A ‘New’ Congenital Haemorrhagic Condition due to the Presence of an Abnormal Factor X (Factor X Friuli): Study of a Large Kindred

Abstract

Summary Three related patients are presented who show a congenital coagulation disorder with laboratory features intermediate between classical factor‐VII and factor‐X deficiencies. A woman and two men had suffered from bleeding since early childhood, with epistaxis, bleeding from the gums, post‐traumatic haemarthroses, bleeding after tooth extractions and other surgical procedures. Investigation demonstrated a prolonged prothrombin time, prolonged partial thromboplastin time, abnormal prothrombin consumption and abnormal thromboplastin generation corrected by normal serum. Platelet and vascular tests were normal and no hyperfibrinolysis was found. Factors I, II, V, VII, IX, XI and XII were within normal limits in all three patients. Mutual correction was demonstrated with a known factor‐VII‐deficient plasma but not with Stuart (X‐deficient) plasma. Factor‐X assay yielded low (4–9%) levels using tissue whole thromboplastin or tissue partial thromboplastin; but the results were normal with a Stypven‐cephalin mixture. In agreement with these results, the Stypven‐cephalin clotting time, the Stypven clotting time and the factor II + factor X level using a Stypven‐cephalin mixture were normal, ‘correction’ being attributable to the Russell's Viper venom. These results were thought to indicate an abnormal factor X rather than a real deficiency. The presence of abnormal factor X was demonstrated by the antibody neutralization technique and by the immunodiffusion studies. The defect, like classical factor X deficiency, is transmitted as an autosomal incompletely recessive trait. The heterozygote population has factor‐X levels varying from 32% to 55% of normal and are usually asymptomatic. The term ‘Factor X Friuli’ is proposed for the abnormality, due to a locally common mutant gene.

Reduced von Willebrand factor survival in type Vicenza von Willebrand disease

“…16 Factor VIII (FVIII) coagulant (FVIII:C) was measured by a one-stage method, using cephaloplastin as activated cephalin, as reported elsewhere. 18 Platelet VWF:Ag was evaluated by ELISA.…”

A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor

“…Factor VIII (FVIII) coagulant was measured using a one-stage method, with cephaloplastin as activated cephalin, as reported elsewhere. 27 VWF collagen binding (VWF:CB) activity was assessed by ELISA using type I and type III collagen diluted in acetic acid solution (95% and 5%, respectively), as described elsewhere. 28 Briefly, after overnight coating with collagen, microtiter plates were incubated with plasma VWF for 1 hour at room temperature; bound VWF was evaluated with HRP-conjugated anti-VWF antibody (DAKO).…”

An Arg760Cys mutation in the consensus sequence of the von Willebrand factor propeptide cleavage site is responsible for a new von Willebrand disease variant

“…24 FVIII activity was measured by a one-stage method, as previously described. 25 FVIII binding activity of VWF (VWF:FVIIIB) was evaluated by using an ELISA method as previously reported. 26 Briefly, after coating anti-VWF polyclonal antibody to microtiter plates, plasma VWF was added and incubated for 1 hour at room temperature.…”