Anti- and procoagulant activities in factor VII-deficient subjects.
The clinical feature in patients with congenital factor VII deficiency is in part dependent on the underlying genetic defect, but the mechanisms influencing the genotype-phenotype correlation remain to be fully elucidated. In addition, thromboembolic events have been reported. Compensatory mechanisms involving vitamin K-dependent factors have been suggested. We have measured anticoagulant activities in 25 factor VII-deficient subjects (factor VII activity < or =36%) and 23 age-matched controls and correlated these to the vitamin K-dependent procoagulant activities. Two of the patients had a history of thromboembolism. The factor VII-deficient patients were found to have a significantly lower protein C activity than the controls [0.84 U/ml (95% CI 0.78; 0.89) vs. 0.98 U/ml (95% CI 0.91; 1.05), P=.004]. In addition, the protein C activity was correlated to that of factor VII (r=.36; P=.014), factor IX (r=.45; P=.002) and factor X (r=.50; P=.0006), respectively. The level of prothrombin fragment 1+2 was correlated to the protein C (r=.40; P=.012) and to the factor VII activity (r=.42; P=.011). No differences between patients and controls were seen regarding total and free protein S, antithrombin, plasminogen activator inhibitor-1 (PAI-1) and tissue factor pathway inhibitor (TFPI). Seven of the patients were found to have the Factor V Leiden mutation, but none of them had experienced any thromboembolic event. The present data support the notion that compensatory hemostatic mechanisms might exist in that the protein C activity was found to be decreased in the factor VII-deficient subjects. Whether this could influence the clinical feature, including the risk of thromboembolic events in association with replacement therapy, remains to be evaluated.
Astermark
J
J
Department of Coagulation Disorders, University Hospital, University of Lund, Malmö, Sweden. jan.astermark@medforsk.mas.lu.se
Tengborn
L
L
Hedner
U
U
Berntorp
E
E
D020016:Activated Protein C Resistance; D000328:Adult; D000367:Age Factors; D000368:Aged; D000925:Anticoagulants / Q000097:blood*; D005168:Factor VII Deficiency / Q000097:blood* / Q000151:congenital; D005170:Factor X / Q000378:metabolism; D005260:Female; D006487:Hemostasis; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D017293:Protein S / Q000378:metabolism; D019851:Thrombophilia / Q000097:blood / Q000209:etiology; D013927:Thrombosis / Q000097:blood / Q000209:etiology
D000925:Anticoagulants; D017293:Protein S; D005170:Factor X