Haemophilia is a rare and congenital bleeding disorder caused by a genetic defect, resulting in a lack of or insufficient coagulation factors VIII or IX in the body. In affected individuals, this causes an inability to clot blood, leading to bleeds in the joints, muscles and soft tissues. If left untreated, this can lead to disability and sometimes death. It is widely agreed that the optimal st...

A high plasma concentration of coagulation factor VIII (FVIII) is an important risk factor for venous thromboembolism (VTE) (1-4). In the Leiden Thrombophilia study for example, FVIII levels above 1500 IU/L conferred an almost 5-fold risk for a first episode of deep-vein thrombosis (1). Most importantly, high FVIII is also associated with a very high risk of recurrent venous thromboembolism (4,...

cerebral vein thrombosis (cvt) is an infrequent condition with a large variety of causes that can lead to serious disabilities. however, in 20% to 35% of cases, no cause is found. in this study we evaluated the hereditary (p & c proteins, antithrombin, mutation of prothrombin g20210a and factor v leiden), other risk factors (hyperhomocycteinemia, factor viii, acl-ab, apl-ab, and ocp) and clinic...

Development of neutralizing Abs to blood coagulation factor VIII (FVIII) provides a major complication in hemophilia care. In this study we explored whether modulation of the uptake of FVIII by APCs can reduce its intrinsic immunogenicity. Endocytosis of FVIII by professional APCs is significantly blocked by mAb KM33, directed toward the C1 domain of FVIII. We created a C1 domain variant (FVIII...

Combined deficiency of factors V and VIII is an autosomal recessive bleeding disorder resulting from alterations in an unknown gene on chromosome 18q, distinct from the factor V and factor VIII genes. ERGIC-53, a component of the ER-Golgi intermediate compartment, was mapped to a YAC and BAC contig containing the critical region for the combined factors V and VIII deficiency gene. DNA sequence ...

This paper reports an asymptomatic coagulation defect responsible for an abnormality at the contact phase of blood coagulation in vitro, distinct from Hageman factor and Fletcher factor deficiencies. Coagulation studies in a 50-yr-old French woman without bleeding tendency revealed the following results: whole-blood clotting time in glass tubes and activated partial thromboplastin time with kao...

Advances in recombinant technology and knowledge about coagulation factor VIII (FVIII) are building a platform for new therapeutic options in patients with hemophilia A. The development of turoctocog alfa, a novel, high-purity, third-generation, B-domain truncated recombinant FVIII, has been produced and formulated without the use of animal-derived or human serum-derived components, in the wake...

The classification of factor VIII deficiency, generally used based on plasma levels of factor VIII, consists of severe (<1% normal factor VIII activity), moderate (1% to 4% factor VIII activity), or mild (5% to 25% factor VIII activity). A recent communication described four individuals bearing identical factor VIII mutations. This resulted in a severe bleeding disorder in two patients who carr...