#196 Thromboembolism in Pregnancy Flashcards
What is the risk of thromboembolism in pregnant women compared to non pregnant (fold change)?
4-5 fold increase
What % of thromboembolic events in pregnancy are venous?
80%
What is the prevalence of thromboembolic events in pregnancy?
0.5-2 per 1,000 pregnant women
What % of all maternal deaths in US are caused by VTE?
9.3%
What % of VTE are due to PE during pregnancy?
20-25%
When during pregnancy/postpartum period is greatest risk for VTE?
Greatest within the weeks immediately after delivery
What is May-Thurner anatomy?
Compression of the left iliac vein by the right iliac artery, leading to increased venous stasis in the left leg
Is fibrinogen increased or decreased during pregnancy?
Increased
Is factor VII increased or decreased during pregnancy?
Increased
Is Factor VIII increased or decreased during pregnancy?
Increased
Is Factor X increased or decreased during pregnancy?
Increased
Is Von Willebrand factor increased or decreased during pregnancy?
Increased
Is Plasminogen activator inhibitor-1 increased or decreased during pregnancy?
Increased
Is Plasminogen activator inhibitor-2 increased or decreased during pregnancy?
Increased
Is Factor II increased or decreased during pregnancy?
No change
Is Factor V increased or decreased during pregnancy?
No change
Is Factor IX increased or decreased during pregnancy?
No change
Is free protein S increased or decreased during pregnancy?
Decreased
Is protein C increased or decreased during pregnancy?
No change
Is antithrombin increased or decreased during pregnancy?
No change
What is the most important individual risk factor for VTE in pregnancy?
Personal history of thrombosis
What % of all cases of VTE in pregnancy are recurrent events?
15-25%
What is the second most important individual risk factor for VTE in pregnancy?
Presence of thrombophilia. (first is personal hx)
What % of women with VTE in pregnancy have a thrombophilia?
20-50%
Does preeclampsia affect the risk of VTE?
Increases risk
Does heart disease affect the risk of VTE?
Increases risk
Does sickle cell disease affect the risk of VTE?
Increases risk
Does multiple gestation increase the risk of VTE?
Increases risk
Does autoimmune disease affect risk of VTE?
Increases risk
What is the incidence of VTE after cesarean delivery?
3 in 1000
What is the risk of VTE after cesarean compared with vaginal delivery (fold change)?
4 fold increase
Does heparin cross the placenta?
No
What is the % increase in maternal blood volume during pregnancy?
40-50%
How does pregnancy affect the use of heparin (due to changes of maternal physiology)?
Increased GFR leads to increased renal excretion. Increase in protein binding of heparin. Overall shorter half life and lower peak plasma concentrations; usually necessitating higher dose and increased frequency
What is the dosing of prophylactic enoxaparin?
40mg SC once daily
What is the dosing of prophylactic dalteparin?
5,000u SC once daily
What is the prophylactic dosing of Tinzaparin?
4,500u SC once daily
What is the prophylactic dosing of Nadroparin?
2,850u SC once daily
What is the intermediate-dose of enoxaparin?
40mg SC q12h
What is the intermediate-dose of dalteparin?
5,000u SC every 12h
What is the therapeutic dose of enoxaparin?
1mg/kg q12h
What is the therapeutic dose of dalteparin?
200u/kg once daily
What is the therapeutic dose of Tinzaparin?
175u/kg once daily
What is the therapeutic dosing of Dalteparin?
100u/kg every 12h
What is the target anti-Xa level for therapeutic anticoagulation?
0.6-1.0 unit/mL 4 hr after last injection for BID regimen; slightly higher doses may be needed for once daily regimen
What lab test can you check in someone receiving LMWH to assess if they are therapeutic?
Anti-Xa levels
What is the prophylactic dosing of unfractionated heparin per trimester?
First: 5-7.5k SC q12h
2nd: 7.5-10k SC q12h
3rd: 10k SC q12h, unless aPTT is elevated
What is the therapeutic dose of unfractionated heparin?
10k units or more SC q12h adjusted to target aPTT in therapeutic range (1.5-2.5x control) 6h after injection
What are the benefits of LMWH compared to UFH?
Fewer bleeding episodes, more predictable therapeutic response, lower risk of heparin-induced thrombocytopenia, longer half-life, less bone mineral density loss.
What is the mechanism of action of warfarin?
Vitamin K antagonist
During which weeks of gestation is warfarin exposure at highest risk of fetal harm?
6-12wks
In which patients would you consider continuing warfarin in pregnancy?
Patients with mechanical heart valves (high risk of thrombosis even with heparin and LMWH therapy)
How would you manage a woman with mechanical heart valve during pregnancy?
Multidisciplinary team. Consider adjusted-dose LMWH or UFH from 6 wk until 13 wk > warfarin until close to delivery when switch to LMWH or UFH.
What is the concern for women receiving warfarin near time of delivery, what should you consider?
Apart from maternal bleeding; risk for fetal hemorrhage. Cesarean delivery may be required and the neonate may require administration of vitamin K and FFP
What medication is an oral direct thrombin inhibitor?
Dabigatran
What type of medication is dabigatran?
Oral direct thrombin inhibitor
What are anti-Xa inhibitors?
Rivaroxaban, apixaban, edoxaban, betrixaban
Can oral direct thrombin inhibitors and anti-Xa inhibitors be used in pregnancy? Lactation?
Avoided in pregnancy and lactation d/t insufficient data on safety
What are the two most common initial symptoms of DVT and in what % of women with pregnancy-associated DVT do these present?
Pain and swelling in an extremity. In more than 80% of women.
A difference in calf circumference of what cm is suggestive of DVT in lower extremity?
2cm or more
What is the initial recommended diagnostic test for pregnant/postpartum woman with sign/symptoms suggestive of new onset DVT?
Compression ultrasonography of the proximal veins
In a non pregnant population, are DVTs typically proximal or distal?
Distal
In pregnant patients with DVT, what is the frequency of ileofemoral and iliac thromboses?
Ileofemoral (64%), iliac (17%)
What is next step if pregnant woman with signs/symptoms highly suggestive of DVT, but compression ultrasonography is negative?
Additional imaging with doppler ultrasonography of the iliac vein, venography, or MRI; alternatively, empiric anticoagulation may be a reasonable option
What lab is a useful screening tool to exclude DVT?
D-dimer level, not useful for pregnant women or postpartum
Is D-dimer recommended in pregnancy/postpartum in evaluation for DVT?
Not recommended as part of evaluation
Does a V/Q scan or helical CT for work up for PE during pregnancy expose the fetus to lower radiation?
Helical CT has a lower radiation exposure for fetus
Does a V/Q scan or helical CT for work up for PE have lower radiation exposure for mom (particularly the breast)?
VQ scan has lower radiation exposure for mom
What does the American Thoracic Society and the Society of Thoracic Radiology recommend for the evaluation of suspected PE in pregnancy?
Chest XRay as initial evaluation with progression to VQ scan if CXR normal, and CTA is CXR is abnormal.
How should you treat someone with acute VTE during pregnancy; for how long do you treat?
Full-dose anticoagulation for 3-6 months (dependent upon type of VTE), anticoagulation intensity can be decreased to intermediate or prophylactic dose for the remainder of the pregnancy and for at least 6wks postpartum
What is the risk of heparin-induced thrombocytopenia in the obstetric population?
Estimated at less than 0.1%
Do obstetric patients placed on heparin need to undergo platelet monitoring?
Most will not require platelet monitoring as risk is < 0.1%; only need to monitor if risk >1% (in absence of other risk factors do not need monitoring)
At what % risk of heparin-induced thrombocytopenia do you need to start platelet monitoring?
> 1%
In cases of severe cutaneous allergies or heparin-induced thrombocytopenia in pregnancy, what may be the preferred anticoagulant?
Fondaparinux
Do pregnant patients with newly diagnosed VTE need to be hospitalized?
May be indicated in cases of hemodynamic instability, large clots, or maternal comorbidities
In which pregnant patients with PE, should initial treatment be with IV unfractionated hepatin?
In situations in which delivery, surgery, or thrombolysis (indicated for life-threatening or limb-threatening thromboembolism)
Do weight-based anticoagulation (therapeutic) regimens need to be adjusted throughout pregnancy?
Evidence is not clear.
Do pregnant patients requiring prophylactic anticoagulation require monitoring (anti Xa levels) during treatment? Why or why not?
Not required, optimal antifactor Xa levels during LMWH ppx in pregnancy have not been determined
For women who are receiving prophylactic LMWH when should you discontinue in setting of scheduled IOL or CS?
12h before
For women who are receiving therapeutic LMWH when should you discontinue in setting of scheduled IOL or CS?
24h before
What is the reason for transitioning to unfractionated heparin closer to delivery?
Less to do with any risk of maternal bleeding at time of delivery, but rather the risk of an epidural or spinal hematoma with regional anesthesia
What can be used to reverse unfractionated heparin?
Protamine sulfate
What can be used to reverse LMWH?
Protamin sulfate, although less predictable than when reversing UFH
What is the risk of VTE with cesarean delivery compared o vaginal delivery (fold increase)? What is incidence of VTE after CS?
4 fold increase in VTE with cesarean section. VTE in 3 per 1,000 patients.
In healthy pregnancy woman without any additional VTE risk factors going for CS, what DVT ppx should be given?
Pneumatic compression devices before CS and early ambulation. Pneumatic compression devices in place until ambulatory
Can you place an IVC filter during pregnancy?
Yes, if high risk of recurrent VTE. Risks include filter migration and IVC perforation
When should you resume anticoagulation therapy postpartum?
No sooner than 4-6h after vaginal delivery or 6-12h after cesarean delivery
When can you initiate therapeutic anticoagulation with LMWH after neuroaxial blockade and after epidural catheter removal?
24h after neuroaxial blockade. 4 hours after catheter removal
Can you start someone on warfarin postpartum?
Yes, after heparin bridge; typically wait until 1-2 pp once postpartum bleeding has subsided
How do you do a heparin bridge to start warfarin?
Therapeutic LMWH or UFH until an INR of 2-3 is achieved for 2 consecutive days with warfarin started concurrently
What is the risk of starting warfarin without heparin bridge, why?
Paradoxical thrombosis and skin necrosis from the early antiprotein C effect
Is warfarin compatible with breastfeeding?
Yes