Pulmonary Embolism in Acquired Hemophilia A: A Rare Complication With Factor VIII Inhibitor Bypassing Activity Therapy

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.

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Acquired Hemophilia A: A Single Institution’s Experience.

Blood ◽

10.1182/blood.v106.11.4103.4103 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4103-4103

Author(s):

Devinderpal Randhawa ◽

Ibrahim Sidhom ◽

Gunwant Guron ◽

Trevor Layne

Keyword(s):

Factor Viii ◽

Immunosuppressive Therapy ◽

Hemophilia A ◽

Treatment Modalities ◽

Factor Viii Inhibitor ◽

Acquired Hemophilia A ◽

Acquired Hemophilia ◽

Mortality And Morbidity ◽

Life Threatening ◽

Viii Inhibitor

Abstract Background: Acquired Hemophilia A (AH) due to factor VIII inhibitor is a rare life threatening disorder. If not diagnosed and treated urgently, significant mortality and morbidity results. AH can occur in setting of old age, autoimmune diseases, pregnancy, medication, malignancy, and lymphoproliferatve disorders. In majority of cases it is idiopathic. Objective: Review the treatment modalities and outcome of AH patients at our institution. Methods: A retrospective review of the data pertaining to patients who were diagnosed with AH at our institution between 1993–2004. Results: There were 5 patients diagnosed with AH, 3 female and 2 male. The median age was 67 years (range 30–84 years) the setting for development of AH in these patients was as follows: 1- postpartum, 1-HIV, 3 idiopathic. All patients presented with varying degree of spontaneous hemorrhage. The median Factor VIII inhibitor level was 16 Bethesda Unit (BU)(range 7. 2–31). Acute control of hemorrhage was achieved in all patients using either FEIBA (Factor eight inhibitor bypass activity) alone (1 patient), FEIBA and Novo seven (VIIa)(4 patients). Chronic immunosuppressive therapy was given as follows: Steroid alone (2 patients), Steroid and IVIG (1 patients), Steroid and Cyclophospamide (1 patient) and Steroid, Cyclophospamide and Rituximab (1 patient). Complete remission (CR) was obtained in 4 patients and with the final patient still receiving treatment. In one patient, the dose of Cyclophospamide was decreased due to Leucopenia. The median time to elimination of inhibitors was 5 month (range 1–10 month). There have been no mortalities. Conclusions: AH is a life threatening condition if not promptly diagnosed and treated, mortality remains significantly high. Treatment with factors replacement and immunosuppressive therapy was effective in all our patients

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Acquired Factor VIII Inhibitor (Acquired Hemophilia A) Presenting as Spontaneous Blood-filled Scrotum

Southern Medical Journal ◽

10.1097/smj.0b013e3182142d1d ◽

2011 ◽

Vol 104 (5) ◽

pp. 368-370 ◽

Cited By ~ 1

Author(s):

Rajanshu Verma ◽

Jill Noack ◽

Radhakrishna Vemuri ◽

Mark E. Loehrke

Keyword(s):

Factor Viii ◽

Hemophilia A ◽

Factor Viii Inhibitor ◽

Acquired Hemophilia A ◽

Acquired Hemophilia ◽

Viii Inhibitor ◽

Acquired Factor Viii Inhibitor

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Acquired hemophilia A: A rare cause of gross hematuria

Canadian Urological Association Journal ◽

10.5489/cuaj.3306 ◽

2015 ◽

Vol 9 (11-12) ◽

pp. 905

Author(s):

Gregory W Hosier ◽

Ross J Mason ◽

K Sue Robinson ◽

Gregory G Bailly

Keyword(s):

Factor Viii ◽

Hemophilia A ◽

Rare Condition ◽

Factor Vii ◽

Factor Viii Inhibitor ◽

Acquired Hemophilia A ◽

Acquired Hemophilia ◽

Recombinant Activated Factor Vii ◽

Activated Factor Vii ◽

Viii Inhibitor

Acquired hemophilia A is a rare condition caused by spontaneous development of factor VIII inhibitor. This condition most commonly presents with multiple hemorrhagic symptoms and isolated hematuria is exceedingly rare. Early diagnosis is important, as this condition carries a high mortality rate (13‒22%). We present a case of an 82-year-old man with isolated hematuria caused by a factor VIII inhibitor who was successfully treated with recombinant activated factor VII concentrate, as well as prednisone and cyclophosphamide.

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Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

Case Reports in Hematology ◽

10.1155/2014/484563 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4

Author(s):

Nicholas B. Abt ◽

Michael B. Streiff ◽

Christian B. Gocke ◽

Thomas S. Kickler ◽

Sophie M. Lanzkron

Keyword(s):

Factor Viii ◽

Hemophilia A ◽

Term Therapy ◽

Factor Viii Inhibitor ◽

Factor Viii Activity ◽

Acquired Hemophilia A ◽

Acquired Hemophilia ◽

Fviii Activity ◽

Viii Inhibitor ◽

Acquired Factor Viii Inhibitor

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.

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Acquired hemophilia A developing cerebral infarction 36 days after the frequent administration of bypass hemostatic agents

Hematology Reports ◽

10.4081/hr.2018.7453 ◽

2018 ◽

Vol 10 (2) ◽

Cited By ~ 1

Author(s):

Makoto Saito ◽

Hajime Senjo ◽

Minoru Kanaya ◽

Koh Izumiyama ◽

Akio Mori ◽

...

Keyword(s):

Cerebral Infarction ◽

Factor Viii ◽

Hemophilia A ◽

Activity Level ◽

High Dose ◽

Factor Viii Inhibitor ◽

Acquired Hemophilia A ◽

Acquired Hemophilia ◽

Hemostatic Agents ◽

Frequent Administration

A 74-years-old male who was a smoker and received treatment for hypertension, dyslipidemia, peripheral arterial disease and idiopathic interstitial pneumonia complained of subcutaneous hemorrhage of the right lower thigh. Marked anemia (hemoglobin 5.5 g/dL) and prolonged activated partial thromboplastin time (≥130 seconds) were noted. The factor VIII activity level was reduced to 1.2 %, and the factor VIII inhibitor titer was 285.3 BU/mL, a diagnosis of acquired hemophilia A (AHA) was made. Then, hematomas of 5 intra-muscles were recurred. Hemostasis became difficult despite frequent and high-dose administration of recombinant human coagulation factor VIIa (total: 18 days, 305 mg). Hemostasis was achieved by switching to activated prothrombin complex concentrate (for 3 days, 18,000 units), however, cerebral infarction occurred after 36 days. After the frequent administration of bypass hemostatic agents on elderly AHA patients with several risk factors for ischemic stroke, the risk of subsequent thrombotic events may persist for 1 month.

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ACQUIRED HEMOPHILIA A IN DIABETIC WOMAN, Case Report

Berkala Ilmiah Kedokteran Duta Wacana ◽

10.21460/bikdw.v3i2.108 ◽

2018 ◽

Vol 3 (2) ◽

pp. 107

Author(s):

Wiwiek Probowati

Keyword(s):

Diabetes Mellitus ◽

Factor Viii ◽

Hemophilia A ◽

World Federation ◽

Acquired Hemophilia A ◽

Acquired Hemophilia ◽

History Of ◽

Viii Inhibitor ◽

Faktor Viii ◽

Hemofilia A

Background Acquired hemophilia is a rare condition in which autoantibodies, usually IgG class are produced against factor VIII or IX. Age distribution is bimodal. Although hemophilia is a hereditary disease, approximately 20-30% of patients have no family history of clotting disorders. Case report A 55-year-old lady with major complaints of gums bleeding, bruises on the both of leg and thighs that are varying colour (multiple spontaneus haematomas. No previous history of bleeding and no history of blood clotting disorders in the family. She has diabetes mellitus for 8 years was treated metformin three times a day, and )controlled level of blood glucose. Laboratory findings showed decreased haemoglobin (5,7 mg/dl) with prolonged aPTT 129 s(28 s control) but still got the normal PPT that is 17.2 s (14.4 s control) and normal INR 1,3, factor VIII activity got decrease with result of 1,5% (control 91,1%) but factor IX activity still normal 118,7% (control 108%). The Factor VIII inhibitor was 19.52 Bethesda Unit. After exclusion of other possible pathological condition and on the basis of lab criteria we diagnosed the case as acquired hemophilia A. Discussion The diagnosis of Acqured hemophlia A (AHA) shoud be considered in patient who present with bleeding and prolonged aPPT. The pattern of bleeding in AHA differs from that in congenital hemophilia A. Bleeding tends to occur in soft tissue, muscle, retroperitoneal space, iatrogenic bleeding is also common. The diagnosis is then confirmed by a Bethesda positive assay for F VIII inhibitor titre. Diagnostic test in AHA are clotting factor measurement (isolated low FVIII level) and quantification of the inhibitor titer (presence of inhibitor). Most often the cause is idiopathic in 50% of patient or it can be associated with autoimun disorders, hepatitis and diabetes. Chronic disease or diabetes mellitus makes misrecognition tends to self antigen.1,3 Conclusion A 55-years-old lady with diabetes got symptoms gum bleeding, multiple spontaneuos hematomes and very low in factor VIII activity and presence of factor VIII inhibitor. It is concluded that this patient is diagnosed of acquired hemophilia A. Keywords: Acquired Haemophilia A, activated partial thromboplastin time (APTT), Factor VIII. Multiple haematomes in acquired haemphilia References 1. Ma AD, Carrizosa D. Acquired Factor VIII Inhibitors: Pathophysiology and Treatment. American Society of Hematology. 2006. 2. Antonela Tufano, Antonio Copola, Anna Guida, Acquired Hemophilia in Elderly, Current Gerontology and Geriatric Research volume 2010 3. Giangrande P. Acquired Hemophilia. World Federation of Hemophilia. 2012. 4. Sakurai Y, Takeda T. Acquired Hemophilia A: A Frequently Overlooked Autoimmune Hemorrhagic Disorder. Journal of Immunology Research. 2014. 5. Srivastava A, et al. Guidelines for the Management of Hemophilia 2nd edition. World Federation of Hemophilia. 2012 6. Rotty LWA. Hemofilia A dan B dalam Buku Ajar Ilmu Penyakit Dalam. Interna Publishing. Jakarta. 2014. Laporan Kasus ACQUIRED HEMOPHILIA A PADA WANITA PENDERITA DIABETES Wiwiek Probowati1, Mardiah Suci Hardanti2 1 Bagian Penyakit Dalam, Rumah Sakit Bethesda, Yogyakarta 2 Bagian Haematologi Onkologi Medik, Bagian Penyakit Dalam Universitas Gadjah Mada, Rumah Sakit Umum Pusat Sardjito Yogyakarta Latar Belakang Acquired Hemofilia adalah kondisi sangat jarang di mana autoantibodi, IgG diproduksi terhadap faktor VIII atau IX. Distribusi usia adalah bimodal. Meskipun hemofilia adalah penyakit keturunan, sekitar 20-30% pasien tidak memiliki riwayat keluarga gangguan pembekuan. Laporan kasus Seorang wanita berusia 55 tahun dengan keluhan utama perdarahan gusi, memar di kedua kaki dan paha yang warnanya bervariasi (multiple spontaneus hematoma). Tidak ada riwayat perdarahan sebelumnya dan tidak ada riwayat gangguan pembekuan darah dalam keluarga. Ia menderita diabetes mellitus selama 8 tahun diterapi dengan metformin dan kadar glukosa darah terkontrol. Hasil laboratorium menunjukkan penurunan hemoglobin (5,7 mg / dl) dengan PT 129 (kontrol 28), PPT normal yaitu 17,2 s (kontrol 14,4 s) dan INR normal 1,3, aktivitas faktor VIII mengalami penurunan dengan hasil 1,5% (kontrol 91,1%) tetapi aktivitas faktor IX masih normal 118,7% (kontrol 108%). Inhibitor Faktor VIII adalah 19,52 Unit Bethesda. Berdasarkan kriteria laboratorium, diagnosis kasus ini adalah acquired hemofilia A. Diskusi Diagnosis Acqured hemophlia A (AHA) harus dipertimbangkan pada pasien yang datang dengan perdarahan dan pemanjangan PPT. Pola perdarahan pada AHA berbeda dari pada hemofilia kongenital A. Perdarahan cenderung terjadi pada jaringan lunak, otot, ruang retroperitoneal, perdarahan iatrogenik juga sering terjadi. Tes Bethesda positif untuk titer inhibitor F VIII. Tes diagnostik dalam AHA adalah dengan mengukur faktor pembekuan (tingkat FVIII rendah terisolasi) dan kuantifikasi titer inhibitor (inhibitor). Penyebab tersering pasien dikaitkan dengan gangguan autoimun, hepatitis dan diabetes. Penyakit kronis atau diabetes mellitus menimbulkan misrecognition terhadap antigen penderita.1,3 Kesimpulan Seorang wanita 55 tahun dengan diabetes mengalami gejala perdarahan gusi, hematom spontan di paha dan perut dengan aktivitas faktor VIII yang sangat rendah dan munculnya faktor VIII inhibitor. Pasien ini didiagnosis menderita Acquired hemofilia A. Kata kunci: Acquired Haemophilia A, activated partial thromboplastin time (APTT), Factor VIII. Hematom multipel pada acquired hemofilia Daftar Pustaka 1. Ma AD, Carrizosa D. Acquired Factor VIII Inhibitors: Pathophysiology and Treatment. American Society of Hematology. 2006. 2. Antonela Tufano, Antonio Copola, Anna Guida, Acquired Hemophilia in Elderly, Current Gerontology and Geriatric Research volume 2010 3. Giangrande P. Acquired Hemophilia. World Federation of Hemophilia. 2012. 4. Sakurai Y, Takeda T. Acquired Hemophilia A: A Frequently Overlooked Autoimmune Hemorrhagic Disorder. Journal of Immunology Research. 2014. 5. Srivastava A, et al. Guidelines for the Management of Hemophilia 2nd edition. World Federation of Hemophilia. 2012 6. Rotty LWA. Hemofilia A dan B dalam Buku Ajar Ilmu Penyakit Dalam. Interna Publishing. Jakarta. 2014.

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Simultaneous Deep Venous Thrombosis and Acquired Factor VIII Inhibitor

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602960200800410 ◽

2002 ◽

Vol 8 (4) ◽

pp. 375-379 ◽

Cited By ~ 4

Author(s):

Steven R. Deitcher ◽

Teresa L. Carman ◽

Kandice Kottke-Marchant

Keyword(s):

Venous Thrombosis ◽

Factor Viii ◽

Deep Venous Thrombosis ◽

Hemophilia A ◽

Duplex Ultrasound ◽

Factor Viii Inhibitor ◽

Acquired Hemophilia A ◽

Acquired Hemophilia ◽

Prolonged Aptt ◽

Life Threatening

Acquired hemophilia A is a life-threatening immune-mediated hemorrhagic disorder that is most often found in individuals older than 50 who present with an unexplained activated partial thromboplastin time (aPTT) prolongation and clinically significant bleeding. The prolonged aPTT associated with acquired hemophilia A reflects factor VIII activity deficiency due to neutralizing or clearing autoantibodies. Deep venous thrombosis, in contrast, is a veno-occlusive disorder associated with several distinct hypercoagulable states that can result in significant morbidity and mortality due to pulmonary embolism, thrombus extension, and the post-thrombotic syndrome. A prolonged a PYI in the setting of thrombosis may reflect the presence of a lupus anticoagulant. In the absence of accurate diagnosis and the immediate institution of specific therapy, both disorders can be fatal. Three cases of acquired factor VIII inhibitors that included a prolonged aPTT, bleeding, and duplex ultrasound evidence of deep venous thrombosis are presented. The diagnostic and therapeutic challenges posed by these cases as well as a proposed mechanism by which pathologic thrombosis can develop in a patient with a life-threatening bleeding disorder are discussed.

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A Case of a Patient Who Is Diagnosed with Mild Acquired Hemophilia A after Tooth Extraction Died of Acute Subdural Hematoma due to Head Injury

Case Reports in Dentistry ◽

10.1155/2018/7185263 ◽

2018 ◽

Vol 2018 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Tomohisa Kitamura ◽

Tsuyoshi Sato ◽

Eiji Ikami ◽

Yosuke Fukushima ◽

Tetsuya Yoda

Keyword(s):

Factor Viii ◽

Subdural Hematoma ◽

Tooth Extraction ◽

Hemophilia A ◽

Coagulation Factor ◽

Acute Subdural Hematoma ◽

Factor Viii Inhibitor ◽

Activity Levels ◽

Acquired Hemophilia A ◽

Acquired Hemophilia

Background. Acquired hemophilia A (AHA) is a rare disorder which results from the presence of autoantibodies against blood coagulation factor VIII. The initial diagnosis is based on the detection of an isolated prolongation of the activated partial thromboplastin time (aPTT) with negative personal and family history of bleeding disorder. Definitive diagnosis is the identification of reduced FVIII levels with evidence of FVIII neutralizing activity. Case report. We report a case of a 93-year-old female who was diagnosed as AHA after tooth extraction at her home clinic. Prolongation of aPTT and a reduction in factor VIII activity levels were observed with the presence of factor VIII inhibitor. AHA condition is mild. However, acute subdural hematoma of this patient occurred due to an unexpected accident in our hospital. Hematoma was gradually increased and the patient died 13 days after admission. Discussion. Although AHA is mild, intracranial bleeding is a life-threatening condition. We also should pay attention to the presence of AHA patients when we extract teeth.

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Surgery-associated acquired hemophilia A: a report of 2 cases and review of literature

BMC Surgery ◽

10.1186/s12893-020-00872-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Umar Zeb Khan ◽

Xiangwu Yang ◽

Matiullah Masroor ◽

Abdul Aziz ◽

Hui Yi ◽

...

Keyword(s):

Mortality Rate ◽

Factor Viii ◽

Hemophilia A ◽

Factor Viii Inhibitor ◽

Haemophilia A ◽

Bleeding Site ◽

Acquired Hemophilia A ◽

Acquired Hemophilia ◽

Acquired Haemophilia ◽

Upper Abdominal

Abstract Background Acquired Hemophilia A (AHA) is a rare bleeding diathesis in patients with no previous personal or family bleeding history. The diagnosis of this disease often delays due to unfamiliarity of physicians with it, which leads to its high mortality rate. Case presentation Two cases (one 12 years old female and another 18 years old male) were admitted for right upper abdominal mass and right upper abdominal pain respectively at different times. Pre-operative diagnosis of both cases was congenital choledochal cyst. They suffered continuous gastrointestinal bleeding (hematemesis and melena) with reduced hemoglobin to 54 g/L and 60 g/L after Roux-en-Y anastomosis respectively. To investigate the exact bleeding site, Digital subtraction angiography (DSA) of case 1 showed contrast overflow at small branch of proper hepatic artery but had unremarkable result for case 2, whereas gastroscopy of both cases showed unremarkable results. Multiple surgeries were also performed for hemostatic purpose but each time no active bleeding site was found. Finally, hematologists consultation was mandated in both cases and they were diagnosed as acquired haemophilia A. However, unfortunately case 1 patient could not survive because of sever hemorrhage and infection while Case 2 of 18 years old male survived after proper haemophilia treatment catalog. Conclusion Awareness about surgery associated acquired haemophilia A (SAHA) can facilitate quick diagnosis and lifesaving management because the mortality rate in SAHA is high due to lake of knowledge or late recognition of the disease. Bleeding always occurs at surgical sites and it can occur immediately within few hours after surgery in some cases. Hemorrhage may be severe or even life threatening and it presents a special challenge for diagnosis and treatment in a patient who has just undergone a surgical procedure. The treatment strategies for AHA include resumption of hemostasis with either recombinant porcine factor VIII (rpFVIII) or bypassing agents and immunosuppressive therapy to suppress the production of the factor VIII inhibitor.

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