REDUCED THROMBUS FORMATION IN NATIVE BLOOD OF HOMOZYGOUS FACTOR VII-DEFICIENT PATIENTS AT HIGH ARTERIAL-WALL SHEAR RATE

Inhibition of thrombin formation in flowing native blood reduces throm bus formation on subendothelium, dacron, or collagen fibrils at arteri al wall shear rates of 450 to 650 s(-1). In the present study, we have investigated the role of low levels of factor VII (FVII) in thrombus formation on collagen fibrils at arterial wall shear rates of 650 s(-1 ) (coronary arteries), 2,600 s(-1) (mildly stenosed arteries), and 10, 510 s(-1) (severely stenosed arteries) in parallel-plate perfusion cha mbers. In the perfusion chamber with the highest wall shear rate, thro mbus formation took place at the apex of an eccentric stenosis, which reduced the cross-sectional area of the blood flow channel by 80%, thu s simulating thrombus formation at an atherosclerotic plaque rupture. Native blood from 21 healthy volunteers and 12 homozygous FVII-deficie nt patients was drawn by a pump directly from an antecubital vein over a surface of fibrillar collagen positioned in the respective perfusio n chambers. The patients had FVII coagulant activities ranging from 1. 3% to 4.5% and FVII antigen levels of 16% to 23% of normal. Immunoaffi nity purification of the patients' FVII followed by electrophoresis (s odium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]) a nd immunoblotting showed a protein with similar molecular mass as norm al FVII. In the perfusion studies, a reduction in thrombus volume of 5 4% of normal (P < .007) at 10,510 s(-1) was observed. The deposition o f fibrin on the thrombogenic surface and the plasma level of fibrinope ptide A (FPA) in blood samples collected distal to the perfusion chamb er were concomitantly reduced (P < .002 and P < .04, respectively). Th e plasma FPA level was also reduced at 2,600 s(-1) (P < .04), but not at 650 s(-1). However, at the lower shear conditions, the thrombus vol ume and the fibrin deposition were within the ranges observed in norma l blood. The platelet-collagen adhesion was not affected at any of the three shear conditions. Thus, low plasma levels of FVII result in sig nificantly less formation of thrombin and fibrin in and around growing platelet masses at high shear condition. This may weaken the thrombus stability and reduce platelet recruitment, thereby lowering thrombus volume. In support of this theory, one patient with afibrinogenemia ha d an 83% reduction in thrombus volume at this high shear condition. (C ) 1994 by The American Society of Hematology.