scholarly journals Role of B Cells in Breaking and Maintaining Tolerance to Clotting Factor VIII in Congenital and Acquired Hemophilia A

Antibodies ◽  
2014 ◽  
Vol 3 (2) ◽  
pp. 192-204 ◽  
Author(s):  
Amanda Actor ◽  
Claire Holley ◽  
Keri Csencsits-Smith
Keyword(s):  
B Cells ◽  
Factor Viii ◽  
Hemophilia A ◽  
Clotting Factor ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia

scholarly journals Clinical case of an acquired hemophilia

The Clinician ◽  
2020 ◽  
Vol 13 (3-4) ◽  
pp. 74-77
Author(s):  
P. N. Barlamov ◽  
E. R. Vasilyeva ◽  
M. E. Golubeva ◽  
V. G. Zhelobov ◽  
A. A. Shutylev ◽  
...  
Keyword(s):  
Factor Viii ◽  
Blood Clotting ◽  
Clinical Case ◽  
Hemophilia A ◽  
Clotting Factor ◽  
Clotting Factors ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Left Femur ◽  
Submandibular Region

The aim of the work is to describe the clinical case of formation, diagnosis and treatment of the acquired form of blood clotting factor VIII deficiency – of acquired hemophilia A.Material and methods. Patient R., 71 years, from April 2018, was found an acute hemorrhagic syndrome in the hematomic type of large hematomas manifested submandibular region, neck, chest, right breast, pubic and inguinal regions on the right, the anterior-medial surface of the left femur, anterior surface of left tibia. Standard laboratory tests, computed tomography of soft tissues of the neck, lungs, abdomen; coagulogram; blood clotting factors; inhibitor of factor VIII were evaluated in dynamics during the patient’s stay in the hospital; platelet aggregation function.Results. Typical gematomny type of bleeding, prolongation of coagulation indicators, the presence of the inhibitor factor VIII (7,0 BAA), the decrease in factor VIII (2 %) allowed diagnosis of acquired hemophilia A. Anti-inhibitory coagulant complex, fresh frozen plasma was successfully used for treatment. The patient is under observation in the regional Hematology center. The hematomas were not renewed.Conclusion. Our clinical observation demonstrates the features of the course, the algorithm of diagnosis and management of patients with of acquired hemophilia A.

Acquired hemophilia A: review and case report

2018 ◽  
Author(s):  
Н.Т. . Ватутин ◽  
Е.В. . . Склянная ◽  
М.А. Эль-Хатиб
Keyword(s):  
Case Report ◽  
Factor Viii ◽  
Successful Treatment ◽  
Hemophilia A ◽  
Coagulation Factors ◽  
Clotting Factor ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Blood Disease

Резюме. Классическая гемофилия — наследственное заболевание крови, причиной развития которого является дефицит факторов свертывающей системы. Приобретенная же гемофилия относится к редким патологиям; в ее основе лежит продукция аутоантител, которые приводят к инактивации эндогенного фактора VIII. В статье представлен обзор литературы по этиологии, эпидемиологии, патогенезу, клинике, диагностике и лечению приобретенной гемофилии А. Приведено собственное клиническое наблюдение успешного лечения пациентки с приобретенной послеродовой гемофилией. Summary. Classical hemophilia is a hereditary blood disease caused by defi ciency of coagulation factors. Hemophilia A is a rare pathology caused by inactivation of plasma clotting factor VIII with autoantibodies. The review summarizes what is currently known about the epidemiology, pathogenesis, clinical peculiarities, diagnostics, treatment and prognosis of acquired hemophilia A. Case report of successful treatment of patient with acquired postpartum hemophilia is presented.

scholarly journals Postpartum Acquired Hemophilia: A Rare Cause of Postpartum Hemorrhage

2013 ◽  
Vol 2013 ◽  
pp. 1-2 ◽  
Author(s):  
Srikanth Seethala ◽  
Sumit Gaur ◽  
Elizabeth Enderton ◽  
Javier Corral
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Factor Vii ◽  
Normal Vaginal Delivery ◽  
Factor Viii Inhibitor ◽  
Activity Levels ◽  
Factor Viii Activity ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Viii Inhibitor

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.

scholarly journals Acquired hemophilia A and plasma cell neoplasms: a case report and review of the literature

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Katarzyna A. Jalowiec ◽  
Martin Andres ◽  
Behrouz Mansouri Taleghani ◽  
Albulena Musa ◽  
Martina Dickenmann ◽  
...  
Keyword(s):  
Factor Viii ◽  
Plasma Cell ◽  
Hemophilia A ◽  
High Titer ◽  
Coagulation Factor ◽  
Laboratory Diagnostics ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Plasma Cell Neoplasm ◽  
Cell Neoplasm

Abstract Background Acquired hemophilia A is a rare autoimmune disease with clinically often significant bleeding diathesis resulting from circulating autoantibodies inhibiting coagulation factor VIII. Half of acquired hemophilia A cases are associated with an underlying disorder, such as autoimmune diseases, cancer, or use of certain drugs, or occur during pregnancy and in the postpartum period. In the other half, no underlying cause is identified. An association of acquired hemophilia A with plasma cell neoplasm seems to be extremely rare. Case presentation We describe a case of a 77-year-old Swiss Caucasian man who was diagnosed with acquired hemophilia A and smoldering multiple myeloma as an underlying cause. Acquired hemophilia A was treated with prednisolone, cyclophosphamide, and immunoadsorption. Extensive workup revealed a plasma cell neoplasm as the only disorder associated with or underlying the acquired hemophilia A. For long-term control of acquired hemophilia A, we considered treatment of the plasma cell neoplasm necessary, and a VRD (bortezomib, lenalidomide, and dexamethasone) regimen was initiated. Due to multiple complications, VRD was reduced to VRD-lite after two cycles. After nine cycles of induction therapy and five cycles of consolidation therapy, the patient is in complete remission of his acquired hemophilia A and very good partial remission of the plasma cell neoplasm. We conducted a literature review to identify additional cases of this rare association and identified 15 other cases. Case descriptions, including the sequence of occurrence of acquired hemophilia A and plasma cell neoplasm , treatment, evolution, and outcome are presented. Discussion and conclusions Our case, together with 15 other cases described in the literature, underscore the possibility of plasma cell neoplasm as an underlying cause of acquired hemophilia A. Physicians should consider including protein electrophoresis, immunofixation, and analysis of free light chains in laboratory diagnostics when treating a patient with acquired hemophilia A. The occurrence of excessive and unexplained bleeding in patients diagnosed with plasma cell neoplasm should raise suspicion of secondary acquired hemophilia A and trigger the request for coagulation tests, particularly in patients treated with immunomodulatory drugs such as thalidomide or lenalidomide. Additionally, early intervention with immunoadsorption can be lifesaving in cases with high-titer factor VIII inhibitors, especially when surgical interventions are necessary.

scholarly journals Cross‐reacting inhibitors against recombinant porcine factor VIII in acquired hemophilia A: Data from the GTH ‐ AH 01/2010 Study

2019 ◽  
Vol 18 (1) ◽  
pp. 36-43 ◽  
Author(s):  
Halet Türkantoz ◽  
Christoph Königs ◽  
Paul Knöbl ◽  
Robert Klamroth ◽  
Katharina Holstein ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia

scholarly journals Anti–factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study

Blood ◽  
2016 ◽  
Vol 127 (19) ◽  
pp. 2289-2297 ◽  
Author(s):  
Andreas Tiede ◽  
Christoph J. Hofbauer ◽  
Sonja Werwitzke ◽  
Paul Knöbl ◽  
Saskia Gottstein ◽  
...  
Keyword(s):  
Factor Viii ◽  
Specific Antibody ◽  
Immunoglobulin G ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Hemophilia A ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Potential Marker ◽  
Key Points

Key Points This study is the first to assess the prognostic value of FVIII-specific antibody data in patients with AHA. Anti-FVIII IgA, but not immunoglobulin G, autoantibodies at baseline are potential predictors of recurrence and poor outcome of AHA.

Distribution of Th1- and Th2-induced Anti-factor VIII IgG Subclasses in Congenital and Acquired Hemophilia Patients

2002 ◽  
Vol 88 (10) ◽  
pp. 568-575 ◽  
Author(s):  
Sijin Lei ◽  
Howard Lei ◽  
Daid Green ◽  
Joan Gill ◽  
Bianca Conti-Fine ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Igg Subclasses ◽  
T Cell Subsets ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Acquired Hemophilia ◽  
Th1 And Th2

SummaryDevelopment of antibodies (Ab) that inhibit the procoagulant function of factor VIII (fVIII) seriously complicates the treatment of hemophilia A patients. It also causes acquired hemophilia, a rare yet serious autoimmune disease. The design of effective fVIII-specific tolerizing procedures will require elucidation of the role of the different CD4+ T cell subsets that drive inhibitor synthesis. To examine the contribution of Th1 and Th2 cells in the anti-fVIII Ab response, we measured the concentration of Th1- and Th2-driven anti-fVIII IgG subclasses in 17 patients with severe hemophilia A and 18 patients with acquired hemophilia. We found that both congenital and acquired hemophilia patients had similar and comparable proportions of Th1- and Th2-induced anti-fVIII Ab, suggesting a more important role of Th1 cells in the immune response to fVIII than previously appreciated. The distribution of anti-fVIII IgG subclasses was stable for periods of up to six months. More intense anti-fVIII Ab responses and higher inhibitor titers correlated with a predominance of Th2-driven subclasses. In contrast, Th1-driven anti-fVIII Ab were predominant in patients who had low anti-fVIII Ab concentrations, even when this was the result of successful immune tolerance or immunosuppressive therapy, which had caused drastic reduction or disappearance of inhibitors.Thus, synthesis of Th2-driven inhibitors occurs when the anti-fVIII Ab response is intense, while Th1 cells may be involved in the long-term maintenance of anti-fVIII Ab synthesis.

scholarly journals The Frequency and Effect of Baseline Cross-Reacting and De Novo Inhibitors to Recombinant Porcine FVIII in Patients with Congenital and Acquired Hemophilia a

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1128-1128
Author(s):  
Carolyne Elbaz ◽  
Katerina Pavenski ◽  
Hina Chaudhry ◽  
Jerome M. Teitel ◽  
Michelle Sholzberg
Keyword(s):  
Factor Viii ◽  
Research Funding ◽  
Hemophilia A ◽  
De Novo ◽  
Factor Viia ◽  
Case Series ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
C2 Domains ◽  
Inhibitor Development

Background Patients with severe congenital hemophilia A (CHA) have a 25-40% lifetime risk of alloantibody (inhibitor) development to FVIII. Patients with acquired hemophilia A (AHA) spontaneously develop neutralizing autoantibodies to factor VIII. In both cases, patients require pro-hemostatic therapy with bypassing agents: recombinant factor VIIa (rFVIIa), activated prothrombin complex concentrate (aPCC) and more recently recombinant porcine factor VIII (rpFVIII). Anti-human FVIII (hFVIII) inhibitors typically bind to the A2 and C2 domains of the FVIII molecule. RpFVIII is an effective pro-hemostatic treatment for AHA and CHA given the immunologic difference in the A2 and C2 domains of the rpFVIII while maintaining sufficient hFVIII homology to act as an effective cofactor to human FIX in the intrinsic tenase. However, some anti-hFVIII antibodies cross-react with rpFVIII and may interfere with its hemostatic function. Cross-reacting antibodies were reported in 35% of subjects in a phase II/III trial prior to initiation of rpFVIII. Moreover, de novo rpFVIII inhibitors may develop during or after the treatment with rpFVIII and may affect its hemostatic function. Here we describe the largest case series to date on baseline cross-reactivity of rpFVIII inhibitors and post-treatment de novo inhibitor development in patients with CHA and AHA to address the paucity of published literature in this area. Aim First, we describe the frequency of baseline cross-reacting rpFVIII inhibitors in patients with AHA and CHA (with inhibitors) at our institution. Second, we describe the effect of baseline rpFVIII antibodies on FVIII recovery after treatment with rpFVIII. We also describe the frequency and timing of de novo rpFVIII inhibitor development after exposure to rpFVIII. Methods Institutional research ethics board approval was obtained. Electronic charts of patients admitted to our institution with AHA or CHA who underwent testing for rpFVIII inhibitors were reviewed retrospectively. RpFVIII inhibitor assay is performed in the special coagulation laboratory using the Nijmegen modified Bethesda assay. The patient sample is initially heat-treated at 57 Results Twenty-seven patients (7 CHA, 20 AHA) underwent testing for porcine inhibitors since assay availability in 2016. 61% (5/7 CHA, 11/20 AHA) of patients had a detectable rpFVIII inhibitor prior to exposure to rpFVIII; median titer 1.6 BU/ml (range 0.6-192). Eight patients with AHA with baseline cross-reacting inhibitors received rpFVIII. Of those, three achieved an initial FVIII recovery beyond 100% (132%, 148% and 177%) after approximately 100U/kg of rpFVIII and all three had very low anti-rpFVIII Bethesda titers (0.70, 0.85 and 0.9 BU/ml). Five patients did not achieve a FVIII recovery above 50% (46%, 46%, 40%, 36% and 0%) despite approximately 100U/kg of rpFVIII. Most patients who received rpFVIII were tested weekly for the duration of their treatment or hospital stay. Upon discharge, patients who were seen in clinic for follow up were tested for anti-hFVIII and anti-rpFVIII. Two AHA patients without a baseline inhibitor who received rpFVIII treatment developed a de novo inhibitor after 20 days (1 BU/ml) and 133 days (12 BU/ml), respectively. One AHA patient had a rise in baseline anti-rpFVIII titer after exposure to rpFVIII. Conclusion In conclusion, we found that 61% of patients with AHA and CHA tested for rpFVIII inhibitors had a detectable baseline cross-reacting inhibitor which is higher than previously described. Of those patients with a baseline inhibitor treated with rpFVIII, only 37.5% of patients had an appropriate rise in FVIII. Finally, 13% of patients without baseline inhibitors developed a de novo inhibitor after exposure to rpFVIII, an incidence comparable to previously published findings. Disclosures Pavenski: Bioverativ: Research Funding; Alexion: Honoraria, Research Funding; Octapharma: Research Funding; Shire: Honoraria; Ablynx: Honoraria, Research Funding. Teitel:BioMarin: Consultancy; CSL Behring: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Shire: Consultancy; Pfizer: Consultancy, Research Funding; Bayer: Consultancy, Research Funding. Sholzberg:Takeda: Honoraria, Research Funding; Baxter: Honoraria, Research Funding; Baxalta: Honoraria, Research Funding. OffLabel Disclosure: Recombinant porcine factor VIII is used to treated patients with congenital hemophilia A with allo inhibitors

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