|Year : 2017 | Volume
| Issue : 2 | Page : 75-78
Postpartum-acquired hemophilia: A challenging disease to manage
Mohammed A Karish1, Amr Hanbali2, Hazzaa Al Zahrani2, Rahaf Al Sahli3
1 Medical Resident R3, KFSHRC, Riyadh, KSA
2 Hematologist, KFSHRC, Riyadh, KSA
3 Medical Student, Alfisal University, Riyadh, KSA
|Date of Web Publication||17-Jul-2017|
Mohammed A Karish
Internal Medicine Resident R3, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Source of Support: None, Conflict of Interest: None
Acquired hemophilia is a severe bleeding diathesis that affects both males and females. It is caused by suddenly appearing autoantibodies that interfere with the coagulation factor VIII activity. This disorder is characterized by spontaneous and post-traumatic subcutaneous bleeds and massive mucosal hemorrhages. We report a case of postpartum-acquired hemophilia with a compartment syndrome of right (Rt.) forearm in a 29-year-old woman. Hemostatic tests indicated a prolonged activated partial thromboplastin time (APTT) to 99 s (normal 30.4–40 s), the prothrombin time was 7.8 s (normal 12–14 s), and the platelet count was 271,000 (normal 155,000–450,000). Further workup demonstrated the presence of autoantibody against factor VIII in a titer of 15 Bethesda Units/ml (BU/ml) and a decreased factor VIII activity to 0.04 IU/ml (normal 0.6–1.5 IU/ml). Immunosuppressive treatment with oral prednisone at 60 mg/24 h was initiated, but she was refractory to steroids; therefore, rituximab was added on a weekly basis for 4 weeks. At the same time, factor eight inhibitor bypassing activity (FEIBA), an anti-inhibitor coagulant complex, has been used as a bypassing agent. Reduction of the factor VIII inhibitor titer to 0 BU/ml and an increase of factor VIII activity to 0.38 were achieved. This led to normalization of hemostatic parameters (APTT 38.9 s, factor VIII activity 0.38).
Keywords: Acquired hemophilia, hemophilia, postpartum
|How to cite this article:|
Karish MA, Hanbali A, Al Zahrani H, Al Sahli R. Postpartum-acquired hemophilia: A challenging disease to manage. J Appl Hematol 2017;8:75-8
| Introduction|| |
Acquired hemophilia (AH) is a rare autoimmune disorder characterized by a severe bleeding caused by autoantibodies, which impair the function of the coagulation factor VIII. These antibodies are defined as the circulating anticoagulant, or the factor VIII inhibitor.
AH is a very serious disorder and can be fatal. This is because bleeding can be severe and unexpected, and health care professionals may not recognize that an antibody has developed. While it is unknown just how many patients with AH die as a consequence of the bleeding or other complications, the estimates from some large studies are between 8 and 22 percent. In both classic and AH, the cause of bleeding tendency is the same − a decrease in the factor VIII activity in the patient’s plasma. However, the clinical manifestation of both diseases is not identical. Spontaneous bleeding into joints is typical in classic hemophilia, whereas in AH, massive subcutaneous blood extravasations and mucosal hemorrhages are usually observed. In a patient with AH, with normal prothrombin, thrombin, and bleeding time values, normal platelet count, and fibrinogen concentration, a 2- or 3-fold prolongation of the activated partial thromboplastin time (APTT) is usually observed. The first manifestation of AH is often a massive hemorrhage. In such a situation, only a quick diagnosis and the immediate administration of appropriate treatment can save the patient’s life.
A 29-year-old female patient with no known medical illnesses presented with a history of right hand pain and swelling along with scattered ecchymosis in different parts of her body. She underwent a cesarean section 10 months before admission with no significant bleeding and no history of complication during pregnancy. Five months after delivery, the patient started noticing multiple ecchymosis, which started from the buttock with extension to the lower extremities, variable in size from 3 cm to about 6 cm, associated with on and off gum bleeding. Five days before admission, the patient had a history of right hand pain of sudden onset and swelling. This swelling increased progressively until the patient was unable to move her fingers with numbness and decreased sensation. None of these shortcomings were present such as significant bleeding history, history of metrorrhagia or menorrhagia, family history of abnormal bleeding, history of skin rashes, joint pain, or fever, and history of headache, dizziness, or loss of consciousness. The patient’s mother had history of systemic lupus erythematouses (SLE), but there was no family history of bleeding or thrombosis.
Two days before admission, she went to a private hospital, and there they found that partial thromboplastin time (PTT) was prolonged reaching 99 s.
The patient was admitted to a hospital as a case of bleeding diathesis requiring further work up with a presentation of right forearm early compartment syndrome.
At the time of admission, she was afebrile, pulse rate was 91 beats/min, respiratory rate was 19 breaths/min, and blood pressure was 129/76 mmHg, with oxygen saturation of 98% in room air. Her weight was 68 kg. On examination, she was conscious, oriented to time, place, and person, and not in distress but was in pain. Cardiovascular, chest, abdominal, and neurological examination results were normal. Right forearm was tense with bruises in flexion posture. She felt pain with passive extension, but she had good capillary refilling and strong pulses; there were three ecchymosis in the lower extremity, with the largest one on the left lower limb 5 cm above the left ankle measured about 3–4 cm.
Work up of bleeding was performed including mixing study which showed:
- PTT = 52 s with no correction with mixing study.
- Factor VIII activity = 0.04 IU/ml.
- Factor VIII inhibitors = 15 Bethesda Units (BU).
Renal and hepatic profiles were normal.
Computed tomography (CT) abdomen, chest, and pelvis with contrast were taken to rule out any underline malignancy, and it was negative for any signs of malignancy.
Rest of the laboratory results are shown in [Table 1]. Therefore, she was started on factor VII 7 mg q.2h and then de-escalated to 7 mg q.8h; methylprednisolone 100 mg was given, and prednisolone 60 mg daily was started after that. The patient was checked by a plastic surgeon, and the recommendation was no surgical intervention at that moment.
Her PTT increased up to 71.4 s in 5 days after admission, but the factor VIII activity was still low with 0.06 IU/ml, and the factor VIII inhibitor was still high with 10 BU. As the patient was refractory to steroid, rituximab 600 mg weekly total of four doses was initiated; the factor VIII inhibitor decreased to 0.5 BU, but 1 week after finishing the last dose of rituximab, it increased again reaching 20 BU with normal PTT, which was suspicious for lab error; the test was repeated, and result was 0.0 BU [Figure 1].
|Figure 1: Showed improvement of PTT and factor VIII inhibitors levels with using rituximab, FEIBA and tapered steroid.|
Click here to view
The patient was discharged in a good condition, and treating her as an outpatient, factor eight inhibitor bypassing activity (FEIBA), an anti-inhibitor coagulant complex, was started as a bypassing agent.
After 1 month, the factor VIII inhibitor was 0; PTT became normal (38.9), and the factor VIII activity increased to 0.38.
| Discussion|| |
Postpartum-acquired hemophilia is a rare disorder that accounts for 7% of the cases presenting with AH. It usually presents as a severe bleeding disorder, which can sometimes be life-threatening. The diagnosis should be considered in any postpartum patient presenting with an isolated, unexplained, prolongation of PTT. Diagnosis can be made with mixing study and by measuring the factor VIII level and the factor VIII inhibitor level.
The incidence of AH is reported as about one per million annually,, but it represents the most common type of spontaneously acquired inhibitors against a clotting factor. Both sexes are affected equally., The incidence increases with age, the majority of patients being over 50 years of age. There is a second small peak of incidence in the 3rd decade, accounted for by women affected around parturition. A wide range of associated conditions has been described in the literature. In a large survey of 215 patients with the factor VIII inhibitors, 18% had concomitant autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus, 7% were postpartum women, 7% had malignancies, 5% had been treated with drugs (penicillin and phenytoin), 5% had skin disorders such as psoriasis and pemphigus, and 12% had various conditions such as asthma, multiple transfusions, diabetes, or hepatitis. In 46%, no associated disease could be identified. Beside this case series, both various solid tumors, and hematologic malignancies, such as plasma cell dyscrasias and lymphoproliferative disease are reported frequently in the literature in conjunction with the factor VIII inhibitors, whereas in autoimmune disorders and hematologic malignancies, a causal relation between autoantibody formation and associated disease seems possible, as there is both a plausible pathogenesis and clinical evidence;, the nature of this correlation is less clear for most of the other conditions. Further, the fact that most of them tend to occur in the elderly may indicate a coincidental relationship.
Management of postpartum-acquired hemophilia can be challenging since it requires restoration of hemostasis and inhibitor eradication at the same time. The level of the factor VIII inhibitor and the severity of bleeding can help in deciding which agent to use to restore hemostasis. If bleeding is not severe, and inhibitor level is low, the factor VIII concentrates can be used; if the bleeding is severe or the inhibitor level is high, then the agent of choice will be either FEIBA (the factor VIII inhibitor bypassing activity) or recombinant factor VIIa, and both of which work as bypassing agents for the factor VIII. For inhibitor eradication, corticosteroids continue to be the first line agents of choice. If refractory condition is found, then second-line therapies include rituximab or other immunosuppressive therapy. There is no relation between the level of inhibitor at presentation and response rate to immunosuppressive therapy. In a case series published by Shaffer and Phillips, the association of oral cyclophosphamide and prednisone was successful in achieving a complete remission in all of the nine consecutively enrolled AH patients. Other combinations, such as prednisone with azathioprine or prednisone with cyclophosphamide and vincristine, were also proven effective., A number of case reports have described such a type of cases wherein the patients with AH refractory to first-line immunosuppressive treatments responded to rituximab.
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| References|| |
Buczma A, Windyga J. Hemofilia nabyta. Pol Arch Med Wewn 2007;117:241-6.
Delgado J, Jimenez-Yuste V, Hernandez-Navarro F, Villar A. Acquired haemophilia: Review and meta-analysis focused on therapy and prognostic factors. Brit J Haematol 2003;121:21-35.
Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to Factor VIII. Thromb Haemost 1981;45:200-3.
Feinstein D, Green D, Federici A, Goodnight S. Diagnosis and management of patients with spontaneous acquired inhibitors of coagulation. In: Hematology. Louisiana: American Society of Hematology Education Program Book; 1999. p. 192-208.
Lottenberg L, Kentro K, Kitchens C. Acquired hemophilia. A natural history study of 16 patients with factor VIII inhibitors receiving little or no therapy. Arch Intern Med 1987;147:1077-81.
Hultin B. Acquired inhibitors in malignant and nonmalignant disease states. Am J Med 1991;91:9-13S.
Hauser I, Lechner K. Solid tumors and factor VIII antibodies. Thromb Haemost 1999;82:1005-7.
Endo T, Yatomi Y, Amemiya N, Mizoe A, Lino M, Ozawa H et al.
Antibody studies of factor VIII inhibitor in a case with Waldenström’s macroglobulinemia. Am J Hematol 2000;63:145-8.
Komiya I, Ito T, Ogata K, Yamada T, Dan K, Kuriya S et al.
Diverse hemostatic abnormalities in a patient with biclonal multiple myeloma. Rinsho Ketsueki 1990;31:62-5.
Baudo F, De Cataldo F, Bari SM et al.
Acquired factor VIII inhibitors in pregnancy: data from the Italian Haemophilia Register relevant to clinical practice. BJOG 2003;110:311-4.
Shaffer LG, Phillips MD. Successful treatment of acquired hemophilia with oral immunosuppressive therapy. Ann Intern Med 1997;127:206-9.
Söhngen D, Specker C, Bach D, Kuntz BM, Burk M, Aul C et al.
Acquired factor VIII inhibitors in nonhemophilic patients. Ann Hematol 1997;74:89-93.
Lian EC, Larcada AF, Chiu AY. Combination immunosuppressive therapy after factor VIII infusion for acquired factor VIII inhibitor. Ann Intern Med 1989;110:774-8.
Garvey B. Rituximab in the treatment of autoimmune haematological disorders. Br J Haematol 2008;141:149-69.