Acquired inhibitor against coagulation factor V with severe hematuria

A 42-year-old man was admitted with hematuria after a common cold. No purpura could be observed but there was oozing on the site of the forearm where blood had been taken in a previous hospital. Platelet count was 292 x 10(3)/microliter, examination of coagulation system showed abnormalities; prolonged prothrombin time: PT (99.7 sec) and activated partial thromboplastin time: APTT (more than 200 sec), which suggested deficiency of coagulation factor II (FII), factor V (FV) or factor X (FX). In fact, the FV activity was only 2% of the pooled normal plasma. Mixing test of patient's plasma with normal pooled plasma revealed the existence of an FV inhibitor (FVI), which was IgA with an activity levels of 3 Bethesda unit/ml. Although hematuria stopped soon after beginning treatment with steroids (PSL), the abnormalities in PT and APTT improved very slowly and incompletely. At the time of writing, FVI is still observed ten months after onset. The patient had no underlying disease, and in this case FVI appeared following a common cold. Previous reports have said that FVI can cause mild bleeding, and it disappear in a short time. This case showed the possibility of the hidden presence of FVI in patients with hematuria.     

Multimodality therapy of an acquired factor V inhibitor

Acquired inhibitors of factor V are rare causes of clinical bleeding, whose severity ranges from mild to life-threatening. Optimal treatment of patients with factor V inhibitors is uncertain. We report on our successful treatment approach in a patient with spontaneous, life-threatening intracranial bleeding caused by a factor V inhibitor. The patient deteriorated after initial treatment with fresh-frozen plasma and platelet transfusions. He was subsequently treated with a combination of plasma exchange and chemotherapy, which led to complete recovery. Our experience suggests that plasma exchange may be life-saving in cases of severe bleeding caused by factor V inhibitors. The use of plasmapheresis in conjunction with chemotherapy is an efficacious and well-tolerated treatment and should be considered in patients with factor V inhibitors. © 1996 Wiley-Liss, Inc.     

Spontaneous resolution of acquired factor V inhibitor associated with ovarian carcinoma

A 74-year-old lady who presented initially with loin pain and haematuria, then melaena was found to have a prothrombin time ratio (PTR) > 10 and activated partial thromboplastin time ratio (APTTR) > 7. A factor V inhibitor was diagnosed. She was managed with supportive care and the FV inhibitor resolved. A few weeks later she developed abdominal swelling and ascites and was found to have an ovarian tumour. This is the first case, as far as we are aware, of a malignancy-associated FV antibody that has spontaneously remitted before overt presentation of the tumour and illustrates the value of adopting an expectant approach to the management of acquired FV inhibitors.     

Successful treatment with rituximab in a patient with an acquired factor V inhibitor

Rituximab has already been successfully used to treat immune-mediated bleeding disorders such as acquired factor VIII inhibitor. We report here a case of severe acquired factor V (FV) inhibitor deficiency due to FV inhibitor which has been dramatically improved after rituximab.     

Platelet factor V supports hemostasis in a patient with an acquired factor V inhibitor, as shown by prothrombinase and tenase assays.

A woman with gross hematuria was shown to have a severe isolated factor V deficiency due to a factor V inhibitor of 200 U/ml titer. Hematuria persisted despite multiple infusions of plasma but, after one transfusion with 1 U platelets, urine red blood cells decreased by more than 98%. To evaluate the patient's platelet function we performed prothrombinase and tenase assays with platelets from the patient and from normal donors. By prothrombinase assay, ionophore-activated patient platelets showed 42% of the activity of normal platelets in their ability to support prothrombin activation by activated factor X; whereas in a 'tenase' assay, which measures the platelets' ability to support factor X activation by activated factor IX + activated factor VIII, their activity was 117% of normal. The addition of excess bovine activated factor V to the prothrombinase assay fully corrected the defect. The results demonstrate the benefit of platelet transfusion and indicate that in this case the platelets are the primary source of factor V for hemostasis.     

Hemarthrosis in patients with acquired factor VIII inhibitor

We describe 2 patients who presented with hemarthrosis and were found to have an underlying Factor VIII inhibitor. One case was associated with a renal cell carcinoma. Factor VIII inhibitor should be included in the differential diagnostic lists of causes of hemarthrosis.     

Multiple myeloma presenting with acquired factor VIII inhibitor

An initial presentation of hematological malignancies associated with autoantibodies is not common, and there is only one documented case of multiple myeloma presenting with acquired FVIII inhibitor for multiple myeloma. In this paper, we describe a second case of multiple myeloma who presented with acquired FVIII inhibitor. A 43-year-old woman was referred to our hematology unit for anemia and an elevated erythrocyte sedimentation rate. Two months before her admission, she had undergone an operation at a local hospital because of ovarian cyst rupture complicated by severe postoperative bleeding. Because coagulation tests had revealed a prolonged partial thromboplastin time which could not be corrected by a mixing test and a decreased FVIII level, a diagnosis of acquired FVIII inhibitor had been made. The patient was hospitalized in our unit for further evaluation. The erythrocyte sedimentation rate was 110 mm/h, serum albumin level 2.5 g/dL, globulin level 5.6 g/dL, and C-reactive protein 47.8 mg/L (0–6). Serum IgG was high, and serum protein electrophoresis showed a monoclonal spike in the gamma region. An IgG-kappa paraprotein was identified by immunofixation of the urine and serum. X-ray films of the bones revealed lytic areas in the skull, pelvis, and lumbar vertebrae. Bone marrow aspiration showed normal cellularity with 40% plasma cell infiltration. The patient was diagnosed with the IgG kappa type of multiple myeloma associated with acquired FVIII inhibitor. In patients presenting with severe bleeding, autoantibodies against FVIII should be considered for the differential diagnosis of bleeding. Clinicians should be alert to the presence of rare underlying neoplastic diseases such as multiple myeloma, in patients with acquired FVIII inhibitor.     

High-titer acquired factor V inhibitor responsive to corticosteroids and cyclophosphamide in a patient with two malignant tumors

We report a 79-year-old man with two simultaneous malignant tumors (buccal epidermoid carcinoma and prostatic adenocarcinoma) who developed a severe bleeding complication at the site of the buccal tumor as well as a massive cerebral hematoma after a skull trauma. Laboratory findings showed the presence of a high-titer specific factor V inhibitor. The patient failed to respond to intravenous immunoglobulins, but both clinical and laboratory improvement was obtained after treatment with corticosteroids and cyclophosphamide.     

High-titer idiopathic acquired factor V inhibitor patient showing decreased activities of multiple coagulation factors

A 72-year-old male presented with oral bleeding resulting from acquired factor V (FV) inhibitor. We observed abnormalities in prothrombin time (PT) (8%) and activated partial thromboplastin time (APTT) (>200 seconds). FV activity was less than 3%, and a mixing test did not correlate with PT. FV inhibitor assay demonstrated 240 Bethesda units/ml. The patient also showed markedly decreased activity of Factors II (13%) and X (14%). Oral bleeding disappeared and coagulation abnormalities improved with prednisolone therapy. High titer FV inhibitor might affect coagulation assays even in a patient with normal factor activity.     

Successful treatment of acquired factor VIII inhibitor with cyclosporin

Acquired factor VIII inhibitor causes a rare but life-threatening form of bleeding disorder, owing to the formation of auto-antibodies against FVIII. Treatment modalities include the use of immunosuppressive drugs such as cyclophosphamide and corticosteroids, plasmapheresis and i.v. immunoglobulin. A patient with idiopathic acquired FVIII inhibitor presented with serious bleeding complications resistant to all the above therapeutic modalities. Treatment with cyclosporin, however, resulted in a prompt and complete response. The lack of side-effects and the relatively quick response suggest that cyclosporin may be tried as front line treatment for patients with acquired FVIII inhibitors.     

Management of bleeding in severe factor V deficiency with a factor V inhibitor

Factor V (FV) inhibitor arises rarely after using fresh frozen plasma (FFP) to treat inherited FV deficiency and is often a real therapeutic challenge. Here, we report a patient with a severe FV deficiency who developed such an inhibitor and was then treated with recombinant activated FVII (rFVIIa) and platelet concentrates (PC). Monitoring was assessed by thrombin generation assay (TGA). PC were more effective than rFVIIa in treating bleeding, but there was no correlation between the TGA results and clinical efficacy.