vte pregnancy oct 2011
TRANSCRIPT
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VTE Pregnancy
Kami M. Dixon, MD
October 2011
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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
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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
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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
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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
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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%)
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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)
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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)
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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)
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Pregnancy & Delivery Risk Factors
Factor OR (95% CI)Preeclampsia & GHTN 0.9 (0.7-1.0)Preterm labor 0.9 (0.7-9.5)
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VTE RISK FACTOR #2
ACOG #2: Thrombophilia (inherited & acquired)
– 20-50% ♀ with VTE peripartum
Thrombophilia OR: 51.8 (38.7-69.2)
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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
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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
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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
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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
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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
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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
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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
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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
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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…”
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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
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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
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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
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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.
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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
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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
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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
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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
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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
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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
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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!