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 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 A case of serious bleeding

2015 ◽  
Vol 5 (2S) ◽  
pp. 15-19
Author(s):  
Irene Ricca ◽  
Marisa Coggiola ◽  
Silvia Destefanis ◽  
Claudio Pascale
Keyword(s):  
Mortality Rate ◽  
Autoimmune Diseases ◽  
Factor Viii ◽  
Coagulation Factor ◽  
The Elderly ◽  
Severe Anaemia ◽  
Severe Bleeding ◽  
Haemophilia A ◽  
Acquired Haemophilia ◽  
History Of

Acquired haemophilia A (AHA) is a rare disorder with a high mortality rate. It occurs due to autoantibodies against coagulation factor VIII (FVIII) which neutralise its procoagulant function resulting in severe bleeding. This disease may be associated with autoimmune diseases, malignancies, infections or medications and occurs most commonly in the elderly. Diagnosis is based on the isolated prolongation of aPTT which does not normalise after the addition of normal plasma along with reduced FVIII levels. Treatment involves eradication of antibodies and maintaining effective haemostasis during bleeding. We report a case of a 76-year-old patient with a history of haemorrhage with severe anaemia. The article describes difficulties and complexities of clinical and therapeutic management of the patient.

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.

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.

Factor VIII Inhibitors in Mild and Moderate-severity Haemophilia A

1998 ◽  
Vol 79 (04) ◽  
pp. 762-766 ◽  
Author(s):  
C.A. Ludlam ◽  
B.T. Colvin ◽  
F.G.H. Hill ◽  
F.E. Preston ◽  
N. Wasseem ◽  
...  
Keyword(s):  
Factor Viii ◽  
Tolerance Induction ◽  
Haemophilia A ◽  
Missense Mutations ◽  
Bleeding Pattern ◽  
Spontaneous Bleeding ◽  
Familial Predisposition ◽  
Inhibitor Development ◽  
Acquired Haemophilia ◽  
History Of

SummaryTwenty six patients with mild or moderate haemophilia A and inhibitors are described. The inhibitor was detected at a median age of 33 years, after a median of 5.5 bleeding episodes. This usually following intensive replacement therapy. The median presenting inhibitor titre was antihuman 11.6 BU/ml, antiporcine 1.45 BU/ml. Plasma basal factor VIII level declined from a median of 0.08 IU/ml to 0.01 IU/ml following the inhibitor development. This caused spontaneous bleeding in 22 and a bleeding pattern similar to acquired haemophilia in 17. Bleeding was often severe and caused two deaths.The inhibitor disappeared spontaneously, or following immune tolerance induction, in 16 cases after a median of 9 months (range 0.5-46), with a return to the original baseline VIIIC level and bleeding pattern accompanied inhibitor loss. The inhibitor persisted in the remainder of the cases over a median period of 99 months (range 17-433 months) of follow-up. Inhibitors are an uncommon complication of mild haemophilia which frequently persist and may be associated with severe, life-threatening, haemorrhage.Forty-one percent of treated haemophilic family members had a history of factor VIII inhibitors, suggesting a familial predisposition to develop inhibitors in these kindreds. Sixteen patients from 11 families were genotyped. Seven different missense mutations affecting the light chain were detected and two in the A2 domain. Five patients from three families had a mutation causing a substitution of Trp2229 by Cys in the C2 domain which appears to predispose to inhibitor formation since 7 of the 18 affected individuals have a history of inhibitor development.

scholarly journals Acquired haemophilia A in women postpartum: management of bleeding episodes and natural history of the factor VIII inhibitor

2009 ◽  
Vol 59 (2) ◽  
pp. 105-109 ◽  
Author(s):  
J. J. Michiels ◽  
K. Hamulyak ◽  
H. K. Nieuwenhuis ◽  
I. Novakova ◽  
H. H. D. M. Vliet
Keyword(s):  
Natural History ◽  
Factor Viii ◽  
Factor Viii Inhibitor ◽  
Haemophilia A ◽  
Acquired Haemophilia ◽  
History Of ◽  
Bleeding Episodes ◽  
Viii Inhibitor

Doxycycline-induced acquired haemophilia A

2021 ◽  
Vol 14 (10) ◽  
pp. e244748
Author(s):  
Ejaz Shah ◽  
Calvin Abro ◽  
Fawwad Zaidi ◽  
Ruchika Goel
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Failure ◽  
Factor Viii ◽  
Distress Syndrome ◽  
Therapeutic Agents ◽  
Activated Partial Thromboplastin Time ◽  
Factor Vii ◽  
Haemophilia A ◽  
Acquired Haemophilia ◽  
History Of

An 80-year-old man with no personal or family history of bleeding, presented to hospital with extensive haematomas and skin bruising after using doxycycline. His basic lab workup was concerning for a coagulopathy with an elevated activated partial thromboplastin time and significant anaemia. Mixing studies and other factor levels were tested that led to the diagnosis of acquired haemophilia A with low factor VIII levels and high factor VIII antibodies. He was started on steroids, but his haemoglobin level continued to drop. Later, during his treatment, he was given multiple therapeutic agents, including cyclophosphamide, rituximab and recombinant factor VII (NovoSeven-R). Gradually factor VIII levels increased and haemoglobin stabilised. The hospital course was complicated by COVID-19 pneumonia leading to acute respiratory distress syndrome; the patient eventually expired due to respiratory failure.

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.

Rituximab in der Behandlung der erworbenen Hämophilie A bei einem Patienten mit Polymyalgia rheumatica

2010 ◽  
Vol 30 (S 01) ◽  
pp. S40-S43
Author(s):  
M. Bruegel ◽  
C. Pfrepper ◽  
J. Thiery ◽  
D. Niederwieser ◽  
L. Braunert
Keyword(s):  
Factor Viii ◽  
Clinical Improvement ◽  
Polymyalgia Rheumatica ◽  
Oral Prednisone ◽  
Immunosuppressive Treatment ◽  
Coagulation Factor ◽  
Fviii Inhibitor ◽  
Acquired Haemophilia ◽  
Fviii Activity ◽  
Activated Prothrombin Complex Concentrates

SummaryAcquired hemophilia A is a rare but potentially life-threatening bleeding disorder. It is caused by the development of autoantibodies directed against coagulation factor VIII in adults or elderly patients, who do not have a personal or family history of bleeding. Case: A man (age: 76 years) on prednisone and leflunomide for polymyalgia rheumatica developed spontaneous severe haematomas. The patient was diagnosed with acquired factor VIII deficiency (FVIII activity 1.2%, FVIII inhibitor 31.7 BU). Due to the active bleeding diathesis, treatment was administered with activated prothrombin complex concentrates (FEIBA®, Baxter). Immunosuppressive treatment with a combination of oral prednisone (1 mg/kg daily) and cyclophosphamide (1,5 mg/kg daily) was administered to reduce the FVIII inhibitor. However, after two weeks of treatment, FVIII was only 3% and no clinical improvement was observed. Treatment with the anti CD20 monoclonal antibody rituximab intravenously at 375 mg/m2 once weekly for four consecutive weeks was started. The patient showed rapid clinical improvement following rituximab treatment. He achieved a complete remission defined as return to normal FVIII activity and undetectable FVIII inhibitor titer. After a follow-up of six months no relapse occurred. Conclusion: Rituximab appears an effective and well-tolerated treatment for patients with acquired haemophilia.

Acquired haemophilia: an easy diagnosis to miss in a patient taking warfarin

2015 ◽  
Vol 14 (3) ◽  
pp. 122-124
Author(s):  
Avraneel Talapatra ◽  
◽  
Michael J. Nash ◽  
Charles R. M. Hay ◽  
Jecko Thachil ◽  
...  
Keyword(s):  
Factor Viii ◽  
Warfarin Therapy ◽  
Soft Tissues ◽  
Bleeding Disorder ◽  
Spontaneous Bleeding ◽  
Acquired Haemophilia

Acquired Haemophilia (AH) is an autoimmune bleeding disorder, which despite being rare, can be fatal. It occurs in patients with previously normal haemostasis who spontaneously develop IgG autoantibodies against factor VIII. Unlike congenital haemophilia, it manifests as spontaneous bleeding into skin and soft tissues. The presentation can be masked in patients who are receiving warfarin where the bleeding is often attributed to warfarin therapy, as in the case described in this report. Consideration of AH is important in patients taking anticoagulants, when coagulopathy and bleeding fails to correct with usual measures.

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