Obgyno Wino Podcast Episode 32 - Thromboembolism in Pregnancy
"Whereas the beautiful is limited, the sublime is limitless, so that the mind in the presence of the sublime, attempting to imagine what it cannot, has pain in the failure but pleasure in contemplating the immensity of the attempt." - Immanuel Kant
PB#196 - Published July 2018
VTE risk is 4-5x higher in pregnancy due to hypercoagulability, venous stasis, and decreased venous outflow
C-section is an independent risk factor for VTE postpartum, especially in the setting of infection or hemorrhage
LMWH has significant advantages over unfractionated heparin, including longer half-life, more predictable therapeutic response, less risk of heparin-induced thrombocytopenia, and less risk of bone mineral density loss
If a patient using unfractionated heparin needs urgent surgery, protamine sulfite can reverse the effects. This is not so for LMWH. Switch to heparin close to delivery.
The only patients in which anticoagulation is recommended throughout pregnancy are those at highest risk of VTE in pregnancy: inherited thrombophilias, personal history of VTE, or patients with acute VTE in pregnancy. Data is limited otherwise.
Before you get started, you may want to review the intrinsic and extrinsic clotting pathways that I outlined in Episode 28 on Thrombophilias in Pregnancy...
VTE is more commonly seen in pregnancy. Why?
- 11-132/ 100,000 is annual incidence in general population
- pregnant women at 4-5x increased risk of VTE
- most important risk factor for VTE in pregnancy is personal history
- 3-4 fold greater risk of recurrence in pregnancy
- risk is also increased in presence of thrombophilias
- 75-80% of VTE in pregnancy is secondary to DVT
- 50/50 in pregnancy versus postpartum, though greatest risk is in the first few days postpartum
- hypercoagulability (increased clotting factors secondary to high estrogen), increased venous stasis (secondary to uterine compression of inferior vena cava), decreased venous outflow (due to increased vascular compliance and decreased mobility)
Fun fact: Venous stasis is more pronounced in the left lower extremity compared to the right, which is thought to be due to compression of the left iliac vein by the right iliac artery. DVT thus more likely in left lower extremity compared to right.
- c-section is an independent risk factor postpartum (3 in 1000 cases, a fourfold increased risk over vaginal delivery), particularly in the event of hemorrhage or infection or other medical factors such as obesity, hypertension, autoimmune disease, heart disease, sickle cell disease, multiple gestation, and preeclampsia
- despite the overall increased risk of VTE in pregnancy and postpartum, there isn't sufficient evidence to recommend thromboprophylaxis in all women
Anticoagulation medications in pregnancy
- if she require anticoagulation before pregnancy, continue it through pregnancy (risks versus benefits)
- select patients may require it de novo (e.g. new DVT)
- neither LMWH nor unfractionated heparin cross placenta
- increased blood volume and GFR (thus increased clearance of the drugs from the blood) mean that higher doses or more frequent dosing may be required in pregnancy to therapeutic serum levels
- dose-adjusted regimens will be dependent on either maternal BMI (LMWH) or aPTT (unractionated heparin)
- LMWH has a few advantages over unfractionated heparin: fewer bleeding episodes, more predictable therapeutic response, lower risk of heparin-induced thrombocytopenia, a longer half-life, less likelihood of skin reaction at injection site, and less bone mineral density loss (though both have low risk to bones at prophylactic doses)
- primary disadvantage is the longer half-life around time of delivery and lack of quick reversal in a pinch (remember protamine sulfate can be used to reverse unfractionated heparin)
- vitamin K antagonist, meaning clotting factors II, VII, IX, X, and proteins S/C are affected (I reviewed clotting at length in episode 28)
- crosses placenta
- exposure of the fetus between 6-12 weeks can lead to significant embryopathy (low birth weight, abnormal bone and connective tissue development, deafness, neurodevelopmental issues, among other things like fetal hemorrhage)
- switch patients to LWMH if they are taking warfarin prior to pregnancy, UNLESS they have mechanical heart valves, in which case the risk of thrombus may outweigh risk to fetus (risks versus benefits)
- generally best to avoid Warfarin around time of delivery if possible, as this is the time at which risk of fetal hemorrhage is highest
- if delivery must happen while patient taking Warfarin, c-section may be required and the newborn may require Vitamin K injections and FFP
Oral direct thrombin inhibitors and anti-Xa inhibitor
- oral direct thrombin inhibitors (dabigatran) and anti-Xa inhibitors (rivaroxaban, apixaban) are generally avoided in pregnancy due to lack of safety data
- crosses placenta, and it's detectible in breast milk
- best to transition patients to LMWH if taking any of these agents prior to pregnancy
How to assess for VTE risk?
- no universally accepted scoring system
- RCOG's 2015 green top guidelines are a great example, though
How is DVT diagnosed in pregnancy?
- same as outside of pregnancy, silly
- 80% of patients w/ DVT will present with pain and swelling in affected extremity
- look for one calf >2cm in circumference compared to the unaffected calf
- compression ultrasound of the proximal veins is diagnostic
- DVT generally affect distal veins, but it's more common to find DVTs in proximal veins like ileofemoral and iliac in pregnant compared to nonpregnant women
- if compression ultrasound is negative or equivocal and the entire leg is swollen and painful, this may be a false negative for an iliac DVT; follow-up w/ MRI or repeat sono in 3 days and again in 7 days should be considered
- D-dimers aren't helpful as they are physiologically elevated in pregnancy
How is pulmonary embolism (PE) diagnosed in pregnancy?
- again, same as outside pregnancy
- benefits of ventilation-perfusion scanning (VQ scan) or CT angiogram (CTA) outweigh the risks of the relatively low radiation exposure to the fetus
- overall radiation exposure with VQ scan is lower than CTA, so start with CXR or VQ scan
- follow-up with VQ scan if CXR normal but suspicion is high
- follow-up with CTA if CXR is abnormal
- Cochrane doesn't think there's a significant difference of predictive accuracy between VQ scan and CTA in pregnancy
PEARL: You don't want to miss a PE, so just order the damn study!
What if your patient has a history of VTE prior to pregnancy?
- screen for antiphospholipid antibodies and inherited thrombophilias
- why? your anticoagulation dosage may change as these conditions are associated with even higher risks than regular ol' pregnant women
How much anticoagulant do I give? and to whom?
- any pregnant woman with an acute VTE should be started on anticoagulation at adjusted dosing
- continue it for 3-6 months (total therapy); it's safe to decrease to intermediate or prophylactic dosing for the remained of pregnancy and at least 6 weeks postpartum
- other candidates: inherited thrombophilias, presence of mechanical heart valves, or personal history of VTE (also adjusted dosing)
- no consensus to guide anticoagulation prescribing in other patient populations
- unfractionated heparin should be administered at least twice daily whereas LMWH can generally be administered once (data suggests no difference in benefit between once or twice daily dosing)
What if my patient can't tolerate heparin products? (e.g. allergy or history of HIT)
- Risk of HIT is <0.1%, so checking platelets once early after initiation (when the risk is highest) is sufficient
- Fondaparinux could be a reasonable alternative, but it can cross placenta (risks versus benefits)
- if patient has a true allergy, best to consult hematology...cause that's weird
How do I ensure my anticoagulation is therapeutic?
- prophylactic dosing doesn't require monitoring (though may be reasonable for extremely obese patients)
- LMWH: keep anti-Xa levels between 0.6 and 1.0 units/mL (check 4-6 hrs after injection)
- unfractionated heparin: keep aPTT between 1.5 and 2.5x control (check 6 hrs after injection)
Patient is on anticoagulation, and they present for delivery. What do I do?
- if patient is on LMWH, convert them to unfractionated heparin a few days before delivery
- this is meant to prevent epidural or spinal hematomas in the event of regional anesthesia
What about patients undergoing c-section?
- as mentioned before, fourfold increased risk (but absolute risk is still low)
- sequential compression devices for all
- if on anticoagulation for any reason in pregnancy, best to continue it until 6 weeks postpartum
- anticoagulation for 6 weeks postpartum may also be prudent for patients at higher risk of VTE even if not on anticoagulation in pregnancy (c-section + hemorrhage + obesity + immobility + infection = disaster)
- highest risk patients could benefit from placement of inferior vena cava (IVC) filter placement prior to discharge
Patient is now delivered. How soon after delivery do I restart anticoagulation?
- 4-6 hrs after vaginal delivery
- 6-12 hrs after c-section
- if epidural catheter is left in place, hold anticoagulation until 4 hrs after catheter removal, or 24 hrs after neuraxial blockade
Do they have to inject that stuff for 6 weeks postpartum?!
- No. You could also bridge to Warfarin (safe in breastfeeding) OR start a direct antithrombin inhibitor (may not be safe in breastfeeding)
- how do I bridge to Warfarin again? check daily INR while giving patient both Warfarin (start with 5 mg daily for two days straight) and heparin product until the INR stabilizes between 2.0 and 3.0 for 2 consecutive days, then you can discontinue the heparin/LMWH