Measurement of Markers of Activated Coagulation in Antithrombin III Deficient Subjects

Summary

Functional antithrombin III levels were measured by factor Xa inhibition in 63 members of a large family with type 2 antithrombin III deficiency and individuals were classified as antithrombin III deficient or non-deficient according to the results. FI+2 and TAT complexes were measured using an ELISA and FPA levels were measured by radioimmunoassay.

Thirty subjects (48%) were classified as antithrombin III deficient and 33 (52%) as antithrombin III non-deficient. The mean level of FI+2 was significantly higher in the deficient adults (0.87 ± 0.26) compared to both the non-deficient adults (0.70 ± 0.21) (p = 0.03) and the deficient adults receiving warfarin (0.16 ± 0.01) (p <0.001). The differences in the mean values of TAT complexes and FPA between deficient and non-deficient individuals were not statistically significant.

These findings suggest that untreated antithrombin III deficient subjects generate more thrombin than their non-deficient family members and that warfarin inhibits this thrombin formation. In this cross-sectional study, it is not possible to correlate the levels of the surrogate makers with future clinical outcome.

• References

• 1 Thaler E, Lechner K. Antithrombin III deficiency in thromboembolism. Clin Haematol 1981; 10: 369-390
• 2 Bauer KA, Goodman TL, Kass BL, Rosenberg RD. Elevated factor Xa activity in the blood of asymptomatic patients with congenital antithrombin deficiency. J Clin Invest 1985; 76: 826-836
• 3 Leroy-Matheron C, Gouault-Heilmann M, Levent M. Prothrombin fragment 1+2 levels in patients with inherited deficiency in coagulation inhibitors. Thromb Haemostas 1991; 65: 1208a
• 4 Bauer KA, Barzegar S, Rosenberg RD. Influence of anticoagulants used for blood collection on plasma prothrombin fragment F₁₊₂ measurements. Thromb Res 1991; 63: 617-628
• 5 Devraj-Kizuk R, Chui DHK, Prochownik EW, Carter CJ, Ofosu FA, Blajchman MA. Antithrombin-III-Hamilton: a gene with a point mutation (guanine to adenine) in codon 382 causing impaired serine protease reactivity. Blood 1988; 72: 1518-1523
• 6 Kahle LH, Schipper HG, Jenkins CSP, ten Cate JW. Antithrombin III. Evaluation of an automated antithrombin III method. Thromb Res 1978; 12: 1003-1014
• 7 Nossel HL, Yudelman I, Canfield RE. et al Measurement of fib-rinopeptide A in human blood. J Clin Invest 1974; 54: 43-53