Anticoagulation in pregnancy

Overview
Anticoagulation in pregnancy is an issue that occurs in women who are at risk for clot formation and subsequently become pregnant. While the general consensus among physicians is that the safety of the mother supersedes the safety of the developing fetus, changes in the anticoagulation regimen during pregnancy can be performed to minimize the risks to the developing fetus while maintaining therapeutic levels of anticoagulation in the mother.

The main issue with anticoagulation in pregnancy is that warfarin, the most commonly used anticoagulant in chronic administration, is known to have teratogenic effects on the fetus if administered in early pregnancy.

Indications
In general, the indications for anticoagulation during pregnancy are the same as the general population. This includes (but is not limited to) a recent history of deep venous thrombosis or pulmonary embolism, a metallic prosthetic heart valve, and atrial fibrillation in the setting of structural heart disease.

In addition to these indications, anticoagulation may be of benefit in individuals with SLE and a history of previous spontaneous abortions, individuals who have a history of deep venous thrombosis (DVT) or pulmonary embolism (PE) associated with a previous pregnancy, and even with individuals with a history of coagulation factor deficiencies and DVT not associated with a previous pregnancy.

In a normal pregnancy, there is progressive increase in plasma thrombin-antithrombin III levels and decrease in protein S levels. This may contribute to the increased incidence of thrombosis in certain individuals during pregnancy.

Strategies
There is no consensus opinion on the correct anticoagulation regimen during pregnancy. Treatment is tailored to the particular individual based on their risk of complications. Because of the teratogenic effects associated with warfarin and other vitamin K inhibiting agents during the first trimester of pregnancy, women who are on chronic anticoagulation may be given the option of conversion to either heparin or low molecular weight heparin (LMWH) prior to a planned conception. Delaying the conversion from warfarin to another agent until pregnancy is confirmed is also an acceptable policy.

While unfractionated heparin is typically given in an intravenous formulation, this is inconvenient for the prolonged period of administration required in pregnancy. In these cases, subcutaneous heparin at doses of 10,000 to 20,000 IU every 12 hours may be given, titrating to an aPTT of 1.5 times the control when measured 6 hours after dosing.

Whether warfarin can be re-initiated after the twelfth week of pregnancy is unclear. In a recent retrospective analysis, it was suggested that resumption of warfarin after the first trimester is completed is associated with increased risk of loss of the fetus. However, this analysis included only individuals who were anticoagulated for mechanical heart valves, which generally require high levels of anticoagulation.

Mechanical heart valves
The optimal anticoagulation regimen for mechanical heart valves in pregnancy is particularly unclear. It is clear from prior studies that anticoagulation with subcutaneous heparin in this setting is associated with a high incidence of thrombosis of the valve and death. Similar issues are likely associated with the use of enoxaparin (a low molecular weight heparin) in these high-risk individuals.