Evaluation of an optimal dose of low-molecular-weight heparin for thromboprophylaxis in pregnant women at risk of thrombosis using coagulation activation markers.

There is no consensus on the dose of low-molecular-weight (LMW) heparin for thromboprophylaxis in pregnant women at increased risk of thrombosis. Based upon monitoring with anti-factor Xa activity, the studies showed conflicting results suggesting either fixed dosages throughout the pregnancy or dosages adapted to the gestational age. We tested whether monitoring thromboprophylaxis with D-dimers and thrombin-antithrombin complexes (TAT) would provide additional information on the optimal dose of LMW heparin. Women (165 women and 202 pregnancies) with hereditary or acquired thrombophilia or a history of thrombosis were considered to receive prophylactic LMW heparin therapy. All women received initially 5,000 IU/day of dalteparin s.c. All further dosages were determined solely on the basis of TAT and/or D-dimer values which were determined every 2-3 weeks. As soon as one of these values increased above the normal range, the dose of LMW heparin was adjusted. In 84.6% of all pregnancies, TAT and/or D-dimer values increased above the normal range once or more during the pregnancy. Consequently, the dose of LMW heparin had to be adjusted at least once over the course of the pregnancy. The mean daily dose of LMW heparin increased from 5,000 to 11,200 U between the 6th and 40th week of gestation. Adverse effects included one major bleeding and six local complications, but no thromboembolic event. In conclusion, increasing doses of LMW heparin are needed to keep TAT and D-dimers within the normal range during pregnancy. Hence, to suppress thrombin generation, apparently, the dosage of LMW heparin should be adjusted to the gestational age rather than using fixed doses throughout the pregnancy. However, it remains to be further established whether elevated TAT and D-dimers truly reflect a prothrombotic state during pregnancy.

Coagulation activation markers do not correlate with the clinical risk of thrombosis in pregnant women.

OBJECTIVE: Because coagulation activation markers have been shown to indicate an increased risk of thrombosis, we tested whether thrombin-antithrombin III complexes and D-dimers correlated with the risk assessment in pregnant women on the basis of clinical data. STUDY DESIGN: We divided a group of 261 pregnant women (305 pregnancies) into low- and high-risk groups according to the personal and family histories of thrombosis and the presence of a hereditary or an acquired thrombophilia. Women with a thrombotic event in the current pregnancy formed a separate group. All pregnancies with or without heparin therapy were closely monitored with thrombin-antithrombin III and D-dimer values for the entire course of the pregnancy. Retrospectively, the data were then correlated with the different groups and subgroups. RESULTS: The course of the mean thrombin-antithrombin III values of all 305 pregnancies was close to or slightly above the upper cutoff line, whereas the D-dimer values were well within the normal range. Independent of heparin, there was no difference in the course of the thrombin-antithrombin III and D-dimer values between the low- and high-risk groups. Only women with ongoing thrombosis during pregnancy had significantly higher thrombin-antithrombin III and D-dimer values with or without heparin therapy. Among those individuals with elevated thrombin-antithrombin III or D-dimer values, there were no specific, recognizable patients who had elevated markers more often than others. CONCLUSIONS: Thrombin-antithrombin III and D-dimer values do not correlate with a risk stratification assessed by clinical criteria. There are many women at low clinical risk who have elevated markers, and there are many women at very high clinical risk who have normal markers. Thus thromboprophylaxis would often be used inadequately if the indication were based on coagulation markers.