scholarly journals Acquired haemophilia syndrome: Pathophysiology and therapy

2010 ◽  
Vol 138 (suppl. 1) ◽  
pp. 64-68 ◽  
Author(s):  
Ivo Elezovic
Keyword(s):  
Soft Tissues ◽  
Coagulation Factor ◽  
Prior History ◽  
Haemophilia A ◽  
Acute Bleeding ◽  
Fviii Inhibitor ◽  
Acquired Haemophilia ◽  
Life Threatening ◽  
Bleeding Episodes ◽  
Inhibitor Titer

Acquired inhibitors against coagulation factor VIII (FVIII), also termed acquired haemophilia A, neutralize its procoagulant function and result in severe or often life-threatening bleeding. The antibodies arise in individuals with no prior history of clinical bleeding. Acquired haemophilia occurs rarely with the incidence of approximately 1 to 4 per million/ year, with severe bleeds in up to 90% of affected patients, and high mortality between 8-22%. About 50% of diagnosed patients were previously healthy, while the remaining cases may be associated with postpartum period, autoimmune diseases, malignancy, infections, or medications. Most patients have spontaneous haemorrhages into the skin, muscles or soft tissues, and mucous membranes, or after trauma and surgery, whereas haemarthroses are uncommon. The diagnosis of acquired haemophilia A based on the prolongation of activated partial thromboplastin time which does not normalize after the addition of normal plasma, reduced FVIII, with evidence of FVIII inhibitor measured by the Bethesda assay (Nijmegen modification). The treatment of acute bleeding episodes and the long-term eradication of the autoantibodies in acquired haemophilia are the main therapeutic strategy. Two options are currently available for acute bleeding control: the use rFVIIa or FEIBA in patients with higher inhibitor titer (>5 BU), or to raise the level of FVIII by administration of DDAVP or concentrates of FVIII in patients with low level of inhibitors (<5 BU). Treatment with FEIBA (50-100 IU/ kg every 8-12 hours) has shown good haemostatic response in 76-89% of the bleeding episodes. Patients treated with rFVIIa (90 ?g/kg every 2-6 hours) have achieved good response in 95-100% as a first-line, and 75-80% as a salvage therapy. Patients with low inhibitor titer and lower response can be treated with concentrate of FVIII in the recommended dose of 40 IU/kg plus 20 IU/kg for each BU of inhibitor. The treatment of non-life-threatening haemorrhages with desmopressin (DDAVP 0.3 ?g/kg) may increase both FVIII and vWF. Sometimes inhibitors disappear spontaneously, but longterm management is necessary for eradication of inhibitors by immunosuppression (prednisone 1 mg/kg 3 weeks alone or in combination cyclophosphamide 2 mg/kg), immunomodulation, intravenous immunoglobulin (HD IgG 2g/kg 2 or 5 d), physical removal of antibodies (plasmapheresis or immunoadsorption), or various combinations. Recently, a therapy with rituximab, an anti-CD20 monoclonal antibody, has shown to be effective in acquired haemophilia.

scholarly journals Progressive Intramuscular Haematoma in a 12-Year-Old Boy: A Case of Acquired Haemophilia A

2018 ◽  
Vol 2018 ◽  
pp. 1-3
Author(s):  
Manori Gamage ◽  
Sadeepa Weerasinghe ◽  
Mohamed Nasoor ◽  
A. M. P. W. Karunarathne ◽  
Sashi Praba Abeyrathne
Keyword(s):  
Factor Viii ◽  
Soft Tissues ◽  
Coagulation Factor ◽  
Bleeding Disorder ◽  
Haemophilia A ◽  
Fviii Inhibitor ◽  
Acquired Haemophilia ◽  
High Antibody Titer ◽  
History Of ◽  
The Right

Acquired hemophilia A (AHA) is a rare bleeding disorder due to acquired antibodies against coagulation factor VIII (FVIII). It is rare in children less than 16 years old, and the incidence is 0.45/million/year. An otherwise healthy, 12-year-old boy was admitted to the ward with a history of swelling of the right and left forearms, for 1 day duration. He did not have any history of trauma or bleeding disorder. He had prolonged APPTT level with very high antibody titer against factor VIII. His gene expression for factor VIII was found to be normal. He was managed with FEIBA and recombinant FVII activated complexes and prednisolone 1 m/kg/day regime to control bleeding. AHA is associated with several underlying pathologies such as pregnancy, autoimmune diseases, malignancy, medications and infections; however, up to 50% of reported cases are idiopathic. In contrast to congenital haemophilia A, in which haemarthrosis is the hallmark clinical presentation, patients with AHA mainly bleed in to the skin, muscles, and soft tissues. High mortality rate of more than 20% is either to retroperitoneal or intracranial bleeds. Diagnosis is confirmed on isolated prolongation of activated partial thromboplastin time which does not normalize after addition of normal plasma, reducing the factor VIII levels with evidence of FVIII inhibitor activity. They have normal prothrombin time and platelet functions. Management of AHA involves two aspects, namely, eradication of antibodies and maintaining effective haemostasis during a bleeding episode.

scholarly journals A Case of Acquired Haemophilia A in a Patient with Chronic Myelomonocytic Leukaemia

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Takeshi Araki ◽  
Shinya Ohata ◽  
Kohei Okamoto ◽  
Kazuhide Morimoto ◽  
Mana Hiraishi ◽  
...  
Keyword(s):  
Bone Marrow Failure ◽  
Laboratory Data ◽  
Coagulation Factor ◽  
Haemophilia A ◽  
Bleeding Tendency ◽  
Normal Range ◽  
Fviii Inhibitor ◽  
Acquired Haemophilia ◽  
Fviii Activity ◽  
Chronic Myelomonocytic Leukaemia

A 67-year-old male, with a known diagnosis of myelodysplastic syndromes with multilineage dysplasia (MDS-MLD) was admitted to our hospital with a primary complaint of subcutaneous bleeding in his left thigh. Laboratory data showed anaemia and prolongation of activated partial thromboplastin time (85.8 s, normal range 24–39 s) without thrombocytopenia. Coagulation factor VIII (FVIII) activity was less than 1% (normal range 60–150%), and a FVIII inhibitor was identified and quantified at 166 BU/mL to indicate a diagnosis of acquired haemophilia A (AHA). A recent, but sustained circulating monocytosis (>1 × 109/L) was observed, which combined with elevated numbers of neutrophil and monocytic cells in the marrow, suggested evolution of MDS-MLD to chronic myelomonocytic leukaemia (CMML), coinciding with AHA. Further analysis revealed a karyotype of 46, XY, i(14) (q10), which was the same abnormality previously identified in the patient. To treat bleeding caused by AHA, steroid and activated prothrombin complex concentrate were administered. Azacitidine (AZA) was used to treat CMML. During the clinical course, bleeding partially improved; however, subsequent acute myocardial infarction occurred on day 87. Worsening bone marrow failure was observed 4 months after the original admission, despite administration of AZA therapy, and the patient died due to bleeding from AHA. This case suggests that the evolution of MDS to CMML status can be associated with AHA conferring a bleeding tendency.

scholarly journals Acquired haemophilia a presenting in postpartum period - case report

2008 ◽  
Vol 136 (Suppl. 3) ◽  
pp. 214-217
Author(s):  
Mirjana Mitrovic-Vasiljevic ◽  
Darko Antic ◽  
Ivo Elezovic ◽  
Jelena Bila ◽  
Milena Todorovic
Keyword(s):  
Vaginal Delivery ◽  
Postpartum Period ◽  
Case Reports ◽  
Rare Complication ◽  
Factor Vii ◽  
Prior History ◽  
Haemophilia A ◽  
Fviii Inhibitor ◽  
Acquired Haemophilia ◽  
Small Series

INTRODUCTION. Acquired haemophilia A is a rare autoimmune disorder caused by factor VIII (FVIII) inhibitors. Patients may present with catastrophic bleeding, despite having no prior history of bleeding disorders. Acquired haemophilia A is a rare complication of pregnancy, typically appearing in the postpartum period. The patients usually present with bleeding related to vaginal delivery or Caesarean section. Management includes control of haemorrhage and eradication of the FVIII inhibitor. CASE OUTLINE. Acquired haemophilia A was diagnosed in our patient after profuse vaginal bleeding related to vaginal delivery (FVIII level 2%; FVIII inhibitor titar 16 BJ). Red cell, fresh frozen plasma and cryoprecipitate transfusions, as well as vaginal packing were ineffective. The administration of recombinant activated factor VII (rFVIIa) (NovoSeven) proved effective in stopping the bleeding. To facilitate eradication of the inhibitor prednisone (30 mg orally/d) was added. After 3 weeks of treatment, the inhibitor FVIII titar was reduced to 50%. CONCLUSION. Acquired postpartum haemophilia must be always considered in the differential diagnosis of postpartum haemorrhage. According to our experience and reported literature (case reports and small series), initial haemodynamic stabilization after rFVIIa (NovoSeven) administration followed by immunosuppressive therapy is highly successful. Thus, most women presenting with acguired hemophilia A in the portpartum period has favourable prognosis.

scholarly journals Acquired haemophilia – A diagnosis not to be missed

2008 ◽  
Vol 7 (2) ◽  
pp. 70-72
Author(s):  
S J Kitson ◽  
◽  
N F Grigoropoulos ◽  
Keyword(s):  
Autoimmune Diseases ◽  
Factor Viii ◽  
Coagulation Factor ◽  
Clinical History ◽  
Haemophilia A ◽  
Haematological Malignancies ◽  
Acquired Haemophilia ◽  
Wide Range ◽  
Life Threatening ◽  
History Of

Acquired haemophilia is a rare, life threatening bleeding disorder characterised by the development of auto-antibodies to coagulation factor VIII. Diagnosis is based upon the clinical history of mucocutaneous haemorrhages combined with a selective prolongation of the APTT. The condition is associated with a wide range of conditions, such as autoimmune diseases , solid and haematological malignancies. Treatment involves controlling the bleeding manifestations and eliminating the inhibitor antibodies. Three cases from our recent practice are used to highlight the variable severity of this condition.

scholarly journals Efficacy and safety of the drug Octofactor in prophylactic treatment in patients with severe haemophilia A

2018 ◽  
Vol 5 (3) ◽  
pp. 60-73 ◽  
Author(s):  
T. A. Andreeva ◽  
V. Yu. Zorenko ◽  
I. L. Davydkin ◽  
V. N. Konstantinova ◽  
O. E. Zalepukhina ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Bleeding Episode ◽  
Coagulation Factor ◽  
Preventive Treatment ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Efficacy And Safety ◽  
Spontaneous Bleeding ◽  
Bleeding Episodes ◽  
Blood Coagulation Factor Viii

Relevance.The development of a new recombinant blood coagulation factor VIII preparation is a promising step towards optimizing the treatment of hemophilia A. An introduction of a new medication into clinical practice precedes a clinical trials to evaluate the efficacy and safety.Materials and methods.The efficacy and safety of the domestic recombinant B-domain deleted blood coagulation factor VIII (FVIII) (moroctocog alfa, Octofactor®, JSC “GENERIUM”) were studied in the preventive treatment of 31 patients aged 21 to 52 years with severe haemophilia A. The Octofactor was administered in doses of 40 ± 5 IU/kg 3 times per week at intervals of at least 48 hours for 21 ± 1 weeks.Results.The efficacy of therapy was evaluated in 30 patients, since 1 patient refused to participate in the trial after the first injection of the study medication. There were registered 43 episodes of bleeding among 11 patients in the course of the preventive treatment with Octofactor. The average number of bleeding episodes was 1.4 ± 2.58. There were 43 bleeding episodes, 9 (20.9 %) of them were posttraumatic, 34 (79.1 %) of them were spontaneous. The average number of the spontaneous bleeding episodes (a major criterion of the efficacy) was 1.13 ± 2.19, which showed a low incidence of exacerbations of the hemorrhagic syndrome in the course of preventive treatment with Octofactor. Among all registered bleeding episodes there were 6 (14 %) mild episodes, 37 (86 %) moderate episodes. Among all spontaneous bleedings there were 6 mild episodes (17.6 %), 28 (82.4 %) moderate episodes. All posttraumatic bleedings were moderate. The vast majority (36, or 83.7 %) of bleeding episodes were stopped with administration of the Octofactor. The average number of administrations of the Octofactor for arresting 1 bleeding episode was 1.2 ± 0.56, for 1 spontaneous bleeding episode – 1.2 ± 0.59. On average, it was required to administer 3534.9 ± 2329.02 IU of the Octofactor to stop 1 episode of bleeding. In the vast majority of patients with severe hemophilia A (83.3–86.7 %),  the remaining activity FVIII was 1 % or more after the administration of the Octofactor in 48 hours. The total amount of the Octofactor, introduced for the prevention of bleeding, was 6,107,000 IU, to stop bleeding – 152,000 IU. The safety of therapy was evaluated in 31 patients. There were recorded 25 adverse events (AE) in 17 patients. Among them the laboratory ones prevailed in 23 (92 %) cases, which is not associated with the use of the trial medication. There were noted nausea and an unpleasant aftertaste in the mouth in 1 patient during the first administration of the Octofactor, and therefore he refused to continue to participate in the trial. Causality 2 AE with the study drug was regarded as definite. Such AE are expected and described in the instructions to the preparation. All AE were not serious and mild and resolved without outcomes. There were no presented thromboembolic events and immunogenic reactions.Conclusions.The obtained data testify to the efficacy and safety of the Octofactor both for preventive measures and for stopping bleeding in adult patients with severe hemophilia A.

scholarly journals Acquired Haemophilia A. Which is the best therapeutic choice in older adults? Single center study of 4 cases

Reumatismo ◽  
2019 ◽  
Vol 71 (1) ◽  
pp. 37-41 ◽  
Author(s):  
E. Mauro ◽  
E. Garlatti Costa ◽  
A. Zanier ◽  
M. Maset ◽  
A. Ermacora ◽  
...  
Keyword(s):  
Coagulation Factor ◽  
Factor Vii ◽  
Haemophilia A ◽  
Recombinant Activated Factor Vii ◽  
Acquired Haemophilia ◽  
Activated Factor Vii ◽  
Activated Prothrombin Complex Concentrate ◽  
Therapeutic Choice ◽  
Single Center Study ◽  
Thrombotic Complications

Acquired haemophilia A (AHA) is a rare bleeding disorder due to autoantibodies directed against coagulation factor VIII. The treatment is based on recombinant activated factor VII and activated prothrombin complex concentrate. However, mainly in older patients, severe thrombotic complications have been reported. Here we report the different therapeutic approaches in 4 cases of elderly patients with AHA and co-morbidities.

Neutralisation of factor VIII inhibitors by anti-idiotypes isolated from phage-displayed libraries

2016 ◽  
Vol 116 (07) ◽  
pp. 32-41 ◽  
Author(s):  
Anja Schmidt ◽  
Kerstin Brettschneider ◽  
Jörg Kahle ◽  
Aleksander Orlowski ◽  
Karin Becker-Peters ◽  
...  
Keyword(s):  
Factor Viii ◽  
Tolerance Induction ◽  
Coagulation Factor ◽  
Cross Reactivity ◽  
Hybridoma Cells ◽  
Haemophilia A ◽  
Immune Tolerance Induction ◽  
Fviii Inhibitor ◽  
Antiidiotypic Antibody

SummaryFollowing replacement therapy with coagulation factor VIII (FVIII), up to 30 % of haemophilia A patients develop FVIII-specific inhibitory antibodies (FVIII inhibitors). Immune tolerance induction (ITI) is not always successful, resulting in a need for alternative treatments for FVIII inhibitor-positive patients. As tolerance induction in the course of ITI appears to involve the formation of anti-idiotypes specific for anti-FVIII antibodies, such anti-idiotypes might be used to restore haemostasis in haemophilia A patients with FVIII inhibitors. We isolated antiidiotypic antibody fragments (scFvs) binding to murine FVIII inhibitors 2-76 and 2-77 from phage-displayed libraries. FVIII inhibitor/anti-idiotype interactions were very specific as no cross-reactivity with other FVIII inhibitors or isotype controls was observed. ScFvs blocked binding of FVIII inhibitors to FVIII and neutralised their cognate inhibitors in vitro and a monoclonal mouse model. In addition, scFv JkH5 specific for FVIII inhibitor 2-76 stained 2-76-producing hybridoma cells. JkH5 residues R52 and Y226, located in complementary determining regions, were identified as crucial for the JkH5/2-76 interaction using JkH5 alanine mutants. SPR spectroscopy revealed that JkH5 interacts with FVIII inhibitor 2-76 with nanomolar affinity. Thus, FVIII inhibitorspecific, high-affinity anti-idiotypes can be isolated from phagedisplayed libraries and neutralise their respective inhibitors. Furthermore, we show that anti-idiotypic scFvs might be utilised to specifically target inhibitor-specific B cells. Hence, a pool of anti-idiotypes could enable the reestablishment of haemostasis in the presence of FVIII inhibitors in patients or even allow the depletion of inhibitors by targeting inhibitor-specific B cell populations.

scholarly journals Acquired Haemophilia A in Association with Influenza A and Urinary Tract Infection

2020 ◽  
Author(s):  
Felipe Peña-Muñoz ◽  
Ernesto Parras ◽  
Olga Compan ◽  
Nora Gutierrez ◽  
Celestino Martin ◽  
...  
Keyword(s):  
Influenza A ◽  
Coagulation Factor ◽  
Autoimmune Disorder ◽  
Immunosuppressive Drugs ◽  
Bleeding Complications ◽  
Haemophilia A ◽  
Acquired Haemophilia ◽  
Haemostatic Agents ◽  
Inhibitor Titre ◽  
Prolonged Aptt

Acquired haemophilia A (AHA) is a rare autoimmune disorder caused by an autoantibody against any circulating coagulation factor, especially factor VIII (FVIII). The lack of awareness of this condition suggests that diagnosis is a challenge and usually delayed, which leads to suboptimal treatment. Consequently, early diagnosis is mandatory to prevent potentially life-threatening bleeding complications. We present the case of an 85-year-old woman admitted to hospital with symptoms of respiratory infection who 12 hours later developed haematuria which required transfusion. Laboratory assays showed an isolated prolonged aPTT, a moderately reduced FVIII and a high inhibitor titre. Influenza A and Escherichia coli were also identified. Antivirals, antibiotics, immunosuppressive drugs and haemostatic agents were started. Two weeks later, the inhibitor was not detected, and bleeding and symptoms of infection had resolved. Immunosuppressive drugs were stopped on day 45 and there has been no recurrence since then. To date, no FVIII inhibitors have been reported in concomitant infection with influenza A and urinary E. coli. The identification of conditions potentially associated with AHA is essential to achieve complete remission.

Paraneoplastic acquired haemophilia A in extensive-stage small cell lung cancer (ES-SCLC) in the era of immunotherapy

2021 ◽  
Vol 14 (1) ◽  
pp. e236973
Author(s):  
Mehrnoosh Pauls ◽  
Natalia Rydz ◽  
Nancy A Nixon ◽  
Doreen Ezeife
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
High Dose ◽  
Haemophilia A ◽  
Small Cell Lung ◽  
Fviii Inhibitor ◽  
Acquired Haemophilia ◽  
Extensive Stage

Small cell lung cancer (SCLC) is a deadly and rapidly progressive disease that can present with various paraneoplastic syndromes on initial workup. Acquired factor VIII (FVIII) deficiency, also known as acquired haemophilia A (AHA), has been identified as a rare paraneoplastic syndrome in SCLC. Here, we present a 61-year-old woman with a massive gastrointestinal bleed and prolonged activated partial thromboplastin time (PTT) in the emergency department. She was diagnosed with rare paraneoplastic AHA secondary to extensive-stage SCLC (ES-SCLC). She was treated with high-dose steroids and factor bypassing agents, which led to the resolution of bleeding and undetectable FVIII inhibitor levels. She was subsequently treated for ES-SCLC with carboplatin, etoposide and atezolizumab. This case report highlights a rare clinical presentation of paraneoplastic AHA that necessitates prompt recognition in patients with SCLC with ongoing bleeding and elevated PTT.

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