Inherited Thrombophilias and Anticoagulation in Pregnancy
/Check out PB 196 and PB 197 for the primary reading on this topic!
Remember way back when, when we talked about physiologic changes of pregnancy (Part I and Part II)? Recall that pregnant women are 4-5x more likely than non-pregnant women to experience VTE, owing in part to factors we can trace back to Virchow’s Triad: hypercoagulability, venous stasis, and endothelial injury. In pregnancy we have hypercoagulability: increased clotting potential, decreased anticoagulant activity, and decreased fibrinolysis And we certainly have venous stasis, particularly in the lower extremities due to compression of the IVC by the uterus. Persons with inherited thrombophilias are at even higher risk of VTE owing to these factors.
Inherited Thrombophilas
There are lots of different types of inherited thrombophilias:
Factor V Leiden:
The most common mutation is factor V leiden heterozygosity, and is responsible for about 40% of all VTEs during pregnancy.
By itself, it doesn’t really put you at that much of an increased risk for VTE (only about 5-12/1000 deliveries), but if you have a personal history of VTE as well, then risk goes up to about 10%.
Prothrombin Gene
Heterozygote is next most common mutation; like factor V Leiden, if you are a homozygote, you’re at higher risk of VTE than heterozygote.
Antithrombin gene deficiency
Unommon (only 0.02% prevalence), but it is highly thrombotic
In non pregnant people, the risk of VTE is 25x normal.
More severe deficiencies is associated with increased VTE risk; so, if you have a personal history of VTE, and you have a severe antithrombin deficiency (<60% activity), your risk of VTE in pregnancy could be as high as 40%.
Testing for Inherited Thrombophilias
Testing is generally considered in two scenarios: either a patient who has a history of VTE herself, or the patient has a family member with a known high risk inherited thrombophilia. Screening is generally not recommended for women who have experienced fetal loss or various adverse pregnancy outcomes, outside of those meant for antiphospholipid syndrome testing.
ACOG PB 196
Basis for Anticoagulation in Inherited Thrombophilias
We can divide these mutations in to high and low risk thrombophilias:
High risk = Factor V Leiden homozygosity, prothrombin gene homozygosity, antithrombin deficiency, or factor V leiden + prothrombin gene heterozygosity (meaning one mutation of each gene)
Low risk = Factor V Leiden heterozygosity, prothrombin gene heterozygosity, protein C or protein S deficiency, and antiphospholipid antibody
It is important to realize that according to ACOG, there is insufficient evidence that anticoagulation use will prevent adverse pregnancy outcomes in patients with inherited thrombophilias, such as preeclampsia, FGR, or placental abruption. The indication for anticoagulation is for the purpose of preventing VTE.
Choice of Anticoagulant Agent
Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) - neither cross the placenta and are safe, and are first line choices.
Warfarin - we KNOW that there are harmful fetal effects, especially in first trimester, so don’t use it as first line. The only case that this is used in pregnancy is for women with mechanical heart valves because there is a higher risk of VTE even with LMWH or UFH.
Usually will use LMWH or UFH from weeks 6- 13 in pregnancy and switch back to warfarin later.
Oral direct thrombin inhibitors should be avoided in pregnancy and postpartum because insufficient data on safety.
When and How Much Anticoagulation?
In the Practice Bulletins, there is a large table of conditions with recommendation for anticoagulation. We’ve broken it down a bit for you, as the progression actually is logical once it’s written out.
For inherited thrombophilias, you’ll need to remember the high risk and low risk groupings:
(c) CREOGS Over Coffee, 2020
The other group that should be considered for anticoagulation are patients who may have had a VTE in the past, but do not have evidence of inherited thrombophilia:
(c) CREOGS Over Coffee, 2020
Delivery Considerations on Anticoagulation
Peri-delivery, the use of anticoagulation can be challenging if patients desire or require neuraxial analgesia. PB 196 reviews recommendations for holding anticoagulation before delivery. In general:
Prophylactic doses of UFH or LMWH should be held 12 hours prior to anticipated delivery/admission.
Therapeutic doses of UFH or LMWH should be held for 24 hours prior to anticipated delivery/admission.
UFH may be resumed 1 hour after catheter removal or neuraxial blockade, whether at prophylactic or therapeutic doses.
LMWH may be resumed:
12 hours after neuraxial blockade and 4 hours after catheter removal, whichever is longer, at prophylactic doses.
24 hours after neuraxial blockade and 4 hours after catheter removal, whichever is longer, at therapeutic doses.