The APTT response of pregnant plasma to unfractionated heparin.

Pregnancy is associated with a physiological increase in coagulation factors and heparin binding proteins; both can affect the activated partial thromboplastin time (APTT) in response to unfractionated heparin (UFH) invalidating the use of a non-pregnant APTT therapeutic range. We compared the anticoagulant response of UFH added in vitro to the plasma of 13 pregnant (third trimester) and 15 nonpregnant women to determine whether the measured APTT and antifactor Xa activities are lower in pregnancy. Increasing concentrations of UFH were added to platelet-poor plasma from each subject and the APTT and anti-factor Xa activity were measured. The amount of UFH which was reversibly bound and neutralised by plasma heparin binding proteins was assessed by comparing the anti-factor Xa activity before and after addition of low affinity heparin (LAH). Fibrinogen, von Willebrand factor antigen (vWF Ag) and factor VIII levels, were also measured. The APTT response, assessed by the slope of the regression line of log APTT versus added heparin concentration, was attenuated in pregnant plasma (0.76 s/U/mL versus 1.2 s/U/mL, p = 0.005) and was highly correlated to increased non-specific plasma protein binding (47% versus 35% p <0.01) and increased fibrinogen (5.1 g/L versus 2.8 g/L, p < 0.01) and factor VIII activity (2.7 U/mL versus 1.2 U/mL, p <0.01). Thus, to achieve the same heparin level, pregnant women require higher daily doses of UFH than non-pregnant women. However, if UFH dose adjustments during the third trimester are based upon a non-pregnant APTT therapeutic range, systematic overdosing of pregnant women will result, possibly increasing the risk of bleeding and osteoporosis.

Antithrombotic therapy during pregnancy.

Antithrombotic therapy is required during pregnancy for the prevention and treatment of venous and arterial thromboembolism and for the prevention of pregnancy loss in women at risk. The choice of anticoagulant for venous thromboembolism during pregnancy is limited to unfractionated heparin or low molecular weight heparin because the use of warfarin is relatively contraindicated. Much of the information surrounding the pharmacokinetics and dosing of unfractionated heparin and low molecular weight heparin obtained from non-pregnant patients has been applied to pregnant women. Whether this is appropriate in the presence of significant physiological changes in pregnancy is unclear. Specific to pregnancy and unfractionated heparin use, activated partial prothrombin time may be unreliable. In addition, the appropriate dosing of low molecular weight heparin is uncertain. Because venous thromboembolism can cause significant maternal morbidity and mortality, these important issues surrounding appropriate drug dosing of anticoagulants should be addressed.