Maternal VTE

Question 1

Extinsince and Intrinsic Pathway

Answer 1

Question 2

Which side of DVT is more common in pregnancy?

Answer 2

L»R

Question 3

What is the increase of risk for VTE in CD vs SVD

Answer 3

CD has a 2-5 fold risk, compared to SVD

Question 4

What is the rates of PE after a DVT and the associated mortality in patients who are and are NOT treated

Answer 4

• PE occurs in 25% of untreated DVT with mortality of 15%
• PE occurs in 5% of treated DVT with mortality rate of 1%

Question 5

How to the factors change in pregnancy

Answer 5

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

Question 6

Thrombophilias (inherited) and the tests

Answer 6

• 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

Question 7

What are the inherited thrombophilias

Answer 7

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

Question 8

What is anticoagulation dosing for LMWH, Coumadin and how to monitor? What are the risks

Answer 8

• 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

Question 9

How do you anticoagulate for mechanical heart vavles

Answer 9

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