Maternal VTE Flashcards
Extinsince and Intrinsic Pathway
Which side of DVT is more common in pregnancy?
L»R
What is the increase of risk for VTE in CD vs SVD
CD has a 2-5 fold risk, compared to SVD
What is the rates of PE after a DVT and the associated mortality in patients who are and are NOT treated
- PE occurs in 25% of untreated DVT with mortality of 15%
- PE occurs in 5% of treated DVT with mortality rate of 1%
How to the factors change in pregnancy
Pregnancy associated with 20-200% increase in levels of fibrinogen and factors 2, 7, 8, 10, and 12
o Reduced protein S levels
o Impaired fibrinolysis (increase in PAI 1 and 2)
o Reduced TAFI levels (thrombin activatable fibrinolysis inhibitor)
o Increased resistance to activated Protein C
Thrombophilias (inherited) and the tests
- Inherited: genetic conditions that increase the risk of thromboembolic disease
o Most common: FVL, PT G20210A mutation, MTHFR (most common cause of hyperhomocysteinemia)
o Rare: anti-thrombin deficiency, Protein C and Protein S deficiency - Acquired: antiphospholipid antibodies
o ACL antibodies, LA, beta 2 glycoprotein 1 - Up to 50% with DVT during pregnancy have a thrombophilia
What are the inherited thrombophilias
FVL:
- Mutation in nucleotide position 1691 of FVL gene’s 10th exon
- Substitution of glutamine for arginine at position 506 in FV polypeptide
- Impairs activated PC and PS complex inactivation of factor Va
- Autosomal dominant inheritance
- Carrier rate: 6% Caucasians (1.7% Hispanics, 0.8% AA)
PT 20210A
- Mutation in promoter of the prothrombin gene
- Increased 150-200% circulating levels of prothrombin
- AD inheritance
- Homozygosity confers risk equivalent to FVL homozygosity
Antithrombin Def
- Most thrombogenic; 70-90% lifetime risk of VTE; results from numerous point mutations, deletions, insertions
- AD inheritance
- Risk of VTE in pregnancy is up to 60% and 33% in puerperium
Protein C/S
- Results from numerous mutations
- AD inheritance
- Protein S decreases due to estrogen induced decreases in total protein S and increases in complement 4b binding protein (which beinds protein S)
Perinatal implications:
- Examination of uteroplacental vessels from such pregnancies displays:
o Increased fibrin deposition, thrombosis, hypoxia-associated endothelial/trophoblast change
- Screening:
o For APLAS: RPL < 10 weeks;
o For inherited thrombophilias:
With late fetal loss? (no role with IUGR, PEC, abruption)
- Who to treat?
o APLA and RPL (lack of clear consensus); prophylactic LMWH with ASA
What is anticoagulation dosing for LMWH, Coumadin and how to monitor? What are the risks
- Prophylactic: 40mg QD (can be adjusted with weight)
- Intermediate: 40 SQ BID
- Therapeuric: weight adjusted or full treatment = 1mg/kg q12 hours
- Increased metabolic clearance in pregnancy
Treatment: - LMWH improved efficacy and safety compared to UFH
- Monitor anti-Xa levels 4-6 hours after dose; measure q2-3 days until therapeutic (antiXa 0.6-1.0IU/mL)
- Can switch to prophylactic dose after 4 months (anti Xa 0.2-0.5IU/mL)
- D/C 24 hours prior to delivery
o if high risk patient, IV UFH until 4-6 hours prior to delivery - restart LMWH 6 hours after SVD, 12 hours after CD if no bleeding
- Coumadin: INR 2.0 (concurrent heparin due to initial inhibitory effect on protein C)
- Duration of 3-6 months
- Thrombolytic therapy should be reserved for life-threatening acute PE
- HIT (type II, immune mediated)
o 5-10 days after heparin started; monitory platelets for 3 weeks (LMWH lower risk of HIT); skin necrosis
o Osteoporosis – need Ca++ supplementation
How do you anticoagulate for mechanical heart vavles
Mechanical heart valves:
- Therapeutic LMWH BID (monitor anti Xa)
- Therapeutic UFH to achieve aPTT 2x normal or anti-Xa 0.35-0.7 units/mL (or 0.5-1.0 wider range) , for mitral mechanical Xa should be 1.0-1.2
- Therapeutic UFH or LMWH until 13 weeks, then Vitamin K antagonist until close to delivery, then resume UFH or LMHW
- INR: 2.5 mechanical, 3.0 for mechanical mitral valve
