Acquired haemophilia

Acquired haemophilia (AH) is a severe bleeding diathesis that affects both males and females. It is caused by suddenly appearing autoantibodies that interfere with coagulation factor VIII (FVIII) activity. Although some conditions such as autoimmune diseases, cancer and puerperium seem likely to induce AH, in more than half of the observed cases autoantibodies to FVIII are idiopathic. The clinical picture is characterized by spontaneous and post-traumatic subcutaneous bleeds as well as massive mucosal membrane hemorrhages (from the genitourinary and gastrointestinal tracts). Typical abnormalities in AH are prolonged activated partial thromboplastin time and normal results of the other haemostatic tests (platelet count, prothrombin and thrombin times, fibrinogen concentration). Acquired haemophilia is definitely confirmed by quantification of FVIII neutralizing antibodies. Bleeds are usually treated with activated prothrombin complex concentrates and activated recombinant factor VII. In most patients with AH, the use of immunosuppressive agents results in autoantibody elimination and restoration of normal FVIII plasma activity.     

Acquired haemophilia A as a blood transfusion emergency

Introduction

Acquired haemophilia is a rare autoimmune disorder caused by autoantibodies directed in the majority of the cases against clotting factor VIII. This disorder is characterised by the sudden onset of bleeding that not rarely may be life-threatening and need transfusion support. Most reports on this condition describe the need for blood transfusions during the acute, haemorrhagic phase, but the number of transfused red cell units is often unknown.

Patients and methods

In the last 5 years, 14 patients with acquired haemophilia A were identified in the transfusion and haemophilia centres of Verona and Castelfranco Veneto. The transfusion support for these 14 patients was analyzed in this retrospective survey.

Results

The 14 patients required a total of 183 red cell units. The average transfusion requirement was 13 red cells units/patient, with a range from 0 to 38 units.

Conclusions

Eleven of the 14 patients studied needed strong transfusion support to enable any further management of the haemorrhages, as well as for eradication treatment of the autoantibodies to factor VIII. A relevant part of the management of haemorrhagic symptoms as well as the first choice for any further treatment (bleeding or the cure of the underlying disease) is transfusion of red blood cells.     

Acquired haemophilia and PM-Scl antibodies

SIR, We read with interest the recent case report by Trottaet al. [1] about long-lasting remission and the successful treatmentof acquired factor VIII inhibitors using cyclophosphamide ina patient with systemic lupus erythematosus. There is a recognized association between the development ofacquired antibodies to factor VIII and a number of diseaseswith an autoimmune basis (bullous pemphigoid, rheumatoid arthritis,Sjögren     

Living donor liver transplantation for hepatitis C related hepatocellular carcinoma in a haemophilia A patient

We report the first case of unrelated living liver transplantation for hepatitis C related hepatocellular carcinoma (HCC) in a Chinese patient with haemophilia A. The development of cirrhosis and HCC was insidious in this patient, who has previously failed interferon treatment despite low viral load and genotype 6a. With factor VIII and novoseven support, there were no operative complications and there was no need for blood transfusion. Postoperative pegulated interferon treatment resulted in viral clearance with no increased cellular rejection. The use of living donors represent a potential life saving therapeutic options for hepatitis C virus related complications in haemophiliac, especially in countries of organ shortage. Careful patient and donor choice, meticulous surgical expertise and proper counselling, however, are prudent requirements.     

Acquired haemophilia masked by warfarin therapy

Acquired haemophilia is a rare phenomenon and prompt diagnosis is essential for successful treatment. Early laboratory detection could minimize its potentially devastating consequences and reduce mortality but when a masking element such as anticoagulant therapy is present, delay in diagnosis is not uncommon. A prolonged activated partial thromboplastin time (APTT) may be falsely attributed to warfarin alone, particularly when it is associated with oral anticoagulant overdose. We describe two patients on treatment with warfarin who presented with a bleeding diathesis and disproportionately prolonged APTT, which led to the diagnosis of antibodies directed against factor VIII.     

Acquired haemophilia in cancer: A systematic and critical literature review

Aim

There is a paucity of data on the clinical presentation and management of cancer patients with acquired haemophilia (AH), we here report a systematic literature review on acquired haemophilia in the context of cancer.

Methods

Treatment outcomes of AH were defined as complete response (CR), partial response (PR) or no response (NR), based on inhibitor eradication, coagulation factor VIII levels and bleeding control. Reported deaths were either related to cancer or bleeding.

Results

Overall, 105 cases were collected and analyzed according to classification of cancer and efficacy of treatments for inhibitor and malignancy. The mean age was 68 years for both males (range 37‐86 years) and females (range 43‐89 years), 39 patients were female subjects and 66 were males. A solid cancer was diagnosed in 60 subjects, while 45 patients suffered a haematological malignancy. Solid cancers affected mainly males; however, the incidence of solid tumours vs haematological malignancies was not statistically significant (P = .09). Not all patients were treated for their underlying cancer, bleeding and/or inhibitor, in two cases outcome is unavailable. CR was reported in 62.1% (64/103) cases, PR in 9.7% (10/103) cases, NR with or without death was reported in 28.1% (29/103) cases.

Conclusion

CR was best achieved when successful and complete elimination of autoantibodies occurred contemporaneously with the successful treatment of the underlying malignancy. In some cases, recurrent autoantibodies were harbingers of relapsed cancer. Type of cancer, inhibitor titer, treatments administered for bleeding control and inhibitor eradication did not significantly affect clinical outcome of analyzed cases.     

Acquired haemophilia in recipients of depot thioxanthenes.

We present two cases in which the occurrence of acquired haemophilia is associated with the use of depot preparations of the thioxanthenes zuclopenthixol and flupenthixol. These drugs have not previously been implicated in the aetiology of acquired haemophilia.     

Acquired haemophilia in South Australia: a case series

Abstract
Of eight cases of acquired haemophilia presenting over an 8-year period, six received immunosuppressive treatment, five with cyclophosphamide, vincristine and prednisolone (CVP). Five patients (four on immunosuppressive treatment) entered remission, two patients died and one was lost to follow up. Initially, the remissions were only partial. The median duration until partial remission was 10 weeks (range 1–55 weeks) and until complete remission was 35 weeks (range 2–59 weeks). Partial remission may proceed to complete remission without further chemotherapy. (Intern Med J 2001; 31: 556–559)     

Acquired haemophilia: experiences with a standardized approach

Acquired haemophilia is a rare, life-threatening, acquired bleeding diathesis. No general consensus exists on the best therapeutic approach. We report on the standardized approach at our institution evaluated in ten patients with acquired haemophilia. Factor VIII inhibitors were found in all patients, activities ranging from 1 to 648 Bethesda units (BU). Eight of the ten patients presented with severe bleeding. Two patients died during the acute phase, one from intracranial bleeding and one due to Mycoplasma pneumonia. One patient with mild bleeding was treated with immunosuppression alone. Two patients with factor VIII inhibitor activities below 5 BU were started on factor VIII concentrate therapy. Therapy was successful in one and was changed to recombinant human activated factor VII infusion (rFVIIa) in the other, owing to insufficient factor VIII recovery. Six patients with factor VIII inhibitor activities above 5 BU were started on activated prothrombin complex concentrate (APCC) therapy. APCC treatment was successful initially in all six patients and was changed to rFVIIa infusion in one for rebleeding. One patient did not receive any specific therapy. Immunosuppression with prednisolone (2 mg kg(-1)) was begun in nine patients and was continued with cyclophosphamide (2 mg kg(-1)) in six. A complete remission of the acquired haemophilia was found in seven of the eight patients surviving the acute phase, one had a partial remission. All patients with acquired haemophilia could be managed effectively following our standardized approach. Routine administration of immunosuppression was associated with high inhibitor elimination rates.     

Safety and complications of interventional radiology for hepatocellular carcinoma in patients with haemophilia and cirrhosis

Many patients with haemophilia have been chronically infected with hepatitis virus owing to multiple transfusions and the prevalence of hepatocellular carcinoma will probably increase in this population. We evaluated the safety and complications of radiological intervention for hepatocellular carcinoma in eight patients with haemophilia and cirrhosis. Radiological interventions can be performed safely in all patients with haemophilia. Unexpectedly, the most common complication was bleeding from the gastrointestinal tract. Attention should be paid to this potential problem in order to take appropriate steps to minimize its occurrence.