VTE and Pregnancy

Huma Khan MDMCH fellow

August 3rd, 2011

objectivesEpidemiology of VTE in pregnancy

to be able to identify the causes of vte

To understand and identify the different diagnostic tools

Understand prenatal management

To be aware of the different pharmacotherapies

Identify risk factors for post natal management

Case 1AK is a 24 yr old obese AA G2P0010, who comes for an initial prenatal visit. She is very sure of her lmp which places her at about 8wk 3d GA. She states this a planned pregnancy and that she has been taking pnv’s.

Pmhx: DVT in her left leg 4yrs ago,

Pshx: none

Meds: pnv

Case 1

Fhx: DM, cHTN

Shx: married, employed, no smoking, no etoh, hx of thc in college with occasional addition of other substances which she denies using once she graduated

Obhx: SAB 2 yrs ago at 6 wks different partner

epidemiology

VTE( DVT & PE) occurs in 5 -12 per 10,000 pregnanciesPostpartum 3 -7 per 10,000 deliveries7-10 fold increase in antepartum15- 35 fold in post partumPE leading cause of death in developing countries current deaths from PE: 1.1 -1.5 per 100,000 deliveries

anatomy

virchow’s triadVenous stasis

hypercoagulability

Vascular damage

pathophysiology Virchow's triad

Venous stasis:

1st trimester to 36wk Progesterone induced venodilation Right iliac artery over left iliac vein Gravid uterus Immobilization

pathophysiology Virchow's triad

Vascular damage: Compression at delivery Assisted or operative delivery

Hypercoagulability: procoagulant factors anticoagulant activity fibrinolytic activity = more thrombin generation + less clot dissolution

Other risk factors black raceHeart diseaseSickle cell diseaseDiabetesLupus

SmokingMultiple pregnancyAmaObesity ( BMI > 30)C-section( especially emergent or after long labor)

Thrombophilic disorders disorder of hemostasis predisposing to thrombotic event

Inherited Factor V Leiden Prothrombin G20210A

Acquired Antiphospholipid antibody syndrome Lupus anticoagulant

Thrombophilic disorders cause 50 % of VTE in pregnancy Occur only in 0.1% of pregnancies

Universal screening not cost effective

Screening affected in pregnancy protein S levels fall in 2nd trimester Massive thrombus & nephrotic syndrome decrease

antithrombin levels Liver disease decrease protein C & S levels

Screening should be done after pregnancy and when no longer taking anticoagulants

Thrombophilic disorders

Complications

Early and late losses IUGR Placental abruption

Presentation of vteDifficult to differentiate from pregnancy sx’s

DVT: Unilateral leg pain and swelling, especially left leg ≥ 2 cm calf circumference difference 1st trimester Homan’s sign

Diagnosis tree

Dresand et al. aafp,77:1709-16, 2008

Diagnostic tools for DTVVCUS ( venous compression ultrasonagraphy)

Sensitivity : 89 - 97% Specificity : 94 - 99% Less accurate for isolated calf and iliac vein thrombosis

D-Dimer Levels increase during pregnancy Usually positive and hence of little use Negative test with low clinical probability has a NPV of 99.5 %

when highly sensitive assay used. positive test sensitivity is 100% & specificity is 60% hence

additional testing is needed

MRI and ct can be done in high probability pts

presentationDifficult to differentiate from pregnancy sx’s

PE: Dyspnea Chest pain Unexplained tachycardia

PE diagnosis tree

Dresand et al. aafp,77:1709-16, 2008

Diagnostic tools for PEv/q scan

PPV when combined with high clinical pretest is 96% Only 56% with low clinical pretest Radiation dose : 0.003 -.077 mGY

ct In one study PPV’s in

Lobar: 97% segmental:68% Subsegmental: 25%

False positive rates: 30% , detected incorrectly in segmental/ subsegmental

Radiation dose: 0.02 -0.06 gy

Case 1AK is a 24 yr old obese AA G2P0010, who comes for an initial prenatal visit. She is very sure of her lmp which places her at about 8wk 3d GA. She states this a planned pregnancy and that she has been taking pnv’s. Pmhx: DVT in her left leg 4yrs ago, Pshx: noneFhx: DM, cHTNMeds: pnvShx: married, employed, no smoking, no etoh, hx of thc in college with occasional addition of other substances which she denies using once she graduatedObhx: SAB 2 yrs ago at 6 wks different partner

Case 1 : extra stuffOn further examination you find

BP: 140/85BMI of 32A few varicose veins on her right calfOn US she is 10wk with twin gestation

Case 1 managementIdentify the risk factors

prenatal management

What do do during labor and delivery

Identify risk factor for post partum management

Rcog Green- top guideline 37, 2009

management prophylaxis in pregnancy

Marik & Plante nejm,359:2025-33, 2008

Therapeutic dosing in pregnancy

Vena caval filters

Marik & Plante nejm,359:2025-33, 2008

Which heparin???LMWH

More predictable dose responseMore dose independent mechanisms of clearanceLong plasma half lifeOnce or twice daily dosingNo lab visitsLower risk of bleeding, HIT & fracturesNot easily reversed

UFHDose dependent responseClearance is dependent on renal / liver functionHalf life is short and dose dependentMultiple dosingLabs for PLTSHigh risk of bleeding and HITEasily reversed by protamine sulphate

Why not Warfarin ?!Crosses placentaIncreases miscarriage, stillbirth, embryopathy (midface hypoplasia,stippled epiphyses) if exposed in 1st trimesterIn 2nd and 3rd trimester causes CNS abnormalities and hemorrhage

It is compatible with breast feeding

During labor and deliverySwitch to UFH several wks before

stop all anticoagulation with onset of labor

If planned IOL or c-section then stop 24 hrs prior to

Management varies based on prophylaxis /treatment doses

Anticoagulation & Anesthesia neuroaxial anesthesia contra-indicated in spontaneous labor with full anticoagulation

Spinal anesthesia placed 12 hrs after prophylactic dose of LMWH 24 hrs after therapeutic dose of LMWH 6 hrs after UFH dose and confirmed normal activated partial-

thromboplastin time

General preferred if emergent c-section Anticipate larger blood loss

reversal of UFH and LMWH

Bourjeily et al. lancet 375:500-12, 2010

After birthPost partum thromboprophylaxis not routinely indicatedASA not usedThromboprophylaxis for 6-12 wksWarfarin can be used

Post OPIncidence of PE higher by a factor of 2.5 to 20Incidence of fatal PE by a factor of 10

Thromboprophylaxis highly effective in reducing the high incidence

Duration is 3-7 days for intermediate riskUp to 6 wks for high risk.

Rcog Green- top guideline 37, 2009

Thank you