Weight-adjusted LMWH prophylaxis provides more effective thrombin inhibition in morbidly obese pregnant women.

INTRODUCTION: Low molecular weight heparin (LMWH) prophylaxis has been recommended for morbidly obese pregnant women (>40kg/m(2)). There is very little data on the anticoagulant effects of LMWH in this group. We investigated two different dosing regimens; fixed dose and weight-adjusted dose on the anticoagulant effects of the LMWH tinzaparin used for thromboprophylaxis in obese pregnant women. MATERIALS AND METHODS: Twenty morbidly obese pregnant women were started on a fixed dose of tinzaparin (4,500 iu/day) at 32weeks gestation and then changed to a weight-adjusted dose (75iu/kg/day) for the remainder of their pregnancy. Four-hour post LMWH, venous bloods were taken after each initial dose and repeated every two weeks until delivery. Twenty normal weight women who did not receive LMWH at the same gestation were used as controls. RESULTS: Prior to LMWH prophylaxis, tissue factor pathway inhibitor (TFPI) levels in the obese group at 32weeks were significantly lower (p<0.001) and endogenous thrombin potential (ETP) and peak thrombin levels in obese group were significantly higher, compared with controls (p<0.0001; p<0.001). There was no significant difference between ETP levels before and after fixed LMWH. However, ETP levels were significantly lower post weight-adjusted dose compared with post fixed dose. There was a significant effect of LMWH on TFPI levels, (p<0.0001). ETP correlated positively with total body weight prior to LMWH (r=0.631) (p<0.05) and at fixed dose (r=0.578) (p<0.05). CONCLUSION: Morbidly obese pregnant women have increased thrombin generation and reduced natural anticoagulant in third trimester. This prothrombotic state was more effectively attenuated by weight-adjusted than fixed LMWH doses.

Thrombin generation post elective caesarean section: effect of low molecular weight heparin.

INTRODUCTION: Caesarean section (CS) is a significant risk factor for venous thromboembolism.. Low molecular weight heparin (LMWH) is commonly used for thromboprophylaxis post emergency caesarean delivery. However, no consensus exists regarding LMWH thromboprophylaxis following elective caesarean section. Measures of thrombin formation may indicate the full anticoagulant activity of LMWH in this setting. MATERIALS AND METHODS: Anti-Xa, tissue factor pathway inhibitor (TFPI), thrombin anti-thrombin complex (TAT) and endogenous thrombin potential (ETP) were measured in twenty healthy women who received 4,500 IU tinzaparin 6 hours post CS (CS1), twenty women who received 4,500 IU tinzaparin at 10-12 hours post delivery (CS2) and twenty women post spontaneous vaginal delivery (SVD). RESULTS: Prior to initiation of LMWH, TAT levels at 6 hours post delivery were significantly higher in the CS1 and CS2 groups than the SVD group (P<0.002); TAT levels were significantly reduced up to 24 hours post LMWH treatment despite declining anti-Xa levels (P<0.001). In CS1, peak thrombin and ETP were significantly reduced following LMWH prophylaxis (P<0.0001; P<0.002) and reverted to pre-delivery levels 10 hours post LMWH. TFPI levels mirror anti-Xa levels during the 24 hours following LMWH treatment in CS1 group with peak levels coinciding with peak anti-Xa levels 4 hours post injection. CONCLUSION: In women post caesarean section, anti-Xa levels do not reflect the full anticoagulant effects of LMWH. In-vivo thrombin production (TAT) is effectively reduced even when anti-Xa levels are negligible. LMWH thromboprophylaxis in this healthy cohort of patients appears to have a sustained effect in reducing excess thrombin production post elective caesarean section.