Thrombophilias in Pregnancy Workup

Updated: Jun 14, 2018
  • Author: Edward H Springel, MD, FACOG; Chief Editor: Ronald M Ramus, MD  more...
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Approach Considerations

ACOG recommends screening a patient for thrombophilia only if test results are likely to alter management. Screening should be performed when the presence of a thrombophilia may alter the intensity or duration of anticoagulation therapy. Screening is unnecessary when treatment is indicated for other reasons. [19]

ACOG recommends that screening for thrombophilia may be considered (1) in patients with a personal history of VTE that occurred in the setting of a transient nonrecurrent risk factor (eg, fractures, surgery, prolonged immobility) that was not estrogen- or pregnancy-related [19] and (2) in patients with a first-degree relative with a prior VTE that occurred before age 50 years or with a prior diagnosis of high-risk thrombophilia.

In the absence of thrombophilia, pregnant patients with prior VTE not associated with estrogen and/or pregnancy may undergo surveillance and postpartum anticoagulation therapy. [15] In patients with a low-risk thrombophilia who have a history of VTE, management includes surveillance or prophylactic or intermediate-dose heparin therapy antepartum. Postpartum anticoagulation is recommended.

In patients with prior VTE and a high-risk thrombophilia, prophylactic or low- or intermediate-dose heparin therapy is recommended antepartum and postpartum. [15, 19]

It is controversial whether thrombophilia is associated with adverse pregnancy events other than VTE. Few obstetric indications for screening exist. Indications for screening for antiphospholipid antibody syndrome are discussed above.

There is currently insufficient evidence to suggest that thromboprophylaxis in patients with thrombophilia prevents recurrence of adverse pregnancy events such as recurrent pregnancy loss, IUFD, abruption, or preeclampsia. [15, 19]

Confounding variables in testing

Ideally, evaluation for thrombophilia should occur when the patient is not pregnant, does not have an acute thrombotic event, and is not on anticoagulation therapy. Protein S deficiency testing is less reliable in pregnancy, as levels decrease with increasing gestational age. [55] Suggested threshold reference values for diagnosis are discussed under Protein S deficiency. [35] Protein C, protein S, and antithrombin levels are not reliable in the setting of acute thrombosis or anticoagulation therapy. [19]

First-generation activated protein C resistance assay for factor V Leiden is unreliable during pregnancy. [56] ACOG has recommended screening for factor V Leiden in pregnancy using the second-generation activated protein resistance assay, followed by DNA analysis for the Leiden mutation if the results are abnormal. [19] Alternatively, proceeding directly to genetic testing for factor V Leiden mutation may be considered. Activated protein C resistance assays are also unreliable during anticoagulation, so genetic testing is used in this setting. [19]

The test panel is as follows:

  • Factor V Leiden: Second-generation activated protein C resistance assay is reliable in pregnancy; if results are abnormal, evaluate for genotype for factor V Leiden mutation; if the patient is on anticoagulation therapy, consider evaluation of factor V Leiden mutation via genotype testing

  • Prothrombin G20210A mutation DNA analysis

  • Protein C functional activity level

  • Protein S free, total, and functional levels

  • Antithrombin-heparin cofactor assay

  • Antiphospholipid antibody syndrome (abnormalities must be present at least twice and at least 12 weeks apart; anticardiolipin antibodies and anti-beta2 glycoprotein I antibodies must be present in medium to high titers, corresponding to >99th percentile for the general population, or greater than 40 IgG phospholipid [GPL] or IgM phospholipid [MPL] units): (1) Lupus anticoagulant, (2) anticardiolipin antibodies (IgG and IgM), and (3) anti-beta2 glycoprotein antibodies (IgG and IgM)

Diagnosis of antiphospholipid antibody syndrome: please see above. Diagnosis of this syndrome relies on both clinical and laboratory criteria.