One of the major binding sites for factor VIII inhibitors is located within the A2 domain. In this study, phage display technology was used to isolate 2 human monoclonal antibodies, termed VK34 and VK41, directed toward the heavy chain of factor VIII. The V(H) domain of a single-chain variable domain antibody fragment (scFv) VK34 is encoded by germline gene segment DP-10. Epitope-mapping studie...

We report a 54-year-old male presenting with a history or recurrent nose bleeds and ecchymoses. The coagulation study showed a prolonged partial thromboplastin time, a factor VIII of 8% and a high inhibitor titer (193 Bethesda units). A diagnosis of acquired hemophilia A was reached. The patient was initially treated with cyclophosphamide for seven months without response. Therefore rituximab i...

This report describes a patient without evident underlying disease, in whom an acquired von Willebrand's syndrome was discovered before surgery. Coagulation abnormalities included a borderline bleeding time, a low retention of platelets on glass beads, decreased levels of factor VIII procoagulant activity (VIIIAHF), factor VIII-related antigen (VIIIAg), and ristocetin-induced agglutination cofa...

Previous studies using immunoneutralization techniques have shown that many factor VIII inhibitors are IgG antibodies of a single light chain type. We have investigated this apparent homogeneity by immunoneutralization assay and liquid isoelectric focusing of inhibitor fractions from five hemophiliacs and two nonhemophiliacs. By immunoneutralization assay, inhibitors from four hemophiliacs and ...

Lactadherin, a glycoprotein of the milk-fat globule membrane, contains tandem C domains with homology to discoidin-type lectins and to membrane-binding domains of blood-clotting factors V and VIII. We asked whether the structural homology confers the capacity to compete for the membrane-binding sites of factor VIII and factor V and to function as an anticoagulant. Our results indicate that lact...

Lactadherin, a glycoprotein of the milk-fat globule membrane, contains tandem C domains with homology to discoidin-type lectins and to membrane-binding domains of blood-clotting factors V and VIII. We asked whether the structural homology confers the capacity to compete for the membrane-binding sites of factor VIII and factor V and to function as an anticoagulant. Our results indicate that lact...

Acquired hemophilia is a very rare disease characterized by the presence of an autoantibody (mainly IgG) to factor VIII, with a clinical presentation resembling hemophilia A. It is associated with various autoimmune or dermatologic diseases, pregnancy, cancer, or drug ingestion, but in almost 50% of patients no underlying disorder is found. The treatment of acquired hemophilia is particularly c...

We studied the activation of factor X by the intrinsic pathway of blood coagulation using a new assay of factor X activation. When factor X tritiated in its sialic acid residues is activated, activation can be measured by the release of tritiated activation peptide, and the initial rate of activation can be determined under varying conditions. In the presence of phospholipid and calcium ions, f...

BACKGROUND: Acquired hemophilia is a rare condition which can be associated with lymphoproliferative disease. CASE REPORT: Eleven years after the diagnosis of immunocytoma had been made, a 72-year-old man developed a high-titer factor VIII inhibitor. At this time, the lymphoma was without significant progress and there was no paraprotein in the serum. Partial thromboplastin time (PTT) was 83s, ...

daily for 1 week), pulse therapy with methylprednisolone (1000 mg/day for 3 days) and rituximab (100 mg/week for 2 weeks) were initially used for correcting the coagulopathy. Prednisolone (1 mg/kg/day) and cyclophosphamide (100 mg/ day) were prescribed as maintenance therapy. The coagulatory disorder improved after 2 months of treatment associated with reduction of factor VIII inhibitor to 35 B...