination of PSL and cyclophosphamide in case 2. In case 3, treatment involving five courses of weekly rituximab (RTX) reduced the activity of factor III inhibitor to 3.5 BU/ml (and subsequently to zero). During this time, the patient achieved hemostasis without using a specific hemostatic agent, and was again referred to the previous hospital for the treatment of hepatocellular carcinoma. Although PSL is often chosen as a first-line therapy to suppress the production of factor VIII inhibitor, which may cause acquired hemophilia A, RTX may be another therapeutic option in some patients.
Josiane Bazzo de Alencar
Full Text Available Hemophilia A is a disease caused by a deficiency of coagulation factor VIII resulting from genetic inheritance linked to chromosome X. One treatment option is the administration of plasma or recombinant FVIII. However, some patients develop inhibitors or antibodies against this factor. Inhibitors are alloantibodies that bind to the epitope of factor VIII causing it to be recognized by the immune system as a foreign peptide. This is the most serious complication in hemophilia patients in respect to replacement therapy. Some studies have suggested that genetic factors influence the development of factor VIII inhibitors such as ethnicity, family history, mutations in the factor VIII gene and in genes of the immune system. The aim of this study was to conduct a literature review to assess the influence of genetic factors of immune response genes, especially genes of the major histocompatibility complex and cytokines, which may be related to the development of factor VIII inhibitors in hemophilia A patients. Understanding these risk factors will help to determine future differential treatment in the control and prevention of the development of inhibitors.
Gorski, Marcin M; Blighe, Kevin; Lotta, Luca A; Pappalardo, Emanuela; Garagiola, Isabella; Mancini, Ilaria; Mancuso, Maria Elisa; Fasulo, Maria Rosaria; Santagostino, Elena; Peyvandi, Flora
The development of neutralizing antibodies (inhibitors) against coagulation factor VIII (FVIII) is the most problematic and costly complication of FVIII replacement therapy that affects up to 30% of previously untreated patients with severe hemophilia A. The development of inhibitors is a multifactorial complication involving environmental and genetic factors. Among the latter, F8 gene mutations, ethnicity, family history of inhibitors, and polymorphisms affecting genes involved in the immune response have been previously investigated. To identify novel genetic elements underling the risk of inhibitor development in patients with severe hemophilia A, we applied whole-exome sequencing (WES) and data analysis in a selected group of 26 Italian patients with (n = 17) and without (n = 9) inhibitors. WES revealed several rare, damaging variants in immunoregulatory genes as novel candidate mutations. A case-control association analysis using Cochran-Armitage and Fisher's exact statistical tests identified 1364 statistically significant variants. Hierarchical clustering of these genetic variants showed 2 distinct patterns of homozygous variants with a protective or harmful role in inhibitor development. When looking solely at coding variants, a total of 28 nonsynonymous variants were identified and replicated in 53 inhibitor-positive and 174 inhibitor-negative Italian severe hemophilia A patients using a TaqMan genotyping assay. The genotyping results revealed 10 variants showing estimated odds ratios in the same direction as in the discovery phase and confirmed the association of the rs3754689 missense variant (OR 0.58; 95% CI 0.36-0.94; P = .028) in a highly conserved haplotype region surrounding the LCT locus on chromosome 2q21 with inhibitor development. © 2016 by The American Society of Hematology.
Full Text Available Nikos Eleftheriadis, Pantelis MakrisHemostatic Unit of The First Propedeutic Department of Internal Medicine, AHEPA Hospital, Aristotles University of Thessaloniki, GreeceAbstract: The relation of hemophilia A with thrombophilia V Leiden is extremely rare in the literature. Furthermore, hemophiliac patients have an increased risk of severe life-threatening hemorrhage, blood transfusions, and therefore hepatitis transmission, mainly hepatitis C (HCV.Aims and methods: We present a 54-year-old male with a 5-year history of decompensated liver cirrhosis on the grounds of HCV hepatitis, hemophilia A, and thrombophilia V Leiden. He was admitted to our department because of severe abdominal distension, resembling ‘tense ascites’ despite the use of diuretics. Clinical examination showed shifting dullness and a protuberant abdomen, while hematological and blood chemistry results revealed thrombopenia (platelets: 77000/mL and hypoalbuminemia. Repeated abdominal paracentesis (under factor VIII administration failed to remove ascitic fluid, while abdominal echosonography and computed tomography revealed severe edema of mesenterium and intraabdominal viscus and the absence of free ascitic fluid, atrophic cirrhotic liver, and splenomegaly. Moreover, abdominal doppler echosonography revealed signs of portal hypertension, previous portal vein thrombosis, and revascularization of the portal vein. Gastroscopy showed esophageal varices grade II, without signs of bleeding. A-FP and all other laboratory examinations were normal.Results: Our patient was intravenously treated with albumine and diuretics (furosemide with mild improvement of his abdominal distension. During his hospitalization he presented an episode of spontaneous bacterial peritonitis and hepatic encephalopathy, which were successfully treated with lactulose clysmas and ciprofloxacine. He was discharged in a good general condition.Conclusion: According to our case we consider the false clinical
Kamphuis, AGA; Baur, CHJCM; Freling, NJM
A 73-yr-old woman on anticoagulant therapy experienced progressive dyspnea and dysphagia due to a large compressing mass in the posterior mediastinum. Because her clinical condition deteriorated rapidly surgery was performed. A large intramural hematoma along the full length of the esophagus with
Butterfly hematoma after traumatic intercourse. F Hajji, A Ameur. Abstract. No Abstract. http://dx.doi.org/10.11604/pamj.2015.20.317.6660 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use · Contact ...
Ni, Wei; Mao, Shanshan; Xi, Guohua; Keep, Richard F; Hua, Ya
Enhancing hematoma clearance through phagocytosis may reduce brain injury after intracerebral hemorrhage. In the current study, we investigated the role of cluster of differentiation 47 (CD47) in regulating erythrophagocytosis and brain injury after intracerebral hemorrhage in nude mice. This study was in 2 parts. First, male adult nude mice had an intracaudate injection of 30 μL saline, blood from male adult wild-type (WT) mice, or blood from CD47 knockout mice. Second, mice had an intracaudate injection of 30 μL CD47 knockout blood with clodronate or control liposomes. Clodronate liposomes were also tested in saline-injected mice. All mice then had magnetic resonance imaging to measure hematoma size and brain swelling. Brains were used for immunohistochemistry and Western blot. Erythrophagocytosis occurred in and around the hematoma. Injection of CD47 knockout blood resulted in quicker clot resolution, less brain swelling, and less neurological deficits compared with wild-type blood. Higher brain heme oxygenase-1 levels and more microglial activation (mostly M2 polarized microglia) at day 3 were found after CD47 knockout blood injection. Co-injection of clodronate liposomes, to deplete phagocytes, caused more severe brain swelling and less clot resolution. These results indicated that CD47 has a key role in hematoma clearance after intracerebral hemorrhage. © 2016 American Heart Association, Inc.
French, Keisha L; Daniels, Eldra W; Ahn, Uri M; Ahn, Nicholas U
Spinal epidural hematoma and spinal epidural abscess are rare surgical emergencies resulting in significant neurologic deficits. Making the diagnosis for spinal epidural hematoma and spinal epidural abscess can be challenging; however, a delay in recognition and treatment can be devastating. The objective of this retrospective analysis study was to identify risk factors for an adverse outcome for the provider. The LexisNexis Academic legal search database was used to identify a total of 19 cases of spinal epidural hematoma and spinal epidural abscess filed against medical providers. Outcome data on trial verdicts, age, sex, initial site of injury, time to consultation, time to appropriate imaging studies, time to surgery, and whether a rectal examination was performed or not were recorded. The results demonstrated a significant association between time to surgery more than 48 hours and an unfavorable verdict for the provider. The degree of permanent neurologic impairment did not appear to affect the verdicts. Fifty-eight percent of the cases did not present with an initial deficit, including loss of bowel or bladder control. All medical professionals must maintain a high level of suspicion and act quickly. Physicians who are able to identify early clinical features, appropriately image, and treat within a 48 hour time frame have demonstrated a more favorable medicolegal outcome compared with their counterparts in filed lawsuits for spinal epidural hematoma and spinal epidural abscess cases. Copyright 2013, SLACK Incorporated.
Kim, Sam Soo [Seoul City Boramae Hospital, Seoul (Korea, Republic of); Han, Moon Hee; Kim, Hyun Beom [College of Medicine, Seoul National University, Seoul (Korea, Republic of)] [and others
To describe the MR imaging and clinical findings of spontaneous spinal epidural hematoma. The MR and clinical findings in six patients (M:F=3D4:2;adult:child=3D3:3) with spontaneous spinal epidural hematoma were reviewed. Five patients without any predisposing factor which might cause the condition and one with acute myelogenous leukemia were included. Emergency surgery was performed in two patients, and the other four were managed conservatively. The epidural lesion involved between three and seven vertebrae (mean:4.5), and relative to the spinal cord was located in the posterior-lateral (n=3D4), anterior (n=3D1), or right lateral (n=3D1) area. The hematoma was isointense (n=3D1) or hyperintense (n=3D5) with spinal cord on T1-weighted images, and hypointense (n=3D2) or hyperintense (n=3D4) on T2-weighted images. It was completely absorbed in four of five patients who underwent follow-up MR imaging, but not changed in one. The clinical outcome of these patients was complete recovery (n=3D4), spastic cerebral palsy (n=3D1), or unknown (n=3D1). Because of the lesion's characteristic signal intensity; MR imaging is very useful in the diagnosis and evaluation of spontaneous spinal epidural hematoma. (author)
INTRODUCTION. Retroperitoneal hemorrhage or retroperitoneal hematoma (RH) refers to an accumulation of blood found in the retroperitoneal.. The retroperitoneum is a large space bounded anteriorly by the posterior parietal peritoneum, posteriorly be the transversalis fascia, and superiorly by the diaphragm. Inferiorly ...
Loomans, J. I.; Fijnvandraat, K.
With great interest we read the letter of Dr. Patil et al. (1) in which they present the number and percentage of hemophilia patients registered in the Mumbai hemophilia center who died from (intracranial) bleeding between 2002 and 2015. We thank Dr. Patil et al. for sharing their data and for
van Velzen, A.S.
Hemophilia A is an inherited X-linked bleeding disorder that occurs in male offspring of carrier females. In these individuals a mutation in the F8 gene, located on the X-chromosome, causes a deficiency of the factor VIII protein, clotting factor VIII. The worldwide prevalence of hemophilia is 1 in
Biere-Rafi, S.; Tuinenburg, A.; Haak, B.; Peters, M.; De Groot, E.; Verhamme, P.; Peerlinck, K.; Visseren, F.; Kruip, M.; Gorkom, B.L.-V.; Buller, H.; Gerdes, V.; Schutgens, R.; Kamphuisen, P.
Introduction: Hemophilia A patients have a 50% lower cardiovascular mortality than the general population. Whether this is caused by less atherosclerosis due to hypocoagulability is unclear. We assessed whether hemophilia A patients with obesity, a major atherosclerotic risk factor, have a lower
Full Text Available Inhibitor development is a lifelong challenge for patients with bleeding disorders who received replacement therapy. Most commonly, inhibitor formation was observed in hemophilia A patients but patients with rare bleeding disorders (RBD especially patients with deficiency of factor XIII (FXIII and factor V (FV can develop an inhibitor against exogenous factors. Several factors considered as risk factors for inhibitor formations in these patients. Genetic risk factors are the main accused that can cause inhibitor formation in hemophilia patients but are less important in RBDs.For this review study, we searched MEDLINE and Web of Science databases for English sources and the following key words: hemophilia, inhibitor, rare bleeding disorder, rare inherited disorder, acquired hemophilia, acquired rare bleeding disorders, treatment complication, genetic in hemophilia, polymorphism in rare bleeding disorder, mutation in hemophilia and other required keywords.Hemophilia A (HA patients who had large deletion, nonsense mutation or intron 22 inversion are more susceptible for inhibitor development. Gene polymorphisms in immune system are also considered as other risk factors in HA patients.Keywords: Hemophilia, rare bleeding disorder, inhibitor
Full Text Available The etiologies of Fournier's gangrene are well described into four groups: anorectal, genitourinary, dermatologic, and idiopathic. Here, we present the case of a hematoma and acute osteomyelitis (related to a closed fracture of the pubis, which progressed to Fournier's gangrene 1 month after trauma. A 68-year-old woman was admitted to our emergency department because she had sustained a left side pubic bone fracture from a fall. On her first admission to our emergency department, conservative treatment had been prescribed; however, she was readmitted to our emergency department due to septic shock, local swelling, and pus discharge from the pubis and the left labium majus. A whole abdomen computed tomography scan revealed fluid accumulation in the left suprapubic and perineum region in addition to acute osteomyelitis of the pubis. Acute osteomyelitis-related Fournier's gangrene and sepsis were suspected; hence, she underwent urgent fasciotomy and sequestrectomy. After three rounds of sequestrectomies, partial wound reconstruction with local flap and 24-day hospitalization, she was discharged from our hospital with continuing wound care management. Conservative treatment of closed stable fractures of the pelvic bone along with bed rest is suggested by most orthopedists. However, surgical drainage of hematoma is necessary due to the poor hematoma absorption owing to pelvic fracture. The patient subsequently contracted acute osteomyelitis, a secondary infection associated with the etiology of Fournier's gangrene, particularly in the case of patients with diabetes mellitus. We concluded that this was a rare etiology of Fournier's gangrene and examined the complications of pelvic bone fracture in this context.
Staber, Janice M; Pollpeter, Molly J
Hemophilia A animal models have helped advance our understanding of factor VIII deficiency. Previously, factor VIII deficient mouse models were reported to have a normal life span without spontaneous bleeds. However, the bleeding frequency and survival in these animals has not been thoroughly evaluated. To investigate the survival and lethal bleeding frequency in two strains of E-16 hemophilia A mice. We prospectively studied factor VIII deficient hemizygous affected males (n = 83) and homozygous affected females (n = 55) for survival and bleeding frequency. Animals were evaluated for presence and location of bleeds as potential cause of death. Hemophilia A mice had a median survival of 254 days, which is significantly shortened compared to wild type controls (p hemophilia A mice experienced hemorrhage in several tissues. This previously-underappreciated shortened survival in the hemophilia A murine model provides new outcomes for investigation of therapeutics and also reflects the shortened lifespan of patients if left untreated.
Gopalakrishnan, Natarajan; Usha, Thiruvengadam; Thopalan, Balasubramaniyan; Dhanapriya, Jeyachandran; Dineshkumar, Thanigachalam; Thirumalvalavan, Kaliaperumal; Sakthirajan, Ramanathan
Hemophilia A is a hereditary X-linked recessive disease caused by mutations in the gene encoding factor VIII (FVIII), occurring in 1 out of 10,000 persons. Life expectancy and quality of life have dramatically improved recently in patients with hemophilia. Chronic kidney disease and need for renal replacement therapy in these patients are rare. The development of inhibitors to FVIII is the most serious complication of hemophilia and makes treatment of bleeds very challenging. We describe here a 28-year-old male patient with severe hemophilia A with presence of factor VIII inhibitor, who had end stage renal disease. Central venous access device was inserted along with infusion of factor eight inhibitor bypass activity before and after the procedure. He is currently on thrice weekly hemodialysis and doing well for 6 months without bleeding episodes. To our knowledge, hemophilia A with factor VIII inhibitor managed with hemodialysis has not been reported so far. © 2016 International Society for Hemodialysis.
Werwitzke, S; Geisen, U; Nowak-Göttl, U; Eichler, H; Stephan, B; Scholz, U; Holstein, K; Klamroth, R; Knöbl, P; Huth-Kühne, A; Bomke, B; Tiede, A
Essentials Factor VIII (FVIII) binding IgG detected by ELISA could be an alternative to the Bethesda assay. We studied the performance of anti-FVIII IgG ELISA in patients with acquired hemophilia and controls. Anti-FVIII IgG > 99th percentile of controls was highly sensitive and specific. Patients with high anti-FVIII IgG have a lower chance of achieving remission. Background Acquired hemophilia A is a severe bleeding disorder that requires fast and accurate diagnosis as it occurs often unexpectedly in previously healthy men and women of every age. The Nijmegen-modified Bethesda assay is the diagnostic reference standard for detecting neutralizing autoantibodies against factor VIII (FVIII), but is not widely available, not ideal for quantifying the complex type 2 inhibitors seen in acquired hemophilia, and suffers from high inter-laboratory variability. Objectives To assess the diagnostic and prognostic value of FVIII-binding antibodies as detected by ELISA compared with the Nijmegen Bethesda assay. Methods Samples from the time of first diagnosis and clinical data were available from 102 patients with acquired hemophilia enrolled in the prospective GTH-AH 01/2010 study. Controls (n = 102) were matched for gender and age. Diagnostic cut-offs were determined by receiver-operator curve analysis. The prognostic value was assessed in 92 of the 102 patients by Cox regression analysis of time to partial remission. Results Anti-FVIII IgG above the 99th percentile (> 15 arbitrary units per mL) revealed high sensitivity and specificity (both 0.99; 95% confidence interval, 0.95-1.0) for diagnosing acquired hemophilia. The likelihood of achieving partial remission was related to anti-FVIII IgG concentration ( 1050, 0.39). The Bethesda titer was only associated with the likelihood of partial remission when analyzed in the central laboratory, but not when data from local GTH study sites were used. Conclusion Although the Nijmegen-modified Bethesda assay is the reference
Li, Qi; Zhang, Gang; Xiong, Xin; Wang, Xing-Chen; Yang, Wen-Song; Li, Ke-Wei; Wei, Xiao; Xie, Peng
Early hematoma growth is a devastating neurological complication after intracerebral hemorrhage. We aim to report and evaluate the usefulness of computed tomography (CT) black hole sign in predicting hematoma growth in patients with intracerebral hemorrhage. Patients with intracerebral hemorrhage were screened for the presence of CT black hole sign on admission head CT performed within 6 hours after onset of symptoms. The black hole sign was defined as hypoattenuatting area encapsulated within the hyperattenuating hematoma with a clearly defined border. The sensitivity, specificity, and positive and negative predictive values of CT black hole sign in predicting hematoma expansion were calculated. Logistic regression analyses were used to assess the presence of the black hole sign and early hematoma growth. A total of 206 patients were enrolled. Black hole sign was found in 30 (14.6%) of 206 patients on the baseline CT scan. The black hole sign was more common in patients with hematoma growth (31.9%) than those without hematoma growth (5.8%; Phole sign in predicting early hematoma growth were 31.9%, 94.1%, 73.3%, and 73.2%, respectively. The time-to-admission CT scan, baseline hematoma volume, and the presence of black hole sign on admission CT independently predict hematoma growth in multivariate model. The CT black hole sign could be used as a simple and easy-to-use predictor for early hematoma growth in patients with intracerebral hemorrhage. © 2016 American Heart Association, Inc.
Wang, Yong; Zhang, Jiliang
Subperiosteal hematoma is the accumulation of blood between the periosteum and the skull, which commonly occurs in the neonatal period but rarely in other ages. Subperiosteal hematoma can be self-absorbed in most cases and occasionally may cause ossification. This study reports a case of subperiosteal hematoma formed in a 16-year-old adolescent boy after a minor trauma. Because the hematoma did not disappear for more than a month after the trauma, the patient was treated with multiple hematoma punctures. However, the hematoma recurred and led to ossification. Finally, the patient underwent surgical treatment. Finally, the ossification associated with the hematoma was treated through surgery. The head contour recovered normally. The occurrence of hematoma ossification in the 16-year-old patient suggests that the periosteum has great potential for osteogenesis. This is likely caused by the joint action of some active factors in the blood and a certain tension of the hematoma on the local periosteum. This case provides the following thoughts. (1) A subperiosteal hematoma that has not been absorbed after 1 month should be treated promptly to avoid ossification. Once ossification has occurred, the hematoma should be treated surgically. (2) The potential for periosteal osteogenesis is great, which may provide a new thought for cranioplasty.
Buvanendran, Asokumar; Byrne, Richard W; Kari, Maruti; Kroin, Jeffrey S
The authors report the case of a 56-year-old previously healthy man who presented with a 4-month history of postural headache accompanied by nausea and vomiting. The results of initial imaging studies of the brain were normal. Repeated MR imaging demonstrated bilateral subdural hematomas which were drained and reaccumulated over a period of time. Spinal myelography revealed a cerebrospinal fluid leak at the C1-2 level. A cervical epidural blood patch, with repeated injections of 10 ml autologous blood at the site of the leak, dramatically improved the headache within 24 hours and eliminated the recurrent subdural hematomas. The results of follow-up computed tomography of the brain at 1, 4, 8, and 16 weeks were normal, and at 1-year follow-up the patient was completely free of symptoms and working.
Cicvarić, Tedi; Sustić, Alan; Miletić, Damir; Veselko, Matjaz; Mozetic, Vladimir; Spanjol, Josip
Strain of the medial head of the gastrocnemius muscle (GM) is a common injury that can be confirmed by ultrasound (US) or magnetic resonance imaging. We report a case of strain injury of the medial head of the GM, with a hematoma between the soleus muscle and the GM. US revealed an enlarged hypoechoic area between the soleus and the GM. By US-guided puncture, only a small amount of old blood was evacuated. Hence we undertook a surgical approach. It was performed under general endotracheal anesthesia, in the prone position. The most superficial area of hematoma was shown by US. A sharp 4-mm trocar was inserted in the posteromedial side of the calf and the hematoma was partially evacuated by suction. The cavity was washed out with saline solution. The arthroscope was then inserted. A second portal was made laterally and a shaver was inserted under optic control. The inflow pressure was not allowed to exceed 45 mm Hg. The shaver was used to remove blood coagula and fibrin septa that divided the cavity. The fibrous cavity membrane was debrided. By the end of the procedure, the circumference of the leg was reduced by 3 cm and the skin was softer on palpation. The patient was discharged the next day. One week after surgery, US examination revealed only a thin hypoechoic area in place of the previous collection. Two weeks after surgery, he was able to walk painlessly, and at 6 weeks he had regained normal walking activity.
Lane, Jérôme; McLaren, Paul J.; Dorrell, Lucy; Shianna, Kevin V.; Stemke, Amanda; Pelak, Kimberly; Moore, Stephen; Oldenburg, Johannes; Alvarez-Roman, Maria Teresa; Angelillo-Scherrer, Anne; Boehlen, Francoise; Bolton-Maggs, Paula H.B.; Brand, Brigit; Brown, Deborah; Chiang, Elaine; Cid-Haro, Ana Rosa; Clotet, Bonaventura; Collins, Peter; Colombo, Sara; Dalmau, Judith; Fogarty, Patrick; Giangrande, Paul; Gringeri, Alessandro; Iyer, Rathi; Katsarou, Olga; Kempton, Christine; Kuriakose, Philip; Lin, Judith; Makris, Mike; Manco-Johnson, Marilyn; Tsakiris, Dimitrios A.; Martinez-Picado, Javier; Mauser-Bunschoten, Evelien; Neff, Anne; Oka, Shinichi; Oyesiku, Lara; Parra, Rafael; Peter-Salonen, Kristiina; Powell, Jerry; Recht, Michael; Shapiro, Amy; Stine, Kimo; Talks, Katherine; Telenti, Amalio; Wilde, Jonathan; Yee, Thynn Thynn; Wolinsky, Steven M.; Martinson, Jeremy; Hussain, Shehnaz K.; Bream, Jay H.; Jacobson, Lisa P.; Carrington, Mary; Goedert, James J.; Haynes, Barton F.; McMichael, Andrew J.; Goldstein, David B.; Fellay, Jacques
Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979–1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this population. PMID:23372042
Full Text Available O aparecimento do anticorpo contra fator VIII é um fenômeno bem estabelecido na hemofilia A, ocorrendo em 5 a 15% dos pacientes hemofílicos dos Estados Unidos, Inglaterra, Suécia e França. Nos pacientes não-hemofílicos o seu aparecimento é raro, podendo ocorrer em indivíduos saudáveis, principalmente idosos e mulheres no puerpério, pacientes com neoplasia maligna ou doenças autoimunes, como lúpus eritematoso sistêmico, artrite reumatoide e síndrome de Sjögren. Descrevemos o caso de uma paciente de 64 anos de idade, portadora de artrite reumatoide soropositiva há 23 anos, que há 10 dias desenvolveu equimoses e hematomas progressivos cuja investigação foi compatível com a presença de anticorpo contra fator VIII. Foi instituída terapia com metilprednisolona, ciclofosfamida endovenosa, imunoglobulina e reposição de complexo protrombínico, com remissão do quadro hemorrágico e negativação do anticorpo contra o fator VIII. Concluímos com esse caso que, apesar de ser rara, a presença de inibidores adquiridos do fator VIII deve ser pesquisada quando pacientes portadores de doença autoimune desenvolvem manifestações hemorrágicas associadas ao prolongamento do TTPA com TAP e contagem plaquetária normais.The occurrence of the antibody against factor VIII is a well-known phenomenon in hemophilia A, occuring in 5 to 15% of the hemophilic patients in the United States, England, Sweden and France. The development of factor VIII in non-hemophilic patients is rare and may occur in healthy individuals, mostly elderly and women in postpartum period, and in patients with malignant neoplasia or autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome. We described the case of a 64-year-old female patient who has had seropositive rheumatoid arthritis for 23 years and presented with a ten-day history of progressive ecchymosis. Therapy with methylprednisolone, intravenous
Chen, Chi-Ya; Fransson, Boel A; Nylund, Adam M
CASE DESCRIPTION A 2-year-old castrated male mixed-breed dog was evaluated because of a 1-week history of respiratory distress and abdominal distension. Thoracic radiography and echocardiography at that time revealed an enlarged cardiac silhouette and pericardial effusion; abdominal radiography and ultrasonography revealed ascites. CLINICAL FINDINGS At the initial referral examination 5 weeks later, the dog weighed 37.5 kg (82.5 lb) and appeared clinically normal. The only abnormality detected was a grade I/VI systolic murmur on the left side of the thorax. Echocardiography revealed a large fat- and fluid-filled cystic structure located next to the right ventricle with scant pericardial effusion. Computed tomography revealed a bilobed peripherally contrast-enhancing structure within the right ventral aspect of the pericardium; the right ventricle appeared compressed by the cyst. TREATMENT AND OUTCOME Initial treatment consisted of pericardiocentesis and abdominocentesis to alleviate clinical signs. Thoracoscopic subtotal pericardectomy was performed 6 weeks after the initial treatment. The cyst was completely excised, and multiple adhesions between the visceral and parietal pericardium were transected, without surgical or anesthetic complications. Histologic examination of the cyst revealed chronic inflammation with histiocytic infiltration, suggesting possible foreign body reaction or chronic inflammation and hemorrhage. These findings supported a diagnosis of cystic hematoma of the pericardium. The dog remained clinically normal for at least 16 months after surgery. CLINICAL RELEVANCE This report represents a rare case of intrapericardial cystic hematoma in a dog. Minimally invasive surgery was performed without complications, suggesting that thoracoscopic subtotal pericardectomy is a feasible treatment option for affected dogs.
Ahmed M. Abbas
Full Text Available Ectopic pregnancy is a major cause of maternal morbidity and mortality in the first trimester. Interstitial type is the most dangerous variety with a high risk of life-threatening internal hemorrhage. Obstetricians need a high index of suspicion to diagnose such rare type. We are reporting a rare case of ruptured interstitial ectopic pregnancy presented with a large broad ligament hematoma early in the first trimester. A 25-year-old woman was presented with gradual onset of increasing abdominal pain after 6 weeks of amenorrhea. She had a positive urinary pregnancy test. Abdominal ultrasound revealed bulky empty uterus and ill-defined mass at the right side of the uterus. On exploration, incision and drainage of broad ligament hematoma were performed in addition to right salpingectomy. Interstitial ectopic pregnancy represents a diagnostic and therapeutic challenge and frequently constitutes an obstetrical emergency. Its rupture early in the first trimester should be expected. Early diagnosis and proper management are the most important issues to avoid its catastrophic consequences.
Barrios, Lucia; Clément, Renaud; Visseaux, Guillaume; Bord, Eric; Le Gall, Francois; Rodat, Olivier
In forensic medicine, a chronic subdural hematoma (SDH) usually results from trauma, sometimes minimal for elderly people. The case reported here is a forensic medical description of an atypical chronic subdural hematoma. A woman aged of 40-year-old died following a coma. The autopsy and histological analyses revealed the hemorrhagic disintegration of a lymphoid nodule, a metastasis from generalized lymphoma. The combination of chronic symptomatic SDH and a tumor of the dura mater have been described, but are very rare. The possibility of trauma, even minimal, has never been excluded in these cases. In fact, the clinical picture of these patients suggested a significant movement of the brain within the cranial cavity due to the physiological decrease in brain volume. In the reported case, this particular process was excluded since the spontaneous hemorrhagic effusion produced by the meningeal lymphoid nodule was the cause of the chronic SDH. This pathophysiological explanation was possible because the entire brain and meninges were removed for histological analysis. Trauma, even minimal trauma, is not always involved in the formation of a chronic SDH. Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
Full Text Available Nissrine Louhab,1 Nawal Adali,1 Mehdi Laghmari,2 Wafae El Hymer,2 Said Ait Ben Ali,2 Najib Kissani11Neurology Department, 2Neurosurgery Department, University Hospital of Mohammed the VIth, Cadi Ayyad University, Marrakech, MoroccoIntroduction: Spontaneous intracranial hypotension is an infrequent cause of secondary headache due to cerebrospinal fluid (CSF hypovolemia.Objective: To describe a case of headache revealing spontaneous intracranial hypotension complicated by subdural hematoma following lumbar puncture.Observation: A 34-year-old man presented with acute postural headache. The first cerebral computed tomography scan was normal. Lumbar puncture showed hyperproteinorachy at 2 g/L with six lymphocytic cells. The headache became very intense. At admission, clinical examination was normal. Ophthalmological examination did not show any abnormalities. Encephalic magnetic resonance imaging (MRI showed bilateral subdural hematoma with tonsillar descent simulating Chiari type I malformation. After surgical drainage and symptomatic treatment, the patient was discharged with no recurrence.Conclusion: Spontaneous intracranial hypotension is associated with simple clinical presentation, orthostatic headache, and characteristic MRI findings. Misdiagnosed, it leads to unnecessary procedures.Keywords: intracranial hypotension, headache, magnetic resonance imaging
Full Text Available We present a rare case of spinal epidural hematoma (SEH after thoracolumbar posterior fusion without decompression surgery for a thoracic vertebral fracture. A 42-year-old man was hospitalized for a thoracic vertebral fracture caused by being sandwiched against his back on broken concrete block. Computed tomography revealed a T12 dislocation fracture of AO type B2, multiple bilateral rib fractures, and a right hemopneumothorax. Four days after the injury, in order to promote early orthostasis and to improve respiratory status, we performed thoracolumbar posterior fusion surgery without decompression; the patient had back pain but no neurological deficits. Three hours after surgery, he complained of acute pain and severe weakness of his bilateral lower extremities; with allodynia below the level of his umbilicus, postoperative SEH was diagnosed. We performed immediate revision surgery. After removal of the hematoma, his symptoms improved gradually, and he was discharged ambulatory one month after revision surgery. Through experience of this case, we should strongly consider the possibility of preexisting SEH before surgery, even in patients with no neurological deficits. We should also consider perioperative coagulopathy in patients with multiple trauma, as in this case.
Full Text Available Abstract A 68 year-old male patient was hospitalized for radical prostatectomy. He had no abnormal medical history including neurological deficit before the operation. Prior to general anesthesia, an epidural catheter was inserted in the L3-4 interspace for intraoperative and postoperative analgesia. After surgery for nine hours, he developed confusion and flaccid paralysis of bilateral lower extremities occurred. No pathology was detected from cranial computed tomography and diffusion magnetic resonance imaging no pathology was detected. His thoracic/lumbar magnetic resonance imaging. Intraabdominal pressure was shown to be 25 mmHg, and abdominal ultrasonography revealed progression in the inflammation/edema/hematoma in the perirenal region. The Bromage score was back to 1 in the right foot on the 24th hour and in the left foot on the 26th hour. Paraplegia developed in patients after epidural infusion might be caused by potentiated local anesthetic effect due to retroperitoneal hematoma and/or elevated intra-abdominal pressure.
Matsui, Hideto; Fujimoto, Naoko; Sasakawa, Noriko; Ohinata, Yasuhide; Shima, Midori; Yamanaka, Shinya; Sugimoto, Mitsuhiko; Hotta, Akitsu
Viral vectors have been used for hemophilia A gene therapy. However, due to its large size, full-length Factor VIII (FVIII) cDNA has not been successfully delivered using conventional viral vectors. Moreover, viral vectors may pose safety risks, e.g., adverse immunological reactions or virus-mediated cytotoxicity. Here, we took advantages of the non-viral vector gene delivery system based on piggyBac DNA transposon to transfer the full-length FVIII cDNA, for the purpose of treating hemophilia A. We tested the efficiency of this new vector system in human 293T cells and iPS cells, and confirmed the expression of the full-length FVIII in culture media using activity-sensitive coagulation assays. Hydrodynamic injection of the piggyBac vectors into hemophilia A mice temporally treated with an immunosuppressant resulted in stable production of circulating FVIII for over 300 days without development of anti-FVIII antibodies. Furthermore, tail-clip assay revealed significant improvement of blood coagulation time in the treated mice. piggyBac transposon vectors can facilitate the long-term expression of therapeutic transgenes in vitro and in vivo. This novel gene transfer strategy should provide safe and efficient delivery of FVIII.
Full Text Available Viral vectors have been used for hemophilia A gene therapy. However, due to its large size, full-length Factor VIII (FVIII cDNA has not been successfully delivered using conventional viral vectors. Moreover, viral vectors may pose safety risks, e.g., adverse immunological reactions or virus-mediated cytotoxicity. Here, we took advantages of the non-viral vector gene delivery system based on piggyBac DNA transposon to transfer the full-length FVIII cDNA, for the purpose of treating hemophilia A. We tested the efficiency of this new vector system in human 293T cells and iPS cells, and confirmed the expression of the full-length FVIII in culture media using activity-sensitive coagulation assays. Hydrodynamic injection of the piggyBac vectors into hemophilia A mice temporally treated with an immunosuppressant resulted in stable production of circulating FVIII for over 300 days without development of anti-FVIII antibodies. Furthermore, tail-clip assay revealed significant improvement of blood coagulation time in the treated mice. piggyBac transposon vectors can facilitate the long-term expression of therapeutic transgenes in vitro and in vivo. This novel gene transfer strategy should provide safe and efficient delivery of FVIII.
Follenzi, Antonia; Raut, Sanj; Merlin, Simone; Sarkar, Rita
To better understand cellular basis of hemophilia, cell types capable of producing FVIII need to be identified. We determined whether bone marrow (BM)–derived cells would produce cells capable of synthesizing and releasing FVIII by transplanting healthy mouse BM into hemophilia A mice. To track donor-derived cells, we used genetic reporters. Use of multiple coagulation assays demonstrated whether FVIII produced by discrete cell populations would correct hemophilia A. We found that animals receiving healthy BM cells survived bleeding challenge with correction of hemophilia, although donor BM-derived hepatocytes or endothelial cells were extremely rare, and these cells did not account for therapeutic benefits. By contrast, donor BM-derived mononuclear and mesenchymal stromal cells were more abundant and expressed FVIII mRNA as well as FVIII protein. Moreover, injection of healthy mouse Kupffer cells (liver macrophage/mononuclear cells), which predominantly originate from BM, or of healthy BM-derived mesenchymal stromal cells, protected hemophilia A mice from bleeding challenge with appearance of FVIII in blood. Therefore, BM transplantation corrected hemophilia A through donor-derived mononuclear cells and mesenchymal stromal cells. These insights into FVIII synthesis and production in alternative cell types will advance studies of pathophysiological mechanisms and therapeutic development in hemophilia A. PMID:22368271
Radcliff, Kris; Morrison, William B; Kepler, Christopher; Moore, Jeffrey; Sidhu, Gursukhman S; Gendelberg, David; Miller, Luciano; Sonagli, Marcos A; Vaccaro, Alexander R
Retrospective case series. To identify specific magnetic resonance imaging (MRI) characteristics of epidural fluid collections associated with infection, hematoma, or cerebrospinal fluid (CSF). Interpretation of postoperative MRI can be challenging after lumbar fusion. The purpose of this study was to identify specific MRI characteristics of epidural fluid collections associated with infection, hematoma, or CSF. The study population includes consecutive patients between 2006 and 2010 who had MRIs performed within 2 weeks after elective surgery for evaluation of possible CSF fluid collection, hematoma, or infection. Patients with known previous infection (discitis/osteomyelitis) or inadequate MRIs were excluded from the study. Medical records were reviewed to determine the diagnosis (infection, hematoma, or pseudomeningocele) underlying the fluid collection. MRIs were retrospectively evaluated by a musculoskeletal radiologist and orthopedic spine attending who were blinded to the pathologic diagnosis for characteristics of the fluid collection. MRI characteristics include location of lesion: osseous involvement, disk location, anterior versus posterior versus anteroposterior, soft-tissue involvement, and iliopsoas involvement. Characteristics of the lesion include: volume of lesion, loculation, satellite lesions, multiple loci, destructive characteristics, and mass effect upon thecal sac. Enhancement was scored based upon the following variables: rim enhancement, smooth versus irregular, thin versus thick, heterogeneity, diffuse enhancement, nonenhancement, and rim thickness. General fluid collection intensity and complexity on T1, T2, and T1 postcontrast images was scored as high, medium, and low. The χ test was used to compare the incidence of imaging characteristics between patient groups (infection, hematoma, and CSF). Thirty-three patients were identified who met inclusion criteria. There were 13 (39%) with infection, 9 (27%) with hematoma, and 11 (33%) with
Tony Wing-Cheong Chi
Full Text Available We present the case of a 64-year-old female treated surgically for ligamentum flavum hematoma that caused progressive radiculopathy. Initially, she suffered from an acute onset of lower back pain. Only a history of minor back injury was discovered. She rapidly became unable to walk. Magnetic resonance imaging demonstrated an epidural mass lesion at L3 to L4 that was continuous with the left ligamentum flavum. The mass was hypointense on T1-weighted images and centrally hyperintense and marginally hypointense on T2-weighted images. The margin was well enhanced by gadopentetate dimeglumine administration. After removal of the mass, the patient's symptoms completely resolved. Before surgery, we believe accurate diagnosis of ligamentum flavum hematoma can be based on magnetic resonance imaging.
Full Text Available We report the case of a 25-year-old woman, who received epidural analgesia for labor pain and subsequently presented post-dural puncture headache. Conservative treatment was applied and epidural blood patch was performed. In the absence of clinical improvement and due to changes in the postural component of the headache, a brain imaging test was performed showing a bilateral subdural hematoma. The post-dural puncture headache is relatively common, but the lack of response to established medical treatment as well as the change in its characteristics and the presence of neurological deficit, should raise the suspicion of a subdural hematoma, which although is rare, can be lethal if not diagnosed and treated at the right time.
Sanders, Rebecca A; Bendel, Markus A; Moeschler, Susan M; Mauck, William D
We present a case report of a patient who developed an epidural hematoma following an interlaminar epidural steroid injection with no risk factors aside from old age and aspirin use for secondary prevention. A 79-year-old man developed an epidural hematoma requiring surgical treatment following an uncomplicated interlaminar epidural steroid injection performed for neurogenic claudication. In the periprocedural period, he continued aspirin for secondary prophylaxis following a myocardial infarction. For patients taking aspirin for primary or secondary prophylaxis, the American Society of Regional Anesthesia and Pain Medicine antiplatelet and anticoagulation guidelines for spine and pain procedures recommend a shared assessment and risk stratification when deciding to hold the medication for intermediate-risk neuraxial procedures. Cases such as this serve to highlight the importance of giving careful consideration to medical optimization of a patient even when a low- or intermediate-risk procedure is planned.
Full Text Available Spontaneous spinal epidural hematoma is a rare cause of acute spinal cord compression. A 25-year-old male presented with a history of sudden onset of complete quadriplegia with sensory loss below the neck along with loss of bowel and bladder control. He had no history of any constitutional symptoms. He reported 10 days later. He was managed conservatively and after two weeks of intensive rehabilitation he had complete neural recovery. The spontaneous recovery of neurological impairment is attributed to the spreading of the hematoma throughout the epidural space, thus decreasing the pressure with partial neural recovery. Conservative treatment is a fair option in young patients who present late and show neurological improvement. The neurological status on presentation will guide the further approach to management.
Burkhardt, Jan-Karl; Kockro, Ralf A; Dohmen-Scheufler, Hildegard; Woernle, Christoph M; Bellut, David; Kollias, Spyros; Bertalanffy, Helmut
A 16-year-old boy presented with an unusual case of a supratentorial, extraaxial small round blue cell tumor of the central nervous system, which was most likely a primitive neuroectodermal tumor (PNET). Preoperative computed tomography and magnetic resonance imaging showed a large multistage hematoma in the left central region. Intraoperatively, a small, superficial tumorous lesion was found between the sagittal sinus and a large cortical vein hidden by the hematoma. The histological diagnosis was PNET. This tumor is one of the most aggressive intracerebral tumors, not only in children, so treatment strategies must be early, profound, and interdisciplinary. This case represents an important example of atypical extraaxial appearance of this lesion, which should be considered in the differential diagnosis of cortical or subcortical hemorrhage, since complete resection of this lesion is critical for the successful treatment and outcome.
Shetty, Shrimati; Bhave, Manali; Ghosh, Kanjaksha
Acquired hemophilia A (AHA) is a rare disorder with an incidence of approximately 1 per million/year with a high mortality rate of more than 20%. The disease occurs due to autoantibodies against coagulation factor VIII (FVIII) which neutralize its procoagulant function and result in severe, often life-threatening bleeding. The antibodies arise in individuals with no prior history of hemophilia A. AHA may be associated with pregnancy, autoimmune diseases, malignancy, infections or medication and occurs most commonly in the elderly. Approximately 50% of the patients remain idiopathic with no known underlying pathological condition. Clinical manifestations include spontaneous hemorrhages into the skin, muscles or soft tissues or excessive bleeding during surgery. Hemarthrosis which is the hallmark of congenital severe hemophilia A seldom occurs in AHA. The diagnosis of AHA is based on the isolated prolongation of activated partial thromboplastin time (APTT) which does not normalize after the addition of normal plasma along with reduced FVIII levels. The treatment involves two aspects-eradication of antibodies and maintaining effective hemostasis during a bleeding episode. The protocols for eradication of antibodies include immunoadsorption, immunosuppression or immune tolerance induction (ITI). The treatment of acute bleeding episodes involves use of different bypassing agents like recombinant activated factor VIIa (rFVIIa, NovoSeven®) and activated prothrombin complex concentrate (aPCC, (FEIBA®) in case of patients with high titer inhibitors or with antifibrinolytics,1-deamino-8-D-arginine vasopressin (DDAVP) or FVIII concentrates in low titer inhibitor patients. The anti CD20 monoclonal antibody, rituximab, has shown very good results either singly or in combination with immunosuppressive regimens in patients who do not respond to standard immunosuppressors. The present review summarizes the diagnostic, aetiological, clinical and treatment aspects of AHA focusing
Pino Rivero, V; Pantoja Hernández, C G; González Palomino, A; Pardo Romero, G; Trinidad Ramos, G; Montero García, C; Blasco Huelva, A
We report the case ofa 61 years old woman with multiple pathologies: HTA, diabetes, relapsing polychondritis, hypercholesterolemia, iatrogenic Cushing, cardiopathy, cystic fibrosis, etc. She began, an increment of TA (220/130 mm Hg) or hypertensive crisis, with a sudden left cervical hematoma located on the carotid bifurcation according to CT imaging. We oractice an arteriography that was informed as normal and the patient was admitted and controlled of an ORL as Vascular Surgeon. The bleeding stop spontaneously we treat the patient conservativity.
Full Text Available Traumatic optic neuropathy is an uncommon, yet serious, result of facial trauma. The authors present a novel case of a 59-year-old gentleman who presented with an isolated blunt traumatic left optic nerve hematoma causing vision loss. There were no other injuries or fractures to report. This case highlights the importance of early recognition of this rare injury and reviews the current literature and management of traumatic optic neuropathy.
Puetz, John; Soucie, J. Michael; Kempton, Christine L.; Monahan, Paul E.
Summary Background Several risk factors for inhibitors have recently been described for hemophilia A. It has been assumed that similar risk factors are also relevant for hemophilia B, but there is limited data to confirm this notion. Objectives To determine the prevalence of and risk factors associated with inhibitors in hemophilia B Methods The database of the Universal Data Collection (UDC) project of the Centers for Disease Control for the years 1998 – 2011 was queried to determine the prevalence of inhibitors in hemophilia B subjects. In addition, disease severity, race/ethnicity, age, factor exposure, and prophylaxis usage were evaluated to determine their impact on inhibitor prevalence. Results Of the 3800 male subjects with hemophilia B enrolled in the UDC database, 75 (2%) were determined to have an inhibitor at some point during the study period. Severe disease (OR 13.1, 95% CI 6.2-27.7), black race (OR 2.2, 95% CI 1.2-4.1), and age less than 11 (OR 2.5, 95% CI 1.5-4.0) were found to be significantly associated with having an inhibitor. There was insufficient data to determine if type of factor used and prophylaxis were associated with inhibitors. Conclusions Inhibitors in hemophilia B are much less prevalent than hemophilia A, especially in patients with mild disease. Similar factors associated with inhibitors in hemophilia A also seem to be present for hemophilia B. The information collected by this large surveillance project did not permit evaluation of potential risk factors related to treatment approaches and exposures, and additional studies will be required. PMID:23855900
Mao, Jianhua; Xi, Xiaodong; Kapranov, Philipp; Dong, Biao; Firrman, Jenni; Xu, Ruian; Xiao, Weidong
Hemophilia A is a hereditary disorder caused by various mutations in factor VIII gene resulting in either a severe deficit or total lack of the corresponding activity. Recent success in gene therapy of a related disease, hemophilia B, gives new hope that similar success can be achieved for hemophilia A as well. To develop a gene therapy strategy for the latter, a variety of model systems are needed to evaluate molecular engineering of the factor VIII gene, vector delivery efficacy and safety-related issues. Typically, a tissue culture cell line is the most convenient way to get a preliminary glimpse of the potential of a vector delivery strategy. It is then followed by extensive testing in hemophilia A mouse and dog models. Newly developed hemophilia A sheep may provide yet another tool for evaluation of factor VIII gene delivery vectors. Hemophilia models based on other species may also be developed since hemophiliac animals have been identified or generated in rat, pig, cattle and horse. Although a genetic nonhuman primate hemophilia A model has yet to be developed, the non-genetic hemophilia A model can also be used for special purposes when specific questions need to be addressed that cannot not be answered in other model systems. Hemophilia A is caused by a functional deficiency in the factor VIII gene. This X-linked, recessive bleeding disorder affects approximately 1 in 5000 males [1-3]. Clinically, it is characterized by frequent and spontaneous joint hemorrhages, easy bruising and prolonged bleeding time. The coagulation activity of FVIII dictates severity of the clinical symptoms. Approximately 50% of all cases are classified as severe with less than 1% of normal levels of factor VIII detected . This deficiency may lead to spontaneous joint hemorrhages or life-threatening bleeding. In contrast, patients with 5-30% of normal factor VIII activity exhibit mild clinical manifestations.
Atci Ibrahim Burak
Full Text Available Background: In this study, the patients who were operated in two clinics due to traumatic cranial epidural hematoma (EDH were assessed retrospectively and the factors that increase the costs were tried to be revealed through conducting cost analyses. Methods: The patients who were operated between 2010 and 2016 with the diagnosis of EDH were assessed in terms of age, sex, trauma etiology, Glasgow coma scale (GCS at admission, the period from trauma to hospital arrival, trauma-related injury in other organs, the localization of hematoma, the size of hematoma, length of stay in the intensive care unit (ICU, length of antibiotherapy administration, number of consultations conducted, total cost of in-hospital treatments of the patients and prognosis. Results: Distribution of GCS were, between 13-15 in 18 (36% patients, 9-13 in 23 (46% patients and 3-8 in 9 (18% patients. The reasons for emergency department admissions were fall from high in 29 (58% patients, assault in 11 (22% patients and motor vehicle accident in 10 (20% patients. The average cost per ICU stay was 2838 $ (range=343-20571 $. The average cost per surgical treatment was 314 $. ICU care was approximately 9 times more expensive than surgical treatment costs. The mortality rate of the study cohort was 14% (7 patients. Conclusion: The prolonged period of stay in the ICU, antibiotherapy and repeat head CTs increase the costs for patients who are surgically treated for EDH.
Full Text Available Adriana Aparecida Ferreira,1 Isabel Cristina Gonçalves Leite,2 Maria Teresa Bustamante-Teixeira,2 Maximiliano Ribeiro Guerra2 1Foundation and Center for Hematology and Hemotherapy of Minas Gerais (Hemominas, 2Department of Collective Health, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, BrazilAbstract: Hemophilia A is an inherited disorder characterized by deficiency of coagulation factor VIII, which predisposes patients to bleeding events. Treatment is based on replacement of the deficient factor, in a therapeutic or prophylactic manner. Brazil is the country with the third largest population of people with hemophilia, for which the public health system provides free comprehensive care. Maintaining an updated registry of patients, documenting the prevalence of complications, and assessing the effectiveness of resource use are indispensable elements in the design of a well-coordinated national program. According to sociodemographic, clinical, and laboratory data collected by the computerized Brazilian system on coagulopathies, in June 2013, there were 9,122 registered patients with hemophilia A in Brazil, of which 36.1% had a severe form of the disease. Clotting factor inhibitors were present in 7.5%, but 25.7% of records did not provide this type of data. Around 70% of the patients belonged to the economically active population, being between 15 and 59 years old. Infection by the human immunodeficiency virus was present in 23.4% of the patients tested and infection by hepatitis C virus antibodies in 59.3%. Infection by the hepatitis B virus and human T-lymphotropic virus was also reported. The high percentage of incomplete records regarding serological data shows the fragility of the information system to date. There was also no information available on the prevalence of permanent or disabling joint damage. Although few hemophiliacs receive adequate care in developing countries, and despite Brazil exhibiting great social
Rangarajan, Savita; Walsh, Liron; Lester, Will; Perry, David; Madan, Bella; Laffan, Michael; Yu, Hua; Vettermann, Christian; Pierce, Glenn F; Wong, Wing Y; Pasi, K John
Patients with hemophilia A rely on exogenous factor VIII to prevent bleeding in joints, soft tissue, and the central nervous system. Although successful gene transfer has been reported in patients with hemophilia B, the large size of the factor VIII coding region has precluded improved outcomes with gene therapy in patients with hemophilia A. We infused a single intravenous dose of a codon-optimized adeno-associated virus serotype 5 (AAV5) vector encoding a B-domain-deleted human factor VIII (AAV5-hFVIII-SQ) in nine men with severe hemophilia A. Participants were enrolled sequentially into one of three dose cohorts (low dose [one participant], intermediate dose [one participant], and high dose [seven participants]) and were followed through 52 weeks. Factor VIII activity levels remained at 3 IU or less per deciliter in the recipients of the low or intermediate dose. In the high-dose cohort, the factor VIII activity level was more than 5 IU per deciliter between weeks 2 and 9 after gene transfer in all seven participants, and the level in six participants increased to a normal value (>50 IU per deciliter) that was maintained at 1 year after receipt of the dose. In the high-dose cohort, the median annualized bleeding rate among participants who had previously received prophylactic therapy decreased from 16 events before the study to 1 event after gene transfer, and factor VIII use for participant-reported bleeding ceased in all the participants in this cohort by week 22. The primary adverse event was an elevation in the serum alanine aminotransferase level to 1.5 times the upper limit of the normal range or less. Progression of preexisting chronic arthropathy in one participant was the only serious adverse event. No neutralizing antibodies to factor VIII were detected. The infusion of AAV5-hFVIII-SQ was associated with the sustained normalization of factor VIII activity level over a period of 1 year in six of seven participants who received a high dose, with
Sedigh, Omidreza; Lasaponara, Fedele; Dalmasso, Ettore; Gai, Massimo; Hayashi, Yoshiki; Bosio, Andrea; Pasquale, Giovanni; Lillaz, Beatrice; Biancone, Luigi; Frea, Bruno
A 67-year-old man presented to the emergency department 22 hours after a trauma to his kidney graft. He was asymptomatic during the first 10 hours, then he became anuric. His serum creatinine level was 2.73 mg/dL (baseline, 0.7 mg/dL), and his hemoglobin concentration was 13.1 g/dL. Computer tomography showed a 4-cm subcapsular hematoma without active bleeding. He underwent urgent decompression of the hematoma, and we did not find any active bleeding or parenchymal laceration. Urinary output had already recovered by the end of surgery without early or late complications. In conclusion, subcapsular hematoma, complicating a traumatic event on a kidney graft, can lead to a progressive parenchymal compression resulting in anuria. So, although in the absence of anemia, such events require urgent surgical decompression. Symptoms cannot be immediate, so all the graft trauma should be investigated with early ultrasound. Little is known in the case of major renal trauma but mildly symptomatic. Probably surgical exploration is better than observation to prevent possible early and late complications such as organ rejection or a Page kidney.
Andersen-Ranberg, Nina Christine; Poulsen, Frantz Rom; Bergholt, Bo; Hundsholt, Torben; Fugleholm, Kåre
OBJECTIVE Bilateral chronic subdural hematoma (bCSDH) is a common neurosurgical condition frequently associated with the need for retreatment. The reason for the high rate of retreatment has not been thoroughly investigated. Thus, the authors focused on determining which independent predictors are associated with the retreatment of bCSDH with a focus on surgical laterality. METHODS In a national database of CSDHs (Danish Chronic Subdural Hematoma Study) the authors retrospectively identified all bCSDHs treated in the 4 Danish neurosurgical departments over the 3-year period from 2010 to 2012. Univariate and multivariate analyses were performed to determine the relationship between retreatment of bCSDH and clinical, radiological, and surgical variables. RESULTS Two hundred ninety-one patients with bCSDH were identified, and 264 of them underwent unilateral (136 patients) or bilateral (128 patients) surgery. The overall retreatment rate was 21.6% (57 of 264 patients). Cases treated with unilateral surgery had twice the risk of retreatment compared with cases undergoing bilateral surgery (28.7% vs 14.1%, respectively, p = 0.002). In accordance with previous studies, the data also showed that a separated hematoma density and the absence of postoperative drainage were independent predictors of retreatment. CONCLUSIONS In bCSDHs bilateral surgical intervention significantly lowers the risk of retreatment compared with unilateral intervention and should be considered when choosing a surgical procedure.
Chaari, Mourad; Bouhlel, Riadh; Kallel, Samy; Aïdi, Zied; Makni, Faiza; Gerotziafas, Grigoris T; Elalamy, Ismail; Karoui, Abdelhamid; Kallel, Choumous
We report the case of a 19-year-old women who developed on post partum day 1 a large hematoma in the vaginal wall. A surgical intervention for evacuating the hematoma was complicated with profuse bleeding of the genital and abdominal cavities. Postoperative coagulation studies revealed a prolonged activated partial thromboplastin time (87/30 s; ratio: 2.9), a decreased factor VIII level at 7% and the presence of an anti-factor VIII inhibitor in a titer of 64 Bethesda Unit (BU). Due to the active bleeding, the patient received Novoseven(®) (recombinant factor VIIa: 2 doses on post partum day 3 and 1 dose on day 6) and Feiba(®) (activated prothrombin complex concentrates: 1 dose on post partum day 8). These few administrated doses were not enough efficacious to achieve a continuous control of the bleeding. Immunosuppressive treatment used prednisone alone for 3 days, then combined to cyclophosphamide. The outcome was marked by the aggravation of the bleeding and an increase in the inhibitor level (132 BU). Finally, the patient died on post partum day 8 following an hemorrhagic shock.
Antonio Guevara Melcón
Full Text Available Se presenta una paciente portadora de un hematoma subdural crónico postraumático, que se trató médicamente y se logró su desaparición en el curso de varios meses, sin tratamiento quirúrgico y sin signos evolutivos de empeoramiento neurológico. La furosemida fue usada como medicamento básico en su tratamiento. Se adjuntan imágenes que confirman el valor de este punto de vista terapéutico.This is the case of a patient carrier of a post-traumatic chronic subdural hematoma clinically treated achieving its disappearance over some months without surgical treatment and evolutionary signs of neurologic worsening. The furosemide was used as basic drug in its treatment. The images confirming the value of this point of therapeutical view are enclosed.
Full Text Available A 33-year-old male patient experienced temporary sensory loss and weakness in the right lower extremity one month prior to admission. The patient was admitted to a private clinic with a three-day history of acute onset of sensory loss and weakness in both lower extremities and was treated and followed up with a prediagnosis of transverse myelitis and the Guillain-Barre syndrome (GBS. The patient was subsequently transferred to our clinic and the neurologic examination revealed paraplegia in both lower extremities, positive bilateral Babinski signs, and hypesthesia below the T10 dermatome with saddle anesthesia. The patient had urinary incontinence and thoracic magnetic resonance imaging (MRI showed an image of a mass compressing the medulla.
Nicholas B. Abt
Full Text Available Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII inhibitor was undetectable. Methods. The patient’s plasma was comprehensively studied to determine the cause of the acquired coagulopathy. Using the Nijmegen modification of the Bethesda assay, no factor VIII autoantibody was measureable despite varying the incubation time from 1 to 3 hours. Results. The aPTT was prolonged at 46.8 seconds, which did not correct in the 4 : 1 mix but did with 1 : 1 mix. Using a one stage factor VIII activity assay, the FVIII activity was 16% and chromogenic FVIII activity was also 16%. The patient was treated with recombinant FVII and transfusion, significantly reducing bleeding. Long-term therapy was initiated with cyclophosphamide and prednisone with normalization of FVIII activity. Conclusions. Physicians can be presented with the challenging clinical picture of an acquired factor VIII inhibitor without a detectable inhibitor by the Bethesda assay. Standard therapy for an acquired hemophilia A should be considered.
Full Text Available Acquired hemophilia A (AHA is a rare hemorrhagic disease in which autoantibodies against coagulation factor VIII- (FVIII- neutralizing antibodies (inhibitors impair the intrinsic coagulation system. As the inhibitors developed in AHA are autoantibodies, the disease may have an autoimmune cause and is often associated with autoimmune disease. Although acute hemorrhage associated with AHA may be fatal and is costly to treat, AHA is often unrecognized or misdiagnosed. AHA should thus be considered in the differential diagnosis particularly in postpartum women and the elderly with bleeding tendency or prolonged activated partial thromboplastin time. Cross-mixing tests and measurement of FVIII-binding antibodies are useful to confirm AHA diagnosis. For treatment of acute hemorrhage, hemostatic therapy with bypassing agents should be provided. Unlike in congenital hemophilia A with inhibitors, in which immune tolerance induction therapy using repetitive infusions of high-dose FVIII concentrates is effective for inhibitor eradication, immune tolerance induction therapy has shown poor efficacy in treating AHA. Immunosuppressive treatment should thus be initiated to eradicate inhibitors as soon as the diagnosis of AHA is confirmed.
Sakurai, Yoshihiko; Takeda, Tomohiro
Acquired hemophilia A (AHA) is a rare hemorrhagic disease in which autoantibodies against coagulation factor VIII- (FVIII-) neutralizing antibodies (inhibitors) impair the intrinsic coagulation system. As the inhibitors developed in AHA are autoantibodies, the disease may have an autoimmune cause and is often associated with autoimmune disease. Although acute hemorrhage associated with AHA may be fatal and is costly to treat, AHA is often unrecognized or misdiagnosed. AHA should thus be considered in the differential diagnosis particularly in postpartum women and the elderly with bleeding tendency or prolonged activated partial thromboplastin time. Cross-mixing tests and measurement of FVIII-binding antibodies are useful to confirm AHA diagnosis. For treatment of acute hemorrhage, hemostatic therapy with bypassing agents should be provided. Unlike in congenital hemophilia A with inhibitors, in which immune tolerance induction therapy using repetitive infusions of high-dose FVIII concentrates is effective for inhibitor eradication, immune tolerance induction therapy has shown poor efficacy in treating AHA. Immunosuppressive treatment should thus be initiated to eradicate inhibitors as soon as the diagnosis of AHA is confirmed.
Brown, Larry K; Schultz, Janet R; Forsberg, Ann D; King, Gary; Kocik, Susan M; Butler, Regina B
Health care professionals working with individuals with chronic medical illness, especially those infected with the Human Immunodeficiency Virus (HIV), may be at risk for burnout and departure due to various job stresses such as the death of patients and social stigma. Factors that prevent burnout and employee attrition are seldom studied. Two hundred thirteen staff (doctors, nurses and mental health workers) at a representative sample of Hemophilia Treatment Centers (HTC) completed instruments to measure Burnout (Maslach Burnout Inventory), and perceived job stresses and satisfaction (job tasks, interactions with colleagues and patient care). The staff were surveyed again after two years and their job status determined after 4 years. After 4 years, 35% of the staff had left the field of Hemophilia/HIV care. Univariate tests found that retention was significantly associated with initial job satisfaction, being married and low levels of stress with colleagues. Burnout, as measured by the Maslach Burnout Inventory, at baseline, was unrelated to job retention over 4 years. An adjusted multiple logistic regression of all significant variables found that colleague support was most related to retention (OR=2.8, CI=1.49,5.1). We conclude that attrition of highly trained staff is a significant issue for patients and HTCs. These data suggest the important role that a well-functioning team can have in buffering the inevitable stresses associated with HIV care. Mental Health professionals have considerable expertise in addressing these issues.
Rafael Py Gonçalves Flores
equipo multidisciplinar. CONTENIDO: Están definidas las características de la hemofilia en cuanto a la clínica y a los hallazgos laboratoriales, la terapia farmacológica actual y las atenciones con el manoseo del paciente hemofílico en el intra-operatorio. CONCLUSIONES: El manoseo del paciente hemofílico fue perfeccionado. Como consecuencia de ese avance, se percibe la importancia y la necesidad de que nuevos conocimientos, principalmente con relación a la terapia de reposición, sean dominados por hematologistas y por todo el cuerpo clínico-quirúrgico. Cuando pacientes hemofílicos se someten a procedimientos quirúrgicos, es necesario el envolvimiento de un equipo multidisciplinar de la cual el anestesiologista hace parte. A este profesional cabe la responsabilidad de tomar las conductas más adecuadas frente al paciente hemofílico, participando y comunicándose activamente con los miembros del equipo multidisciplinar.BACKGROUND AND OBJECTIVES: For more than 25 years, there has been no discussion in the Brazilian Journal of Anesthesiology about hemophiliac patients' perioperative management. Hemophilia has been described as a disease from the early 19th Century, but still today there are many hemophilia-related breakthroughs. This review aimed at pointing hemophilia patient-related perioperative care, focusing on hemophilia A management and the role of the anesthesiologist as part of the multidisciplinary team. CONTENTS: Hemophilia features are described in terms of clinical and laboratory findings, current pharmacological therapy and intraoperative care of hemophilia patients. CONCLUSIONS: Hemophiliac patients management has improved. As a consequence of this advance, it is important that new knowledge, especially related to replacement therapy, be mastered not only by hematologists but also by the whole clinical-surgical team. A multidisciplinary team of which the anesthesiologist is part has to be involved when hemophilia patients are submitted to surgical
Chouhan, Varun; Mandliya, Alok; Chouhan, Kiran
Introduction: Obturator internus hematoma(OIH) is a very rare entity. In past it has been reported in hemophilics, we firstly report obturator internus hematoma in a patient of stroke on antiplatelet drugs. Obturator internus hematoma can cause severe hip pain with normal X-rays, so it should kept in differential diagnosis of hip pain with normal radiographs. Case report: 74 year old male with history of recent onset stroke presented to us with left side weakness and left hip pain. Radiograph...
Full Text Available Movement disorders are atypical and rare presentation of chronic subdural hematomas. We report a case of 60 year man who presented with intention tremors and altered sensorium. The patient had Kernohan-Woltman notch phenomenon on clinical examination. CT scan brain showed a large left fronto-temporo-parietal chronic subdural hematoma with significant mass effect and midline shift. His symptoms relieved completely after surgical evacuation of the hematoma.
Full Text Available Traumatic subdural hematomas of the posterior fossa are rare but dangerous neurosurgical emergencies that require prompt diagnosis and management to avoid the uniformly poor outcome. We present a case of a teenager with severe TBI and acute subdural hematoma of the posterior fossa that deteriorated rapidly before surgery but eventually made a good recovery. We also the review the literature concerning traumatic posterior fossa subdural hematomas [PFSDH].
Jauch, Edward C; Lindsell, Christopher J; Adeoye, Opeolu; Khoury, Jane; Barsan, William; Broderick, Joseph; Pancioli, Arthur; Brott, Thomas
Early hematoma expansion in spontaneous intracerebral hemorrhage (ICH) is associated with worse clinical outcome. We hypothesized that hemodynamic parameters are associated with the increase in hematoma volume owing to their relationship to blood vessel wall stresses. We performed a post hoc analysis of clinical and computed tomography (CT) data from patients enrolled in a prospective observational study of ICH patients presenting within 3 hours from symptom onset. Hematoma volumes were measured at hospital arrival and at 1 and 20 hours from presentation. Blood pressure and heart rate, recorded at 19 time points between presentation and 20 hours, were used to derive hemodynamic variables. Multivariable logistic-regression models were constructed to assess the relation between hemodynamic parameters and hematoma growth, adjusted for clinical covariates. From the original study, 98 patients underwent baseline and 1-hour CT scans; of these, 65 had 20-hour CT scans. Substantial hematoma growth was observed in 28% within the first hour. Of the 65 patients not undergoing surgery within 20 hours, 37% experienced hematoma growth by 20 hours. Neither baseline or peak hemodynamic parameters nor changes in hemodynamic parameters were significantly associated with hematoma growth at either 1 or 20 hours. We found no blood pressure or heart rate parameters, individually or in combination, that were associated with hematoma growth. Our data suggest the influence of hemodynamic parameters on vessel wall stress to be an unlikely target for intervention in reducing the risk of early hematoma growth in ICH.
Sanne Jensen Dich
Conclusion: Rectal bleed after trauma, in a patient receiving anticoagulant treatment, should raise suspicion of a penetrating hematoma, and such patients should be managed at highly specialized facilities.
R, Cuesta-Barriuso; A, Torres-Ortuño; S, Pérez-Alenda; J, Carrasco Juan; F, Querol; J, Nieto-Munuera; Ja, López-Pina
Numerous measuring instruments for the evaluation of hemophilic arthropathy have been developed. One of the most used systems is the Hemophilia Joint Health Score (HJHS) given its sensitivity to clinical changes appearing in the joints because of recurrent hemarthrosis. Assessing the interrater reliability, using the Spanish version of the HJHS (version 2.1) in children with hemophilia. Reliability study to assess the interrater reliability of the Spanish version of HJHS. A sample of 36 children aged 7-13 years diagnosed with hemophilia A or B was used. Two physiotherapists performed physical assessments with the Spanish version of the HJHS. Descriptive statistics (range, mean, standard deviation) and the analysis of interrater reliability were calculated. The interrater reliability was heterogeneous since the Kappa coefficient range (ĸ), although significant (p reliability of the Spanish population version of the HJHS is high. This scale should be used generically in evaluating musculoskeletal pediatric patients with hemophilia.
Franchini, Massimo; Lippi, Giuseppe
Thanks to considerable progresses made over the last 30years, hemophilia benefits from the most efficacious and safe treatment among the many monogenic inherited disorders. The most challenging complication of replacement therapy in hemophilia A is the occurrence of alloantibodies against infused factor VIII (FVIII), thus predisposing the patients to increased morbidity and disability. Extensive research in this field has definitively unraveled that development of inhibitors in hemophilia A is a complex and multifactorial process, in which inherited and environmental factors dynamically interact. This narrative review, after providing a concise overview about the main genetic and non-genetic risk factors, is aimed to focus on prediction risk models and preventive strategies for minimizing the risk of developing inhibitors in hemophilia A patients. Copyright © 2016 Elsevier Ltd. All rights reserved.
Fabiane de Amorim Almeida; Tássia de Oliveira Vidal
Objectives: To identify the limitations faced by the hemophiliac child, according to his/her parents, and how they deal with these limitations, and to verify how parents approach the problem of hemophilia...
Liu, Jiajia; Sato, Yusuke, E-mail: email@example.com [Akita University Graduate School of Medicine, Department of Thoracic Surgery (Japan); Takahashi, Satoshi [Akita University Graduate School of Medicine, Department of Radiology (Japan); Motoyama, Satoru; Yoshino, Kei; Sasaki, Tomohiko; Imai, Kazuhiro; Saito, Hajime; Minamiya, Yoshihiro [Akita University Graduate School of Medicine, Department of Thoracic Surgery (Japan)
Mediastinal aneurysms are rare but potentially life-threatening. Among these, bronchial artery aneurysms are most frequently reported, whereas up to now aneurysms of the proper esophageal artery had never been reported. A 69-year-old woman was referred to our hospital for treatment of a massive mediastinal hematoma. Enhanced computed tomography and selective proper esophageal arteriography revealed a 5-mm aneurysm in the proper esophageal artery that arises from the thoracic aorta at the Th8 level and has an anastomotic branch with the bronchial artery peripherally. Transcatheter arterial embolization was successfully performed using a mixture of N-butyl cyanoacrylate and lipiodol (1:3 ratio, 0.3 ml). Post-embolization angiography showed no filling into the aneurysm. The patient recovered with no complications and was discharged on the 25th post-procedure day.
Full Text Available Diaphragmatic injury following blunt thoracoabdominal trauma is rare and is usually associated with key radiological features like dependent viscera sign, collar sign, diaphragmatic thickening and defects. It may also be associated with secondary signs like intrathoracic herniation of abdominal viscera. Diaphragmatic crura, which are attached to the upper lumbar vertebra represent prominently thickened folds along the posterior diaphragm, are usually inconspicuous on routine Computed Tomography (CT scans. We present a case of a young patient who sustained a motor vehicle accident and developed difficulty in breathing. CT scan of the patient revealed bilateral crural hematomas, with splenic and renal lacerations and no other sign of diaphragmatic injury. The patient was operated and blunt diaphragmatic rupture was confirmed at surgery.
Jha, Abhishek; Ahmad, Ibne; Gupta, Prakhar; Gupta, Gagan; Ahmad, Mehtab; Said, Mohd
Diaphragmatic injury following blunt thoracoabdominal trauma is rare and is usually associated with key radiological features like dependent viscera sign, collar sign, diaphragmatic thickening and defects. It may also be associated with secondary signs like intrathoracic herniation of abdominal viscera. Diaphragmatic crura, which are attached to the upper lumbar vertebra represent prominently thickened folds along the posterior diaphragm, are usually inconspicuous on routine Computed Tomography (CT) scans. We present a case of a young patient who sustained a motor vehicle accident and developed difficulty in breathing. CT scan of the patient revealed bilateral crural hematomas, with splenic and renal lacerations and no other sign of diaphragmatic injury. The patient was operated and blunt diaphragmatic rupture was confirmed at surgery.
Limperg, P.F. (P. F.)
In this thesis, three major elements in the research around growing up with hemophilia are presented: development and evaluation of instruments (Part I), HRQOL and psychosocial outcomes (Part II) and psychosocial care (Part III). This thesis is the first to describe what it is like to grow up with hemophilia, in terms of HRQOL and psychosocial functioning, for both patients and their mothers. The development and evaluation of several HRQOL and psychosocial instruments (Part I) showed us that ...
NOOASHIN BEHESHTIPOOR; SHIRIN GHANAVATI; MITRA EDRAKI; MEHRAN KARIMI; SEZANEH HAGHPANAH
As hemophilia is a chronic bleeding disease and can interfere with daily performance of children, these children require continuous training to prevent bleeding and take timely action (1). Since children nurses play an important role in the education of involved children and their Selfefficacy and also due to today’s approach which is using educational computer games, the use of educational games in respect to teach hemophilia children how to have self-efficacy can ...
Washino, Satoshi; Hirai, Masaru; Kobayashi, Yutaka; Saito, Kimitoshi; Miyagawa, Tomoaki
Hemophilia A is an X-linked recessive disorder caused by a deficiency in factor VIII. Hemophilia A affects 1 in 5,000-10,000 males. Hematuria is frequent in hemophilia. Hematuria in hemophilia is generally considered benign and manageable with conservative therapy; however, severe hematuria requiring surgical therapy has rarely been reported. A 60-year-old male with hemophilia A presented with persistent gross hematuria of unknown cause. He was treated with recombinant factor VIII products, followed by several conservative therapies as follows: clot evacuation by vesicoclysis, continuous bladder irrigation with normal saline, and intravesical instillation of aluminum hydroxide/magnesium hydroxide (Maalox); however, these failed to resolve the hemorrhaging. The patient was offered and consented to cystectomy with an ileal conduit. Intraoperative clotting was normal with the infusion of adequate recombinant factor VIII products and transfusion of fresh-frozen plasma, and the procedure was performed safely. After surgery, the patient had blood in his stool several times. No bleeding site was demonstrated in the colon by colonoscopy and (99m)Technetium-human serum albumin-diethylenetriaminepenta-acetic acid scintigraphy demonstrated that the extravasation of radioactive isotope was detected at the anal side of terminal ileum but not at the oral side. These findings were suspected to be bleeding from the ileoileal anastomosis. However, the bleeding was managed with recombinant factor VIII products. Cystectomy in hemophilia may be safe, if monitored appropriately. Urinary diversion using the intestine may be avoided because anastomotic hemorrhage may become a problem.
Ichikawa, Satoshi; Kohata, Katsura; Okitsu, Yoko; Suzuki, Makiko; Nakajima, Shinji; Yamada, Minami F; Onishi, Yasushi; Yamamoto, Joji; Suzuki, Sozo; Ishizawa, Kenichi; Kameoka, Junichi; Harigae, Hideo
Acquired hemophilia A is a rare and potentially fatal condition of coagulopathy caused by autoantibodies against clotting factor VIII (factor VIII inhibitor). We report a case of a 63-year-old woman, who presented with a sudden onset of severe hemorrhagic tendency with exclusively prolonged activated partial thromboplastin time (APTT). She was diagnosed with acquired hemophilia A due to a decrease in factor VIII activity and a high titer of factor VIII inhibitor. Hemorrhage was well controlled by recombinant activated factor VII. Although the level of factor VIII inhibitor did not decline with prednisolone and cyclophosphamide, it became undetectable with rituximab. In parallel with controlling hemorrhage, malignancy, which may cause acquired hemophilia A, was searched for and sigmoid colon cancer was found. After the eradication of factor VIII inhibitor, surgical resection was performed uneventfully. Thereafter, acquired hemophilia A has been in complete remission without any additional therapy. The present case suggests the efficacy of rituximab for refractory acquired hemophilia A and the importance of the identification of underlying diseases that can cause acquired hemophilia A.
Kumar, Riten; Dunn, Amy; Carcao, Manuel
Management of hemophilia has evolved significantly in the last century-from recognition of the causative mechanism in the 1950s to commercially available clotting factor concentrates in the 1960s. Availability of lyophilized concentrates in the 1970s set the stage for home-based therapy, followed by introduction of virally attenuated plasma-derived, and then recombinant factor concentrates in the 1980s and 1990s, respectively. The subsequent years saw a paradigm shift in treatment goals from on-demand therapy to prophylactic factor replacement starting at an early age, to prevent hemarthrosis becoming the standard of care for patients with severe hemophilia. In the developed world, the increasing use of home-based prophylactic regimens has significantly improved the quality of life, and life expectancy of patients with severe hemophilia. Seminal developments in the past 5 years, including the commercial availability of extended half-life factor concentrates and the publication of successful results of gene therapy for patients with hemophilia B, promise to further revolutionize hemophilia care over the next few decades. In this review, we summarize the evolution of management for hemophilia, with a focus on extended half-life factor concentrates and gene therapy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Petrov, Andrey; Wynne, Karon E.; Prough, Donald S.; Dewitt, Douglas S.; Petrov, Yuriy; Petrov, Irene Y.; Parsley, Margaret A.; Esenaliev, Rinat O.
Patients with acute intracranial hematomas often require surgical drainage within the first four hours after traumatic brain injury (TBI) to avoid death or severe neurologic disability. CT and MRI permit rapid, noninvasive diagnosis of hematomas, but can be used only at a major health-care facility. At present, there is no device for noninvasive detection and characterization of hematomas in pre-hospital settings. We proposed to use an optoacoustic technique for rapid, noninvasive diagnosis and monitoring of hematomas, including intracranial hematomas. Unlike bulky CT and MR equipment, an optoacoustic system can be small and easily transported in an emergency vehicle. In this study we used a specially-designed blast device to inflict TBI in rats. A near-infrared OPO-based optoacoustic system developed for hematoma diagnosis and for blood oxygenation monitoring in the superior sagittal sinus (SSS) in small animals was used in the study. Optoacoustic signals recorded simultaneously from the SSS and hematomas allowed for measurements of their oxygenations. The presence of hematomas was confirmed after the experiment in gross pictures of the exposed brains. After blast the hematoma signal and oxygenation increased, while SSS oxygenation decreased due to the blastinduced TBI. The increase of the oxygenation in fresh hematomas may be explained by the leakage of blood from arteries which have higher blood pressure compared to that of veins. These results indicate that the optoacoustic technique can be used for early diagnosis of hematomas and may provide important information for improving outcomes in patients with TBI or stroke (both hemorrhagic and ischemic).
Park, Joon-Hee; Li, Guohua; Kim, Minjae
Retrospective cohort. The purpose of the present study was to examine the incidence and risk factors for postoperative hematoma requiring reoperation in patients undergoing single-level lumbar fusion surgery. Postoperative hematoma can cause devastating neurological consequences after spine surgery. Risk factors for hematoma in specific spine procedures have not been well established. A cohort of patients undergoing single-level lumbar fusion surgery was constructed from the 2012 to 2013 American College of Surgeons National Surgical Quality Improvement Program dataset using Current Procedural Terminology codes (22533, 22558, 22612, 22630, and 22633). In cases requiring reoperation within 30 days after initial surgery, postoperative hematoma was identified using the ICD-9 code 998.1. Risk factors for postoperative hematoma were assessed with logistic regression modeling. Of 5280 patients undergoing single-level lumbar fusion surgery, 27 patients (0.5%) developed a postoperative hematoma requiring reoperation for hematoma evacuation. A heightened incidence of postoperative hematoma was found in patients who were smokers (1.0% vs. 0.4% for nonsmokers, P = 0.016) or who had a diagnosis of bleeding disorder (3.8% vs. 0.5% for those without bleeding disorder, P = 0.007). Multivariate logistic regression analysis indicated that the adjusted odds ratios for postoperative hematoma associated with smoking and bleeding disorder were 3.34 (95% confidence interval, 1.15-9.71) and 10.2 (95% confidence interval, 1.9-54.8), respectively. Smoking and bleeding disorder appear to be major risk factors for postoperative hematoma requiring reoperation after single-level lumbar fusion surgery. Intervention programs targeting patients with these risk factors are needed to reduce their excess risk of postoperative hematoma. 3.
Sharma, Anurag; Bhatia, Sonia; Singh, Rajendra Pratap; Malik, Gaurav
Dengue fever, also known as breakbone fever, is an infectious tropical disease caused by the Dengue virus. It is associated with a number of complications, which are well documented. However, Dengue fever associated with rectus sheath hematoma (RSH) is a very rare complication. Only one case report has been published prior supporting the association of Dengue fever with RSH. We report a case of Dengue fever who presented with RSH and was successfully treated conservatively. RSH is also an uncommon cause of acute abdominal pain. It is accumulation of blood in the sheath of the rectus abdominis, secondary to rupture of an epigastric vessel or muscle tear.
MILAGRES ANTONIO CARLOS DE PÁDUA
Full Text Available The authors report the case of a 50 year-old hypertensive male patient with a pontine hematoma. The clinical presentation was characterized by pure pyramidal deficit signs (no other signs or symptoms were present. A pure hemiplegia syndrome, although common in supratentorial lesions, is considered to be a rare event in pontine vascular lesions. The pathophysiologic mechanisms of these neurological findings are unclear. The exclusive involvement of the pyramidal tract in this case is likely due to a variation in the vascular anatomy of the pons but, in some cases, a vascular malformation may be the cause.
Zizka, J.; Elias, P.; Michl, A. [Dept. of Radiology, Charles University Hospital, Hradec Kralove (Czech Republic); Harrer, J. [Dept. of Cardiac Surgery, Charles University Hospital, Hradec Kralove (Czech Republic); Cesak, T. [Dept. of Neurosurgery, Charles University Hospital, Hradec Kralove (Czech Republic); Herman, A. [1. Dept. of Internal Medicine, Charles University Hospital, Hradec Kralove (Czech Republic)
Development of collateral circulation belongs among the typical signs of aortic coarctation. Cerebral or spinal artery aneurysm formation with increased risk of subarachnoid hemorrhage represent the most common neurovascular complication of this disease. We report a case of a 20-year-old sportsman who developed acute non-traumatic paraplegia as a result of extensive spinal epidural hemorrhage from collateral vessels accompanying aortic coarctation which was unrecognized up to that time. To the best of our knowledge, acute spinal epidural hematoma as a complication of aortic coarctation has not been previously reported. (orig.)
MANUEL JESÚS NÚÑEZ FERNÁNDEZ
Full Text Available Mujer de 83 años portadora de cardiopatía isquémica, insuficiencia mitral moderada, fibrilación auricular crónica. A tratamiento con nitroglicerina transdérmica, diuréticos, calcioantagonistas, estatinas y anticoagulantes orales (acenocumarol.Ingresa en nuestro Servicio por infección respiratoria e insuficiencia respiratoria, con tos frecuente y expectoración amarillenta en los 4 días previos. En el noveno día de su ingreso refiere la presencia de un hematoma espontáneo a nivel abdominal acompañado de dolor a dicho nivel.
Full Text Available Hussain I Saba, Duc Quang Tran, JrDepartment of Medicine, University of South Florida Medical Center, Tampa, FL, USAAbstract: In the past, patients with severe hemophilia have suffered a substantially reduced quality of life with frequent bleeding episodes, disabling arthropathy, and shorter life expectancy. In addition, methods of treatment and management have been costly and time-consuming, and have placed a considerable burden on patients' physical and psychological well-being. With the advent of the on-demand therapy and prophylactic treatment paradigm, patients have been able to receive care with less interruption of daily activities. Treatments may be more challenging for hemophiliacs with inhibitors to replacement factor; however, recent advances in the use of bypassing agents and immune tolerance therapy have enabled them to aggressively manage their disease while maintaining their independence. This review focuses on the challenges of treating such a severe hemophiliac through examination of the lifetime experience of a young adult male with a severe form of congenital hemophilia A. At this stage of his life, the patient has minimal disabilities and is inhibitor-free through optimal care and strong family support. His aspiration to pursue a productive life has led him to a career in medicine. After receiving his medical degree, he pursued a specialty in the treatment of hemophilia. By assisting other hemophilia patients, he exemplifies both the rewards of persevering through episodes of bleeding and other complications and the fact that disabilities can be minimized when managed meticulously and in a timely fashion to enable a productive and dignified life.Keywords: hemophilia, quality of life, factor VIII inhibitors, hemophilia treatment center, early treatment, bypassing agent
El Ouali Ouarda
Full Text Available Abstract Introduction Bilateral third nerve palsy secondary to a hemorrhagic stroke is exceptional. To the best of our knowledge, no similar case has been reported in the literature. Case presentation We describe the case of a 69-year-old Moroccan man who presented with isolated sudden bilateral third nerve palsy. Computed tomography (CT of the brain revealed a midbrain hematoma. The oculomotor function gradually and completely improved over eight months of follow-up. Conclusion Stroke should be included in the differential diagnosis of sudden isolated oculomotor paralysis even when it is bilateral because of the severity of the underlying disease and the importance of its therapeutic implications.
Kruse-Jarres, Rebecca; Kempton, Christine L; Baudo, Francesco; Collins, Peter W; Knoebl, Paul; Leissinger, Cindy A; Tiede, Andreas; Kessler, Craig M
Acquired hemophilia A (AHA) is a rare disease resulting from autoantibodies (inhibitors) against endogenous factor VIII (FVIII) that leads to bleeding, which is often spontaneous and severe. AHA tends to occur in elderly patients with comorbidities and is associated with high mortality risk from underlying comorbidities, bleeding, or treatment complications. Treatment, which consists of hemostatic management and eradication of the inhibitors, can be challenging to manage. Few data are available to guide the management of AHA-related bleeding and eradication of the disease-causing antibodies. Endorsed by the Hemostasis and Thrombosis Research Society of North America, an international panel of experts in AHA analyzed key questions, reviewed the literature, weighed the evidence and formed a consensus to update existing guidelines. AHA is likely underdiagnosed and misdiagnosed in real-world clinical practice. Recommendations for the management of AHA are summarized here based on the available data, integrated with the clinical experience of panel participants. © 2017 Wiley Periodicals, Inc.
Ward, Peter; Walsh, Christopher E
Here we review the recent literature on Hemophilia gene transfer/therapy. Gene therapy is one of several new technologies being developed as a treatment for bleeding disorders. We will discuss current and pending clinical efforts and attempt to relate how the field is trending. In doing so, we will focus on the use of recombinant Adeno-associated viral (rAAV) vector-mediated gene transfer since all currently active trials are using this vector. Recent exciting results embody nearly 20 years of preclinical and translational research. After several early clinical attempts, therapeutic factor levels that can now be achieved reflect several modifications of the original vectors. Patterns of results are slowly starting to emerge as different AAV vectors are being tested. As with any new technology, there are drawbacks, and the potential for immune/inflammatory and oncogenic risks have emerged and will be discussed.
Josué M. Avecillas-Chasín
Full Text Available Spinal intradural hematoma is a rare complication of diagnostic lumbar puncture or spinal anesthesia. This complication could be overlooked with devastating neurological consequences due to a delay in diagnosis. Here, we reported a case of a patient with a lumbar spinal intradural hematoma as a result of a difficult spinal anesthesia.
Yu, Zhiyuan; Zheng, Jun; Guo, Rui; Ma, Lu; Li, Mou; Wang, Xiaoze; Lin, Sen; Li, Hao; You, Chao
Hematoma expansion is independently associated with poor outcome in intracerebral hemorrhage (ICH). Blend sign is a simple predictor for hematoma expansion on non-contrast computed tomography. However, its accuracy for predicting hematoma expansion is inconsistent in previous studies. This meta-analysis is aimed to systematically assess the performance of blend sign in predicting hematoma expansion in ICH. A systematic literature search was conducted. Original studies about predictive accuracy of blend sign for hematoma expansion in ICH were included. Pooled sensitivity, specificity, positive and negative likelihood ratios were calculated. Summary receiver operating characteristics curve was constructed. Publication bias was assessed by Deeks' funnel plot asymmetry test. A total of 5 studies with 2248 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive and negative likelihood ratios of blend sign for predicting hematoma expansion were 0.28, 0.92, 3.4 and 0.78, respectively. The area under the curve (AUC) was 0.85. No significant publication bias was found. This meta-analysis demonstrates that blend sign is a useful predictor with high specificity for hematoma expansion in ICH. Further studies with larger sample size are still necessary to verify the accuracy of blend sign for predicting hematoma expansion. Copyright © 2017 Elsevier B.V. All rights reserved.
Hayashi, Ayato; Matsuda, Norifumi; Horiguchi, Masatoshi; Matsumura, Takashi; Komoto, Masakazu; Natori, Yuhei; Komuro, Yuzo; Mizuno, Hiroshi
Subcutaneous hematoma is commonly caused by trauma or surgery. Proper treatment of the condition is needed to avoid severe complications. The present paper introduces a simple technique of hematoma evacuation, called cylinder syringe suction (CSS). Experiments were also performed to determine the detailed mechanism underlying its effectiveness. The CSS procedure was performed as follows. A cylindrical plastic cylinder syringe was used. Either a few stitches were removed or a very small incision was made on the site of the hematoma. The edge of the syringe was compressed to the skin, which was covered by a thin hydrocolloid dressing. Vacuum aspiration was enforced at the site of the wound or incision, and the hematoma was gradually aspirated.For the experiment, house rabbits were used. Hematoma evacuation was performed in 4 different ways, including needle aspiration alone (group 1), needle puncture followed by CSS (group 2), and creation of a small wound (5 mm) followed by needle aspiration (group 3) or CSS (group 4). The amount of evacuated hematoma and the suction pressure created by each of the 4 methods were compared. Group 4 showed the highest suction pressure and the greatest evacuated amount of hematoma. High suction pressure was also obtained in group 1; however, the amount of evacuated hematoma was small as the other 2 groups. The CSS technique becomes effective mainly by creating high suction pressure, and the opening of a small wound enables the viscous coagula to pass through the skin.
Ali, T; Schved, J F
Creating a national registry for bleeding disorders is a major step in establishing a National Hemophilia Care Program in all countries. Creating such a registry which would contain accurate and regularly updated data, including laboratory analysis confirmed by a reference laboratory established at the Syrian Hemophilia Society. Blood samples were drawn and analysed in the Society reference laboratory for the following screening tests: prothrombin time (PT), APTT and coagulation factor assays. Inhibitor detection and VWF RiCof were performed depending on the result of the screening tests. HBs Ag, anti-HCV, anti-HIV 1+2 and syphilis tests were also performed to detect transfusion transmitted agents (TTA). Diagnosis of the bleeding disorder type was confirmed for 760 of these cases. Among the 760 confirmed patients, 82.5% had haemophilia. Among these, 89.6%were haemophilia A; 10.4% were haemophilia B; 8.3% had VWD; 9.2% had other rare bleeding disorders as follows: 1.2% FVII deficiency, 0.7% FV deficiency, 1.8% F1 deficiency, 0.4% FX deficiency, 1.4% platelets dysfunctions (mainly Glanzmann Thrombasthenia) and 3.7% had combined FVIII and FV deficiency. Eighty (21.3%) cases of 375 screened for transfusion transmitted agents were positive for at least one infection: 0.5% were HBsAg positive, 19.7% were anti-HCV positive, 0.8% had combined HBsAg and anti-HCV positivity and 0.3% was anti-Syphilis positive. All patients were negative for HIV1 and HIV2. The preliminary data presented here follow known data on haemophilia A, haemophilia B and VWD disease. This registry will certainly help in improving haemophilia care in Syria. © 2012 Blackwell Publishing Ltd.
Full Text Available Introduction and Objective: Spontaneous pharyngeal-laryngeal hematoma shows the importance of a complete ENT examination in the face of symptoms of banal appearance and a correct history that, in the case reported, unveiled the therapeutic use of anticoagulants. Case description: A 55 year old woman comes to emergency because of unexplained dysphagia. The inspection shows the presence of a hematoma in the pharyngeal-laryngeal region that, after the anticoagulant therapy was reversed, evolved favorably with conservative treatment. Discussion: In this case, apart from medical management performed by the hematology department, we focus our therapeutic approach in the protection of the airway and the prevention of a possible massive bleeding. Determining which patients require endotracheal intubation or tracheostomy and hemostatic surgery is the key to treatment. Conclusions: The anticoagulant therapy involves several complications that ENT specialists must consider in the face of clinical symptoms of dysphagia, dysphonia, dyspnea or signs of bleeding and they must know the possibilities of performance depending on the severity of each case.
Guo, Cheng; Liu, Lin; Wang, Bing; Wang, Zhigang
The swirl sign is identified as a small area of low attenuation within an intracranial hyperattenuating clot on non-enhanced computed tomography (CT) scans of the brain, which represents active bleeding. The purpose of this study was to evaluate the incidence of the swirl sign among patients with acute epidural hematoma (AEDH) and to identify its prognostic value and impact on surgical treatment. A retrospective review was performed of patients with a diagnosis of traumatic EDH by CT scan who were surgically treated at the Department of Neurosurgery of the First People's Hospital of Jingmen between January 2010 and January 2014. Patients with combined or open craniocerebral injuries and those who did not undergo surgical treatment were excluded. Of the 147 patients evaluated, 21 (14%) exhibited the swirl sign on non-enhanced CT scans of the brain. Univariate analysis revealed a significant correlation between the occurrence of the swirl sign and preoperative Glasgow coma scale scores, preoperative mydriasis, time from injury to CT scan, and intraoperative hematoma volume. Compared with patients without this sign, those exhibiting the swirl sign had a higher mortality rate (24 vs. 6%, respectively; P = 0.028) and a worse outcome (Glasgow Outcome Scale score ≤ 3: 38 vs. 15%, respectively; P = 0.027) at 3 months. An adjusted analysis showed that the occurrence of the swirl sign was an independent predictor of poor outcome (death: odds ratio (OR) = 4.61; 95% confidence interval (CI): 1.34-15.82; P sign on the head CT scan of patients with AEDH was found to be significantly associated with poor outcome. Therefore, early identification of this sign and aggressive management with early surgical evacuation is crucial for improving patient outcome.
Wan, Yi; Fei, Xifeng; Jiang, Dongyi; Chen, Hanchun; Shi, Lei; Wang, Zhimin
The aim of the present study was to explore the clinical effects, including the prevention of complications, of the treatment of chronic subdural hematoma with double needle aspiration. The clinical data of 31 patients with chronic subdural hematoma treated by double YL-1 needle double skull drilling and 31 controls treated by traditional drilling and drainage were analyzed retrospectively. In the YL-1 needle group, only 1 patient was with hematoma recurrence, 1 patient was with intracranial pneumocephalus, and the remaining patients who were followed up for 3 months achieved a clinical cure. In the traditional drilling and drainage group, 13 patients were with hematoma recurrence within 3 months after the operation and 7 patients were with postoperative intracranial pneumocephalus. The method of double YL-1 needle is better than the traditional drilling and drainage method for the treatment of chronic subdural hematoma because it reduces the postoperative recurrence rate and complications.
Full Text Available Sublingual hematoma secondary to anticoagulation is a rare fatal condition. Hemorrhagic complications of warfarin are well-known. This particular case is unique because the patient was on warfarin for the past 2 years but did not develop the sublingual hematoma. However, a trauma by an attrited sharp cusp triggered the episode of the sublingual hematoma in this patient. Being a medical emergency, patient was promptly hospitalized in cardiac care unit and managed by medical team. The patient was transfused with 2 units of fresh frozen plasma and warfarin was temporarily stopped for 4 days. Alternate day regimen of warfarin was started after 4 days, and international normalized ratio dropped to 3. In dental management, enameloplasty of the mandibular first molar tooth was done to prevent trauma and ulcer development in the floor of the mouth. The hematoma resolved, and no new hematoma formation was observed for a period of 6 months.
Full Text Available We describe a case in which a patient with a past medical history of ovarian cancer received a diagnostic renal biopsy for an incidentally discovered renal mass. During left robotic partial nephrectomy (RPN, a perinephric hematoma was encountered. The hematoma was not present on preoperative imaging and was likely a result of the renal biopsy. The renal cell carcinoma (RCC and the associated hematoma were widely excised with negative surgical margins. On follow-up imaging at five months postoperatively, a recurrent renal mass at the surgical resection bed and several new nodules in the omentum were detected. During completion left robotic total nephrectomy and omental excision, intraoperative frozen sections confirmed metastatic RCC. We believe that a hematoma seeded with RCC formed as a result of the renal biopsy, and subsequent disruption of the hematoma during RPN caused contamination of RCC into the surrounding structures.
Full Text Available Subramanian Vaidyanathan,1 Azi Samsudin,2 Gurpreet Singh,3 Peter L Hughes,4 Bakul M Soni,1 Fahed Selmi1 1Regional Spinal Injuries Center, Southport and Formby District General Hospital, Southport, UK; 2Department of Urology, Whiston Hospital, Prescot, UK; 3Department of Urology, 4Department of Radiology, Southport and Formby District General Hospital, Southport, UK Introduction: Paraplegic patients are at greater risk of developing complications following ureteroscopic lithotripsy because of urine infection associated with neuropathic bladder, difficulties in access due to altered anatomy of urinary bladder and urethra, spinal curvature, spasticity, and contractures. We report the occurrence of large subcapsular hematoma following ureteroscopy and discuss lessons we learn from this case.Case report: A 48-year-old male patient with spina bifida underwent ureteroscopy with laser lithotripsy and ureteric stenting for left ureteric stone and staghorn calculus with hydronephrosis; laser lithotripsy was repeated after 3 months; both procedures were performed by a senior urologist and did not result in any complications. Ureteroscopic laser lithotripsy was performed 5 months later by a urological trainee; it was difficult to negotiate the scope as vision became poor because of bleeding (as a result of the procedure. Postoperatively, hematuria persisted; temperature was 39°C. Cefuroxime was given intravenously followed by gentamicin for 5 days; hematuria subsided gradually; he was discharged home. Ten days later, this patient developed temperature, the urine culture grew Pseudomonas aeruginosa, and ciprofloxacin was given orally. Computed tomography (CT of the urinary tract, performed 4 weeks after ureteroscopy, revealed a 9×7 cm subcapsular collection on the left kidney compressing underlying parenchyma. Percutaneous drainage was not feasible because of severe curvature of spine. Isotope renogram revealed deterioration in left renal function from 30
Zakas, P.M.; Vanijcharoenkarn, K.; Markovitz, R.C.; Meeks, S.L.; Doering, C.B.
Summary Background The formation of neutralizing antibodies (inhibitors) directed against human coagulation factor VIII (hFVIII) is a life-threatening pathogenic response that occurs in 20–30% of severe congenital hemophilia A patients and 0.00015% of remaining population (i.e. acquired hemophilia A). Interspecies amino acid sequence disparity among FVIII orthologs represents a promising strategy to mask FVIII from existing inhibitors while retaining procoagulant function. Evidence for the effectiveness of this approach exists in clinical data obtained for porcine FVIII products, which have demonstrated efficacy in the setting of congenital and acquired hemophilia. Objectives In the current study, recombinant (r) ovine FVIII (oFVIII), was evaluated for antigenicity and procoagulant activity in the context of human patient-derived and murine model-generated FVIII inhibitors. Methods The antigenicity of roFVIII was assessed using i) inhibitor patient plasma samples, ii) murine anti-FVIII MAbs, iii) immunized murine hemophilia A plasmas, and iv) an in vivo model of acquired hemophilia A Results Overall, roFVIII demonstrated reduced reactivity to, and inhibition by, anti-hFVIII immunoglobulin in patient plasmas. Additionally, several hFVIII epitopes were predicted and empirically shown not to exist within roFVIII. In a murine hemophilia A model designed to mimic clinical inhibitor formation, it was demonstrated that inhibitor titers to roFVIII were significantly reduced compared to the orthologous immunogens, rhFVIII or rpFVIII. Furthermore in a murine model of acquired hemophilia A, roFVIII administration conferred protection from bleeding following tail transection. Conclusion These data support the investigation of FVIII orthologs as treatment modalities in both the congenital and acquired FVIII inhibitor settings. PMID:25315236
Lim, Ming Y; Pruthi, Rajiv K
With increasing longevity, the prevalence of cardiovascular disease (CVD) risk factors in hemophilia patients is expected to increase; however, evidence-based guidelines on management are lacking. The aim of the study was to determine the prevalence and management of CVD risk factors in hemophilia patients. A retrospective study of 58 adult hemophilia patients (≥35 years) attending Mayo Comprehensive Hemophilia Center between 1 January 2006 and 15 October 2009 were reviewed. The prevalence of CVD risk factors was hypertension 65.5%, diabetes 10.3%, smoking 12.5% and obesity 19.6%. A total of 31% did not have a lipid profile on record. Management of risk factors included antihypertensive medications in 84.2% and lipid-lowering agents in 12.1%. During their medical evaluation, four of seven active smokers received smoking cessation counseling and four of 11 obese patients received lifestyle modification advice. Eight patients (13.8%) experienced a CVD event: myocardial infarction (MI) (n=3), coronary artery disease (n=2), both MI and ischemic stroke (n=1) and hemorrhagic strokes (n=2). Only five of eight patients were on low-dose aspirin, of which aspirin was discontinued in one patient after he was diagnosed with hemophilia following a bleeding work-up. Another patient on dual antiplatelet therapy post stent placement developed epistaxis resulting in clopidogrel cessation. Hemophilia patients are at risk for CVD, similar to the general age-matched male population. Screening for CVD risk factors, with preventive dietary and pharmacologic interventions, play a key role in the prevention and long-term management of CVD. Collaborative efforts between primary care providers, cardiologists and hemophilia center specialists remain essential in managing these complex patients.
Losos, Michael; Scrape, Scott; Joshi, Sarita; Shmookler, Aaron; Chen, Jian
Acquired hemophilia A (AHA) is a rare autoimmune disorder that leads to factor VIII (FVIII) deficiency via autoantibody formation. Standard treatment options include FVIII bypassing factors and immunosuppression. However, the role of therapeutic plasma exchange (TPE) is not clear in the treatment of AHA. We present a case of idiopathic AHA in a 66 year old female with severe bleeding and a FVIII inhibitor of 17.6 Bethesda units (BU). She failed to respond to standard treatment including maximum dose of recombinant FVIIa (rFVIIa), rituximab, and other immunosuppressive agents. Her FVIII inhibitor rapidly increased to 140 BU and FVIII was below 5%. TPE was initiated 3 weeks after admission and her bleeding stabilized after the first treatment and completely stopped after three treatments. Repeat testing revealed increased FVIII to 15% and FVIII inhibitor decreased to 2.0 BU. After an additional TPE treatment, her FVIII increased to 27% and FVIII inhibitor decreased to 0.6 BU and she was discharged without bleeding 40 days after admission. In this case, TPE played a critical role in reducing FVIII inhibitor, which resulted in a recovery of FVIII activity and hemostasis. Therefore, TPE should be initiated early in AHA patients with bleeding and high titer of FVIII inhibitor. © 2016 Wiley Periodicals, Inc.
Full Text Available Abstract Introduction Acquired factor VIII deficiency is a rare entity that can lead to severe and life-threatening bleeding. We describe a case of severe bleeding from the tongue secondary to acquired hemophilia and discuss treatment options, including aminocaproic acid and recombinant factor VIII, which have not been widely reported in the literature for the management of such patients. Case presentation A 94-year-old Caucasian man presented to our institution with diffuse bruising and extensive bleeding from the tongue secondary to mechanical trauma. He had no prior history of bleeding and his medical history was unremarkable except for dementia and hypertension. Coagulation studies revealed a prolonged activated partial thromboplastin time and a mixing study was consistent with the presence of an inhibitor. Quantitative assays revealed a reduced level of factor VIII activity (1% and the presence of a factor VIII inhibitor, measured at seven Bethesda units, in the serum. Oral prednisone therapy (60mg/day was given. He also received intravenous aminocaproic acid and human concentrate of factor VIII (Humate-P and topical anti-thrombolytic agents (100 units of topical thrombin cream. His hospital course was prolonged because of persistent bleeding and the development of profuse melena. He required eight units of packed red blood cells for transfusion. Hospitalization was also complicated by bradycardia of unclear etiology, which started after infusion of aminocaproic acid. His activated partial thromboplastin time gradually normalized. He was discharged to a rehabilitation facility three weeks later with improving symptoms, stable hematocrit and resolving bruises. Conclusions Clinicians should suspect a diagnosis of acquired hemophilia in older patients with unexplained persistent and profound bleeding from uncommon soft tissues, including the tongue. Use of factor VIII (Humate-P and aminocaproic acid can be useful in this coagulopathy but
Tuinenburg, A.; Rutten, A.; Kavousi, M.; Leebeek, F.W.G.; Ypma, P.F.; Laros-Van Gorkom, B.A.P.; Nijziel, M.R.; Kamphuisen, P.W.; Mauser-Bunschoten, E.P.; Roosendaal, G.; Biesma, D.H.; Van Der Lugt A., [No Value; Hofman, A.; Witteman, J.C.M.; Bots, M.L.; Schutgens, R.E.G.
Mortality due to ischemic heart disease is lower in hemophilia patients when compared to the general male population. As coagulation plays a role in the inflammatory pathways involved in atherogenesis, we investigated whether the clotting factor deficiency protects hemophilia patients from
Banis, Hendrika; Suurmeijer, Th.P.B.M.; van Peer, D.R.
This study addresses the relative importance of clinical characteristics of the child and parental emotional reactions, to child-rearing practices towards children who suffer from hemophilia. The variables were assessed in a Dutch sample of 108 zero-to-twelve-year-old boys with hemophilia and their
Boral, Leonard I.; Cohen, Alice J.; Smyth, Susan S.; White, Gilbert C.
With advances in care, increasing numbers of people with hemophilia (PWH) achieve near-normal life expectancies and present with typical age-related cardiovascular conditions. Evidence-based guidelines for medical or surgical management of cardiovascular conditions in individuals with hemophilia are limited. Published recommendations exist for the management of some common cardiovascular conditions (eg, ischemic heart disease, atrial fibrillation), but identifying optimal strategies for anticoagulant or antithrombotic therapy constitutes the primary challenge of managing nonoperative cardiovascular disease (CVD) in PWH. In general, as long as factor concentrates or other hemostatic therapies maintain adequate hemostasis, the recommended medical and surgical management of CVD in PWH parallels that in individuals without hemophilia. The presence of factor inhibitors complicates hemophilia management. Published outcomes of CVD treatment in PWH are similar to those in the general population. Specific knowledge about factor replacement, factor inhibitors, and disease-specific treatment distinguishes the cardiovascular care of PWH from similar care of individuals without this rare bleeding disorder. Furthermore, a multidisciplinary approach incorporating a hematologist with an onsite coagulation laboratory, ideally associated with a hemophilia treatment center, is integral to the management of CVD in PWH. PMID:25436468
Ragni, Margaret V.; Moore, Charity G.
Summary Background Atherosclerotic heart disease (ASHD) is a common cause of morbidity and mortality in Western society. Few studies have determined prevalence and predictors of ASHD in hemophilia (HA), a population whose survival is improving with safer blood products and effective treatments for AIDS and hepatitis C. Objectives The purpose of this study was to determine prevalence and factors associated with ASHD in hemophilia A patients in Pennsylvania. Methods The prevalence of ASHD (myocardial infarction, angina, coronary disease), cardiac catheterization, coronary angiography, co-morbidities, and in-hospital mortality were assessed on statewide ASHD discharge data, 2001–2006, from the Pennsylvania Health Care Cost Containment Council (PHC4). Results The prevalence of hemophilia ASHD admissions fluctuated between 6.5% and 10.5% for 2001 to 2006, p=0.62. Compared to HA without ASHD, HA with ASHD were older and more likely to be hypertensive, hyperlipidemic, and diabetic, all pHemophilia patients with ASHD have similar cardiovascular risk factors, admitting diagnoses, severity of illness, and in-hospital mortality as the general population. These findings suggest cardiovascular prevention measures should be promoted in hemophilia. PMID:21371197
Wang, Xiaomei; Terhorst, Cox; Herzog, Roland W
Current therapy for the X-linked coagulation disorder hemophilia is based on intravenous infusion of the specifically deficient coagulation factor. However, 20-30% of hemophilia A patients (factor VIII, FVIII, deficiency) generate inhibitory antibodies against FVIII. While formation of inhibitors directed against factor IX, FIX, resulting from hemophilia B treatment is comparatively rare, a serious complication that is often associated with additional immunotoxicities, e.g. anaphylaxis, occurs. Current immune tolerance protocols to eradiate inhibitors are lengthy, expensive, not effective in all patients, and there are no prophylactic tolerance regimens to prevent inhibitor formation. The outcomes of recent experiments in animal models of hemophilia demonstrate that regulatory CD4(+) T cells (Treg) are of paramount importance in controlling B cell responses to FVIII and FIX. This article reviews several novel strategies designed to in vivo induce coagulation factor-specific Treg cells and discusses the subsets of Treg that may promote immune tolerance in hemophilia. Among others, drug- and gene transfer-based protocols, lymphocyte transplant, and oral tolerance are reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.
Janice M Staber
Full Text Available Hemophilia A animal models have helped advance our understanding of factor VIII deficiency. Previously, factor VIII deficient mouse models were reported to have a normal life span without spontaneous bleeds. However, the bleeding frequency and survival in these animals has not been thoroughly evaluated.To investigate the survival and lethal bleeding frequency in two strains of E-16 hemophilia A mice.We prospectively studied factor VIII deficient hemizygous affected males (n = 83 and homozygous affected females (n = 55 for survival and bleeding frequency. Animals were evaluated for presence and location of bleeds as potential cause of death.Hemophilia A mice had a median survival of 254 days, which is significantly shortened compared to wild type controls (p < 0.0001. In addition, the hemophilia A mice experienced hemorrhage in several tissues. This previously-underappreciated shortened survival in the hemophilia A murine model provides new outcomes for investigation of therapeutics and also reflects the shortened lifespan of patients if left untreated.
Daniel S. Treister
Full Text Available A 15-year-old male high school football player presented with episodes of headache and complete body stiffness, especially in the arms, lower back, and thighs, immediately following a football game. This was accompanied by severe nausea and vomiting for several days. Viral meningitis was suspected by the primary clinician, and treatment with corticosteroids was initiated. Over the next several weeks, there was gradual symptom improvement and the patient returned to his baseline clinical status. The patient experienced a severe recurrence of the previous myriad of symptoms following a subsequent football game, without an obvious isolated traumatic episode. In addition, he experienced a new left sided headache, fatigue, and difficulty ambulating. He was admitted and an extensive workup was performed. CT and MRI of the head revealed concurrent intracranial and spinal subdural hematomas (SDH. Clinical workup did not reveal any evidence of coagulopathy or predisposing vascular lesions. Spinal SDH is an uncommon condition whose concurrence with intracranial SDH is an even greater clinical rarity. We suggest that our case represents an acute on chronic intracranial SDH with rebleeding, membrane rupture, and symptomatic redistribution of hematoma to the spinal subdural space.
Nichols, Timothy C; Dillow, Aaron M; Franck, Helen W G; Merricks, Elizabeth P; Raymer, Robin A; Bellinger, Dwight A; Arruda, Valder R; High, Katherine A
Dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and factor VII deficiency faithfully recapitulate the severe bleeding phenotype that occurs in humans with these disorders. The first rational approach to diagnosing these bleeding disorders became possible with the development of reliable assays in the 1940s through research that used these dogs. For the next 60 years, treatment consisted of replacement of the associated missing or dysfunctional protein, first with plasma-derived products and subsequently with recombinant products. Research has consistently shown that replacement products that are safe and efficacious in these dogs prove to be safe and efficacious in humans. But these highly effective products require repeated administration and are limited in supply and expensive; in addition, plasma-derived products have transmitted bloodborne pathogens. Recombinant proteins have all but eliminated inadvertent transmission of bloodborne pathogens, but the other limitations persist. Thus, gene therapy is an attractive alternative strategy in these monogenic disorders and has been actively pursued since the early 1990s. To date, several modalities of gene transfer in canine hemophilia have proven to be safe, produced easily detectable levels of transgene products in plasma that have persisted for years in association with reduced bleeding, and correctly predicted the vector dose required in a human hemophilia B liver-based trial. Very recently, however, researchers have identified an immune response to adeno-associated viral gene transfer vector capsid proteins in a human liver-based trial that was not present in preclinical testing in rodents, dogs, or nonhuman primates. This article provides a review of the strengths and limitations of canine hemophilia, VWD, and factor VII deficiency models and of their historical and current role in the development of improved therapy for humans with these inherited bleeding disorders.
Mauro A. Oliveira
Full Text Available Hematomas da fossa posterior são complicação incomum de traumatismo cra-nioencefálico. Quase invariavelmente eles ocorrem após traumatismo da região occipital e estão associados com fraturas de crânio. O diagnóstico e tratamento dessa patologia tem sido grandemente favorecido pela tomografia computadorizada. Na presente série, a maioria dos pacientes teve evolução aguda, indicando o risco potencial de um tratamento conservador. Nossos resultados (29% de mortalidade são similares àqueles previamente relatados para outras séries dessas lesões.
Poulsen, Frantz Rom; Halle, Bo; Pottegård, Anton
PURPOSE: This study aimed to assess the usefulness of Danish patient registers for epidemiological studies of subdural hematoma (SDH) and to describe clinical characteristics of validated cases. METHODS: Using a patient register covering a geographically defined area in Denmark, we retrieved...... hospital contacts recorded under SDH International Classification of Diseases version 10 codes S065 and I620 in 2000-2012. Neurosurgeons reviewed medical records of all potential cases. Based on brain scan results, verified cases were classified by SDH type (chronic SDH (cSDH) or acute SDH (aSDH)). Thirty......-day mortality and preadmission antithrombotic drug use were established through linkage to population-based registers. We calculated the positive predictive value of the SDH code and compared mortality and preadmission antithrombotic drug use of cSDH with those of aSDH (age-adjusted and sex-adjusted odds ratio...
Kin, Hajime; Mukaida, Masayuki; Koizumi, Junichi; Kamada, Takeshi; Mitsunaga, Yoshino; Iwase, Tomoyuki; Ikai, Akio; Okabayashi, Hitoshi
An 86-year-old woman was scheduled to undergo aortic valve replacement and coronary artery bypass graft. On postoperative day 3, she developed sudden-onset neck pain followed by weakness in the right arm. Her symptoms worsened with time, and she developed paraplegia. At 60 h after the first complaint, spontaneous spinal epidural hematoma (SSEH) from C2 to C6 with spinal cord compression was diagnosed from a magnetic resonance image of the cervical region. We decided on conservative therapy because operative recovery was impossible. Delayed diagnosis led to grievous results in the present case. When neurological abnormalities follow neck or back pain after open heart surgery, SSEH must be considered in the differential diagnosis. Further, if it is suspected, early cervical computed tomography/magnetic resonance imaging and surgery should be considered.
Full Text Available Background. Large craniotomy for acute subdural hematoma is sometimes too invasive. We report good outcomes for two cases of neuroendoscopic evacuation of hematoma and contusion by 1 burr hole surgery. Case Presentation. Both patients arrived by ambulance at our hospital with disturbed consciousness after falling. Case 1 was an 81-year-old man who took antiplatelet drugs for brain infarction. Case 2 was a 73-year-old alcoholic woman. CT scanning showed acute subdural hematoma and frontal contusion in both cases. In the acute stage, glycerol was administered to reduce edema; CTs after 48 and 72 hours showed an increase of subdural hematoma and massive contusion of the frontal lobe. Disturbed consciousness steadily deteriorated. The subdural hematoma and contusion were removed as soon as possible by neuroendoscopy under local anesthesia, because neither patient was a good candidate for large craniotomy considering age and past history. 40%~70% of the hematoma was removed, and the consciousness level improved. Conclusion. Neuroendoscopic removal of acute subdural hematoma and contusion has advantages and disadvantages. For patients with underlying medical issues or other risk factors, it is likely to be effective.
Zeb, Muhammad H; Pandian, T K; El Khatib, Moustafa M; Naik, Nimesh D; Chandra, Abhishek; Morris, David S; Smoot, Rory L; Farley, David R
We recently sensed an increase in the frequency of groin hematoma after inguinal hernia repair (IHR) at our institution. The aim of this study was to provide a more updated assessment of the risk factors inherent to this complication. We performed a case-control study of all adult patients (age ≥ 18 y) who developed a groin hematoma after IHR at our institution between 2003 and 2015. Univariate and multivariable analyses were performed to assess for independent predictors for groin hematoma. A total of 96 patients (among 6608 IHR) developed a groin hematoma, (60 were observed, 36 required intervention). The hematoma frequency increased from our previous study (1.4 % versus 0.9%, P hernia (3.7, [1.4-9.7], P hernia were independent predictors of hematoma development. Independent risk factors for the development of groin hematoma after IHR included warfarin use and recurrent hernia. Careful consideration for anticoagulation and surgical hypervigilance remains prudent in all patients undergoing IHR and especially those with recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.
Full Text Available The authors present a rare case of calcified (ossified chronic epidural hematoma developed in a six-and-a-half-year-old female patient who was operated for cerebellar astrocytoma 6 months earlier. There was no history of trauma. Ossified epidural hematoma was seen as an incidental finding in the follow-up in computed tomography scan after 6 months of primary glioma surgery. Ossified chronic epidural hematoma with thick collagenous wall and newly formed bone on dura was excised. The development of calcified chronic subdural hematoma after decompressive intracranial surgery is a well-known occurrence, but the fact that a calcified epidural hematoma, which is rare and which can also develop after decompressive surgery, and the occurrence of calcified (ossified epidural hematoma after postfossa a glioma surgery is not yet reported. The second case is a 9-year-old male anemic child with a history of fall while playing 5 months earlier who presented with headache of 3 months duration. He had bifrontal calcified epidural hematoma operated by craniotomy and excision of calcified dural edge.
Tsukahara, T.; Nishikawa, M.; Kim, S.; Shibata, T.; Iwama, M. (Shizuoka Rohsai Hospital, Hamamatsu (Japan))
Recently we have encountered three cases of small traumatic hematoma in deep middle portion of the cerebrum. Patient 1: A 55-year-old male was admitted to our hospital 2-days after the traffic accident. CT scan showed small hematoma around septum pellucidi and fornix and in the posterior horn of left lateral ventricle. Patient 2: A 54-year-old male was admitted to our hospital a day after the head injury. CT scan showed hematoma in the supraventral portion of the third ventricle. Patient 3: A 27-year-old male was admitted to our hospital a day after the head injury. CT scan showed hematoma around quadrigeminal cistern and midbrain. Three cases reported here are traumatic hematomas without mass effect, which were pointed out only by autopsy. On traumatic hematoma in the deep middle portion of the brain we have only a few reports. On the mechanism of this bleeding Lindenberg and Kohno reported that the bleeding is caused by outward bending of the skull in injury. Lindenberg et al insisted that when traumatic force goes through corpus callosum over stretching of corpus callosum caused bleeding and that shearing force can damage septum pellucidi and fornix. Although these small hematomas are absorbed gradually functional prognosis is poor. Especially Korsakov syndrome and left hemiparesis in patient 1 shows no sign of recovery. In patient 2 and patient 3 decreased mental activity and hemiparesis have continued. Treatment of these cases cannot be surgical, as far as severe brain edema does not appeared.
van Delft, K; Thakar, R; Shobeiri, S Abbas; Sultan, A H
Childbirth causes overstretching of the levator ani muscle (LAM), predisposing to avulsion. LAM avulsion has not been evaluated early postpartum using endovaginal ultrasound (EVUS). The aim of this study was to evaluate the relationship between hematomas and LAM avulsion using EVUS and palpation early and late postpartum. Nulliparous women were studied prospectively at 36 weeks' gestation and within 4 days and 3 months postpartum. Palpation and high-frequency three-dimensional EVUS were performed. Two independent investigators reviewed the scans. No antenatal LAM avulsions were found (n = 269). 114/199 (57.3%) women seen early postpartum agreed to examination. 27/114 (23.7%) had well delineated, hypoechoic areas consistent with hematomas (100% agreement), 26 following vaginal delivery, one following emergency Cesarean section. In total, 38 hematomas were found (11 bilateral, 16 unilateral). Hematomas away from the attachment zone of the LAM to the pubic bone (n = 22) resolved. Hematomas at the attachment zone (n = 16) manifested as pubococcygeus avulsions 3 months postpartum. In addition to these 16 avulsions, we found another 20 at 3 months postpartum. 13/20 were not scanned early postpartum and in seven no hematomas were seen, but avulsion was seen early postpartum. Overall, LAM avulsion was found in 23/191 (12.0%) women (13 bilateral, 10 unilateral) 3 months postpartum. Hematomas were significantly associated with episiotomy, instrumental delivery and increased hiatal measurements. Palpation was unreliable early postpartum as only seven avulsions were diagnosed. Hematomas at the site of LAM attachment to the pubic bone always result in avulsion diagnosed 3 months postpartum. However, one third of avulsions are not preceded by a hematoma at the site of LAM attachment to the pubic bone. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.
Full Text Available Occurrence of chronic subdural hematoma (CSDH in leukemia is rare, and most reported cases occurred in relation with acute myeloid leukaemia; however, occurrence is extremely rare in accelerated phase of chronic myelogenous leukaemia (CML. Seizure as presentation of SDH development in CML cases is not reported in literature. Authors report an elderly male, who was diagnosed as CML, accelerated phase of developing SDH. Initially presented to local physician with seizure; urgent CT scan head was advised, but ignored and sensorium rapidly worsened over next day and reported to our emergency department in deeply comatose state, where imaging revealed chronic subdural hematoma with hypoxic brain injury with fatal outcome. Seizure, progressive worsening of headache, vomiting and papilloedema are harbinger of intracranial space occupying lesion and requires CT head in emergency medical department for exclusion, who are receiving treatment of haematological malignancy
Migeon, B.R.; McGinniss, M.J.; Antonarakis, S.E.; Axelman, J.; Stasiowski, B.A.; Youssoufian, H.; Kearns, W.G.; Chung, A.; Pearson, P.L.; Kazazian, H.H. Jr. (Johns Hopkins Univ., Baltimore, MD (United States)); Muneer, R.S. (Univ. of Oklahoma, Norman (United States))
The authors report studies of a female with severe hemophilia A resulting from a complex de novo translocation of chromosomes X and 17 (46,X,t(X; 17)). Somatic cell hybrids containing the normal X, the der(X), or the der(17) were analyzed for coagulation factor VIII (F8C) sequences using Southern blots and polymerase chain reaction. The normal X, always late replicating, contains a normal F8C gene, whereas the der(X) has no F8C sequences. The der(17) chromosome containing Xq24-Xq28 carries a functional G6PD locus and a deleted F8C allele that lacks exons 1--15. Also, it lacks the DXYS64-X locus, situated between the F8C locus and the Xq telomere. These results indicate that a cryptic breakpoint within Xq28 deleted the 5[prime] end of F8C, but left the more proximal G6PD locus intact on the der(17)chromosome. As the deleted segment includes the 5[prime] half of F8C as well as the subtelomeric DXYS64 locus, F8C must be oriented on the chromosome with its 5[prime] region closest to the telomere. Therefore, the order of these loci is Xcen-G6PD-3[prime]F8C-5[prime]F8C-DXYS64-Xqtel. The analysis of somatic cell hybrids has elucidated the true nature of the F8C mutation in the pro-band, revealing a more complex rearrangement (three chromosomes involved) than that expected from cytogenetic analysis, chromosome painting, and Southern blots. A 900-kb segment within Xq28 has been translocated to another autosome. Hemophilia A in this heterozygous female is due to the decapitation of the F8C gene on the der(17) and inactivation of the intact allele on the normal X. 27 refs., 5 figs., 1 tab.
Bioku Muftau Jimoh
Full Text Available Neonatal scrotal hematoma is a rare genitourinary emergency. Some cases have underlining aetiologic factors such as testicular torsion, adrenal hemorrhage, or birth trauma, and others are idiopathic. Previously, immediate scrotal exploration was considered imperative for diagnosis and treatment. With good imaging techniques, some patients are managed nonoperatively. We report a case of idiopathic scrotal hematoma in a neonate. He was managed conservatively with clinical and radiological follow-up. There was complete resolution of hematoma within two months, thus, avoiding unnecessary exploration.
Full Text Available Spinal subdural hematoma is a rare disorder and can be caused by abnormalities of coagulation, blood dyscrasias, lumbar puncture, trauma, underlying neoplasm, and arteriovenous malformation. We discuss an unusual case of an elderly woman who presented with spontaneous spinal subdural hematoma and developed massive rebleeding on the third day following initial evacuation of hematoma. This case illustrates that a patient with routine normal coagulation profile and adequate hemostasis can still harbor platelet dysfunction (in present case due to polycythemia and later on can manifest as rebleeding and neurological deterioration.
Lee, K.-W. [Department of Pediatrics, Loma Linda Children' s Hospital and University Medical Center, Loma Linda, CA (United States); McLeary, M.S. [Div. of Pediatric Radiology, Loma Linda Children' s Hospital and University Medical Center, Loma Linda, CA (United States); Zuppan, C.W. [Dept. of Pathology, Loma Linda Children' s Hospital and University Medical Center, Loma Linda, CA (United States); Won, D.J. [Div. of Pediatric Neurosurgery, Loma Linda University Children' s Hospital, Loma Linda, CA (United States)
An 8-year-old boy developed vomiting and severe headache following minor head trauma. A CT scan of the head demonstrated a lytic lesion of the skull and adjacent epidural hematoma. Surgical evacuation and removal of the skull lesion and hematoma were carried out, and pathologic evaluation resulted in a diagnosis of Langerhans' cell histiocytosis (LCH). Epidural involvement of Langerhans' cell histiocytosis is very rare, and we report the first case of LCH presenting as an intracranial epidural hematoma. (orig.)
Walsh, Christopher E; Soucie, J Michael; Miller, Connie H
The previously published mortality studies are limited in hemophilia populations but suggest that there is no increased risk of mortality in factor VIII inhibitor patients. This retrospective study analyzed surveillance data collected on 7,386 males with severe hemophilia A over a 13-year period to assess the association between a current inhibitor and death. During the study period, 432 participants died, among whom 48 were patients with an inhibitor. Clinical characteristics most strongly associated with death were increased number of reported bleeds, signs of liver disease, infection with either HIV or HCV, and the presence of inhibitor. Patients who underwent successful tolerization were not considered inhibitor patients in our analysis. In a multivariable analysis, the odds of death were 70% higher among patients with a current inhibitor compared to those without an inhibitor (P hemophilia A and a current inhibitor are at increased risk of death. © 2015 Wiley Periodicals, Inc.
Youjin, Shen; Jun, Yin
Factor VIII (FVIII) is an essential component in blood coagulation, a deficiency of which causes the serious bleeding disorder hemophilia A. Recently, with the development of purification level and recombinant techniques, protein replacement treatment to hemophiliacs is relatively safe and can prolong their life expectancy. However, because of the possibility of unknown contaminants in plasma-derived FVIII and recombinant FVIII, and high cost for hemophiliacs to use these products, gene therapy for hemophilia A is an attractive alternative to protein replacement therapy. Thus far, the adeno-associated virus (AAV) is a promising vector for gene therapy. Further improvement of the virus for clinical application depends on better understanding of the molecular structure and fate of the vector genome. It is likely that hemophilia will be the first genetic disease to be cured by somatic cell gene therapy.
Full Text Available The development of a factor VIII inhibitory is the most serious problem of Hemophilia A. High dose FVIII, recombinant FVIIa or FVIII inhibitor bypass activator (FEIBA only or combined may use in the treatment of hemophilia with inhibitory. We present here 42 year-old male was admitted to our clinic with sign of shock, abdominal tenderness and image of mass. In laboratory, Hemoglobin was found 5 gr/dl, aPTT: 106 sec, FVIII: %0 and inhibitory level was found 14 BU. Abdominal computerized tomography was shown hemorrhage in abdominal cavity and in psoas muscle. In treatment; We used blood transfusion and 100 U/kgx2/d FEIBA along 4 days. General symptoms and signs was healed after 2 days and hematologic parameters turned to normal. Immune tolerans treatment program was planned for patient, later. FEIBA treatment is very useful in hemophilia patients suffered from hemorrhage and inhibitors in addition to supportive treatment.
Xu, Dan; Alipio, Zaida; Fink, Louis M; Adcock, Dorothy M; Yang, Jianchang; Ward, David C; Ma, Yupo
Hemophilia A is caused by mutations within the Factor VIII (FVIII) gene that lead to depleted protein production and inefficient blood clotting. Several attempts at gene therapy have failed for various reasons-including immune rejection. The recent generation of induced pluripotent stem (iPS) cells from somatic cells by the ectopic expression of 3 transcription factors, Oct4, Sox2, and Klf4, provides a means of circumventing the immune rejection barrier. To date, iPS cells appear to be indistinguishable from ES cells and thus provide tremendous therapeutic potential. Here we prepared murine iPS cells from tail-tip fibroblasts and differentiated them to both endothelial cells and endothelial progenitor cells by using the embryoid body differentiation method. These iPS cells express major ES cell markers such as Oct4, Nanog, SSEA-1, alkaline phosphatase, and SALL4. Endothelial/endothelial progenitor cells derived from iPS cells expressed cell-specific markers such as CD31, CD34, and Flk1 and secreted FVIII protein. These iPS-derived cells were injected directly into the liver of irradiated hemophilia A mice. At various times after transplantation (7-90 days) hemophilia A mice and their control mice counterparts were challenged by a tail-clip bleeding assay. Nontransplanted hemophilia A mice died within a few hours, whereas transplanted mice survived for more than 3 months. Plasma FVIII levels increased in transplanted hemophilia A mice during this period to 8% to 12% of wild type and corrected the hemophilia A phenotype. Our studies provide additional evidence that iPS cell therapy may be able to treat human monogenetic disorders in the future.
Matsuda, Ryosuke; Hironaka, Yasuo; Kawai, Hisashi; Park, Young-Su; Taoka, Toshiaki; Nakase, Hiroyuki
Isolated oculomotor nerve palsy is well known as a symptom of microvascular infarction and intracranial aneurysm, but unilateral oculomotor nerve palsy as an initial manifestation of chronic subdural hematoma (CSDH) is a rare clinical condition. We report a rare case of an 84-year-old woman with bilateral CSDH who presented with unilateral oculomotor nerve palsy as the initial symptom. The patient, who had a medical history of minor head injury 3 weeks prior, presented with left ptosis, diplopia, and vomiting. She had taken an antiplatelet drug for lacunar cerebral infarction. Computed tomography (CT) of the head showed bilateral CSDH with a slight midline shift to the left side. She underwent an urgent evacuation through bilateral frontal burr holes. Magnetic resonance angiography (MRA) after evacuation revealed no intracranial aneurysms, but constructive interference in steady-state (CISS) magnetic resonance imaging (MRI) revealed that the left posterior cerebral artery (PCA) ran much more anteriorly and inferiorly compared with the right PCA and the left oculomotor nerve passed very closely between the left PCA and the left superior cerebellar artery (SCA). There is the possibility that the strong compression to the left uncus, the left PCA, and the left SCA due to the bilateral CSDH resulted in left oculomotor nerve palsy with an initial manifestation without unconsciousness. Unilateral oculomotor nerve palsy as an initial presentation caused by bilateral CSDH without unconsciousness is a rare clinical condition, but this situation is very important as a differential diagnosis of unilateral oculomotor nerve palsy. PMID:24067774
Known-group validity of patient-reported outcome instruments and hemophilia joint health score v2.1 in US adults with hemophilia: results from the Pain, Functional Impairment, and Quality of life (P-FiQ) study.
Buckner, Tyler W; Wang, Michael; Cooper, David L; Iyer, Neeraj N; Kempton, Christine L
The Pain, Functional Impairment, and Quality of Life (P-FiQ) study was an observational, cross-sectional assessment of the impact of pain on functional impairment and quality of life in adults with hemophilia in the United States who experience joint pain or bleeding. To describe known-groups validity of assessment tools used in the P-FiQ study. Participants completed 5 patient-reported outcome (PRO) instruments (5-level EuroQoL 5-dimensional questionnaire [EQ-5D-5L] with visual analog scale [VAS], Brief Pain Inventory v2 Short Form [BPI], International Physical Activity Questionnaire [IPAQ], Short-Form Health Survey [SF-36v2], and Hemophilia Activities List [HAL]) and underwent a musculoskeletal examination (Hemophilia Joint Health Score [HJHS]) during a routine clinical visit. P-FiQ enrolled 381 adults with hemophilia (median age, 34 years). Participants were predominantly white/non-Hispanic (69.2%), 75% had congenital hemophilia A, and 70.5% had severe hemophilia. Most (n=310) reported bleeding within the past 6 months (mean [SD] number of bleeds, 7.1 [13.00]). All instruments discriminated between relevant known (site- or self-reported) participant groups. Domains related to pain on EQ-5D-5L, BPI, and SF-36v2 discriminated self-reported pain (acute/chronic/both; Pvalidity and may have practical applicability in evaluating adults with hemophilia in clinical and research settings in the United States.
Chattopadhyay, Probodh K; Nagori, Shakil Ahmed; Menon, Rahul P; Balasundaram, T
Hemophilic pseudotumor is a rare complication occurring in patients with hemophilia, frequently seen in the femur, tibia, pelvic bones, iliac bones, or rarely in the maxillofacial region. A 7-year-old male reported with a spontaneous extra-oral swelling that was managed with pre-operative transfusion of factor IX along with curettage of the lesion. Our report presents only the fourth case in literature wherein this tumor presented in a patient with hemophilia B. Hemophilic pseudotumor is a rare entity in the maxillofacial region. High degree of suspicion is required for diagnosis, and close coordination between the medical and surgical teams aids in management.
Full Text Available Intracranial hemorrhage among term newborns is a rare clinical condition with high morbidity and mortality. Although major bleeding is relatively uncommon, the incidence of intracranial hemorrhage in hemophilic children is higher during the first few days of life than at any other stage in childhood, which relates to the trauma of delive ry. Here, we reported a newborn case diagnosed with moderate hemophilia A, without the presence of a positive family history of hemophilia and presenting with intracranial and extracranial hemorrhage and we aimed to emphasize that the early diagnosis and replacement therapy carries an essential importance.
Verma, Rajanshu; Noack, Jill; Vemuri, Radhakrishna; Loehrke, Mark E
Acquired hemophilia A, also known as acquired factor VIII deficiency, is an exceedingly rare bleeding diathesis that does not require any personal or family history of bleeding or clotting disorder. Because treatment is available, misdiagnosing or completely missing this diagnosis can be life threatening for patients. Clinicians should be aware that acquired forms of hemophilia do exist and are associated with high morbidity and mortality in elderly adults. We present a case of a 74-year-old man who was diagnosed with acquired factor VIII inhibitor during an admission for community-acquired pneumonia.
Tiede, Andreas; Werwitzke, Sonja; Scharf, Rüdiger E
Acquired hemophilia A (AHA) should be suspected in patients with a new onset of bleeding and an isolated prolongation of activated partial thromboplastin time. About 10% of patients do not bleed at the time of diagnosis, but are at risk of future bleeding, particularly during interventions or surgery. Diagnosis of AHA is confirmed by demonstrating markedly reduced factor VIII activity (FVIII:C) and neutralizing anti-FVIII antibodies, so-called inhibitors. Several limitations and pitfalls exist with the assays used to diagnose AHA. Interference can result from anticoagulants or lupus anticoagulant. The Bethesda assay used to measure inhibitor potency assumes a log-linear relationship between inhibitor concentration and effect on residual FVIII:C activity to allow exact quantification. However, this relationship is not present for the type 2 inhibitors typically seen in AHA. Therefore, this assay only provides a rough estimate of inhibitor potency. These limitations can explain, in part, why laboratory data, such as inhibitor potency, failed to predict bleeding or response to treatment in AHA. This article reviews the diagnostic approach to AHA, discusses assay-specific limitations and addresses some of the challenges for future research. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Sborov, Douglas W; Rodgers, George M
Acquired hemophilia A (AHA) is a rare, potentially life-threatening hemorrhagic disorder that presents a complex clinical challenge. The immune-mediated production of autoantibodies, known as factor VIII inhibitors, often results in clinically significant soft tissue or post-procedural bleeding episodes in patients without a previous diagnosis of a bleeding disorder. Acquired antibodies against factor VIII are associated with an extensive list of conditions, including pregnancy, autoimmune disease, and malignancy. There is great potential for morbidity and mortality resulting from autoantibody development. Death is more frequent within the first few weeks after symptomatic manifestation, making prompt recognition and treatment vitally important. Treatment focuses on stabilization of initial bleeding and long-term eradication of the acquired inhibitor. As no randomized clinical trials have been conducted regarding treatment in this patient population, clinical expertise and experience continue to guide treatment recommendations. This report provides an algorithm for the diagnosis of AHA and outlines potential treatment recommendations, most notably concomitant use of recombinant factor VIIa (rF7a) and factor VIII inhibitor bypassing agent to control bleeding in patients not responsive to single-agent therapy, and use of rituximab and prednisone for inhibitor eradication therapy.
Mulliez, S M N; Vantilborgh, A; Devreese, K M J
Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against clotting factor VIII (FVIII). FVIII autoantibody is characterized as polyclonal immunoglobulin G directed against the FVIII procoagulant activity. This disease occurs most commonly in the elderly population and with preponderance of men in nonpregnancy-related AHA. There are well-established clinical associations with AHA such as malignancy, other autoimmune diseases and pregnancy. However, up to 50% of reported cases remain idiopathic. The clinical manifestation of AHA includes mostly spontaneous hemorrhages into skin, muscles and soft tissues, or mucous membranes. AHA should be suspected when a patient with no previous history of bleeding presents with bleeding and an unexplained prolonged activated partial thromboplastin time. The diagnosis is confirmed in the laboratory by the subsequent identification of reduced FVIII levels and FVIII inhibitor titration. There is a high mortality, making prompt diagnosis and treatment vitally important. The principles of treatment consist in controlling the bleeding and eradicating the inhibitor. Because of the overall high relapse rate (15-33%), it is also recommended to follow up these patients. The review summarizes what is currently known about the epidemiology, pathogenesis, clinical features, diagnosis, treatment and prognosis of AHA and starts with a case report. © 2014 John Wiley & Sons Ltd.
Christopher D Porada
Full Text Available Hemophilia A (HA is the most frequent inheritable defect of the coagulation proteins. The current standard of care for patients with HA is prophylactic factor infusion, which is comprised of regular (2-3 times per week intravenous infusions of recombinant or plasma-derived FVIII to maintain hemostasis. While this treatment has greatly increased the quality of life and lengthened the life expectancy for many HA patients, its high cost, the need for lifelong infusions, and the fact that it is unavailable to roughly 75% of the world’s HA patients make this type of treatment far from ideal. In addition, this lifesaving therapy suffers from a high risk of treatment failure due to immune response to the infused FVIII. There is thus a need for novel treatments, such as those using stem cells and/or gene therapy, which have the potential to mediate long-term correction or permanent cure following a single intervention. In the present review, we discuss the clinical feasibility and unique advantages that an in utero approach to treating HA could offer, placing special emphasis on a new sheep model of HA we have developed and on the use of mesenchymal stromal cells (MSC as cellular vehicles for delivering the FVIII gene.
Komiya, Keiji; Sakai, Yasujiro; Horikoshi, Toru; Naganuma, Hirofumi
To elucidate the precise recovery process and prognosis of language functions in aphasic patients with left putaminal hemorrhage, we investigated 48 aphasic patients classified into 4 groups according to the location and extent of hematoma. The hematoma extended to the corona radiata in all patients, extracapsular in type I (12 cases), to the anterior limb in type II (10 cases), to the posterior limb in type III (12 cases), and to both limbs in type IV (14 cases). The Standard Language Test for Aphasia was performed at 1 month, 3 months, and 6 months after the attack. The type II, III, and IV patients were divided into 2 groups, with and without ventricular rupture of the hemorrhage. At 3 and 6 months after the attack, the type I, II, and III patients showed significant improvement (P language modalities compared with the type IV patients. Most improvement in language modalities occurred in the first 3 months. The evaluation of patients with ventricular rupture after 6 months revealed poor recovery (P type II and III patients. In type IV patients, this evaluation showed poor recovery (P < .05) only in oral and written naming (kanji words). No significant difference in prognostic outcome was observed between the surgical treatment group and the nonsurgical treatment group. The classification of hemorrhage may be useful in predicting the outcome of aphasia with putaminal hemorrhage and in guiding clinicians in providing effective instructions to patients and their relatives. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Full Text Available The present report describes an acute subdural hematoma (ASDH associated with subarachnoid hemorrhage (SAH, due to ruptured cortical aneurysm. To our knowledge, extremely rare cases of this sort have been reported so far. A 23-year-old male patient without previous trauma presented with severe headache and rapidly decreasing level of consciousness to decerebrate status. Computed tomography (CT scan has demonstrated an ASDH together with SAH. Hematoma has immediately been evacuated without any evaluation by angiography. After evacuation of the thick subdural clot, a 10-mm aneurysm was revealed on a precentral artery of frontal cortex, which was ligated. However, after 35 days the patient discharged with left side hemiparesis and dysphasia, and just after several months of admission he got symptom free. Ruptured cortical aneurysm should be considered as one of the causes of spontaneous ASDH. Vascular anomaly investigations are suggested for these cases, thus CT angiography or digital subtraction angiography has to be considered if clinical condition allows.
Aparici, F.; Mas, F.; Solera, M. C.; Moro, G. [Hospital Universitario La Fe. Valencia (Spain)
We present the case of a 78-year-old woman with a spontaneous spinal epidural hematoma that presented with sudden interscapular pain accompanied by left hemiparesis and a significant improvement 15 minutes later. Initially diagnosed as angina, the persistence of pain in dorsal cervical spine suggested the need to perform magnetic resonance imaging (MRI). The images demonstrated a lesion in the epidural spinal canal at level C3-D2 that presented a heterogeneous signal intensity, with hyperintense areas in T1-weighted sequences and hypointense areas in gradient-echo sequences, with no sign of compression myelopathy. A diagnosis of epidural hematoma was established and, given the favorable clinical course, conservative treatment was indicated. The second MRI study showed the complete resorption of the epidural hematoma. (Author) 12 refs.
Dedouit, Fabrice; Grill, Stéphane; Guilbeau-Frugier, Céline; Savall, Frédéric; Rougé, Daniel; Telmon, Norbert
A 53-year-old woman suffering from radicular pain due to cervical herniation underwent a spinal surgery consisting of anterior cervical discectomy and fusion with an implantable titanium cage. Five hours after the procedure, the patient developed cervical swelling and dyspnea. An emergency surgery permitted evacuation of a deep cervical hematoma and intubation of the patient, who died some minutes later. The family of the deceased lodged a complaint with the public prosecutor because of unclear circumstances of death. After analysis of the medical records by two forensic pathologists, a medicolegal autopsy was ordered. Massive retropharyngeal and mediastinal hematomas were diagnosed. Pathological study confirmed acute cervical hemorrhage, but failed to detect the source of bleeding. The forensic pathologists concluded that death was due to mechanical asphyxia secondary to pharyngeal compression by the cervical hematoma. To the best of our knowledge, death secondary to retropharyngeal hematoma in this neurosurgical context is rarely encountered. © 2014 American Academy of Forensic Sciences.
Amin, Nikul; Aymat-Torrente, Antonio
Bone-anchored hearing aids (BAHA) are bone conduction hearing aids commonly implantated by Ear, Nose, and Throat surgeons. We present the first documented case of a subdural hematoma secondary to primary fixation of a BAHA. We present a 65-year-old male patient undergoing a left sided BAHA for bilateral chronic ear infections and difficulty wearing conventional hearing aids. The procedure was uneventful, however, the patient developed a postoperative large acute left temporoparietal intracerebral hematoma associated with an ipsilateral acute subdural hematoma. This required emergency transfer to the local tertiary neurosurgical center for a left decompressive craniotomy and evacuation of the hematoma. The patient required a prolonged stay on an intensive care unit and was eventually discharged to the community for on-going neurological rehabilitation. This is a rare and devastating complication BAHA surgery. Otologist, general ENT surgeons, and neurosurgeons should be aware of this life-threatening complication of BAHA surgery.
Oliveira, João Henrique Botto de; Esper, Raiza Samenica; Ocariz, Rodrigo Campos; Sartori, Flora Specian; Freire, Lucas Marcelo Dias; Chaim, Elinton Adami; Callejas-Neto, Francisco; Cazzo, Everton
Spontaneous intramural duodenal hematoma is uncommon and is usually associated with coagulopathy, anticoagulant therapy and endoscopic procedures. The aim here was to describe a case of intramural duodenal hematoma caused by chronic exacerbation of pancreatitis. A 46-year-old male with chronic alcoholic pancreatitis was admitted to hospital due to abdominal pain, melena and low hemoglobin. An intramural duodenal hematoma with active bleeding was detected and selective angioembolization was warranted. The patient evolved with a perforated duodenum and underwent laparotomy with exclusion of the pylorus and Roux-en-Y gastrojejunostomy. He was discharged nine days later. Intramural duodenal hematoma is a rare complication of pancreatitis. Selective embolization is the preferred treatment for hemorrhagic complications of pancreatitis. However, the risk of visceral ischemia and perforation should be considered.
Full Text Available Clinical outcomes are positively associated with hematoma absorption. The monocyte-macrophage scavenger receptor, CD163, plays an important role in the metabolism of hemoglobin, and a soluble form of CD163 is present in plasma and other tissue fluids; therefore, we speculated that serum CD163 affects hematoma absorption after intracerebral hemorrhage. Patients with intracerebral hemorrhage were divided into high- and low-level groups according to the average CD163 level (1,977.79 ± 832.91 ng/mL. Compared with the high-level group, the low-level group had a significantly slower hematoma absorption rate, and significantly increased National Institutes of Health Stroke Scale scores and modified Rankin Scale scores. These results suggest that CD163 promotes hematoma absorption and the recovery of neurological function in patients with intracerebral hemorrhage.
Rodrigo O. M. F Ferreira
Full Text Available São discutidos os aspectos clínicos relativos ao diagnóstico e tratamento dos hematomas epidurals espinais espontâneos. Os dados obtidos em dois casos são apresentados, sendo salientada a localização lombar destes hematomas, os distúrbios neurológicos agudos, geralmente de. irradiação radicular, acompanhados por déficit neurológico de caráter progressivo. A problemática desses hematomas epidurals espinais, principalmente a sua pequena frequência, a demonstração radiológica por mielografia contrastada e o seu tratamento cirúrgico por laminectomia, são ressaltados. O tratamento de escolha é o cirúrgico, laminectomia com dissecção e remoção do hematoma que possibilita a recuperação do paciente.
Dong Hua Cao
Full Text Available OBJECTIVE: Hemophilia B is caused by coagulation defects in the factor IX gene located in Xq27.1 on the X chromosome. A wide range of mutations, showing extensive molecular heterogeneity, have been described in hemophilia B patients. Our study was aimed at genetic analysis and prenatal diagnosis of hemophilia B in order to further elucidate the pathogenesis of the hemophilia B pedigree in China. METHODS: Polymerase chain reaction amplification and direct sequencing of all the coding regions was conducted in hemophilia B patients and carriers. Prenatal diagnosis of the proband was conducted at 20 weeks. RESULTS: We identified the novel point mutation 10.389 A>G, located upstream of the intron 3 acceptor site in hemophilia B patients. The fetus of the proband’s cousin was identified as a carrier. CONCLUSION: Our identification of a novel mutation in the F9 gene associated with hemophilia B provides novel insight into the pathogenesis of this genetically inherited disorder and also represents the basis of prenatal diagnosis.
Full Text Available Background: Hemophilias are groups of blood clotting disorder caused by deficiency of blood clotting factors which is X-linked recessively inherited and explain why mostly man is the affected victim. But on an extremely rare condition a women can have hemophilia due to several reasons and sporadic hemophilia is used to describe when hemophilia appeared without ascent and decent history of hemophilia. A 38 years old women with a peripheral spontaneous bleeding for two days although an open flap and a cauterization to stop the bleeding has been applied. She was the third child of 7 children in the family, 3 of them were man with normal life and 4 women also have no history of bleeding. Her parent and grand-parent were all dead because of aging problems. She also has 2 sons with ages of 10 and 13 years, respectively, live normally. Results: factor VIII activity 192 seconds (control: 80 seconds, factor IX activity 2 seconds (control: 111 seconds, hence patient was considered suffered from sporadic haemophilia-B due to low level of factor IX 1.8% and bleeding episodes mimicking clinical presentation of classical hemophilia patients while no known history of having hemophiliac family. The different diagnose were Von Willebrand Diisease (VWD, symptomatic carriers, acquired hemophilia. After several admissions and repeatedly bleeding episodes patient died because of intra cerebral bleeding.
Aspegren, Oskar P.; Åstrand, Ramona; Lundgren, Maria I.
Chronic subdural hematoma (CSDH) is a common disease among the elderly and with increasing incidence we have chosen to focus on associations between development and recurrence of CSDH and anticoagulation and/or antiplatelet agent therapy.......Chronic subdural hematoma (CSDH) is a common disease among the elderly and with increasing incidence we have chosen to focus on associations between development and recurrence of CSDH and anticoagulation and/or antiplatelet agent therapy....
Abdul-rahman R. Abdel-karim
Full Text Available Interventricular septal hematoma is a rare complication of retrograde chronic total occlusion (CTO percutaneous coronary interventions (PCI with a typically benign course. Here we report two cases of interventricular septal hematoma and coronary-cameral fistula development after right coronary artery (RCA CTO-PCI using a retrograde approach. Both were complicated by development of ST-segment elevation and chest pain. One case was managed actively and the other conservatively, both with a favorable outcome.
Fuse, Takahisa; Takagi, Takuji; Fukushima, Tsuneyuki; Mizuno, Shiroh; Hashimoto, Nobukazu; Suzuki, Osamu (Nagoya City Higashi General Hospital (Japan))
A 9-year-old boy had been diagnosed at the age of 9 months as having a cerebellar medulloblastoma and had received 40 Gy of radiation therapy to the brain after removal of the tumor. Cerebral angiography at the time of initial diagnosis did not show any evidence of occlusive disease involving the internal carotid circulation. At the age of 6 years, the patient developed generalized seizures. On examination, he was drowsy and had right hemiparesis. CT scan demonstrated a low-density area in the left frontal lobe. Cerebral angiography showed a marked narrowing of the bilateral internal carotid arteries with moyamoya vessels. The patient was treated medically with aspirin (100 mg/day) and anticonvulsants. His neurological deficits improved gradually. At the age of 8 years, there was no recurrence of the tumor although a slight left subdural hematoma was seen on CT scan. On August 10, 1993, at the age of 9 years, he was admitted for treatment of a developing subdural hematoma. MRI showed a chronic subdural hematoma with thick outer and inner membranes. Cerebral angiography showed occlusion of the left internal carotid artery which fed the right frontal lobe through moyamoya vessels, marked narrowing of the right internal carotid artery distal to the ophthalmic artery, moyamoya vessels at the base, and cortical revascularization througth the ophthalmic, posterior cerebral and middle meningeal arteries. Trepanation and aspiration of the hematoma were performed. The outer membrane of the hematoma was about 2 mm thick and the hematoma cavity was filled with a partially organized hematoma. In this case, we speculate that development of the chronic subdural hematoma involved the following factors: (1) transdural external-internal carotid anastomosis after radiation-induced cerebrovasculopathy; (2) repeated mild head trauma due to gait disturbance after removal of the cerebellar tumor; and (3) administration of acetylsalicylic acid. (author).
Ovesen, Christian; Christensen, Anders Fogh; Krieger, Derk W
BACKGROUND AND PURPOSE: Early hematoma expansion (EHE) in patients with intracerebral hematoma is a promising treatment target. To date, the time course of EHE has remained poorly described. We prospectively investigated the time course of EHE. METHODS: We included consecutive patients presenting...... occurred within the first 7 to 8 hours after symptom onset. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01472224....
Nermin Görkem Sirin
Full Text Available Spinal subdural hematoma (SDH is a rare condition and can be caused by several factors. Concomitant cranial and spinal SDH is even much less common. We present a 77-year-old male patient with lower back pain, paraparesis, and urinary retention following a sudden onset headache. Imaging revealed concomitant cranial and spinal SDH related to cerebral venous thrombosis (CVT associated with hemorrhagic venous infarct. Laboratory examinations were consistent with polycythemia vera. There was no history of trauma and previous cranial surgery. Brain angiography did not reveal any evidence of arteriovenous fistula or vascular malformation. Since lower back pain occurred shortly after the headache and there was no other reasonable explanation for spinal hemorrhage, we suppose that the mechanism of spinal SDH is the migration of blood from the intracranial compartment. Therefore, this is the first report of concomitant spinal SDH and cerebral hemorrhage associated with CVT in a patient with myeloproliferative disease.
Lineu Cesar Werneck
Full Text Available Foram analisados retrospectivamente 121 pacientes com hematomas intracerebrais espontâneos (HIE: com média de idade de 53,4 ±14,8 anos, 62,8% do sexo masculino, tempo médio de sangramento na admissão de 36 horas (3 horas a 12 dias; 63,5% estavam acima de 7 na escala de Glasgow e 81,9% com grau igual ou maior que 3 na escala de Botterel. Os HIE eram: em gânglios da base em 45,5%, multilobares em 14,7%, lobares em 22,8%, no tronco cerebral em 4% e cerebelares em 2%. Seus diâmetros médios eram de 46,6 mm (16 a 33 e a área média de 1422,9 mm2 (60 a 4818. O LCR em 67 casos revelou pressão inicial média de 234 mmH20 (30 a 700 e concentrarão proteica média de 416,9 mg/dl (30 a 1960. O tratamento foi conservador em 107 casos e cirúrgico em 14. Sobreviveram 55,8% dos pacientes; a maioria dos que faleceram estava em grau acima de 3 na escala de Boterell e abaixo de 9 na de Glasgow. Houve correlação estatística entre a sobrevida e óbito com a escala de Glasgow e com a de Boterell, paralisia de músculos oculares, déficit motor, sinais de descerebração, broncopneumonia, diâmetro e área do hematoma; não houve relação estatística com uso de dexametasona, antifibrinolítico, anticonvulsivantes e diuréticos. O uso de manitol e a queda da pressão arterial nos primeiros dias tiveram relação com maior mortalidade Dos 14 casos submetidos a cirurgia, 11 faleceram. A principal complicação que levou a óbito foi broncopneumonia. São feitos comentários sobre a patogenia dos HIE, incidência atual, sinais clínicos» localização, tamanho, causas de óbito e tratamento empregado em relação ao prognóstico.
Keshava, S; Sundaram, J; Rajulapati, A; Pendurthi, U R; Rao, L V M
ESSENTIALS: The role of tissue factor (TF) in recombinant factor VIIa (rFVIIa) therapy in hemophilia is unclear. An acquired mouse hemophilia model with very low or normal levels of human TF was used in the study. rFVIIa is equally effective in correcting the bleeding in mice expressing low or normal levels of TF. Pharmacological doses of rFVIIa restore hemostasis in hemophilia independent of TF. Recombinant factor VIIa (rFVIIa) has been used widely for treating hemophilia patients with inhibitory autoantibodies against factor VIII or IX. Its mechanism of action is not entirely known. A majority of in vitro studies suggested that pharmacological concentrations of rFVIIa restore hemostasis in hemophilia in a phospholipid-dependent manner, independent of tissue factor (TF). However, a few studies suggested that a TF-dependent mechanism has a primary role in correction of bleeding by rFVIIa in hemophilia patients. Here, we investigated the potential contribution of TF in rFVIIa-induced hemostasis in hemophilia employing a model system of FVIII antibody-induced hemophilia in TF transgenic mice. Mice expressing low levels of human TF (LTF mice), mice expressing relatively high levels of human TF (HTF mice) and wild-type mice (WT mice) had neutralizing anti-FVIII antibodies administered in order to induce hemophilia in these mice. The mice were then treated with varying concentrations of rFVIIa. rFVIIa-induced hemostasis was evaluated with the saphenous vein bleeding model. Administration of FVIII inhibitory antibodies induced the hemophilic bleeding phenotype in all three genotypes. rFVIIa administration rescued the bleeding phenotype in all three genotypes. No significant differences were observed in rFVIIa-induced correction of bleeding between LTF and HTF mice that had FVIII antibodies administered. Our results provide strong evidence supporting the suggestion that the hemostatic effect of pharmacological doses of rFVIIa stems from a TF-independent mechanism. © 2016
Full Text Available The retroperitoneal hematoma can have, mainly, a traumatic etiology - blunt abdominal trauma (falls from height, road accidents, aggression of any kind, etc., or open (incised wounds, puncture, penetration or gunshot wounds. Ruptured arterial aneurysms can cause hemorrhage in the retroperitoneal space. There is also spontaneous retroperitoneal trauma in patients with chronic treatment with anticoagulant or antiaggregant drugs (1. Hemorrhage in the retroperitoneal space can be iatrogenic, after surgical, open or laparoscopic, interventions (2, 3. A particular type of retroperitoneal hematoma is the psoas muscle hematoma in patients with chronic oral anticoagulant treatment (Acenocumarol, Warfarin. The management of the retroperitoneal hematoma, whatever the cause may be, is, for most of the time, difficult. In case of traumatic etiology, the retroperitoneal hematoma is not the only lesion, being frequently associated with severe hollow or parenchymal organs injury or vascular lesions, which highlights the importance of a complete and precise clinical inventory of the lesions. The decision between an aggressive, surgical or interventional attitude and a conservative one, with monitoring, is often taken under pressure. Especially difficult are the cases in which the imaging results of the lesions is uncertain, when the patient presents hemodynamic instability, when other lesions can not be excluded, or when the parietal peritoneum is ruptured and the retroperitoneal hematoma gets into the peritoneal cavity, the patient presenting haemoperitoneum. For most of the time, these cases have indication for exploratory laparotomy, for a diagnostic, not therapeutic, goal.
Chronic subdural hematoma pathophysiology has been extensively studied and discussed. In the last decades, optic and electron microscope observations have successfully described its histopathology and the ultrastructure of internal membranes. Moreover, recent biochemical studies have identified a number of important pathways involved in its development and evolution. Our aim was to review recent literature regarding histopathology, ultrastructure and biochemichal pathways and supply a unifying theory about chronic subdural hematoma pathophysiology. The starting point of chronic subdural hematoma is a mechanical injury. The evolution of the pathology is due to the exclusive anatomy of the dura-arachnoid interface. This is a mechanically weak layer. Fibroblasts contained in this region produce an inflammatory reaction with neoangiogenesis and fibrinolysis. Biochemical pathways involved in these reactions is complex and could contain a number of pharmacological targets. The hematoma evolves in different stages thus recent outlooks consider chronic subdural hematoma as a dynamic process. One of the key points for a good outcome and a low recurrence rate may be the timing of the surgical treatment in relation of hematoma natural history. Surgery performed during active inflammatory stages may be less effective in terms of clinical outcome and recurrence rate.
Young, G; Mahlangu, J; Kulkarni, R; Nolan, B; Liesner, R; Pasi, J; Barnes, C; Neelakantan, S; Gambino, G; Cristiano, L M; Pierce, G F; Allen, G
Prophylactic factor replacement, which prevents hemarthroses and thereby reduces the musculoskeletal disease burden in children with hemophilia A, requires frequent intravenous infusions (three to four times weekly). Kids A-LONG was a phase 3 open-label study evaluating the safety, efficacy and pharmacokinetics of a longer-acting factor, recombinant factor VIII Fc fusion protein (rFVIIIFc), in previously treated children with severe hemophilia A (endogenous FVIII level of hemophilia A. © 2015 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.
Victoria V. Barinova
Full Text Available Background: The role of subchorionic hematoma (SCH in the first trimester of pregnancy remains open for discussion. Some authors claim that SCH does not affect the pregnancy; others have found that it is a serious risk factor for adverse pregnancy outcome. The objective of the present study was to explore the outcomes of pregnancy in patients with SCH diagnosed in the first trimester. Methods and Results: The study involved 194 pregnant women who were in terms of 6 to12 weeks: 115 women with SCH (Group 1 and 79 apparently healthy pregnant women (Group 2. A missed miscarriage was observed in 27/23% women of Group 1 and in 4/5% of Group 2 (P<0.05, recurrent threat of miscarriage in 27/23% and in 4/5%, recurrent bleeding in 14/12% and 2/3%, and the short cervix syndrome in 22/19% and 5/6% women, respectively. Conclusion: The results of our study show that the presence of SCH adversely affects the first half of pregnancy, leading to recurrent threatened abortion, recurrent threat of miscarriage, missed miscarriage until 12 weeks of gestation, and the short cervix syndrome.
Henry, J B; Messerer, M; Thomas, V; Diabira, S; Morandi, X; Hamlat, A
Nontraumatic spinal epidural hematoma (SEH) during pregnancy is rare. Therefore, appropriate management of this occurrence is not well defined. The aim of this study was to extensively review the literature on this subject, to propose some novel treatment guidelines. Electronic databases, manual reviews and conference proceedings up to December 2011 were systematically reviewed. Articles were deemed eligible for inclusion in this study if they dealt with nontraumatic SEH during pregnancy. Search protocols and data were independently assessed by two authors. In all, 23 case reports were found to be appropriate for review. The mean patient age was 28 years and gestational age was 33.2 weeks. Thirteen cases presented with acute interscapular pain. The clinical picture consisted of paraplegia, which occurred approximately 63 h after pain onset. Spinal cord decompression was performed within an average time of 20 h after neurological deficit onset. Fifteen patients had cesarean deliveries, even when the gestational age was less than 36 weeks. This review failed to identify articles, other than case reports, which could assist in the formation of new guidelines to treat SEH in pregnancy. However, we believe that SEH may be managed neurosurgically, without requiring prior, premature, cesarean section.
Kim, Sang Gyun; Shim, Kwang Seok; Lee, Dong Won; Kim, Eun ju; Lee, Sang-Gon; Lee, Ji-Hyang; An, Ji hyun
Abstract Rationale: Although trigger point injection is known as an easy and low-risk procedure, it is contraindicated to patients with hemorrhagic disorders or who regularly take anticoagulants/antiplatelets. However, taking clopidogrel is not a defined contraindication to this low-risk procedure. Patient concerns: The chief complaint of a 76-year old woman regularly taking clopidogrel was low back and left buttock pain which prolonged for several years. Diagnoses: The patient was diagnosed with L4-5 and L5-S1 spinal stenosis at the orthopedics department and was referred for lumbar spinal epidural steroid injection. Intervention: She was treated with trigger point injection. Outcomes: Three hours after the injection, she complained motor weakness and pain in the injection area. A hematoma on left gluteus medium muscle was detected with ultrasonography and ultrasound-guided needle aspiration was accomplished to relieve the symptom. Lessons: Trigger point injection for patients taking clopidogrel should be done with a caution to prevent such complication. PMID:28953648
Hadded, W.; Chang, J.; Rosenbury, T.; Dallum, G.; Welsch, P.; Scott, D.; Duarte, D.; Acevedo-Bolton, V.
A non-invasive microwave device for the detection of epi/subdural hemorrhaging (hematoma) is under current development. The final device will be highly portable and allow real time assessment of head injuries, thereby satisfying early detection needs of the field technician as well as providing a tool for repetitious monitoring of high-risk individuals. The device will adopt the advanced technology of micropower impulse radar (MIR) which is a state of the art low cost ultra wide band (UWB) microwave radar developed here at LLNL. It will consist of a MIR transmitting and receiving module, a computer based signal processing module, and a device-to-patient signal coupling module--the UWB antenna. The prototype design is being guided by the needs of the patient and the practitioner along with the prerequisites of the technology including issues such as the specificity of the device, efficacy of diagnosis, accuracy, robustness, and patient comfort. The prototype development follows a concurrent approach which .includes experiments designed to evaluate requirements of the radar and antenna design, phantom development to facilitate laboratory investigations, and investigation into the limits of adapting pre-existing non-medical MIR devices to medical applications. This report will present the accomplishments and project highlights to date in the fiscal year 1999. Future project projections will also be discussed.
Azizyan, Avetis; Miller, Joseph M; Azzam, Ramzi I; Maya, Marcel M; Famini, Pouyan; Pressman, Barry D; Moser, Franklin G
Pituitary apoplexy is a rare and potentially life-threatening disorder that is most commonly characterized by a combination of sudden headache, visual disturbance, and hypothalamic/hormonal dysfunction. In many cases, there is hemorrhagic infarction of an underlying pituitary adenoma. The resulting clinical symptoms are due to compression of the remaining pituitary, cavernous sinuses, or cranial nerves. However, there are only 2 case reports in the literature describing spontaneous retroclival expansion of hemorrhage secondary to pituitary apoplexy. Ten cases of this entity with a review of the literature are presented here. This is a single-institution retrospective review of 2598 patients with sellar and parasellar masses during the 10-year period between 1999 and 2009. The pituitary and brain MRI and MRI studies were reviewed by 2 neuroradiologists for evidence of apoplexy, with particular attention given to retroclival extension. Eighteen patients (13 men and 5 women; mean age 54 years) were identified with presenting symptoms of sudden onset of headache and ophthalmoplegia, and laboratory findings consistent with pituitary apoplexy. Ten of these patients (8 men and 2 women; mean age 55 years) had imaging findings consistent with retroclival hematoma. Retroclival hemorrhage was seen in the majority of cases of pituitary apoplexy (56%), suggesting that it is more common than previously thought.
Nakao, Shota; Ishikawa, Kazuo; Ono, Hidefumi; Kusakabe, Kenji; Fujimura, Ichiro; Ueno, Masato; Idoguchi, Koji; Mizushima, Yasuaki; Matsuoka, Tetsuya
Lumbar vertebral fracture (LVF) infrequently produces massive retroperitoneal hematoma (RPH). This study aimed to systematically review the clinical and radiographic characteristics of RPH resulting from LVF. For 193 consecutive patients having LVF who underwent computed tomography (CT), demographic data, physiological conditions, and outcomes were reviewed from their medical records. Presence or absence of RPH, other bone fractures, or organ/vessel injury was evaluated in their CT images, and LVF or RPH, if present, was classified according to either the Orthopaedic Trauma Association classification or the concept of interfascial planes. RPH resulting only or dominantly from LVF was found in 66 (34.2%) patients, whereas among the others, 64 (33.2%) had no RPH, 38 (19.7%) had RPH from other injuries, and 25 (13.0%) had RPH partly attributable to LVF. The 66 RPHs resulting only or dominantly from LVF were radiologically classified into mild subtype of minor median (n = 35), moderate subtype of lateral (n = 11), and severe subtypes of central pushing-up (n = 13) and combined (n = 7). Of the 20 patients with severe subtypes, 18 (90.0%) were in hemorrhagic shock on admission, and 6 (30.0%) were clinically diagnosed as dying due to uncontrollable RPH resulting from vertebral body fractures despite no anticoagulant medication. LVF can directly produce massive RPH leading to hemorrhagic death. A major survey of such pathology should be conducted to establish appropriate diagnosis and treatment.
Sherman, Alexandra; Su, Jin; Lin, Shina; Wang, Xiaomei; Herzog, Roland W; Daniell, Henry
Hemophilia A is the X-linked bleeding disorder caused by deficiency of coagulation factor VIII (FVIII). To address serious complications of inhibitory antibody formation in current replacement therapy, we created tobacco transplastomic lines expressing FVIII antigens, heavy chain (HC) and C2, fused with the transmucosal carrier, cholera toxin B subunit. Cholera toxin B-HC and cholera toxin B-C2 fusion proteins expressed up to 80 or 370 µg/g in fresh leaves, assembled into pentameric forms, and bound to GM1 receptors. Protection of FVIII antigen through bioencapsulation in plant cells and oral delivery to the gut immune system was confirmed by immunostaining. Feeding of HC/C2 mixture substantially suppressed T helper cell responses and inhibitor formation against FVIII in mice of 2 different strain backgrounds with hemophilia A. Prolonged oral delivery was required to control inhibitor formation long-term. Substantial reduction of inhibitor titers in preimmune mice demonstrated that the protocol could also reverse inhibitor formation. Gene expression and flow cytometry analyses showed upregulation of immune suppressive cytokines (transforming growth factor β and interleukin 10). Adoptive transfer experiments confirmed an active suppression mechanism and revealed induction of CD4(+)CD25(+) and CD4(+)CD25(-) T cells that potently suppressed anti-FVIII formation. In sum, these data support plant cell-based oral tolerance for suppression of inhibitor formation against FVIII. © 2014 by The American Society of Hematology.
Mesfin, Fassil B; Perkins, Nora W; Brook, Christopher; Foyt, David; German, John W
Epidural hematoma (EDH) has never been reported as a complication after placement of a bone-anchored hearing aid (BAHA). To our knowledge, this is the first case report of an EDH after placement of a BAHA. We report the case of a 15-year-old girl with an EDH after placement of a BAHA. Initially, she presented with a history of right ear conductive hearing loss and had a tympanomastoidectomy and placement of a BAHA at an outpatient surgical facility. Postoperatively, the patient was transferred to the postoperative care unit in stable neurological condition but was subsequently noted to be lethargic with dilated, nonreactive pupils and extensor posturing. A computed tomography scan revealed a large right temporal EDH with midline shift. She was then taken to the operating room emergently for craniotomy and evacuation of the EDH. After evacuation, she was admitted to the pediatric intensive care unit and slowly emerged from her coma with supportive care. She was discharged to inpatient rehabilitation and has made a good recovery. This report emphasizes the need for a high index of suspicion of this rare, but life-threatening complication of an EDH after the placement of a BAHA.
In this thesis, three major elements in the research around growing up with hemophilia are presented: development and evaluation of instruments (Part I), HRQOL and psychosocial outcomes (Part II) and psychosocial care (Part III). This thesis is the first to describe what it is like to grow up with
Plug, I.; van der Bom, J. G.; Peters, M.; Mauser-Bunschoten, E. P.; de Goede-Bolder, A.; Heijnen, L.; Smit, C.; Willemse, J.; Rosendaal, F. R.
Clotting factor products have been safe for HIV since 1985, and for hepatitis C since 1992. Few studies have reported on mortality in the total population of hemophilia patients after the period of risk of viral infection transmission. We studied the mortality, causes of death, and life expectancy
Biere-Rafi, Sara; Zwiers, M.; Peters, Marjolein; Van Der Meer, Jan; Rosendaal, Frits R; Buller, Harry R; Kamphuisen, Pieter W
Background: Patients with hemophilia and von Willebrand disease (VWD) may be protected against arterial thrombosis, through a hy-pocoagulable state or atherosclerosis. We performed a systematic review to assess the association between these clotting disorders, arterial thrombosis and the prevalence
Nakamura, Yuki; Murata, Moe; Takagi, Yuki; Kozuka, Toshihiro; Nakata, Yukiko; Hasebe, Ryo; Takagi, Akira; Kitazawa, Jun-ichi; Shima, Midori; Kojima, Tetsuhito
Hemophilia B is an X-linked recessive bleeding disorder caused by abnormalities of the coagulation factor IX gene (F9). Insertion mutations in F9 ranging from a few to more than 100 base pairs account for only a few percent of all hemophilia B cases. We investigated F9 to elucidate genetic abnormalities causing severe hemophilia B in a Japanese subject. We performed PCR-mediated analysis of F9 and identified a large insertion in exon 6. Next, we carried out direct sequencing of a PCR clone of the whole insert using nested deletion by exonuclease III and S1 nuclease. We identified an approximately 2.5-kb SINE-VNTR-Alu (SVA)-F element flanked by 15-bp duplications in the antisense orientation in exon 6. Additionally, we carried out exontrap analysis to assess the effect of this retrotransposition on mRNA splicing. We observed that regular splicing at exons 5 and 6 of F9 was disturbed by the SVA retrotransposition, suggesting that abnormal FIX mRNA may be reduced by nonsense-mediated mRNA decay. In conclusion, this is the first report of SVA retrotransposition causing severe hemophilia B; only five cases of LINE-1 or Alu retrotranspositions in F9 have been reported previously.
Wu, Runhui; Luke, Koon Hung
Currently full dose prophylaxis is the standard of care in the treatment of hemophilia (World Federation of Hemophilia). However, the high costs prevent the use of standard or intermediate dose prophylaxis in China and other developing countries. Low dose prophylaxis would be a viable alternative treatment. At present global research data on the use of low dose prophylaxis is limited. Areas covered: Since 2007, China has been developing low dose prophylaxis as a high priority (90 % of moderate and severe hemophilia boys suffer joint disease by age 6 - 9). 11 studies were successfully conducted and published results showing evidence of the benefits of low dose prophylaxis to reduce joint bleeding. This new knowledge has been implemented into clinical practice in China. However the long-term outcome of arthropathy remains unclear and obstacles in execution exist. Expert commentary: In 2016, the first phenotype-based individualized prophylaxis study using four escalating low dose regimens on severe Chinese hemophilia A boys (China Individualized Prophylaxis Study (CHIP China)) launched. Using the previously published and imminent CHIP data, the goal for China is to establish an effective escalating low dose prophylaxis protocol for use in China as a standard of care.
Gupta, Samriti; Garg, Kapil; Singh, Jagdish
To evaluate the functional independence of children with hemophilia A and its correlation to radiological joint score. The present cross sectional study was conducted at SPMCHI, SMS Medical College, Jaipur, India. Children in the age group of 4-18 y affected with severe, moderate and mild hemophilia A and with a history of hemarthrosis who attended the OPD, emergency or got admitted in wards of SPMCHI, SMS Medical College were examined. Musculoskeletal function was measured in 98 patients using Functional Independence Score in Hemophilia (FISH) and index joints (joints most commonly affected with repeated bleeding) were assessed radiologically with plain X rays using Pettersson score. The mean FISH score was 28.07 ± 3.90 (range 17-32) with squatting, running and step climbing as most affected tasks. The mean Pettersson score was 3.8 ± 3.2. A significant correlation was found between mean Pettersson score and FISH (r = -0.875, P hemophilia A.
Conclusion: Carrier and prenatal genetic testing for hemophilia is a cost-effective investment in healthcare allocation. A case management system should be integrated in the current practice to facilitate patient care (e.g., collecting family pedigrees and providing genetic counseling.
Goedert, JJ; Eyster, ME; Lederman, MM; Mandalaki, T; de Moerloose, P; White, GC; Angiolillo, AL; Luban, NLC; Sherman, KE; Manco-Johnson, M; Preiss, L; Leissinger, C; Kessler, CM; Cohen, AR; DiMichele, D; Hilgartner, MW; Aledort, LM; Kroner, BL; Rosenberg, PS; Hatzakis, A
Many persons with hemophilia were infected with hepatitis C and B viruses (HCV, HBV) and HIV, but the consequences of these transfusion-acquired infections are poorly defined. We estimated the risk of HCV-related end-stage liver disease (ESLD) and the associations of age, HBV, and HIV with that
Hanyu, Naofumi; Aota, Yasuo; Gotoh, Akihiko; Sakurai, Michio
Acquired hemophilia is a rare bleeding diathesis caused by autoantibodies against clotting factor VIII. Many cases are associated with autoimmune disease, malignancy and an elderly status. Acquired hemophilia is very rare, with a reported annual incidence of 1.48/million/y. However, it is necessary to consider this rare disease when encountering bleeding of unknown cause in elderly patients. An 84-year-old woman was referred to our hospital with subcutaneous bleeding and anemia. The patient had severe anemia and a prolonged activated partial prothrombin time (APTT). Despite the administration of red blood cell transfusions, the decline in hemoglobin continued. Since the activity of coagulation factor VIII was 5 BU/ml, the patient was diagnosed with acquired hemophilia. No underlying diseases were found, and we concluded that this case was idiopathic. Although she was treated with prednisolone at a dose of 40 mg per day, the bleeding tendency did not improve. Therefore, she was given activated prothrombin complex concentrates (APCC) for four days. The subcutaneous bleeding and Hb decline stopped, and the dose of prednisolone was gradually reduced. The patient's clotting function and clinical course were satisfactory, and she was discharged on the 64th day. An early diagnosis and optimal treatment are critical for treating acquired hemophilia. The development of a bleeding tendency related to the appearance of coagulation factor VIII inhibitor is serious in many patients. Therefore, recognizing this disease and providing prompt management are necessary.
Solomon, Gabriele; Greenberg, Jacquie; Futter, Merle; Vivian, Lauraine; Penn, Claire
Hemophilia A and B are X-linked recessive inherited bleeding disorders that have a profound impact on the family of affected individuals. Education is vital to enable women to appreciate the implications of being a carrier and the implications for a prospective child. Prior research has shown that cultural, socio-economic and linguistic issues in South Africa are major barriers to communication for first-language Xhosa-speakers. This exploratory study aimed to investigate the basic knowledge of genetic inheritance among this cultural group in order to promote culturally-sensitive, effective genetic counseling. Ten in-depth interviews were conducted with Xhosa-speaking mothers or caregivers of boys with hemophilia. Results suggest that the participants had a very limited understanding of the clinical management, genetic consequences and cause of hemophilia. While treatment and care by health care service providers was fully accepted, several participants believed that traditional methods would provide them with more satisfactory explanations. These findings suggest that there is a critical need for socio-culturally tailored, language-specific education for families with hemophilia.
Patients with severe hemophilia, a deficiency of functional clotting factor VIII, typically suffer from joint and muscle bleedings spontaneously or after minor trauma. The bleeding tendency can be effectively corrected by intravenous substitution of factor VIII products. However, about 25% of
Baudo, Francesco; Collins, Peter; Huth-Kuehne, Angela; Levesque, Herve; Marco, Pascual; Nemes, Laszlo; Pellegrini, Fabio; Tengborn, Lilian; Knoebl, Paul; Aspoeck, G.; Heistinger, M.; Knobl, P.; Makipernaa, A.; Andre, H; Aouba, A.; Bellucci, S.; Beurrier, P.; Borg, J.Y.; Darnige, L.; Devignes, J.; d'Oiron, R.; Gautier, P.; Gay, V.; Girault, S.; Gruel, Y.; Guerin, V.; Hezard, N.; Khellaf, M.; Koenig, M.; Levesque, H.; Lifermann, F; Marlu, R; Ninet, J.; Peynet, J.; Quemeneur, T.; Rothschild, C.; Schleinitz, N.; Sigaud, M.; Trouillier, S; Voisin, S.; Giebl, A.; Holstein, K.; Huth-Kuhne, A; Loreth, R.M.; Steigerwald, U.; Tiede, A.; Theodossiades, G.; Nemes, L.; Radvanyi, G.; Schlammadinger, A.; Barillari, G.; Pasca, S.; Baudo, F; Caimi, T.; Contino, L.; D'Angelo Armando, C.L.; Fattorini, A.; Di Minno, G.; Cerbone, A.M.; Di Minno, Matteo Nicola Dario; D'inca, M.; Falanga, A.; Maggioni, A.; Lerede, T.; Franchini, M.; Gaidano, G.; De Paoli, L.; Gamba, G.; Ghirardi, R; Girotto, M.; Tasca, D.; Grandone, E.; Tiscia, G.; Imberti, D.; Iorio, A.; Landolfi, R; Di Gennaro, L.; Novarese, L.; Mariani, G.; Lapecorella, M.; Marietta, M.; Pedrazzi, P.; Mazzucconi, M.G.; Santoro, C.; Morfini, M.; Linari, S.; Moratelli, S.; Paolini, R.; Piseddu, G.; Poggio, R.; Pogliani, E.; Carpenedo, M.; Remiddi, C.; Santagostino, E.; Mancuso, M.E.; Santoro, R.; Papaleo, G.; Schinco, P.; Borchiellini, A.; Valeri, F.; Scortechini, A.R.; Siragusa, S.; Sottilotta, G.; Squizzato, A.; Tagariello, G.; Sartori, R; Tagliaferri, A.R.; Di Perna, C.; Rivolta, G.F.; Testa, S.; Paoletti, O.; Toschi, V.; Zanon, E.; Brandolin, B.; Hamulyak, K.; Kamphuisen, P.; Laros-van Gorkom, B.; Leebeek, F.W.; Marten, N.; Novakova, I.; Schutgens, R.; van der Linden, P.W.; van Esser, J.; van der Meer, J.; Ypma, P.; Campos, M.; Aguilar, C.; Altisent, C.; Bermejo, N.; Del Campo, R.; Ferreiro Arguelles, M.; Gonzalez Bolos', R.; Gutierrez Pimentel, M.J.; Jimenez-Yuste, V.; Jose-Felix, L.; Marco, P.; Mingot, M.E.; Perez Garrido, R.; Perez Gonzale, N.Z.; Prieto Garcia, M.; Rodriguez-Huerta, A.M.; Sedano, C.; Tolosa Munoz, A.; Baghaei, F.; Tengborn, L.; Boehlen, F.; Korte, W.; Chowdary, P.; Collins, P.; Evans, G.; Pavord, S.; Rangarajan, S.; Wilde, J.
Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The
Collins, Peter; Baudo, Francesco; Knoebl, Paul; Levesque, Herve; Nemes, Laszlo; Pellegrini, Fabio; Marco, Pascual; Tengborn, Lilian; Huth-Kuehne, Angela; Aspoeck, Gerold; Heistinger, Max; Knobl, Paul; Makipernaa, Anne; Andre, Helene; Aouba, A; Bellucci, Sylvia; Beurrier, Philippe; Borg, Jeanne Yvonne; Darnige, Luc; Devignes, Jean; dOiron, Roseline; Gautier, Philippe; Gay, Valerie; Girault, Stephane; Gruel, Yves; Guerin, Viviane; Hezard, Nathalie; Khellaf, Mehdi; Koenig, Martial; Levesque, Herve; Lifermann, Francois; Marlu, Raphael; Ninet, J.; Peynet, Jocelyne; Quemeneur, Thomas; Rothschild, Chantal; Schleinitz, Nicolas; Sigaud, Marianne; Trouillier, Sebastien; Voisin, Sophie; Giebl, Andreas; Holstein, Katharina; Huth-Kuhne, Angela; Loreth, Ralph M.; Steigerwald, Udo; Tiede, Andreas; Theodossiades, George; Nemes, Laszlo; Radvanyi, Gaspar; Schlammadinger, Agota; Barillari, Giovanni; Pasca, Samantha; Baudo, Francesco; Caimi, T.; Contino, L.; D'Angelo, Armando; Crippa, Luciano; Fattorini, Annalisa; Di Minno, Giovanni; Cerbone, Anna Maria; Di Minno, Matteo Nicola Dario; D'inca, Marco; Falanga, Anna; Maggioni, Anna; Lerede, Teresa; Franchini, Massimo; Gaidano, Gianluca; De Paoli, Lorenzo; Gamba, Gabriella; Ghirardi, Raffaele; Girotto, Mauro; Tasca, Delios; Grandone, Elvira; Tiscia, Giovanni; Imberti, Davide; Iorio, Alfonso; Landolfi, Raffaele; Di Gennaro, Leonardo; Novarese, Linda; Mariani, Guglielmo; Lapecorella, Mario; Marietta, Marco; Pedrazzi, Paola; Mazzucconi, Maria Gabriella; Santoro, Cristina; Morfini, Massimo; Linari, Silvia; Moratelli, Stefano; Paolini, Rossella; Piseddu, Gavino; Poggio, Renzo; Pogliani, Enrico; Carpenedo, Monica; Remiddi, Chiara; Santagostino, Elena; Mancuso, Maria Elisa; Santoro, Rita; Papaleo, Giuseppina; Schinco, Piercarla; Borchiellini, Alessandra; Valeri, Federica; Scortechini, Anna Rita; Siragusa, Sergio; Sottilotta, Gianluca; Squizzato, Alessandro; Tagariello, Giuseppe; Sartori, Roberto; Tagliaferri, Anna Rita; Di Perna, Caterina; Rivolta, Gianna Franca; Testa, Sophie; Paoletti, Oriana; Toschi, Vincenzo; Zanon, Ezio; Brandolin, Barbara; Hamulyak, Karly; Kamphuisen, Pieter; Laros-van Gorkom, Britta; Leebeek, Frank W.G.; Marten, Nijziel; Novakova, Irena; Schutgens, Roger; van der Linden, P.W.G; van Esser, Joost; van der Meer, J.; Ypma, Paula; Campos, Manuel; Aguilar, Carlos; Altisent, Carmen; Bermejo, Nuria; Del Campo, Raquel; Ferreiro Arguelles, M.; Gonzalez Boullosa, Rosario; Gutierrez Pimentel, Maria Jose; Jimenez-Yuste, Victor [No Value; Jose-Felix, Lucia; Marco, Pascual; Mingot, Maria Eva; Perez Garrido, Rosario; Perez Gonzale, Noelia z; Prieto Garcia, Manuel; Rodriguez-Huerta, Ana Maria; Maranon, HGUG [No Value; Sedano, Carmen; Tolosa Munoz, Alexandra; Baghaei, Fariba; Tengborn, Lilian; Boehlen, Francoise; Korte, Wolfgang; Chowdary, Pratima; Collins, Peter; Evans, Gillian; Pavord, Suzanne; Rangarajan, Savita; Wilde, Jonathan
Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive
Collins, Peter; Baudo, Francesco; Knoebl, Paul; Lévesque, Hervé; Nemes, László; Pellegrini, Fabio; Marco, Pascual; Tengborn, Lilian; Huth-Kühne, Angela; Aspoeck, Gerold; Heistinger, Max; Knöbl, Paul; Makipernaa, Anne; André, Hélène; Aouba, Achille; Bellucci, Sylvia; Beurrier, Philippe; Borg, Jeanne Yvonne; Darnige, Luc; Devignes, Jean; d'Oiron, Roseline; Gautier, Philippe; Gay, Valérie; Girault, Stéphane; Gruel, Yves; Guerin, Viviane; Hézard, Nathalie; Khellaf, Mehdi; Koenig, Martial; Lifermann, François; Marlu, Raphael; Ninet, Jacques; Peynet, Jocelyne; Quéméneur, Thomas; Rothschild, Chantal; Schleinitz, Nicolas; Sigaud, Marianne; Trouillier, Sébastien; Voisin, Sophie; Giebl, Andreas; Holstein, Katharina; Loreth, Ralph M.; Steigerwald, Udo; Tiede, Andreas; Theodossiades, George; Radvanyi, Gaspar; Schlammadinger, Agota; Barillari, Giovanni; Pasca, Samantha; Caimi, Teresa; Contino, Laura; D'Angelo Armando, Crippa Luciano; Fattorini, Annalisa; Di Minno, Giovanni; Cerbone, Anna Maria; Di Minno, Dario; D'incà, Marco; Falanga, Anna; Maggioni, Anna; Lerede, Teresa; Franchini, Massimo; Gaidano, Gianluca; de Paoli, Lorenzo; Gamba, Gabriella; Ghirardi, Raffaele; Girotto, Mauro; Tasca, Delios; Grandone, Elvira; Tiscia, Giovanni; Imberti, Davide; Iorio, Alfonso; Landolfi, Raffaele; Di Gennaro, Leonardo; Novarese, Linda; Mariani, Guglielmo; Lapecorella, Mario; Marietta, Marco; Pedrazzi, Paola; Mazzucconi, Maria Gabriella; Santoro, Cristina; Morfini, Massimo; Linari, Silvia; Moratelli, Stefano; Paolini, Rossella; Piseddu, Gavino; Poggio, Renzo; Pogliani, Enrico; Carpenedo, Monica; Remiddi, Chiara; Santagostino, Elena; Mancuso, Maria Elisa; Santoro, Rita; Papaleo, Giuseppina; Schinco, Piercarla; Borchiellini, Alessandra; Valeri, Federica; Scortechini, Anna Rita; Siragusa, Sergio; Sottilotta, Gianluca; Squizzato, Alessandro; Tagariello, Giuseppe; Sartori, Roberto; Tagliaferri, Anna Rita; Di Perna, Caterina; Rivolta, Gianna Franca; Testa, Sophie; Paoletti, Oriana; Toschi, Vincenzo; Zanon, Ezio; Brandolin, Barbara; Hamulyák, Karly; Kamphuisen, Pieter; Laros-van Gorkom, Britta; Leebeek, Frank W. G.; Marten, Nijziel; Novakova, Irena; Schutgens, Roger; van der Linden, P. W. G.; van Esser, Joost; van der Meer, J.; Ypma, Paula; Campos, Manuel; Aguilar, Carlos; Altisent, Carmen; Bermejo, Nuria; del Campo, Raquel; Ferreiro Argüelles, María; González Boullosa, Rosario; Gutiérrez Pimentel, María José; Jiménez-Yuste, Victor; Jose-Felix, Lucia; Mingot, Maria Eva; Perez Garrido, Rosario; Perez Gonzale, Noelia Z.; Prieto Garcia, Manuel; Rodriguez-Huerta, Ana María; Sedano, Carmen; Tolosa Munoz, Alexandra; Baghaei, Fariba; Boehlen, Françoise; Korte, Wolfgang; Chowdary, Pratima; Evans, Gillian; Pavord, Suzanne; Rangarajan, Savita; Wilde, Jonathan
Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive
Baudo, Francesco; Collins, Peter; Huth-Kühne, Angela; Lévesque, Hervé; Marco, Pascual; Nemes, László; Pellegrini, Fabio; Tengborn, Lilian; Knoebl, Paul; Aspoeck, Gerold; Heistinger, Max; Knöbl, Paul; Makipernaa, Anne; André, Hélène; Aouba, Achille; Bellucci, Sylvia; Beurrier, Philippe; Borg, Jeanne Yvonne; Darnige, Luc; Devignes, Jean; d'Oiron, Roseline; Gautier, Philippe; Gay, Valérie; Girault, Stéphane; Gruel, Yves; Guerin, Viviane; Hézard, Nathalie; Khellaf, Mehdi; Koenig, Martial; Lifermann, François; Marlu, Raphael; Ninet, Jacques; Peynet, Jocelyne; Quéméneur, Thomas; Rothschild, Chantal; Schleinitz, Nicolas; Sigaud, Marianne; Trouillier, Sébastien; Voisin, Sophie; Giebl, Andreas; Holstein, Katharina; Loreth, Ralph M.; Steigerwald, Udo; Tiede, Andreas; Theodossiades, George; Radvanyi, Gaspar; Schlammadinger, Agota; Barillari, Giovanni; Pasca, Samantha; Caimi, Teresa; Contino, Laura; D'Angelo Armando, Crippa Luciano; Fattorini, Annalisa; Di Minno, Giovanni; Cerbone, Anna Maria; Di Minno, Dario; D'incà, Marco; Falanga, Anna; Maggioni, Anna; Lerede, Teresa; Franchini, Massimo; Gaidano, Gianluca; de Paoli, Lorenzo; Gamba, Gabriella; Ghirardi, Raffaele; Girotto, Mauro; Tasca, Delios; Grandone, Elvira; Tiscia, Giovanni; Imberti, Davide; Iorio, Alfonso; Landolfi, Raffaele; Di Gennaro, Leonardo; Novarese, Linda; Mariani, Guglielmo; Lapecorella, Mario; Marietta, Marco; Pedrazzi, Paola; Mazzucconi, Maria Gabriella; Santoro, Cristina; Morfini, Massimo; Linari, Silvia; Moratelli, Stefano; Paolini, Rossella; Piseddu, Gavino; Poggio, Renzo; Pogliani, Enrico; Carpenedo, Monica; Remiddi, Chiara; Santagostino, Elena; Mancuso, Maria Elisa; Santoro, Rita; Papaleo, Giuseppina; Schinco, Piercarla; Borchiellini, Alessandra; Valeri, Federica; Scortechini, Anna Rita; Siragusa, Sergio; Sottilotta, Gianluca; Squizzato, Alessandro; Tagariello, Giuseppe; Sartori, Roberto; Tagliaferri, Anna Rita; Di Perna, Caterina; Rivolta, Gianna Franca; Testa, Sophie; Paoletti, Oriana; Toschi, Vincenzo; Zanon, Ezio; Brandolin, Barbara; Hamulyák, Karly; Kamphuisen, Pieter; Laros-van Gorkom, Britta; Leebeek, Frank W. G.; Marten, Nijziel; Novakova, Irena; Schutgens, Roger; van der Linden, P. W. G.; van Esser, Joost; van der Meer, J.; Ypma, Paula; Campos, Manuel; Aguilar, Carlos; Altisent, Carmen; Bermejo, Nuria; del Campo, Raquel; Ferreiro Argüelles, María; González Boullosa, Rosario; Gutiérrez Pimentel, María José; Jiménez-Yuste, Victor; Jose-Felix, Lucia; Mingot, Maria Eva; Perez Garrido, Rosario; Perez Gonzale, Noelia Z.; Prieto Garcia, Manuel; Rodriguez-Huerta, Ana María; Sedano, Carmen; Tolosa Munoz, Alexandra; Baghaei, Fariba; Boehlen, Françoise; Korte, Wolfgang; Chowdary, Pratima; Evans, Gillian; Pavord, Suzanne; Rangarajan, Savita; Wilde, Jonathan
Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The
Alperstein, Warren; Corrales-Medina, Fernando F; Tamariz, Leonardo; Palacio, Ana M; Davis, Joanna A
Improved life expectancy in hemophilia has led to a greater interest in age-related disorders. Hypertension (HTN) as well as cardiovascular disease have been increasingly reported in hemophilic adults but there is currently very limited data in the pediatric population. We conducted a cross-sectional study using data from the 2012 National Health Cost and Utilization Project database to determine the prevalence of HTN and associated cardiovascular risk factors in a hospitalized pediatric hemophilia population, between the ages of 0 to 21 years, in comparison with the general pediatric population. The prevalence of HTN was significantly higher in children with hemophilia (CWH) in comparison with the general pediatric population (1.71% vs. 1.02%, P-value=0.005). When adjusting the analysis for sex, the prevalence of HTN in the hemophilia cohort remained higher, although not statistically significant (1.52% vs. 1.22%, P-value=0.2568). When examining the concomitant presence of ≥1 cardiovascular risk factors in the hypertensive subgroups, CWH had a higher prevalence of obesity (2.64% vs. 1.32%, P-value <0.0001). Interestingly, diabetes mellitus was more prevalent in nonhemophilic children (1.47% vs. 0.56%, P-value=0.0015). These data suggest that cardiovascular risk factors need to be closely monitored in CWH, and a better preventive strategy is likely needed to identify those hemophilic patients at higher risk of developing cardiovascular disease in adulthood.
Loomans, J.I.; Eckhardt, C.L.; Reitter-Pfoertner, S.E.; Holmstrom, M.; Laros-van Gorkom, B.A.; Leebeek, F.W.; Santoro, C.; Haya, S.; Meijer, K.; Nijziel, M.R.; Bom, J.G. Van Der; Fijnvandraat, K.
Essentials Data on bleeding-related causes of death in non-severe hemophilia A (HA) patients are scarce. Such data may provide new insights into areas of care that can be improved. Non-severe HA patients have an increased risk of dying from intracranial bleeding. This demonstrates the need for
Lu, Wei; Zhou, Qingzhang; Yang, Hao; Wang, Hao; Gu, Yexing; Shen, Qi; Xue, Jinglun; Dong, Xiaoyan; Chen, Jinzhong
Hemophilia B is a hemorrhagic disease caused by the deficiency of clotting factor IX (FIX). Gene therapy might be the ultimate strategy for the disease. However, two main problems that should be solved in gene therapy for hemophilia B are immunity and safety. Self-complementary adeno-associated virus serotype 8 (scAAV8), a non-human primate AAV featuring low immunogenicity and high transfection efficiency in liver cells, might be a potential vector for hemophilia B gene therapy. A strong liver-specific promoter-1 (LP1) was inserted and mutant human FIX Arg338Ala was introduced into plasmid scAAV8-LP1 to develop an optimized AAV8 vector that expresses human clotting factor FIX (hFIX). The efficiency of scAAV8-LP1-hFIX administered through normal systemic injection or hydrodynamic injection was compared. A high expression was achieved using hydrodynamic injection, and the peak hFIX expression levels in the 5 × 10(11) and 1 × 10(11) virus genome (vg) cohorts were 31.94% and 25.02% of normal level, respectively, at 60 days post-injection. From the perspective of long-term (200 days) expression, both injection methods presented promising results with the concentration value maintained above 4% of normal plasma. The results were further verified by enzyme-linked immunosorbent assay and activated partial thromboplastin time. Our study provides a potential gene therapy method for hemophilia B.
Kim, Tae-Won; Choi, Hyun Seok; Koo, Jaseong; Jung, So Lyung; Ahn, Kook-Jin; Kim, Bum-Soo; Shin, Yong Sam; Lee, Kwang Soo
The radiologic diagnosis of vertebral artery dissection (VAD) depends on characteristic intraluminal findings on angiography and intramural hematoma or a double-lumen sign on high-resolution vessel wall imaging. We aimed to evaluate the accuracy of intramural hematoma sign on susceptibility-weighted imaging (SWI) in VAD. We retrospectively analyzed SWI, phase map images and brain computed tomography (CT) of the consecutive patients who suffered an ischemic stroke in the vertebral artery territory from August 2010 to July 2012. We divided the patients into 2 groups: the VAD group and the nondissection group. VAD was diagnosed by conventional catheter angiographic findings (aneurysmal dilatation, pearl-and-string or tapered steno-occlusion) and pathognomonic findings such as intramural hematoma or a double-lumen sign on the source images of TOF-MRA, high-resolution T1-weighted MRI or high-resolution T2-weighted MRI. Intramural hematoma sign was considered positive if the patient had an eccentric or concentric hypointense signal lesion in the vertebral artery on SWI, a corresponding hyperintense signal on phase map and no evidence of calcification on the brain CT, suggesting blood products other than calcification. Two experienced neuroradiologists blinded to clinical information and angiographic findings were asked to judge for the presence of intramural hematoma sign on SWI. The accuracy of intramural hematoma sign on SWI was evaluated. Phase value, demographic and clinical data were compared between the VAD and the nondissection groups. Thirty-nine patients were included: 10 in the VAD group and 29 in the non-dissection group. Among the VAD group cases, intramural hematoma sign on SWI was positive in 9 of the 10 VAD cases and in 1 out of the 29 cases in the nondissection group. The intramural hematoma sign on SWI was significantly associated with VAD (p radian vs. -0.42 radian, p < 0.001). The intramural hematoma sign on SWI was significantly associated with VAD
Full Text Available Moniba Nazeef,1,2 John P Sheehan1,2 1Department of Medicine, Division of Hematology/Oncology, 2UW Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA Abstract: Hemophilia B is an X-linked genetic deficiency of coagulation factor IX (FIX activity associated with recurrent deep tissue and joint bleeding that may lead to long-term disability. FIX replacement therapy using plasma-derived protein or recombinant protein has significantly reduced bleeding and disability from hemophilia B, particularly when used in a prophylactic fashion. Although modern factor replacement has excellent efficacy and safety, barriers to the broader use of prophylaxis remain, including the need for intravenous (IV access, frequent dosing, variability in individual pharmacokinetics, and cost. To overcome the requirement for frequent factor dosing, novel forms of recombinant FIX have been developed that possess extended terminal half-lives. Two of these products (FIXFc and rIX-FP represent fusion proteins with the immunoglobulin G1 (IgG1 Fc domain and albumin, respectively, resulting in proteins that are recycled in vivo by the neonatal Fc receptor. The third product has undergone site-specific PEGylation on the activation peptide of FIX, similarly resulting in a long-lived FIX form. Clinical trials in previously treated hemophilia B patients have demonstrated excellent efficacy and confirmed less-frequent dosing requirements for the extended half-life forms. However, gaps in knowledge remain with regard to the risk of inhibitor formation and allergic reactions in previously untreated patient populations, safety in elderly patients with hemophilia, effects on in vivo FIX distribution, and cost-effectiveness. Additional strategies designed to rebalance hemostasis in hemophilia patients include monoclonal-antibody-mediated inhibition of tissue factor pathway inhibitor activity and siRNA-mediated reduction in antithrombin
Jerry S Powell
Full Text Available Jerry S PowellDivision of Hematology and Oncology, University of California Davis Cancer Center, Sacramento, CA, USAAbstract: Hemophilia A is a rare inherited bleeding disorder due to mutation of the gene that encodes the coagulation protein factor VIII. Historically, prior to the availability of treatment with factor VIII preparations, most boys died from uncontrolled bleeding, either spontaneous bleeding or after injury, before reaching 20 years of age. One of the most impressive triumphs of modern medicine is that with current recombinant factor VIII replacement therapy, a boy born in the 21st century with severe hemophilia A can anticipate a normal life expectancy with essentially no permanent complications from bleeding. For severe hemophilia A, current optimal treatment should have two goals: first, to provide sufficient factor VIII to prevent spontaneous bleeding, and second, to provide sufficient factor VIII to have normal coagulation function after any trauma. However, the replacement therapy requires tremendous resources for effective use, and remains extraordinarily expensive. Thus there are opportunities for further advances in therapy for hemophilia A. Two major concerns continue to trouble current optimal treatment approaches: some patients will develop neutralizing antibodies during the first 50 infusions of therapeutic factor VIII, and second, to administer therapeutic factor VIII every other day in young boys often requires placement of a central venous access device, and such use carries the life-threatening risks of infection and thrombosis. Because of the effectiveness of current therapy, any new developments in treatment will require significant concerns for safety, both immediate and in the long term. A number of research groups seek to prolong the biological efficacy of infused recombinant factor VIII. Currently, one such promising development is in the advanced stages of clinical trial. The goals will be to improve
Full Text Available Rubén Cuesta-Barriuso,1–3 Ana Torres-Ortuño,4 Pilar Galindo-Piñana,4 Joaquín Nieto-Munuera,4 Natalie Duncan,5 José Antonio López-Pina6 1Department of Physiotherapy, School of Biomedical and Health Sciences, European University of Madrid, 2Fishemo, Centro Especial de Empleo, Spanish Federation of Hemophilia, 3Royal Foundation Victoria Eugenia, Madrid, 4Department of Psychiatry and Social Psychology, Faculty of Medicine, University of Murcia, Murcia, Spain; 5Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA; 6Department of Basic Psychology and Methodology, Faculty of Psychology, University of Murcia, Murcia, Spain Purpose: We aimed to conduct a validation in Spanish of the Validated Hemophilia Regimen Treatment Adherence Scale – Prophylaxis (VERITAS-Pro questionnaire for use in patients with hemophilia under prophylactic treatment.Patients and methods: The VERITAS-Pro scale was adapted through a process of back translation from English to Spanish. A bilingual native Spanish translator translated the scale from English to Spanish. Subsequently, a bilingual native English translator translated the scale from Spanish to English. The disagreements were resolved by agreement between the research team and translators. Seventy-three patients with hemophilia, aged 13–62 years, were enrolled in the study. The scale was applied twice (2 months apart to evaluate the test–retest reliability.Results: Internal consistency reliability was lower on the Spanish VERITAS-Pro than on the English version. Test–retest reliability was high, ranging from 0.83 to 0.92. No significant differences (P>0.05 were found between test and retest scores in subscales of VERITAS-Pro. In general, Spanish patients showed higher rates of nonadherence than American patients in all subscales.Conclusion: The Spanish version of the VERITAS-Pro has high levels of consistency and empirical validity. This scale can be administered to assess the degree of
Aurioles-Garibay, Alma; Hernandez-Andrade, Edgar; Romero, Roberto; Qureshi, Faisal; Ahn, Hyunyoung; Jacques, Suzanne M; Garcia, Maynor; Yeo, Lami; Hassan, Sonia S
The lesion termed 'placental infarction hematoma' is associated with fetal death and adverse perinatal outcome. Such a lesion has been associated with a high risk of fetal death and abruption placentae. The fetal and placental hemodynamic changes associated with placental infarction hematoma have not been reported. This paper describes a case of early and severe growth restriction with preeclampsia, and progressive deterioration of the fetal and placental Doppler parameters in the presence of a placental infarction hematoma.
Zeng, Yan; Zhou, Ruiqing; Duan, Xin; Long, Dan; Yang, Songtao
Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation factor VIII (FVIII). In most cases, bleeding episodes are spontaneous and severe at presentation. The optimal hemostatic therapy is controversial. To determine the efficacy of hemostatic therapies for acute bleeds in people with acquired hemophilia A; and to compare different forms of therapy for these bleeds. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 4) and MEDLINE (Ovid) (1948 to 30 April 2014). We searched the conference proceedings of the: American Society of Hematology; European Hematology Association; International Society on Thrombosis and Haemostasis (ISTH); and the European Association for Haemophilia and Allied Disorders (EAHAD) (from 2000 to 30 April 2014). In addition to this we searched clinical trials registers. All randomised controlled trials and quasi-randomised trials of hemostatic therapies for people with acquired hemophilia A, with no restrictions on gender, age or ethnicity. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. No randomised clinical trials of hemostatic therapies for acquired hemophilia A were found. Thus, we are not able to draw any conclusions or make any recommendations on the optimal hemostatic therapies for acquired hemophilia A based on the highest quality of evidence. GIven that carrying out randomized controlled trials in this field is a complex task, the authors suggest that, while planning randomised controlled trials in which patients can be enrolled, clinicians treating the disease continue to base their choices on alternative, lower quality sources of evidence, which hopefully, in the future, will also be appraised and incorporated in a Cochrane Review.
Fomin, M E; Togarrati, P P; Muench, M O
Hemophilia A results from an insufficiency of factor VIII (FVIII). Although replacement therapy with plasma-derived or recombinant FVIII is a life-saving therapy for hemophilia A patients, such therapy is a life-long treatment rather than a cure for the disease. In this review, we discuss the possibilities, progress, and challenges that remain in the development of a cell-based cure for hemophilia A. The success of cell therapy depends on the type and availability of donor cells, the age of the host and method of transplantation, and the levels of engraftment and production of FVIII by the graft. Early therapy, possibly even prenatal transplantation, may yield the highest levels of engraftment by avoiding immunological rejection of the graft. Potential cell sources of FVIII include a specialized subset of endothelial cells known as liver sinusoidal endothelial cells (LSECs) present in the adult and fetal liver, or patient-specific endothelial cells derived from induced pluripotent stem cells that have undergone gene editing to produce FVIII. Achieving sufficient engraftment of transplanted LSECs is one of the obstacles to successful cell therapy for hemophilia A. We discuss recent results from transplants performed in animals that show production of functional and clinically relevant levels of FVIII obtained from donor LSECs. Hence, the possibility of treating hemophilia A can be envisioned through persistent production of FVIII from transplanted donor cells derived from a number of potential cell sources or through creation of donor endothelial cells from patient-specific induced pluripotent stem cells. © 2014 International Society on Thrombosis and Haemostasis.
Cannavò, Antonino; Valsecchi, Carla; Garagiola, Isabella; Palla, Roberta; Mannucci, Pier Mannuccio; Rosendaal, Frits R; Peyvandi, Flora
The development of anti-factor VIII (FVIII) neutralizing antibodies (inhibitors) is the major complication in hemophilia A. Nonneutralizing antibodies (NNAs) have been detected in hemophilia patients and also in unaffected individuals. The aim of this study was to assess the prevalence of NNAs and to evaluate whether their presence is associated with the development of inhibitors in a cohort of previously untreated or minimally treated patients with hemophilia A; plasma samples of 237 patients with severe hemophilia A enrolled in the SIPPET trial were collected before any exposure to FVIII concentrates and analyzed for the presence of anti-FVIII NNAs. Patients were observed for the development of neutralizing antibodies. NNAs were found in 18 (7.6%) of 237 patients at screening, and there was a clear age gradient. Of those with NNAs, 7 patients subsequently developed an inhibitor for a cumulative incidence of 45.4% (95% confidence interval [CI], 19.5% to 71.3%); among the 219 patients without NNAs, 64 (29%) developed an inhibitor (cumulative incidence, 34.0%; 95% CI, 27.1%-40.9%). In Cox regression analyses, patients with NNAs at screening had an 83% higher incidence of inhibitor development than patients without NNAs (hazard ratio [HR], 1.83; 95% CI, 0.84-3.99). For high-titer inhibitors, the incidence rate had an almost threefold increase (HR, 2.74; 95% CI, 1.23-6.12). These associations did not materially change after adjustment. The presence of anti-FVIII NNAs in patients with severe hemophilia A who were not previously exposed to FVIII concentrates is associated with an increased incidence of inhibitors. © 2017 by The American Society of Hematology.
Fabiane de Amorim Almeida
Full Text Available Objectives: To identify the limitations faced by the hemophiliac child, according to his/her parents, and how they deal with these limitations, and to verify how parents approach the problem of hemophilia with the child as well as their strategies for disciplining that child and their nonhemophiliac children. Methods: An exploratory descriptive research study with a quantitative approach carried out with 20 parents of hemophiliac children seen at the ambulatory of a medium size public hospital in the city of São Paulo. The data were collected by means of a structured interview, using a form with open-ended and closed questions. Rresults: All the parents (20; 100% reported talking to their children about hemophilia, especially as to the definition of the disease (19; 46,35% and the activities that should be avoided (eight; 19.50%. Most of them (17; 85% also reported talking about hemophilia with their other children. Eighteen parents (90% restricted participation in sports and physical activities for their hemophiliac child, including at school: 11 (55% prohibit participation in physical activities, and 12 (60% ban extracurricular activities. All the parents also reported raising the subject of their child’s hemophilia with the educational professionals at their child’s school. As to discipline, half of them (ten; 50% use different strategies for disciplining their hemophiliac and non-hemophiliac children. Cconclusions: All the parents are concerned with discussing the subject of hemophilia with the child, his/her siblings, and teachers at school, imposing limitations especially as to participation in sports and/or physical activities. Differences were noted as to the strategies used by the parents for the discipline of their hemophiliac and non-hemophiliac children.
Gringeri, A; Lundin, B; von Mackensen, S; Mantovani, L; Mannucci, P M
Prevention of arthropathy is a major goal of hemophilia treatment. While studies in adults have demonstrated an impact of prophylaxis on the incidence of joint bleeds and patients' well-being in terms of improved quality of life (QoL), it is unclear whether or not prophylaxis influences the outcome and perception of well- of children with hemophilia. This randomized controlled study compared the efficacy of prophylaxis with episodic therapy in preventing hemarthroses and image-proven joint damage in children with severe hemophilia A (factor VIII <1%) over a 10-year time period. Forty-five children with severe hemophilia A, aged 1-7 years (median 4), with negative clinical-radiologic joint score at entry and at least one bleed during the previous 6 months, were consecutively randomized to prophylaxis with recombinant factor VIII (25 IU kg(-1) 3 × week) or episodic therapy with ≥25 IU kg(-1) every 12-24 h until complete clinical bleeding resolution. Safety, feasibility, direct costs and QoL were also evaluated. Twenty-one children were assigned to prophylaxis, 19 to episodic treatment. Children on prophylaxis had fewer hemarthroses than children on episodic therapy: 0.20 vs. 0.52 events per patient per month (P < 0.02). Plain-film radiology showed signs of arthropathy in six patients on prophylaxis (29%) vs. 14 on episodic treatment (74%) (P < 0.05). Prophylaxis was more effective when started early (≤36 months), with patients having fewer joint bleeds (0.12 joint bleeds per patient per month) and no radiologic signs of arthropathy. This randomized trial confirms the efficacy of prophylaxis in preventing bleeds and arthropathy in children with hemophilia, particularly when it is initiated early in life. © 2011 International Society on Thrombosis and Haemostasis.
Amelard, Robert; Pfisterer, Kaylen J.; Clausi, David A.; Wong, Alexander
Impact trauma may cause a hematoma, which is the leakage of venous blood into surrounding tissues. Large hematomas can be dangerous as they may inhibit local blood ow. Hematomas are often diagnosed visually, which may be problematic if the hematoma leaks deeper than the visible penetration depth. Furthermore, vascular wound healing is often monitored at home without the aid of a clinician. We therefore investigated the use of near infrared (NIR) re ectance photoplethysmographic imaging (PPGI) to assess vascular damage resulting from a hematoma, and monitor the healing process. In this case study, the participant experienced internal vascular damage in the form of a hematoma. Using a PPGI system with dual-mode temporally coded illumination for ambient-agnostic data acquisition and mounted optical elements, the tissue was illuminated with a spatially uniform irradiance pattern of 850 nm wavelength light for increased tissue penetration and high oxy-to-deoxyhemoglobin absorption ratio. Initial and follow-up PPGI data collection was performed to assess vascular damage and healing. The tissue PPGI sequences were spectrally analyzed, producing spectral maps of the tissue area. Experimental results show that spatial differences in spectral information can be observed around the damaged area. In particular, the damaged site exhibited lower pulsatility than the surrounding healthy tissue. This pulsatility was largely restored in the follow-up data, suggesting that the tissue had undergone vascular healing. These results indicate that hematomas can be assessed and monitored in a non-contact visual manner, and suggests that PPGI can be used for tissue health assessment, with potential extensions to peripheral vascular disease.
Yu, Zhiyuan; Zheng, Jun; Ali, Hasan; Guo, Rui; Li, Mou; Wang, Xiaoze; Ma, Lu; Li, Hao; You, Chao
Hematoma expansion is related to poor outcome in spontaneous intracerebral hemorrhage (ICH). Recently, a non-enhanced computed tomography (CT) based finding, termed the 'satellite sign', was reported to be a novel predictor for poor outcome in spontaneous ICH. However, it is still unclear whether the presence of the satellite sign is related to hematoma expansion. Initial computed tomography angiography (CTA) was conducted within 6h after ictus. Satellite sign on non-enhanced CT and spot sign on CTA were detected by two independent reviewers. The sensitivity and specificity of both satellite sign and spot sign were calculated. Receiver-operator analysis was conducted to evaluate their predictive accuracy for hematoma expansion. This study included 153 patients. Satellite sign was detected in 58 (37.91%) patients and spot sign was detected in 38 (24.84%) patients. Among 37 patients with hematoma expansion, 22 (59.46%) had satellite sign and 23 (62.16%) had spot sign. The sensitivity and specificity of satellite sign for prediction of hematoma expansion were 59.46% and 68.97%, respectively. The sensitivity and specificity of spot sign were 62.16% and 87.07%, respectively. The area under the curve (AUC) of satellite sign was 0.642 and the AUC of spot sign was 0.746. (P=0.157) CONCLUSION: Our results suggest that the satellite sign is an independent predictor for hematoma expansion in spontaneous ICH. Although spot sign has the higher predictive accuracy, satellite sign is still an acceptable predictor for hematoma expansion when CTA is unavailable. Copyright © 2017 Elsevier B.V. All rights reserved.
Full Text Available Objectives In this study, the relationships of residue hematoma volume to brain edema and inflammation factors were studied after intracerebral hematoma was evacuated with a frameless stereotactic aspiration. Methods Eighty-nine patients with hypertensive intracerebral hemorrhage (ICH were treated by frameless stereotactic aspiration. According to residual volume of the hematoma, the patients were divided into gross-total removal of hematoma (GTRH (≤5ml and sub-total removal of hematoma (STRH (≥10ml groups after the operation. The pre-operative and postoperative data of the patients were compared between the two groups. The pre-operative data included age, sex, hematoma volume, time interval from the ictus to the operation, and Glasgow Coma Scale (GCS scores. The post-operative information included edema grade, level of thromboxane B2 (TXB2, 6-keto-prostaglandin F1α(6-K-PGF1α, tumor necrosis factor-α(TNF-α and endothelin (ET in hematoma cavity or cerebral spinal fluid (CSF. Results There were 46 patients in GTRH group and 43 in STRH group respectively. There was no statistical difference in the pre-operative data between the two groups. The levels of TXB2, 6-K-PGF1α, TNF-αand ET were significantly lower in the GTRH group than in the STRH group at different post-operative time points. There was a significant difference between the two groups. The post-operative CT scan at different time points showed that the brain edema grades were better in the GTRH group than in the STRH group. Conclusions GTRH is helpful for decreasing ICH-induced injury to brain tissue, which is related to decreased perihematomal edema formation and secondary injury by coagulation end products activated inflammatory cascade. DOI: 10.11855/j.issn.0577-7402.2016.09.12
Law, Catherine; Alam, Peyman; Borumandi, Farzad
The authors provide a structured review of reported cases of floor-of-mouth hematoma during or after dental implantation and frequent causes and management and present a related case. An online search of the medical literature was conducted from 1990 through 2016. The following search terms were used: floor of mouth hematoma, sublingual hematoma, dental implant hematoma, implant in mandible, and complication of dental implant. Abstracts were screened for relevance to the aims of the review. Relevant reports in the English language were included and referenced. The articles were reviewed for patient demographics, implant location, coagulopathy, pre- or postoperative imaging, airway management, treatment of the hematoma, and management of the offending implant. The literature search identified 25 reported cases. Hemorrhage was caused by perforation of the lingual cortex in 84% of cases (n = 21). Airway obstruction resulted in emergency intubation or tracheostomy in 68% of patients (n = 17). Most cases (n = 18; 72%) required surgical management in the hospital setting. Management of the offending implant was reported inconsistently. Of 17 reported cases, 5 implants had to be removed, 9 remained in situ, and in 3 cases implant placement was abandoned. Only 1 case involved preoperative 3-dimensional (3D) imaging before implant insertion. The authors report on an additional case with a serious floor-of-mouth hematoma that required immediate surgical evacuation and hemostasis. Serious complications, such as floor-of-mouth hematoma after dental implant insertion, can occur, which could be life-threatening. Preoperative 3D imaging helps to visualize the individual mandibular shape, which could decrease the incidence of serious complications. If injury to vessels of the floor of the mouth cannot be confidently excluded, then further assessment and treatment are recommended before the patient is discharged. Copyright © 2017 American Association of Oral and
Hvas, Anne-Mette; Sørensen, Hanne Thykjær; Norengaard, Lisbeth
BACKGROUND: Most patients with severe hemophilia A suffer from a profoundly compromised hemostatic response. In addition to both the delayed and slow development of a clot, previous studies have documented that severe hemophilia A is also associated with reduced clot stability. OBJECTIVES: We...... examined whether the clot stability in hemophiliacs could be improved by treatment with tranexamic acid (TXA) in combination with recombinant factor VIII (rFVIII). PATIENTS/METHODS: Baseline blood samples were obtained from eight males with severe hemophilia A. Thereafter, a bolus injection of r...... the elasticity curve increased 5-fold after rFVIII and 24-fold after addition of TXA. CONCLUSIONS: The study demonstrates that simultaneous treatment with TXA and rFVIII significantly improves the clot stability in patients with hemophilia A. Udgivelsesdato: December...
...; Knoebl, P; Marco, P; Baudo, F; Collins, P; Huth-Kuhne, A; Nemes, L; Pellegrini, F; Tengborn, L; Levesque, H; Aspoek, G; Heistinger, M; Knobl, P; Makipernaa, A; Ane, H; Aouba, A; Bellucci, Sylvia; Beurrier, P; Borg, J.Y; Darnige, L; Devignes, J; D'Oiron, R; Gautier, P; Gay, V; Girault, S; Gruel, Y; Guerin, V; Hezard, N; Khellaf, M; Koenig, M; Lifermann, F; Marlu, R; Ninet, Jacques; Peynet, J; Quemeneur, T; Rothschild, C; Schleinitz, N; Sigaud, M; Trouillier, S; Voisin, S; Giebl, A; Holstein, K; Loreth, R.M; Steigerwald, U; Tiede, A; Theodossiades, G; Radvanyi, G; Schlammadinger, A; Barillari, G; Pasca, S; Caimi, T; Contino, L; Di Minno, G; Cerbone, A.M; Di Minno, Matteo Nicola Dario; D'inca, M; Falanga, A; Maggioni, A; Lerede, T; Franchini, M; Gaidano, G; De Paoli, L; Gamba, G; Ghirardi, R; Girotto, M; Tasca, D; Grandone, E; Tiscia, G; Imberti, D; Iorio, A; Landolfi, R; Di Gennaro, L; Novarese, L; Mariani, G; Lapecorella, M; Marietta, M; Peazzi, P; Mazzucconi, M.G; Santoro, C; Morfini, M; Linari, S; Moratelli, S; Paolini, R; Piseddu, G; Poggio, R; Pogliani, E; Carpenedo, M; Remiddi, C; Santagostino, E; Mancuso, Maria Elisa; Santoro, R; Papaleo, G; Schinco, P; Borchiellini, A; Valeri, Federica; Scortechini, A.R; Siragusa, Sergio; Sottilotta, G; Squizzato, A; Sartori, R; Tagariello, G
Background: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous family or personal history of bleeding...
Wu, S; Li, Y; Cui, H; Xie, Y; Zheng, J; Pan, X; Zhang, H; Zhao, R; Zhang, Q
To explore a scheme of using PCR analysis in the detection of carriers of Hind III polymorphism of factor VIII gene of hemophilia A. Implicating intron 19 of the factor VIII gene of 6 patients with the hemophilia A and 207 unrelated X-chromosomes were amplified by PCR and were analysed by means of Amp-RFLPs of Hind III. The incidence of the polymorphic Hind III sites in the given population was found to be 0.29. The frequence of the Hind III heterozygotes in women calculated according to Hardy-Weinberg equation was 0.41, which proved to be informative enough for carrier detection and prenatal diagnosis of hemophilia A. 2 out of 6 families (33%)examined in this study were informative. The new scheme proved to be effective for hemophilia A carrier detection and prenatal diagnosis.
Conclusion: The results showed that aquatic exercise therapy can be a useful method to improve joints′ strength and range of motion in hemophilia patients in order to improve their daily functioning and quality of life.
Murru, S.; Casula, L.; Moi, P. [Insituto di Clinica e Biologia dell` Eta Evolutiva, Cagliari (Italy)] [and others
In this paper the authors report the molecular characterization of a large deletion that removes the entire Factor VIII gene in a severe hemophilia A patient. Accurate DNA analysis of the breakpoint region revealed that a large DNA fragment replaced the 300-kb one, which was removed by the deletion. Pulsed-field gel electrophoresis analysis revealed that the size of the inserted fragment is about 550 kb. In situ hybridization demonstrated that part of the inserted region normally maps to Xq21 and to the tip of the short arm of the Y chromosome (Yp). In this patient this locus is present both in Xq21 and in Xq28, in addition to the Yp, being thus duplicated in the X chromosome. Sequence analysis of the 3` breakpoint suggested that an illegitimate recombination is probably the cause of this complex rearrangement. 52 refs., 7 figs.
Isik, Arda; Peker, Kemal; Soyturk, Mehmet; Firat, Deniz; Yoruker, Uygar; Yilmaz, Ismayil
To identify clinical characteristics, treatment modalities, and course of spontaneous rectus sheath hematoma (SRSH). In the literature, there is no prospective clinical trial that is intended for treatment in clinical research. Seventeen SRSH patients diagnosed and treated between March 2012 and March 2014 at the general Surgery Department of Erzincan University Training and Research Hospital were included. Age, sex, weight, height, predisposing factors, comorbid diseases, Charlson index, current medical treatment, physical examination signs, imaging methods, lowest hemoglobin value, blood type, SRSH type, INR/Factor V Leiden mutation/Factor VII/Factor VIII/Factor X/Protein S/Protein C values, treatment method, transfusions hospitalization duration, and outcome were studied. Thirteen patients were female. The mean age was 63.3 ± 18.7 years (range, 22-87 years), and the mean BMI was 27.8 ± 3.5 (range, 20.9-33.7). Six patients had Grade I SRSH, 5 had Grade II SRSH, and 6 had Grade III SRSH. Thirteen were hospitalized for a mean duration of 9.3 ± 8.1 days (range, 1-30 days). The death rate attributable to SRSH was 5.8%. Early diagnosis of SRSH by ultrasonography and/or computerized tomography is important for a low mortality rate. Even though medical treatments are important, arterial embolization by interventional radiology, or more radical interventions such as surgery, may be required. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.
Weimer, Jonathan M; Gordon, Errol; Frontera, Jennifer A
Although the incidence of subdural hematoma (SDH) has increased in the US in the last decade, limited prospective data exist examining risk factors for poor outcome. A prospective, observational study of consecutive SDH patients was conducted from 7/2008 to 11/2011. Baseline clinical data, hospital and surgical course, complications, and imaging data were compared between those with good versus poor 3-month outcomes (modified Rankin Scores [mRS] 0-3 vs. 4-6). A multivariable logistic regression model was constructed to identify independent predictors of poor outcome. 116 SDH patients (18 acute, 56 mixed acute/subacute/chronic, 42 subacute/chronic) were included. At 3 months, 61 (53 %) patients had good outcomes (mRS 0-3) while 55 (47 %) were severely disabled or dead (mRS 4-6). Of those who underwent surgical evacuation, 54/94 (57 %) had good outcomes compared to 7/22 (32 %) who did not (p = 0.030). Patients with mixed acuity or subacute/chronic SDH had significantly better 3-month mRS with surgery (median mRS 1 versus 5 without surgery, p = 0.002) compared to those with only acute SDH (p = 0.494). In multivariable analysis, premorbid mRS, age, admission Glasgow Coma Score, history of smoking, and fever were independent predictors of poor 3-month outcome (all p SDH evacuation tended to improve outcomes (adjusted OR 3.90, 95 % CI 0.96-18.9, p = 0.057). Nearly 50 % of SDH patients were dead or moderate-severely disabled at 3 months. Older age, poor baseline, poor admission neurological status, history of smoking, and fever during hospitalization predicted poor outcomes, while surgical evacuation was associated with improved outcomes among those with mixed acuity or chronic/subacute SDH.
Shander, Aryeh; Walsh, Christopher E; Cromwell, Caroline
There are a number of potential etiologies of severe bleeding encountered in the intensive care unit. Although rare, acquired hemophilia is one such etiology that often presents with major bleeding requiring intensive care. Despite the introduction of effective treatments, the reported mortality rate of patients with acquired hemophilia ranges from 6 to 8% and is in part attributable to sequential delays in diagnosis and appropriate treatment. The purpose of this review is to familiarize the intensive care specialist with this underrecognized cause of bleeding, with an emphasis on diagnosis and treatment. As the objective of this article was to provide a concise overview of the diagnosis and management of acquired hemophilia, a directed search of English-language literature was undertaken using the PubMed database, targeting such topics as the differential diagnosis of bleeding in the intensive care unit and the epidemiology, diagnosis, and treatment of acquired hemophilia. Clinical study findings pertaining to the efficacy of specific treatments for acquired hemophilia were summarized. Recognition of acquired hemophilia presents a clinical challenge, given the rarity of this condition, a general lack of familiarity with acquired hemophilia, and the potential for confusion with other more common causes of bleeding in the intensive care unit. Nevertheless, there are sentinel clinical and laboratory findings that should raise suspicion of this diagnosis. The treatment of acquired hemophilia is a multi-step, physiologically focused process aimed at controlling both active and recurrent bleeding. Therefore, prompt diagnosis is central to prognosis. Consultation with a hematologist may facilitate efficient diagnosis and management.
Fletcher, Matthew; Crombet, Ofelia; Morales-Arias, Jaime
Acquired hemophilia A is a very rare, serious bleeding disorder. We describe a 5-year-old female who developed an acquired factor VIII inhibitor, and while under treatment with steroids, had an intestinal perforation with peritonitis and septic shock, making her a poor candidate for further immunosuppression. She was treated with rituximab with rapid, complete eradication of the inhibitor. She represents the first published case of a pediatric patient with acquired hemophilia A successfully treated with rituximab.
Full Text Available Rehabilitation plays an important role in the physical health of patients with hemophilia. However, comprehensive information regarding the utilization of rehabilitation for such patients remains scarce.This population-based study aimed to examine the characteristics, trends, and most important factors affecting rehabilitation usage in patients with hemophilia A using a nationwide database in Taiwan.Data from 777 patients with hemophilia A who were registered in the National Health Insurance Research Database between 1998 and 2008 were analyzed using SAS 9.0.Musculoskeletal or nervous system-related surgical procedures and clotting factor VIII concentrate costs were identified as factors affecting rehabilitation usage; musculoskeletal or nervous system-related surgical procedures (odds ratio = 3.788; P < 0.001 were the most important predictor of whether a patient with hemophilia A would use rehabilitation services. Joint disorders, arthropathies, bone and cartilage disorders, intracranial hemorrhage, and brain trauma were common diagnoses during rehabilitation use. The costs of physical therapy (physiotherapy comprised the majority (71.2% of rehabilitation therapy categories. Increasingly, rehabilitation therapy was performed at physician clinics. The total rehabilitation costs were <0.1% of the total annual medical costs.Musculoskeletal or nervous system-related surgical procedures and increased use of clotting factor VIII concentrate affect the rehabilitation utilization of patients with hemophilia A the most. The findings in this study could help clinicians comprehensively understand the rehabilitation utilization of patients with hemophilia A.
Lytle, Allison M; Brown, Harrison C; Paik, Na Yoon; Knight, Kristopher A; Wright, J Fraser; Spencer, H Trent; Doering, Christopher B
Immune responses to coagulation factors VIII (FVIII) and IX (FIX) represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC) retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV)-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV) vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV. PMID:26909355
Lytle, Allison M; Brown, Harrison C; Paik, Na Yoon; Knight, Kristopher A; Wright, J Fraser; Spencer, H Trent; Doering, Christopher B
Immune responses to coagulation factors VIII (FVIII) and IX (FIX) represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC) retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV)-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV) vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV.
Allison M Lytle
Full Text Available Immune responses to coagulation factors VIII (FVIII and IX (FIX represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV.
Kren, Betsy T; Unger, Gretchen M; Sjeklocha, Lucas; Trossen, Alycia A; Korman, Vicci; Diethelm-Okita, Brenda M; Reding, Mark T; Steer, Clifford J
Liver sinusoidal endothelial cells are a major endogenous source of Factor VIII (FVIII), lack of which causes the human congenital bleeding disorder hemophilia A. Despite extensive efforts, gene therapy using viral vectors has shown little success in clinical hemophilia trials. Here we achieved cell type-specific gene targeting using hyaluronan- and asialoorosomucoid-coated nanocapsules, generated using dispersion atomization, to direct genes to liver sinusoidal endothelial cells and hepatocytes, respectively. To highlight the therapeutic potential of this approach, we encapsulated Sleeping Beauty transposon expressing the B domain-deleted canine FVIII in cis with Sleeping Beauty transposase in hyaluronan nanocapsules and injected them intravenously into hemophilia A mice. The treated mice exhibited activated partial thromboplastin times that were comparable to those of wild-type mice at 5 and 50 weeks and substantially shorter than those of untreated controls at the same time points. Further, plasma FVIII activity in the treated hemophilia A mice was nearly identical to that in wild-type mice through 50 weeks, while untreated hemophilia A mice exhibited no detectable FVIII activity. Thus, Sleeping Beauty transposon targeted to liver sinusoidal endothelial cells provided long-term expression of FVIII, without apparent antibody formation, and improved the phenotype of hemophilia A mice.
Wang, Shuo; Lou, Min; Liu, Tian; Cui, Deqi; Chen, Xiaomei; Wang, Yi
A novel quantitative susceptibility mapping (QSM) processing technology has been developed to map tissue susceptibility property without blooming artifacts. We hypothesize that hematoma volume measurement on QSM is independent of imaging parameters, eliminating its echo time dependence on gradient echo MRI. Gradient echo MRI of 16 patients with intracerebral hemorrhage was processed with susceptibility-weighted imaging, R2* (=1/T2*) mapping, and QSM at various echo times. Hematoma volumes were measured from these images. Linear regression of hematoma volume versus echo time showed substantial slopes for gradient echo magnitude (0.45±0.31 L/s), susceptibility-weighted imaging (0.52±0.46), and R2* (0.39±0.30) but nearly zero slope for QSM (0.01±0.05). At echo time=20 ms, hematoma volume on QSM was 0.80× that on gradient echo magnitude image (R2=0.99). QSM can provide reliable measurement of hematoma volume, which can be performed rapidly and accurately using a semiautomated segmentation tool.
Gupta, Saksham; Iv, Vycheth; Sam, Nang; Vuthy, Din; Klaric, Katherine; Shrime, Mark G; Park, Kee B
Traumatic brain injury is a major cause of morbidity and mortality worldwide, often necessitating neurosurgical intervention to evacuate intracranial bleeding. Since the early 2000s, Cambodia has been undergoing a rapid increase in motorcycle transit and in road traffic accidents, but the prevalence of helmet usage remains low. Epidural hematomas are severe traumatic brain injuries that can necessitate neurosurgical intervention. This is a retrospective cohort study of patients with epidural hematoma secondary to motorcycle accidents who presented to a major national tertiary care center in Phnom Penh, Cambodia, between November 2013 and March 2016. All patients were diagnosed with computed tomography of the head. In this cohort, 21.6% of patients in motorcycle accidents presented with epidural hematoma and 89.1% of patients were men, 47.6% were intoxicated, and were 87.8% were not wearing helmets at the moment of impact. Not wearing a helmet was associated with a 6.90-fold increase in odds of presenting with a moderate-to-severe Glasgow coma scale score and a 3.76-fold increase in odds of requiring craniotomy or craniectomy for evacuation of hematoma. Male sex was also associated with increased odds of higher clinical severity at presentation and indication for craniotomy or craniectomy, and alcohol intoxication at the time of accident was not associated with either. Helmet usage is protective in reducing the severity of presentation and need for neurosurgical intervention for patients with epidural hematoma secondary to motorcycle accidents. Copyright © 2016 Elsevier Inc. All rights reserved.
Ng, D; Churilov, L; Mitchell, P; Dowling, R; Yan, B
Hematoma expansion is an independent determinant of poor clinical outcome in intracerebral hemorrhage. Although the "spot sign" predicts hematoma expansion, the identification requires CT angiography, which limits its general accessibility in some hospital settings. Noncontrast CT, without the need for CT angiography, may identify sites of active extravasation, termed the "swirl sign." We aimed to determine the association of the swirl sign with hematoma expansion. Patients with spontaneous intracerebral hemorrhage between 2007 and 2014 who underwent an initial and subsequent noncontrast CT at a single center were retrospectively identified. The swirl sign, on noncontrast CT, was defined as iso- or hypodensity within a hyperdense region that extended across 2 contiguous 5-mm axial CT sections. A total of 212 patients met the inclusion criteria. The swirl sign was identified in 91 patients with excellent interobserver agreement (κ = 0.87). The swirl sign was associated with larger initial hematoma (P sign compared with those without. The NCCT swirl sign was reliably identified and is associated with hematoma expansion. We propose that the swirl sign be included in risk stratification of intracerebral hemorrhage and considered for inclusion in clinical trials. © 2018 by American Journal of Neuroradiology.
Amorous squeezing of the augmented breast may result in late capsular hematoma formation - A report of two cases (and a review of English-language literature on late hematoma formation in the augmented breast)
van Rijssen, A. L.; Wilmink, Han; van Wingerden, Jan J.; van der Lei, Berend
Late hematoma formation is a rare complication of augmentation mammaplasty. Late hematoma formation related to excessive or vigorous squeezing of the breast during sexual activity has not been described. We present 2 such cases and review the English-language literature on all causes of late
Full Text Available Registro de caso de paciente no oitavo mês de gestação que desenvolveu hematoma epidural espinal espontâneo dorsolombar. A gravidez, determinando aumento da pressão intra-abdominal e, como consequência, aumento da pressão venosa no plexo epidural, poderia ter sido o fator desencadeante no hematoma- A paciente foi submetida a cirurgia precocemente, porém não apresentou recuperação do déficit sensitivo-motor. São discutidos aspectos clínicos, do tratamento cirúrgico, da evolução e da etiologia dos hematomas epidurals espinais espontâneos.
Roy-Gash, F; Engrand, N; Lecarpentier, E; Bonnet, M P
We present a case of arachnoiditis and an intrathecal hematoma after an epidural blood patch. A 24-year-old parturient underwent an epidural blood patch three days after an accidental dural puncture during epidural labor analgesia. Four days later, the patient developed severe lower back pain, bilateral leg pain, persistent headache and fever. Bacterial meningitis was initially suspected and antibiotics started. Lumbar magnetic resonance imaging was performed and showed an intrathecal hematoma, with no blood in the epidural space. This report briefly reviews the few cases in the literature of arachnoiditis caused by an intrathecal hematoma and discusses the mechanism which resulted in blood in the subarachnoid space. Copyright © 2017 Elsevier Ltd. All rights reserved.
Cetin Kursad Akpinar
Full Text Available Spontaneous and non-spontaneous epidural hematomas are among rarely seen emergency diseases which can cause permanent neurological deficits in the event of delays in diagnosis and treatment. They are findings of spinal cord compression that generally develop following a clinical, severe backache. While surgical treatment can be delayed in case of recovery of sudden neurological findings within hours, surgical treatment should be conducted as soon as possible in case of advancement of the findings within hours. Spinal epidural hematoma developed when Case 1 was receiving anticoagulant therapy while it developed in Case 2 when the case was not receiving any therapy. Case 1 recovered with conservative treatment and Case 2 recovered with surgical treatment. In this article, we presented spinal epidural hematoma cases with 2 different etiological causes in which we followed 2 different treatment approaches.
Fingertip crush injuries are common hand injuries in children and often are evaluated initially in an emergency department. Nail bed injuries can be classified into subungual hematomas, simple or stellate lacerations, crush injuries, and avulsions. Emergency department physicians with good knowledge of fingertip anatomy can appropriately manage these injuries so as to prevent long-term fingertip deformities and functional deficits. The management of simple nail bed lacerations and subungual hematomas has remained somewhat controversial with much debate surrounding the necessity of removing the nail plate for repair of a nail bed laceration versus trephination alone of a large subungual hematoma. This article will discuss the management and evaluation of simple nail bed injuries by emergency department physicians to prevent chronic nail and fingertip deformities.
Full Text Available Intra- and subcorneal hematoma, a skin alteration seen palmar and plantar after trauma or physical exercise, can be challenging to distinguish from in situ or invasive acral lentiginous melanoma. Thus, careful examination including dermoscopic and histologic assessment may be necessary to make the correct diagnosis. We here present a case of a 67-year-old healthy female patient who presented with a pigmented plantar skin alteration. Differential diagnoses included benign skin lesions, for example, hematoma or melanocytic nevus, and also acral lentiginous melanoma or melanoma in situ. Since clinical and dermoscopic examinations did not rule out a malignant skin lesion, surgical excision was performed and confirmed an intracorneal hematoma. In summary, without adequate physical trigger, it may be clinically and dermoscopically challenging to make the correct diagnosis in pigmented palmar and plantar skin alterations. Thus, biopsy or surgical excision of the skin alteration may be necessary to rule out melanoma.
Choi, Jung Ju; Chang, Young Jin; Jung, Wol Seon; Lee, Kyung Cheon; Kim, Ju Ho; Jo, Youn Yi
Caudal epidural injection is one of the conventional treatments of chronic back pain. Even though spinal epidural hematoma after caudal epidural injection is rare but it can cause serious neurologic complication. An 83-year-old woman taking cilostazol received caudal epidural steroid injection because of her chronic back pain. Six hours later, she experienced an acute hip pain which worsened with time. Magnetic resonance image showed acute cord compression due to a spinal epidural hematoma at L2-S1 level with concomitant central canal compromise at L2/3, L3/4 level. Emergency decompressive laminectomy and evacuation of the lumbar epidural hematoma were performed. All of her symptoms were resolved over the 72 hours following surgery. Continuous vigilance after caudal epidural injection is important to prevent catastrophic neurologic deterioration with early detection and early treatment.
Millien, J P; Coget, J M
A series of 1,000 patients has been studied. I. HEMATOMAE: They are nearly continuous during internal saphena stripping but depend on various parameters. 1) Anatomical: a) Varicose veins topography. Perforating veins. Perforating veins of the thigh cause haemorrhage but reactions of venous construction are quite important and precocious not to observe subcutaneous bleedings. More or less "soft" stripping creates a reaction of reflex vasoconstriction. Fore saphenous vein of the thigh Hematomae are more and more numerous and important because the fore saphenous vein is a vein whose wall is thinner, more fragile and almost more superficial. b) Type of patient. In an obese patient, hematoma seems to be more spectacular. In the thin patient, it appears faster, if hematic expression is too late. 2) Stripping techniques: It is possible to propose different techniques of stripping, but none of them can lower specifically post-surgical hematomae. 3) Anaesthesiae: a) General anaesthesia. A bilateral surgery under general anaesthesia was helpful to observe in some cases a less important hematoma at the level of the second operated leg. b) Rachi-anaesthesia. Physiological vasoconstriction requires a latent period for this kind of anaethesia which causes a vasomotor paralysis due to a blockade of the sympathetic nerve. c) Local anaesthesia. It is obtained by crural block in association with injection of Xylocaine Adrenalina at the level of perforating veins of the thigh. This technique causes less hematomae. II. ABSCESSES: Only 4 cases out of 1,000 operated legs have been reported. No related pathology have been observed particularly about lymphatic disorders (erysipelas or lymphoedema), no previous infection known which could not have explained such complications. Therapy was simple: incision at mid-thigh and draining by lamina. The patient recovered within two weeks.
Lee, Yeon Soo; Kim, Jong Ok; Choi, Eun Seok [Daejeon St. Mary' s Hospital, The Catholic University of Korea, Daejeon (Korea, Republic of); Kwon, Soon Tae [Chungnam National University, School of Medicine, Daejeon (Korea, Republic of)
We wanted to demonstrate the temporal changes of the magnetic resonance imaging (MRI) findings in experimentally-induced intramuscular hematomas in rats and to correlate these data with the concurrent pathologic observations. Intramuscular hematoma was induced in 30 rats. The MR images were obtained at 1, 4, 7 and 10 days and at 2, 3, 4, 6 and 8 weeks after muscle injury. The characteristic serial MRI findings were evaluated and the relative signal intensities were calculated. Pathologic specimens were obtained at each time point. On the T1-weighted imaging (T1WI), the intramuscular hematomas exhibited isointensity compared to that of muscle or the development of a high signal intensity (SI) rim on day one after injury. The high SI persisted until eight weeks after injury. On the T2-weighted imaging (T2WI), the hematomas showed high SI or centrally low SI on day one after injury, and mainly high SI after four days. A dark signal rim was apparent after seven days, which was indicative of hemosiderin on the pathology. The gradient echo (GRE) imaging yielded dark signal intensities at all stages. Unlike brain hematomas, experimentally-induced intramuscular hematomas show increased SI on both the T1WI and T2WI from the acute stage onward, and this is pathologically correlated with a rich blood supply and rapid healing response to injury in the muscle. On the T2WI and GRE imaging, high SI with a peripheral dark signal rim is apparent from seven days to the chronic stage
Bellut, David; Woernle, Christoph Michael; Burkhardt, Jan-Karl; Kockro, Ralf Alfons; Bertalanffy, Helmut; Krayenbühl, Niklaus
Symptomatic chronic subdural hematoma (scSDH) is one of the most frequent diseases in neurosurgical practice, and its incidence is increasing. However, treatment modalities are still controversial. The aim of this retrospective single-center study is to compare for the first time two surgical methods in the treatment of subdural hematoma that have been proven to be efficient in previous studies in a direct comparison. We analyzed the data of 143 scSDHs in 113 patients undergoing surgery for subdural hematoma with placement of subperiosteal or subdural drainage after double burr-hole trepanation for hematoma evacuation. Overall, there were no statistically significant differences regarding general patient characteristics, preoperative and postoperative symptoms, postoperative hematoma remnant, rates of recurrences, mortality, complications, and outcome at discharge and at 3-month follow up between the groups. There was a close to significant tendency of lower mortality after placement of subperiosteal drainage system and a tendency towards lower rate of recurrent hematoma after placement of subdural drainage system. Our study shows for the first time a direct comparison of two mainly used surgical techniques in the treatment of scSDH. Both methods proved to be highly effective, and general patient data, complications, outcome and mortality of both groups are equal or superior compared with previously published series. Because there is a clear tendency to less mortality and fewer serious complications, treatment with double burr-hole trepanation, irrigation, and placement of subperiosteal drainage is our treatment of choice in patients with predictable high risk of complications. Copyright Â© 2012 Elsevier Inc. All rights reserved.
Chen, Shiwen; Xu, Chen; Yuan, Lutao; Tian, Hengli; Cao, Heli; Guo, Yan
Both delayed posttraumatic intracerebral hemorrhage and epidural hematoma have been well described in the neurosurgical literatures. However, delayed posttraumatic acute subdural hematoma which happens more than a week with a rapid progress after mild traumatic brain injury and causes death of patient is rarely reported. We show two such cases and briefly review the literature and discuss the probable pathogenesis of their rapid progress.
Full Text Available The treatment of chronic back pain is a challenging problem. Facet joint infiltration is an established treatment for chronic low back pain caused by arthrosis of the lumbar facet joints. Due to the increasing number of patients with chronic low back pain, this therapy has become more frequent. We treated a 51-year-old male patient, who developed an epidural hematoma 2 months after infiltration therapy. Our case shows that even a delayed onset of spinal epidural hematoma is possible and should be kept in mind as a possible cause of acute myelopathy after spinal intervention.
Crosi, Gonzalo; Prado, Martín; Huertas, Stella; Imelio, Juan; Piaggio, José; Gil, Andres
Objetivo: Evaluar y caracterizar los hematomas presentes en vacunos faenados en las plantas frigoríficas de Uruguay, habilitadas para exportación. Comparar datos obtenidos con investigaciones anteriores a nivel nacional. Metodología: Se realizó un estudio observacional de las carcasas bovinas luego de la faena, con el fin de evaluar la presencia de hematomas, teniendo en cuenta su localización, área, forma y profundidad. A su vez, se recabó información sobre el sexo y categoría de las tropas ...
Full Text Available Spontaneous coronary dissections are a well described entity which are often difficult to treat. Intramural hematoma is one type of coronary dissection. Previous case reports have described the treatment for angiographically visible dissection. We describe the first report of diffuse intramural hematoma visualized only on intravascular ultrasound with no angiographically obvious evidence of dissection treated with multivessel drug eluting stenting. This case highlights the importance of a high level of suspicion and atypical presentations of coronary dissection, and the use of multimodality imaging with intravascular ultrasound and computerized tomography for both diagnosis and therapy.
Full Text Available Boy 4 years old, hospitalized due to hemorrhagic chickenpox and sepsis during his clinical examination besides hemorrhagic crust, vesicles and bullous he has also a cutaneous red lesion localized at the right proximal nail fold of the big toenail (Fig. 1, dermatoscopic view of the lesion (Fig. 2. The diagnosis of hematoma of the proximal nail fold due to oximeter was done. The proximal nail fold hematomas due to oximeter are uncommon dermatoses at this level that are caused for the pressure of the oximeter and it has been seeing in patient in Unit Intensive or Intermediate Unit Care since 2007.
Adamastor Humberto Pereira
A ruptura dos vasa vasorum tem sido reconhecida como uma das causas do hematoma intramural da aorta há 90 anos. Esta breve revisão apresenta sistematicamente a fisiologia desses vasos e o seu papel na fisiopatologia das alterações parietais da aorta que ocorrem na hipertensão arterial, na arteriosclerose e na síndrome aórtica aguda. A hipótese defendida aqui é a de que a ruptura dos vasa vasorum ocorre como um fenômeno secundário e não como um dos fatores causais na fisiopatologia do hematoma...
Lee, Sung Soo; Han, Jong Kyu; Baek, Byoung Joon; Oh, Mee Hye; Jou, Sung Shick; Kim, Hyung Hwan; Bae, Won Kyung; Kim, Il Young [Soonchunhyang University, Cheonan Hospital, Cheonan (Korea, Republic of)
Subperiosteal hematoma of the orbit is a rare disease and most of the cases occur in young adult males as a result of direct facial or orbital trauma. In the absence of direct facial or orbital trauma, nontranmatic subperiosteal orbital hematoma has rarely been reported in association with a sudden elevation of cranial venous pressure or venous congestion, systemic diseases associated with a bleeding diathesis and paranasal sinusitis. We report here on a rare case of subperiosteal orbital hemaboma associated with ethmoid sinusitis, as was seen on CT imaging.
Full Text Available A 77-year-old man suffered hypoxemic cardiac arrest by supraglottic and tracheal airway obstruction in the emergency department. A previously unknown cervical fracture had caused a traumatic retropharyngeal-mediastinal hematoma. A lifesaving surgical emergency tracheostomy succeeded. Supraglottic and tracheal obstruction by a retropharyngeal-mediastinal hematoma with successful resuscitation via emergency tracheostomy after hypoxemic cardiac arrest has never been reported in a context of trauma. This clinically demanding case outlines the need for multidisciplinary airway management systems with continuous training and well-implemented guidelines. Only multidisciplinary staff preparedness and readily available equipments for the unanticipated difficult airway solved the catastrophic clinical situation.
Escosa Baé, Marcos; Wessling, Heinrich; Salca, Horia Calin; de Las Heras Echeverría, Pedro
Recurrence rates after chronic subdural hematoma (CSDH) evacuation with any of actual techniques [twist-drill craniostomy (TDC), burr-hole craniostomy, craniotomy] range from 5% to 30%. Use of drain has improved recurrence rates when used with burr-hole craniostomy. Now, we analyze predictors of recurrence of TDC with drain. Three hundred twelve consecutive patients with CSDH have been studied in a retrospective study. Operative technique in all patients consisted in TDC with drain. Data recorded included any associated comorbidity. Radiologic measures of the CSDH before and after the procedure were studied. Clinical evaluation included Modified Rankin Scale, Glasgow Coma Scale (GCS), and neurological deficits. Two groups were compared: recurrence group and nonrecurrence group. Follow-up was for at least 1 year. Twelve percent experienced recurrence. Preoperative CSDH width, preoperative midline shift, postoperative midline width, postoperative CSDH width, and residual CSDH 1 month later were significantly associated with CSDH recurrence. The logistic regression model for the multivariate analysis revealed that postoperative midline shift and postoperative neurological deficit were significantly associated with CSDH recurrence. The duration of treatment with dexamethasone was found not to be related with recurrence. Mortality before hospital discharge was 1%. Hospital stay was 2.5 days. TDC with drain has similar results in recurrence rates, morbidity, mortality, and outcome as other techniques as burr-hole craniostomy with drain. Preoperative and postoperative hematoma width and midline shift are independent predictors of recurrence. Brain re-expansion and time of drain maintenance are important factors related with recurrence of CSDH. Future CSDH reservoirs must avoid negative pressure and sudden pressure changes inside the whole closed drain system.
Colegrove, R W; Huntzinger, R M
Examined the intelligence, academic achievement, behavior, and social competency of 37 school-aged boys with hemophilia, 56% with HIV infection. IQ scores fell in the average range, but total reading scores were almost 1 standard deviation below the mean. Parent and teacher ratings of social functioning and behavior fell in the normal range. Absenteeism, an average of 27 days for the previous school year, was inversely correlated with most teacher ratings, indicating that absenteeism may be a significant factor in the academic and social adaptation of children with hemophilia. Overall, boys infected with HIV demonstrated the same level of academic and behavioral adaptation as those uninfected. The need for special education programs and interventions to enhance competency in the school setting is discussed.
Callan, Mary Beth; Haskins, Mark E; Wang, Ping; Zhou, Shangzhen; High, Katherine A; Arruda, Valder R
Severe hemophilia A (HA) is an inherited bleeding disorder characterized by genetic diseases, such as congenital blindness. Here we report our experience with liver gene therapy with AAV-FVIII in two outbred, privately owned dogs with severe HA that resulted in sustained expression of 1-2% of normal FVIII levels and prevented 90% of expected bleeding episodes. A Thr62Met mutation in the F8 gene was identified in one dog. These data recapitulate the improvement of the disease phenotype in research animals, and in humans, with AAV liver gene therapy for hemophilia B. Our experience is a novel example of the benefits of a relevant preclinical canine model to facilitate both translational studies in humans and improved welfare of privately owned dogs.
Ragni, Margaret V.; Ojeifo, Oluseyi; Feng, Jinong; Yan, Jin; Hill, Kathleen A.; Sommer, Steve S.; Trucco, Massimo N.; Brambilla, Donald J.
Background Inhibitor formation is a major complication of hemophilia treatment. Aim In a prevalent case-control study, we evaluated blood product exposure, genotype, and HLA type on hemophilia A inhibitor formation. Methods Product exposure was extracted from medical records. Genotype was determined on stored DNA samples by detection of virtually all mutations-SSCP (DOVAM-S) and subcycling PCR. HLA typing was performed by PCR amplification and exonuclease-released fluorescence. Results Cases experienced higher intensity factor, 455 vs. 200 U per exposure, p0.100. Genotype was not associated with race. Time to immune tolerance was shorter for titers 0.50. Conclusions Inhibitor formation is associated with high intensity product exposure, CNS bleeding, African-American race, and low frequency of missense mutations. The ideal time to initiate prophylaxis to reduce CNS bleeding and inhibitor formation will require prospective studies. PMID:19563499
Badawy, Sherif M; Rossoff, Jenna; Yallapragada, Sushmita; Liem, Robert I; Sharathkumar, Anjali A
Splenic rupture in neonates is a rare event, usually occurring in the setting of underlying predisposing conditions. Here, we present the case of a term neonate who presented with worsening anemia in the setting of known hemolytic disease during the newborn period and was later found to have a spontaneous splenic rupture. He was subsequently diagnosed with severe hemophilia A, and was managed medically with recombinant factor VIII replacement therapy without any surgical intervention. This is the first reported case of a neonate who had spontaneous splenic rupture and severe hemophilia A, and underwent successful medical treatment without any surgical intervention. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.
Sokal, E M; Lombard, C; Mazza, G
Hemophilia remains a non-curative disease, and patients are constrained to undergo repeated injections of clotting factors. In contrast, the sustained production of endogenous factors VIII (FVIII) or IX (FIX) by the patient's own cells could represent a curative treatment. Gene therapy has thus provided new hope for these patients. However, the issues surrounding the durability of expression and immune responses against gene transfer vectors remain. Cell therapy, involving stem cells expanded in vitro, can provide de novo protein synthesis and, if implanted successfully, could induce a steady-state production of low quantities of factors, which may keep the patient above the level required to prevent spontaneous bleeding. Liver-derived stem cells are already being assessed in clinical trials for inborn errors of metabolism and, in view of their capacity to produce FVIII and FIX in cell culture, they are now also being considered for clinical application in hemophilia patients. © 2015 International Society on Thrombosis and Haemostasis.
Miao, Carol H
Approximately 25–30% of the hemophilia A patients develop inhibitory antibodies against Factor VIII (FVIII) following protein-replacement therapy. This problem is also thought to occur following gene-replacement therapy. Recently, many approaches have been investigated to modulate FVIII-specific immune responses in either protein-replacement or gene therapy hemophilia A mouse models. Several promising protocols have been demonstrated to successfully prevent or modulate the formation of anti-FVIII antibodies, including methods to manipulate antigen presentation, development of less immunogenic FVIII proteins, or formulations or gene therapy protocols to evade immune responses, as well as immunomodulation strategies to target either T- and/or B-cell responses. Most of these successful protocols involve the induction of activated Treg cells to create a regulatory immune environment during tolerance induction. Innovative strategies to overcome pre-existing anti-FVIII immune responses and induce long-term tolerance in primed subjects still need to be developed. PMID:20976115
McCain, Stephen; Gull, Sadaf; Ahmad, Jawad; Carey, Declan
A 71-year-old man presented to the emergency department with his first episode of hematemesis. He was anemic and coagulopathic on admission, and became hemodynamically unstable requiring surgical intervention to control the bleeding. Prior to surgery, he required 100% plasma exchange with human plasma derived prothrombin complex concentrate (Octaplex) as the exchange fluid. At induction of anesthesia, he received tranexamic acid, prothrombin complex concentrate, and platelets. At the time of knife to skin, he was given coagulation factor VIIa intravenously as a bolus. This treatment was on the recommendation of the hematology team who suspected a diagnosis of acquired hemophilia on the basis of his history and coagulation screen. His bleeding was controlled and a diagnosis of acquired hemophilia A was confirmed in the postoperative period. This was managed with immunosuppressive therapy, and at the 2 year follow-up he remains well and is off all treatment.
Miao, Carol H
Approximately 25-30% of the hemophilia A patients develop inhibitory antibodies against Factor VIII (FVIII) following protein-replacement therapy. This problem is also thought to occur following gene-replacement therapy. Recently, many approaches have been investigated to modulate FVIII-specific immune responses in either protein-replacement or gene therapy hemophilia A mouse models. Several promising protocols have been demonstrated to successfully prevent or modulate the formation of anti-FVIII antibodies, including methods to manipulate antigen presentation, development of less immunogenic FVIII proteins, or formulations or gene therapy protocols to evade immune responses, as well as immunomodulation strategies to target either T- and/or B-cell responses. Most of these successful protocols involve the induction of activated Treg cells to create a regulatory immune environment during tolerance induction. Innovative strategies to overcome pre-existing anti-FVIII immune responses and induce long-term tolerance in primed subjects still need to be developed.
Moran, Dane; Shrime, Mark G; Nang, Sam; Vycheth, Iv; Vuthy, Din; Hong, Raksmey; Padula, William V; Park, Kee B
Epidural hematoma (EDH) is a common and potentially deadly occurrence following a severe traumatic brain injury. Our aim was to determine whether craniotomy is cost-effective when indicated for the treatment of EDH when a trained neurosurgeon is available. A decision tree was used to model the cost-effectiveness of craniotomy available versus craniotomy unavailable for the management of traumatic EDH from a Cambodian societal and provider perspective. Costs and effectiveness parameters were obtained from patient data at a large government hospital in Cambodia. Outcomes were measured in quality-adjusted life years (QALYs). Incremental cost per QALY and budget impact were calculated for each intervention at a willingness-to-pay (WTP) threshold of $9787.80/QALY (3× GDP per capita PPP). The time horizon reflected full life span, and costs and QALYs were discounted at 3%. Sensitivity analysis was also conducted. Compared to craniotomy unavailable for EDH ($945.80; 11.78 QALYs), craniotomy available came at a higher cost and greater effectiveness ($1520.73; 12.78 QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of $574.93. One-way analysis demonstrated that craniotomy unavailable became more cost-effective than craniotomy available when the percent chance of having a GOS of 4 or 5 was 60% for patients with an EDH where craniotomy was indicated but not performed. Probabilistic sensitivity analysis revealed that craniotomy available was more cost-effective than conservative management in 84.4% of simulations at the WTP threshold. Craniotomy is a cost-effective treatment for patients with a traumatic EDH who meet criteria for operation when trained neurosurgeons are available onsite.
Zhao, Ying; He, Yi Hua; Liu, Wen Xu; Sun, Lin; Han, Jian Cheng; Man, Ting Ting; Gu, Xiao Yan; Chen, Zhuo; Wen, Zhao Ying; Henein, Michael Y
Intramyocardial dissecting hematoma (IDH) after acute myocardial infarction (MI) is a rare form of subacute cardiac rupture and hence management uncertainties. The objective of this study was to describe the clinical course of a small series of IDH patients and to review the available evidence for managing similar cases. Eight IDH patients from our center had echocardiographic, coronary angiographic and clinical outcome data reviewed. PubMed was also searched for IDH following MI. Cases were divided into three groups and compared according to the dissection location. In our 8 patients, 3 had septal, 1 right ventricular (RV), and 4 left ventricular (LV) dissection. Five were medically treated and 3 surgically repaired. Reviewing the literature revealed 68 IDH patients, of mean age 66 ± 10 years, 43 males. The percentage of IDH involving the LV free wall, septal, and RV free wall were 47%, 26.5%, and 26.5%, respectively. In the cohort as a whole, mortality was not different between surgically and medically treated patients (33.3% vs. 54.3%, P = 0.08), neither based on the IDH location (P = 0.49). While surgical and medical treatment of the LV free wall (20.0% vs. 40.9%, P = 0.25) and septal (46.2% vs. 60.0%, P = 0.60) were not different, surgical repair of RV free wall had significantly better survival (30.0% vs. 87.5%, P = 0.015). The LVEF (P = 0.82), mitral regurgitation (P = 0.49) failed to predict mortality. While survival following medical and surgical treatment of LV IDH is not different, patients with RV free wall dissection benefit significantly from surgical repair. © 2016, Wiley Periodicals, Inc.
Ogata, Kyoichi; Selvaraj, Sundar R; Miao, Hongzhi Z; Pipe, Steven W
Summary Background & Objective The factor VIII (FVIII) B domain shares very little amino acid homology to other known proteins and is not directly necessary for procoagulant activity. Despite this, missense mutations within the B domain have been reported in patients with hemophilia A. Given that the B domain is dispensable for secretion and function of FVIII, we hypothesized that these mutations should not be causative of hemophilia A in these patients. Methods Plasmid vectors containing B domain missense mutations that were reported to be associated with moderate/severe hemophilia A (T751S, D826E, V993L, H1047Y, T1353A, N1441K, L1462P, E1579D, A1591S, P1641L and S1669L) were analyzed for their effect on synthesis and secretion compared to FVIII wild-type (WT) following transient transfection into COS-1 and CHO cells in vitro. Further, H1047Y, N1441K and E1579D mutants were expressed in vivo in a hemophilia A mouse model by hydrodynamic tail-vein injection. Results FVIII activity and antigen levels for all mutants expressed into the conditioned media of COS-1 and CHO cells were similar to FVIII WT. Also, plasma expression of these mutants was similar to FVIII WT in hemophilia A mice. An in vivo tail clip bleeding assay also demonstrated that blood loss from hemophilia A mice expressing FVIII WT, H1047Y, N1441K and E1579D were similar. Conclusion We conclude that most missense mutations within the FVIII B domain would be unlikely to lead to severe hemophilia A and that the majority of such missense mutations represent polymorphisms or non-pathologic mutations. PMID:21645226
Iizuka, Shunsuke; Sakurai, Fuminori; Tachibana, Masashi; Ohashi, Kazuo; Mizuguchi, Hiroyuki
Gene therapy during neonatal and infant stages is a promising approach for hemophilia B, a congenital disorder caused by deficiency of blood coagulation factor IX (FIX). An adenovirus (Ad) vector has high potential for use in neonatal or infant gene therapy for hemophilia B due to its superior transduction properties; however, leaky expression of Ad genes often reduces the transduction efficiencies by Ad protein-mediated tissue damage. Here, we used a novel Ad vector, Ad-E4-122aT, which exhibits a reduction in the leaky expression of Ad genes in liver, in gene therapy studies for neonatal hemophilia B mice. Ad-E4-122aT exhibited significantly higher transduction efficiencies than a conventional Ad vector in neonatal mice. In neonatal hemophilia B mice, a single neonatal injection of Ad-E4-122aT expressing human FIX (hFIX) (Ad-E4-122aT-AHAFIX) maintained more than 6% of the normal plasma hFIX activity levels for approximately 100 days. Sequential administration of Ad-E4-122aT-AHAFIX resulted in more than 100% of the plasma hFIX activity levels for more than 100 days and rescued the bleeding phenotypes of hemophilia B mice. In addition, immunotolerance to hFIX was induced by Ad-E4-122aT-AHAFIX administration in neonatal hemophilia B mice. These results indicated that Ad-E4-122aT is a promising gene delivery vector for neonatal or infant gene therapy for hemophilia B.
Full Text Available Gene therapy during neonatal and infant stages is a promising approach for hemophilia B, a congenital disorder caused by deficiency of blood coagulation factor IX (FIX. An adenovirus (Ad vector has high potential for use in neonatal or infant gene therapy for hemophilia B due to its superior transduction properties; however, leaky expression of Ad genes often reduces the transduction efficiencies by Ad protein-mediated tissue damage. Here, we used a novel Ad vector, Ad-E4-122aT, which exhibits a reduction in the leaky expression of Ad genes in liver, in gene therapy studies for neonatal hemophilia B mice. Ad-E4-122aT exhibited significantly higher transduction efficiencies than a conventional Ad vector in neonatal mice. In neonatal hemophilia B mice, a single neonatal injection of Ad-E4-122aT expressing human FIX (hFIX (Ad-E4-122aT-AHAFIX maintained more than 6% of the normal plasma hFIX activity levels for approximately 100 days. Sequential administration of Ad-E4-122aT-AHAFIX resulted in more than 100% of the plasma hFIX activity levels for more than 100 days and rescued the bleeding phenotypes of hemophilia B mice. In addition, immunotolerance to hFIX was induced by Ad-E4-122aT-AHAFIX administration in neonatal hemophilia B mice. These results indicated that Ad-E4-122aT is a promising gene delivery vector for neonatal or infant gene therapy for hemophilia B.
Pasi, K John; Rangarajan, Savita; Georgiev, Pencho; Mant, Tim; Creagh, Michael D; Lissitchkov, Toshko; Bevan, David; Austin, Steve; Hay, Charles R; Hegemann, Inga; Kazmi, Rashid; Chowdary, Pratima; Gercheva-Kyuchukova, Liana; Mamonov, Vasily; Timofeeva, Margarita; Soh, Chang-Heok; Garg, Pushkal; Vaishnaw, Akshay; Akinc, Akin; Sørensen, Benny; Ragni, Margaret V
Current hemophilia treatment involves frequent intravenous infusions of clotting factors, which is associated with variable hemostatic protection, a high treatment burden, and a risk of the development of inhibitory alloantibodies. Fitusiran, an investigational RNA interference (RNAi) therapy that targets antithrombin (encoded by SERPINC1), is in development to address these and other limitations. In this phase 1 dose-escalation study, we enrolled 4 healthy volunteers and 25 participants with moderate or severe hemophilia A or B who did not have inhibitory alloantibodies. Healthy volunteers received a single subcutaneous injection of fitusiran (at a dose of 0.03 mg per kilogram of body weight) or placebo. The participants with hemophilia received three injections of fitusiran administered either once weekly (at a dose of 0.015, 0.045, or 0.075 mg per kilogram) or once monthly (at a dose of 0.225, 0.45, 0.9, or 1.8 mg per kilogram or a fixed dose of 80 mg). The study objectives were to assess the pharmacokinetic and pharmacodynamic characteristics and safety of fitusiran. No thromboembolic events were observed during the study. The most common adverse events were mild injection-site reactions. Plasma levels of fitusiran increased in a dose-dependent manner and showed no accumulation with repeated administration. The monthly regimen induced a dose-dependent mean maximum antithrombin reduction of 70 to 89% from baseline. A reduction in the antithrombin level of more than 75% from baseline resulted in median peak thrombin values at the lower end of the range observed in healthy participants. Once-monthly subcutaneous administration of fitusiran resulted in dose-dependent lowering of the antithrombin level and increased thrombin generation in participants with hemophilia A or B who did not have inhibitory alloantibodies. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov number, NCT02035605 .).