Vte pregnancy oct 2011

VTE Pregnancy

Kami M. Dixon, MD

October 2011

References• Inherited Thrombophilias in Pregnancy ACOG practice bulletin NUMBER 124, September 2011

• Thromboembolism in PregnancyACOG practice bulletin NUMBER 123, September 2011

• Venous Thromboembolism, Thrombophilia, Antithrombotic Therapy, and Pregnancy*American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

Chest 2008;133;844S-886S • Venous thromboembolism during pregnancy and the postpartum period: Incidence, risk factors, and

mortality

AJOG 2006;194:5,1311-5

• Antithrombotic therapy and pregnancy: consensus report and recommendations for prevention and treatment of venous thromboembolism and adverse pregnancy outcomes.

Am J Obstet Gynecol 2007;197:457.e1-457.e21

• Venous Thromboembolic Disease and Pregnancy. N Engl J Med 2008;359:2025-33.

• VTE Treatment & Prevention Regimens June 2011Douglas Montgomery, MD

• Executive Summary: Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy.Regional Anesthesia and Pain Medicine 2010;35,1:102-105

Thromboembolic Events in Pregnancy

• 4-5 Fold increased risk vs. age controlled non-pregnant counterparts– Risk present in 1st trimester increases with

HIGHEST RISK 1st WEEK POSTPARTUM• Absolute risk 2/1000 pregnancies• 80% are venous

– ~80% are DVT– ~20% are PE

• DVT + PE =1.1 deaths /100,000 deliveries– LEADING CAUSE MATERNAL MORBIDITY IN US– 9% of maternal deaths in US

• 50% are Antepartum, 50% Postpartum

Changes in Pregnancy

• ANATOMICAL:– Decreased venous outflow– Compression of IVC and pelvic veins by enlarging

uterus– Decreased mobility

• PHYSIOLOGICAL:– Thrombogenic State

• Procoagulants: – ↑ Fibrinogen, VII, VIII, X, vWF, PAI-1, PAI-2– ↔ II, V, IX

• Anticoagulants:– ↓ Free Protein S– ↔ Protein C and ATIII

PAI: Plasminogen activator inhibitor; ATII: Antithrombin III

ACOG PB# 123: Risk Factors

• #1: Personal history of VTE RR 3.5 (95% CI 1.6 – 7.8)– 15-25% are recurrent

• #2: Thrombophilia (inherited & acquired)– 20-50% ♀ with VTE peripartum

James AH, Jamison MG, Brancazio LR, Myers ER. AJOG 2006 May;194(5):1311-5

American Journal of Obstetrics and Gynecology - Volume 194, Issue 5 (May 2006)

Table I . Frequency of venous thromboembolic events by type and timing in gestation

DVT PE Both Total (%)

DVT PE BOTH TOTAL %

Pregnancy admissions n = 9,058162 5929 1033 215 7177 (50%)

Postpartum admissions n = 73,834 5397 1466 295 7158 (50%)

Total (%) 11326 (79%)

2499 (17%)

510 (4%)

14335 (100%)

RISK FACTORS

Factor OR (95% CI)

Thrombophilia 51.8 (38.7-69.2)

History of thrombosis 24.8 (17.1-36.0)

APS 15.8 (10.9-22.8)

Lupus 8.7 (5.8-13.0)

Sickle cell disease 6.7 (4.4-10.1)

Heart disease 7.1 (6.2-8.3)American Journal of Obstetrics and Gynecology - Volume 194, Issue 5 (May 2006)

RISK FACTORSFactor OR (95% CI)Obesity (BMI >30) 4.4 (3.4-5.7)Diabetes 2.0 (1.4-2.7)Hypertension 1.8 (1.4-2.3)Smoking 1.7 (1.4-2.1)Age

35-39 y 1.4 (1.2-1.8)≥40 y 1.7 (1.3-2.3)

Black Race 1.4 (1.2-1.6)

RISK FACTORS

Factor OR (95% CI)Transfusion 7.6 (6.2-9.4)Disorders of fluid, electrolyte, & acid-base balance 4.9 (4.1-5.9)Postpartum infection 4.1 (2.9-5.7)Anemia 2.6 (2.2-2.9)Hyperemesis 2.5 (2.0-3.2)Antepartum hemorrhage 2.3 (1.8-2.8)

Cesarean vs vaginal delivery 2.1 (1.8-2.4)Postpartum hemorrhage 1.3 (1.1-1.6)Multiple gestation 1.6 (1.2-2.1)

Pregnancy & Delivery Risk Factors

Factor OR (95% CI)Preeclampsia & GHTN 0.9 (0.7-1.0)Preterm labor 0.9 (0.7-9.5)

VTE RISK FACTOR #2

ACOG #2: Thrombophilia (inherited & acquired)

– 20-50% ♀ with VTE peripartum

Thrombophilia OR: 51.8 (38.7-69.2)

THE UGLY

THE UGLY

Prevalence in the general population

%

VTE RISK per Pregnancy (No

History) %

VTE RISK per Pregnancy (Prev

VTE) %

Percentage of ALL VTE %

ATIII Deficiency <60% 0.02 3 - 7 40 1

FVL Homozygous <1 1.5 17 2

PTGM G20210A Homozygous <1 2.8 >17 0.5

PTGM G20210A + FVL Compound

Heteroz0.01 4.7 >20 1 - 3

ACOG PB # 124, September 2011

THE BAD

THE BAD

Prevalence in the general population

%

VTE RISK per Pregnancy (No

History) %

VTE RISK per Pregnancy (Prev

VTE) %

Percentage of ALL VTE %

FVL Heterozygous 1 – 15 <0.3 10 40

PTGM G20210A Heterozygous 2 – 5 <0.5 >10 17

Protein C Activity <60% 0.2 – 0.4 0.1 – 0.8 4 – 17 14

Protein S free antigen <55% 0.03 – 0.13 0.1 0-22 3

ACOG PB # 124, September 2011

THE NOT SO GOOD

Not Good

Prevalence in the general population

%

VTE RISK per Pregnancy (No

History) %

VTE RISK per Pregnancy (Prev

VTE) %

Percentage of ALL VTE %

MTHFR C677TMTHFR A1298C

10 – 16% Euro4 – 6% Euro No increased risk Weak N/A

PTGM G20210A Heterozygous 2 – 5 <0.5 >10 17

Protein C Activity <50% 0.2 – 0.4 0.1 – 0.8 4 – 17 14

Protein S free antigen <55% (non-preg) or <30% in 2nd Tri, or <24% in 3rd

0.03 – 0.13 0.1 0-22 3

ACOG PB # 124, September 2011

PRIOR VTE, NO WORKUP or

TEST FOR INHERITED IF HAVEV A FIRST DEG RELATIVE WITH HR THROMBOPHILIA OR VTE < 50 YO WITHOUT RISK FACTORS

• ANTIPHOSPHOLIPID ANTIBODIES (2% with VTE will have APA, 5-12% Risk developing VTE preg/pp)– Lupus anticoagulant tests

• dilute Russell viper venom time (dRVVT)

– Anticardiolipin antibody ELISA • IgG and/or IgM aCL moderate to high (>40 units GPL or MPL)

– Anti-ß2 glycoprotein-I ELISA• B2-GP-I IgG or IgM >99th %TILE

• INHERITED THROMBOPHILIASAntithrombin III Gene Mutation

Factor V Leiden Gene Mutation

Prothrombin G20210A

MTHFR gene / Fasting homocystine levels, PAI-1 gene, Protein Z deficiency: NOT RECOMMENDED SEPTEMBER 2011

How to TESTThrombophilia Testing Method Reliable During

Pregnancy?Reliable with Acute

Thrombosis?Reliable with

Anticoagulation?

Antithrombin III Deficiency

Antithrombin activity <60% YES NO NO

Factor V Leiden Mutation

Activated Protein C resistance assay

If Abnormal: DNA Analysis

YES

YES

YES

YES

NO

YES

PTGM G20210A Heterozygous DNA ANALYSIS YES YES YES

Protein C Deficiency Activity <60% YES NO NO

Protein S Deficiencyfree antigen <55%

(non-preg) or <30% in 2nd Tri, or <24% in 3rd

YES NO NO

ACOG PB # 124, September 2011

WHO: PREVIOUS VTE & PreventionANTEPARTUM TX POSTPARTUM TX

LOW RISK Temporary RFNO Thrombophilia

Surveillance WITHOUTanticoagulation

Prophylactic Lovenox up to 6 weeks

MODERATE RISK

LRThrombophilia w single VTE-not on long term tx: FVLHet, PTGHet, Prot C/S

Prophylactic or Intermediate Dose Lovenox(or surveillance)

Prophylactic Lovenox 6 weeks post partum

MODERATE RISK

IdiopathicObesityPregnancy or estrogen RelatedAPA (+/- ASA)

Prophylactic or Intermediate Dose Lovenox

Prophylactic Lovenox 6 weeks post partum

ELEVATED RISK HR Thrombophilia w single VTE-not on long term tx: ATIII, Dbl heteroz PTGM/FVL, FVL homoz, PTGM homoz, or persistent APL abs

Intermediate or Adjusted dose (Therapeutic) Lovenox for 6 weeks

Intermediate or Adjusted dose (Therapeutic) Lovenox for 6 weeks

WHO: PREVIOUS VTE & Prevention

ANTEPARTUM TX POSTPARTUM TX

ELEVATED RISK 2+ VTEThrombophilia or no thrombophilia NOT ON LONG TERM THERAPY

Intermediate or Adjusted dose (Therapeutic) Lovenox (ACOG-prophylactic or therapeutic)

Intermediate or Therapeutic Lovenox for 6 weeks

HIGHEST RISK 2+ VTEThrombophilia or no thrombophilia ON LONG TERM THERAPY

Mechanical heart valve

Therapeutic Dose Resume long-term anticoagulation therapy

PP treatment should be greater or equal to antepartum treatmentACOG supports therapy using either LMWH or UFH

WHO: NO VTE BUT OTHER RFANTEPARTUM TX POSTPARTUM TX

Low Risk Low-risk thrombophilia without previous VTEFVLHet, PTGHet, Prot C/S def

APA w/o VTE

Prophylactic Lovenox(ACOG-OR surveillance)

Prophylactic or surveillance + ASA

Prophylactic 6 weeks Lovenox (ACOG if additional RF-1st degree relative, obesity, immobility etc; surveillance ok w acog)

Moderate Risk High-risk thrombophilia NO h/o VTEATIII, Dbl heteroz PTGM/FVL, FVL homoz, PTGM homoz, or persistent APL abs

Prophylactic Lovenox

Prophylactic 6 weeks Lovenox

PP treatment should be greater or equal to antepartum treatmentACOG supports therapy using either LMWH or UFH

What to Use and Why?

Heparin CompoundsCross Placenta

Bleeding episodes

therapeutic response

HIT Bone density

T ½

LMWH No Fewer More predictable

Less Not with prophylactic dose

Longer

UFH No More Less predictable

More Not with prophylactic dose

Shorter

ACOG PB# 124: “Given the risk and benefit ratio of unfractionated heparin, LMWH generally is the preferred agent for prophylaxis in pregnancy…”

WHAT ANTENATAL dosing?

1. Antenatal clinical surveillance

2. Prophylaxis LMWH 40mg SQ/24 hrsLovenox AntiXa

0.2-0.4

3. Intermediate LMWH 40mg SQ/12 hrsLovenox AntiXa 0.4-0.6

4. Adjusted dose LMWH 1mg/Kg/12hrsLovenox AntiXa 0.5-

1.0

Draw Anti-Xa levels 4 hours after dose

IN CASE YOU ARE STUCK WITH HEPARIN

1. Antenatal clinical surveillance

2. Prophylaxis UFH 1st tri: 5000-7500 Heparin units sq q 12 hrs

2nd tri: 7500-10000

units sq q 12 hrs3rd tri: 10000

units sq q 12 hrs

3. Therapeutic UFH 10000 units q 12 hr increase to target aPTT of 1.5-2.5, 6 hours after injection

CONSIDER HIT

• Acute systemic “allergic reaction” fever, chills, hypertension, tachycardia, chest pain, dyspnea

• Bovine>Porcine>LMWH• Post op>Medical>Obstetric• Check platelet count @ initiation of

therapy and weekly for 3 weeks• Day 5 – 7 platelets begin decline < 150K• Day 10 – 14 decrease >50% from baseline

Postpartum Anticoagulation

Prophylactic LMWH/UFH (if stuck) for 6 weeks

OR YOU MUST “BRIDGE”

Vitamin K antagonist for 6 weeks with target INR of 2.0-3.0 with initial LMWH/UFH overlap for 2 days at INR 2.0 or more.

DONT FORGET…Highest Risk for VTE is 1st WEEK

POSTPARTUM

Low Risk Thrombophilia & NSVD:

1-6 weeks prophyl (Lovenox 40 mg qd)

Low Risk Thrombophilia & C/S:

6 weeks Lovenox 40 mg bid

More than 2 risk factors w/o Thrombophilia: 6 weeks postpartum Lovenox 40 mg daily

ACUTE VTE IN PREGNANCY

• Lovenox 1-1.2 mg /Kg q 12 hrs in hospital 3-7 days

• After 3 rd dose check AntiXa levels

Peak AntiXa 4 hrs after sq ( 0.5-1.0)

Trough AntiXa for PE or large proximal DVT 1 hr before sq ( >/= 0.5 )

• Consider temporary Vena-Cava filter for patients @high risk for PE

PE OR PROXIMAL DVT WITHIN 4 WEEKS FROM DELIVERY

• Patients with an acute PE or proximal DVT that developed within a month prior to delivery should have their Sq Lovenox switched to IV UFH, which can be discontinued 4 to 6 hours prior to delivery. An epidural catheter may be placed when the aPTT has returned to normal.

• For patients with reduced cardiopulmonary reserve and a recent PE ; A temporary inferior vena cava (IVC) filter can be inserted or delivery can proceed despite with anticoagulation.

• Total length of anticoagulation should be 6 months, with at least 6 weeks of PP anticoagulation

But I want an Epidural….

• MAINTAIN patients on Lovenox even after 36 weeks UNLESS at risk for PTD

• D/C Full dose Lovenox at least 24 hours prior to procedure

• Start Heparin 5000 units BID and take last dose > 1 hour prior to procedure

Eg Monday 8 am C/S:Saturday d/c Lovenox AM Start Heparin 5000 bid

qhs

Sunday Heparin 5k am Heparin 5k qhs

Monday Heparin 5 k at 6 am Draw preop PTT, CBC

Dr. Can I have an Epidural?

Warfarin INR <1.5 (stop 4-5 days prior to procedure)

Heparin full dose IV aPTT <40

Lovenox full dose Wait 24 hours

Lovenox prophylactic dose Wait 12 hours

Heparin prophylactic dose >5000 sq aPTT <40

Heparin prophylactic dose 5000 bid/tid Wait 1 hour

ASA/NSAIDS NOW

Resume therapy 4-6 hours after NSVD or 6-12 hours after C/S. ASRA DO NOT RESUME LMWH SOONER THAN 2 hours after removal of catheter

Regional Anesthesia and Pain Medicine: Vol 35, No1, Jan-Feb 2010Thanks Dr. LaValle

UNIVERSALPost C/S VTE Prevention

• All women recommended to use graduated elastic compression stockings.

• SCD here @ Riverside before ambulation

(place and have working prior to and during placement of intrathecal medication)

PLUS• Consider Postoperative Lovenox 40 Q day

for at least 7 days but up to 6 weeks if 2 additional risk factors present

SOME of the Risk Factors

• Age >35 yr• Obesity (BMI >30)• Parity >3• Smoker• Gross varicose veins• Current infection• Preeclampsia• Immobility for >4 days before operation• Multiple gestation• Emergency cesarean section during labor or difficult

prolonged surgery• C-HystGo back to the AJOG Slide for OR/Risks!