What is the management of elevated D-dimer (D-dimer) levels in pregnancy?

From the Guidelines

Elevated D-dimer levels in pregnancy should be managed with careful clinical assessment rather than relying solely on D-dimer values, as they naturally increase throughout normal pregnancy and are less specific for diagnosing venous thromboembolism (VTE) in pregnant women. When evaluating a pregnant woman with suspected VTE and elevated D-dimer, clinicians should proceed with appropriate imaging studies such as compression ultrasonography for suspected deep vein thrombosis or CT pulmonary angiography or ventilation-perfusion scanning for suspected pulmonary embolism 1.

Key Considerations

• D-dimer levels increase progressively in pregnancy and peak in the third trimester, with levels of 0.11 to 0.40 μg/mL, 0.14 to 0.75 μg/mL, and 0.16 to 1.3 μg/mL in first, second, and third trimester, respectively 1.
• A level of 2 μg/mL can still be within the normal range for pregnant women, and the significance of mild to moderate D-dimer elevation in pregnancy remains unknown 1.
• Markedly elevated D-dimers several-fold above the upper range of normal for pregnancy should be considered as indicative of coagulopathy 1.

Management Approach

• If VTE is confirmed, therapeutic anticoagulation with low molecular weight heparin (LMWH) such as enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily) is the treatment of choice during pregnancy, as it does not cross the placenta.
• Treatment should continue throughout pregnancy and for at least 6 weeks postpartum, with a minimum total duration of 3 months.
• Regular monitoring of platelet counts is recommended during the first two weeks of therapy to detect heparin-induced thrombocytopenia.
• Warfarin is contraindicated during pregnancy due to teratogenic effects but may be used postpartum.

Diagnostic Approach

• D-dimer should not be used to exclude suspected PE in a pregnant woman, as it has a low specificity and may result in false negatives 1.
• Imaging studies such as compression ultrasonography, CT pulmonary angiography, or ventilation-perfusion scanning should be used to diagnose VTE in pregnant women.
• A chest X-ray (CXR) is recommended as the first radiation-associated procedure in pregnant women with suspected PE 1.

From the Research

Management of Elevated D-Dimer Levels in Pregnancy

The management of elevated D-dimer levels in pregnancy is a complex issue due to the physiological increase in D-dimer levels during pregnancy. Several studies have investigated this topic:

• A study published in 2018 2 found that D-dimer levels increase progressively and significantly throughout pregnancy, with 99% of pregnant women having D-dimer levels above the conventional cut-off point (500 µg/L) in the third trimester.
• Another study published in 2005 3 reported that D-dimer concentrations increase with each trimester, making it difficult to use the conventional cut-off point to rule out venous thromboembolism (VTE) in pregnant women.
• A study published in 2009 4 found that D-dimer levels are significantly higher in pregnant women than in non-pregnant women, and that the positive predictive value of D-dimer for ultrasonographically positive women is 7.4% when D-dimer is set at 3.2 microg/mL.
• A study published in 2012 5 reported that D-dimer concentrations are positively correlated with gestation in normal uncomplicated pregnancy, and that 10% of pregnant women had elevated D-dimer levels over 500 ng/mL, which may indicate an increased risk of thrombosis.
• A study published in 2010 6 found that using higher cut-points for D-dimer assays can improve specificity without compromising sensitivity for the diagnosis of deep vein thrombosis (DVT) in pregnancy.

Key Findings

Some key findings from these studies include:

• D-dimer levels increase progressively throughout pregnancy 2, 3, 4, 5.
• The conventional cut-off point for D-dimer may not be suitable for pregnant women 3, 6.
• Higher cut-points for D-dimer assays may be needed to improve specificity for the diagnosis of DVT in pregnancy 6.
• D-dimer levels may be useful in identifying pregnant women at increased risk of thrombosis 4, 5.

Implications for Management

The implications of these findings for the management of elevated D-dimer levels in pregnancy are:

• Pregnant women with elevated D-dimer levels should be closely monitored for signs and symptoms of VTE 4, 5.
• Higher cut-points for D-dimer assays may be used to improve specificity for the diagnosis of DVT in pregnancy 6.
• Further studies are needed to validate the use of D-dimer assays in pregnancy and to determine the optimal cut-points for different trimesters 2, 3, 6.