|Year : 2017 | Volume
| Issue : 2 | Page : 79-81
Acquired hemophilia A: A case report
Sarita Pradhan1, Adya Kinkar Panda2
1 Assistant Professor, Department of Pathology (Hematology Division), IMS & SUM Hospital, Bhubaneswar, Odisha, India
2 Assistant Professor, Department of Radiology, IMS & SUM Hospital, Bhubaneswar, Odisha, India
|Date of Web Publication||17-Jul-2017|
Department of Pathology (Hematology Division), IMS & SUM Hospital, Bhubaneswar, 751003, Odisha
Source of Support: None, Conflict of Interest: None
Acquired hemophilia A is a rare autoimmune disorder where autoantibodies are produced against factor VIII. Its reported incidence is as low as 1.20 to 1.48 cases per million per years. However, this entity is underreported because diagnosis is often missed in routine practice as its symptoms differ from its congenital counterpart. We report a 25-year-old male who presented with proptosis of left eye and gastric outlet obstruction. Routine workup revealed isolated elevation of activated platelet thromboplastin time. The patient, however, did not have any history of bleeding episodes, and family history was also negative. Mixing studies and inhibitor screening revealed presence of inhibitors. High degree of clinical suspicion is required to correctly diagnose this rare entity presenting with variable bleeding manifestations.
Keywords: Inhibitors, FVIII, mixing study
|How to cite this article:|
Pradhan S, Panda AK. Acquired hemophilia A: A case report. J Appl Hematol 2017;8:79-81
| Introduction|| |
Acquired hemophilia is a rare bleeding disorder caused by autoantibodies against factor VIII. Its incidence varies from 1 to 4 cases per million per year., Age distribution is bimodal, with the first peak in young females in the postpartum period and the second among elderly. It can be idiopathic or secondary to malignancies, autoimmune or dermatological disorders, and postpartum. Here we report a case of acquired hemophilia A in young male presenting with gastric outlet obstruction and proptosis.
| Case Report|| |
A 25-year-old male presented to the hemato-oncology outdoor with a history of repeated vomiting, abdominal pain, and weight loss since 6 months. He had undergone upper gastrointestinal endoscopic biopsy outside and with a provisional diagnosis of MALToma was referred to our center for further management. On examination, he had severe pallor, mild pedal edema, and marked proptosis of left eye that began 1 year ago. His routine hemogram revealed hemoglobin level of 6.5 g/dL, total leukocyte count of 6.38 × 103/μL with normal differential count, and platelet count of 475 × 103/μL. The liver-function tests and serum urea, creatinine, and electrolytes were all normal. Ultrasonography of abdomen revealed diffuse hypoechoic wall thickening, involving whole of stomach with one or two perigastric nodes. No obvious retroperitoneal lymphadenopathy was noted. contrast enhanced computed tomography (CECT) abdomen showed bulky polypoidal moderately enhancing wall thickening involving body, prepyloric region, lesion contiguously extending to lesser, and greater curvature. Perigastric omental infiltrates were seen. Magnetic resonance imaging (MRI) of brain and orbit revealed a trans-spatial lymphoproliferative infiltrates in left orbit with axial proptosis. A provisional diagnosis of gastric lymphoma with lymphomatous infiltrates in the orbit was performed. Upper GI endoscopy showed an ulceronodular growth extending from gastroesophageal junction to the antral region. Coagulation studies were advised before carrying out endoscopic biopsy, which surprisingly revealed a normal prothrombin time of 13.3 s (normal range 10.8–13.9 s) and international normalised ratio (INR) of 1.05 but a significantly raised activated partial thromboplastin time (APTT) of 130 s (normal range 26.8–38.5 s). The patient gave no previous history of bleeding episodes or hemarthrosis, or bleeding following endoscopic procedure. Family history was also negative. Mixing studies were advised, which showed immediate correction of activated partial thromboplastin time to 41 s; however, a time-delayed 1:1 control:patient serum mix could not completely correct the thromboplastin time, which suggested the presence of clotting factor inhibitors. Then clotting factors assay revealed factor VIII deficiency [factor VIII:C < 1% of normal pooled plasma normal 50–150% of normal pooled plasma (NPP)]. Factor VIII:C inhibitor levels by Bethesda assay were more than 32 BU/mL. A diagnosis of acquired hemophilia A was made. Meanwhile, a repeat endoscopic biopsy was planned under coverage of factor VIII concentrate. The upper GI endoscopy was done, and multiple biopsies were taken from the lesion. Procedure was uneventful without any episode of bleeding. Upper GI endoscopic biopsy from the growth revealed only superficial duodenal mucosa, with numerous collections of acute and chronic inflammatory cells with a plasma-cell-rich population. However, the plasma cells were polytypic in nature on immunochemistry. The patient was started on steroids and planned for deeper endoscopic biopsy to confirm gastric lymphoma by histopathological diagnosis. The patient was, however, lost to follow-up.
| Discussion|| |
Acquired hemophilia A is characterized by isolated prolongation of APTT and spontaneous bleeding episodes in a previously asymptomatic patient with negative family history. Its clinical presentation is strikingly variable from congenital hemophilia as hemarthrosis is very rare, and common features are bleeding into skin, muscle, or mucous membrane (epistaxis, melena, hematemesis). Often it is diagnosed after a episode of severe bleeding post surgery or invasive procedure. Even rarer is the scenario where the patients are asymptomatic and are discovered on routine investigations. It either can be idiopathic or secondary to hematological/solid malignancy, autoimmune disorders like SLE, rheumatoid arthritis, ulcerative colitis, drug reaction, dermatological conditions like psoriasis, pemphigus, or can also occur in the postpartum period [Table 1].
Routine coagulation workup shows isolated elevation of APTT with normal PT, TT, and platelet counts. Mixing studies done after mixing a normal plasma to the test plasma in 1:1 ratio shows complete correction if it is due to factor deficiency but fails to correct in presence of inhibitors. However, it is essential to note that sometimes immediate mix may show correction even in presence of inhibitors; hence, it should be performed after incubation at 37° for 2 h. This highlights the fact that the interaction of antibodies and coagulation factor is time and temperature dependant.
If mixing study results are compatible with presence of inhibitors, then factor VIII assay and quantification of inhibitor assay by Bethesda assay is done. The inhibitor titer represents the reciprocal of dilution of patient plasma that produces 50% inhibition of factor VIII. Lupus anticoagulant can also mimic this condition and hence should be excluded. However, unlike acquired factor VIII inhibitors, lupus anticoagulant is not time dependant and causes immediate inhibition.
Treatment is aimed at controlling bleeding symptoms if any and eradicate the inhibitor. Treatment of acquired inhibitors to factor VIII depends on the bleeding manifestations and on the nature of the underlying pathology. As a first line of therapy for eradication of inhibitors, corticosteroids alone, or in combination with cyclophosphamide, is recommended. Rituximab has now emerged as a second-line drug for refractory cases., For control of bleeding episodes, bypassing agents like recombinant FVIIa or aPCC are the drug of choice but are less frequently available in Indian scenario. Therapeutic response is measured by evaluating FVIII level which should turn to normal and undetectable inhibitor titers.
| Conclusion|| |
The aim of reporting this case is to create awareness of this potentially serious and rare disorder among physicians. The index case which had no bleeding manifestations at presentation also highlights the need to evaluate every case of unexplained prolongation of APTT as the clinical manifestations are highly variable.
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Conflicts of interest
There are no conflicts of interest.
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