Vte pregnancy oct 2011

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Vte pregnancy oct 2011

  1. 1. VTE Pregnancy Kami M. Dixon, MD October 2011
  2. 2. References <ul><li>Inherited Thrombophilias in Pregnancy </li></ul><ul><li>ACOG practice bulletin NUMBER 124, September 2011 </li></ul><ul><li>Thromboembolism in Pregnancy </li></ul><ul><li>ACOG practice bulletin NUMBER 123, September 2011 </li></ul><ul><li>Venous Thromboembolism, Thrombophilia, Antithrombotic Therapy, and Pregnancy*American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) </li></ul><ul><li>Chest 2008;133;844S-886S </li></ul><ul><li>Venous thromboembolism during pregnancy and the postpartum period: Incidence, risk factors, and mortality </li></ul><ul><li>AJOG 2006;194:5,1311-5 </li></ul><ul><li>Antithrombotic therapy and pregnancy: consensus report and recommendations for prevention and treatment of venous thromboembolism and adverse pregnancy outcomes. </li></ul><ul><li>Am J Obstet Gynecol 2007;197:457.e1-457.e21 </li></ul><ul><li>Venous Thromboembolic Disease and Pregnancy. </li></ul><ul><li>N Engl J Med 2008;359:2025-33. </li></ul><ul><li>VTE Treatment & Prevention Regimens June 2011 </li></ul><ul><li>Douglas Montgomery, MD </li></ul><ul><li>Executive Summary: Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy. </li></ul><ul><li>Regional Anesthesia and Pain Medicine 2010;35,1:102-105 </li></ul>
  3. 3. Thromboembolic Events in Pregnancy <ul><li>4-5 Fold increased risk vs. age controlled non-pregnant counterparts </li></ul><ul><ul><li>Risk present in 1st trimester increases with HIGHEST RISK 1 st WEEK POSTPARTUM </li></ul></ul><ul><li>Absolute risk 2/1000 pregnancies </li></ul><ul><li>80% are venous </li></ul><ul><ul><li>~80% are DVT </li></ul></ul><ul><ul><li>~20% are PE </li></ul></ul><ul><li>DVT + PE =1.1 deaths /100,000 deliveries </li></ul><ul><ul><li>LEADING CAUSE MATERNAL MORBIDITY IN US </li></ul></ul><ul><ul><li>9% of maternal deaths in US </li></ul></ul><ul><li>50% are Antepartum, 50% Postpartum </li></ul>
  4. 4. Changes in Pregnancy <ul><li>ANATOMICAL: </li></ul><ul><ul><li>Decreased venous outflow </li></ul></ul><ul><ul><li>Compression of IVC and pelvic veins by enlarging uterus </li></ul></ul><ul><ul><li>Decreased mobility </li></ul></ul><ul><li>PHYSIOLOGICAL: </li></ul><ul><ul><li>Thrombogenic State </li></ul></ul><ul><ul><ul><li>Procoagulants: </li></ul></ul></ul><ul><ul><ul><ul><li>↑ Fibrinogen, VII, VIII, X, vWF, PAI-1, PAI-2 </li></ul></ul></ul></ul><ul><ul><ul><ul><li>↔ II, V, IX </li></ul></ul></ul></ul><ul><ul><ul><li>Anticoagulants: </li></ul></ul></ul><ul><ul><ul><ul><li>↓ Free Protein S </li></ul></ul></ul></ul><ul><ul><ul><ul><li>↔ Protein C and ATIII </li></ul></ul></ul></ul>PAI: Plasminogen activator inhibitor; ATII: Antithrombin III
  5. 5. ACOG PB# 123: Risk Factors <ul><li>#1: Personal history of VTE RR 3.5 (95% CI 1.6 – 7.8) </li></ul><ul><ul><li>15-25% are recurrent </li></ul></ul><ul><li>#2: Thrombophilia (inherited & acquired) </li></ul><ul><ul><li>20-50% ♀ with VTE peripartum </li></ul></ul><ul><li>James AH, Jamison MG, Brancazio LR, Myers ER. AJOG 2006 May;194(5):1311-5 </li></ul>
  6. 6. American Journal of Obstetrics and Gynecology - Volume 194, Issue 5 (May 2006) <ul><li>Table I  . Frequency of venous thromboembolic events by type and timing in gestation </li></ul><ul><ul><li> DVT PE Both Total (%) </li></ul></ul>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%)
  7. 7. RISK FACTORS <ul><li>Factor OR (95% CI) </li></ul><ul><li>Thrombophilia 51.8 (38.7-69.2) </li></ul><ul><li>History of thrombosis 24.8 (17.1-36.0) </li></ul><ul><li>APS 15.8 (10.9-22.8) </li></ul><ul><li>Lupus 8.7 (5.8-13.0) </li></ul><ul><li>Sickle cell disease 6.7 (4.4-10.1) </li></ul><ul><li>Heart disease 7.1 (6.2-8.3) </li></ul><ul><li>American Journal of Obstetrics and Gynecology - Volume 194, Issue 5 (May 2006) </li></ul>
  8. 8. RISK FACTORS <ul><li>Factor OR (95% CI) </li></ul><ul><li>Obesity (BMI >30) 4.4 (3.4-5.7) </li></ul><ul><li>Diabetes 2.0 (1.4-2.7) </li></ul><ul><li>Hypertension 1.8 (1.4-2.3) </li></ul><ul><li>Smoking 1.7 (1.4-2.1) </li></ul><ul><li>Age </li></ul><ul><li>35-39 y 1.4 (1.2-1.8) </li></ul><ul><li>≥ 40 y 1.7 (1.3-2.3) </li></ul><ul><li>Black Race 1.4 (1.2-1.6) </li></ul>
  9. 9. RISK FACTORS <ul><li>Factor OR (95% CI) </li></ul><ul><li>Transfusion 7.6 (6.2-9.4) </li></ul><ul><li>Disorders of fluid, electrolyte, </li></ul><ul><li>& acid-base balance 4.9 (4.1-5.9) </li></ul><ul><li>Postpartum infection 4.1 (2.9-5.7) </li></ul><ul><li>Anemia 2.6 (2.2-2.9) </li></ul><ul><li>Hyperemesis 2.5 (2.0-3.2) </li></ul><ul><li>Antepartum hemorrhage 2.3 (1.8-2.8) </li></ul><ul><li>Cesarean vs vaginal delivery 2.1 (1.8-2.4) </li></ul><ul><li>Postpartum hemorrhage 1.3 (1.1-1.6) </li></ul><ul><li>Multiple gestation 1.6 (1.2-2.1) </li></ul>
  10. 10. Pregnancy & Delivery Risk Factors <ul><li>Factor OR (95% CI) </li></ul><ul><li>Preeclampsia & GHTN 0.9 (0.7-1.0) </li></ul><ul><li>Preterm labor 0.9 (0.7-9.5) </li></ul>
  11. 11. VTE RISK FACTOR #2 <ul><li>ACOG #2: Thrombophilia (inherited & acquired) </li></ul><ul><ul><li>20-50% ♀ with VTE peripartum </li></ul></ul><ul><li>Thrombophilia OR: 51.8 (38.7-69.2) </li></ul>
  12. 12. THE UGLY ACOG PB # 124, September 2011 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 Heteroz 0.01 4.7 >20 1 - 3
  13. 13. THE BAD ACOG PB # 124, September 2011 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
  14. 14. THE NOT SO GOOD ACOG PB # 124, September 2011 Not Good Prevalence in the general population % VTE RISK per Pregnancy (No History) % VTE RISK per Pregnancy (Prev VTE) % Percentage of ALL VTE % MTHFR C677T MTHFR A1298C 10 – 16% Euro 4 – 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 2 nd Tri, or <24% in 3rd 0.03 – 0.13 0.1 0-22 3
  15. 15. PRIOR VTE, NO WORKUP or TEST FOR INHERITED IF HAVEV A FIRST DEG RELATIVE WITH HR THROMBOPHILIA OR VTE < 50 YO WITHOUT RISK FACTORS <ul><li>ANTIPHOSPHOLIPID ANTIBODIES (2% with VTE will have APA, 5-12% Risk developing VTE preg/pp) </li></ul><ul><ul><li>Lupus anticoagulant tests </li></ul></ul><ul><ul><ul><li>dilute Russell viper venom time (dRVVT) </li></ul></ul></ul><ul><ul><li>Anticardiolipin antibody ELISA </li></ul></ul><ul><ul><ul><li>IgG and/or IgM aCL moderate to high (>40 units GPL or MPL) </li></ul></ul></ul><ul><ul><li>Anti-ß2 glycoprotein-I ELISA </li></ul></ul><ul><ul><ul><li>B2-GP-I IgG or IgM >99 th %TILE </li></ul></ul></ul><ul><li>INHERITED THROMBOPHILIAS </li></ul><ul><li>Antithrombin III Gene Mutation </li></ul><ul><li>Factor V Leiden Gene Mutation </li></ul><ul><li>Prothrombin G20210A </li></ul><ul><li>MTHFR gene / Fasting homocystine levels, PAI-1 gene, Protein Z deficiency: NOT RECOMMENDED SEPTEMBER 2011 </li></ul>
  16. 16. How to TEST ACOG PB # 124, September 2011 Thrombophilia 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 Deficiency free antigen <55% (non-preg) or <30% in 2 nd Tri, or <24% in 3rd YES NO NO
  17. 17. WHO: PREVIOUS VTE & Prevention ANTEPARTUM TX POSTPARTUM TX LOW RISK Temporary RF NO Thrombophilia Surveillance WITHOUT anticoagulation 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 Idiopathic Obesity Pregnancy or estrogen Related APA (+/- 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
  18. 18. WHO: PREVIOUS VTE & Prevention PP treatment should be greater or equal to antepartum treatment ACOG supports therapy using either LMWH or UFH ANTEPARTUM TX POSTPARTUM TX ELEVATED RISK 2+ VTE Thrombophilia 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+ VTE Thrombophilia or no thrombophilia ON LONG TERM THERAPY Mechanical heart valve Therapeutic Dose Resume long-term anticoagulation therapy
  19. 19. WHO: NO VTE BUT OTHER RF PP treatment should be greater or equal to antepartum treatment ACOG supports therapy using either LMWH or UFH ANTEPARTUM TX POSTPARTUM TX Low Risk Low-risk thrombophilia without previous VTE FVLHet, 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-1 st degree relative, obesity, immobility etc; surveillance ok w acog) Moderate Risk High-risk thrombophilia NO h/o VTE ATIII, Dbl heteroz PTGM/FVL, FVL homoz, PTGM homoz, or persistent APL abs Prophylactic Lovenox Prophylactic 6 weeks Lovenox
  20. 20. What to Use and Why? <ul><li>Heparin Compounds </li></ul>ACOG PB# 124: “Given the risk and benefit ratio of unfractionated heparin, LMWH generally is the preferred agent for prophylaxis in pregnancy…” Cross 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
  21. 21. WHAT ANTENATAL dosing? <ul><li>Antenatal clinical surveillance </li></ul><ul><li>Prophylaxis LMWH 40mg SQ/24 hrs </li></ul><ul><ul><ul><li>Lovenox AntiXa 0.2-0.4 </li></ul></ul></ul><ul><li>Intermediate LMWH 40mg SQ/12 hrs </li></ul><ul><li>Lovenox AntiXa 0.4-0.6 </li></ul><ul><li>Adjusted dose LMWH 1mg/Kg/12hrs </li></ul><ul><li>Lovenox AntiXa 0.5-1.0 </li></ul><ul><li>Draw Anti-Xa levels 4 hours after dose </li></ul>
  22. 22. IN CASE YOU ARE STUCK WITH HEPARIN <ul><li>Antenatal clinical surveillance </li></ul><ul><li>Prophylaxis UFH 1 st tri : 5000-7500 Heparin units sq q 12 hrs </li></ul><ul><li>2nd tri : 7500-10000 </li></ul><ul><li>units sq q 12 hrs </li></ul><ul><li>3 rd tri : 10000 units sq q 12 hrs </li></ul><ul><li>Therapeutic UFH 10000 units q 12 hr increase to target aPTT of 1.5-2.5, 6 hours after injection </li></ul>
  23. 23. CONSIDER HIT <ul><li>Acute systemic “allergic reaction” fever, chills, hypertension, tachycardia, chest pain, dyspnea </li></ul><ul><li>Bovine>Porcine>LMWH </li></ul><ul><li>Post op>Medical>Obstetric </li></ul><ul><li>Check platelet count @ initiation of therapy and weekly for 3 weeks </li></ul><ul><li>Day 5 – 7 platelets begin decline < 150K </li></ul><ul><li>Day 10 – 14 decrease >50% from baseline </li></ul>
  24. 24. Postpartum Anticoagulation <ul><li>Prophylactic LMWH/UFH (if stuck) for 6 weeks </li></ul><ul><li>OR YOU MUST “BRIDGE” </li></ul><ul><li>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. </li></ul>
  25. 25. DONT FORGET… <ul><li>Highest Risk for VTE is 1 st WEEK POSTPARTUM </li></ul><ul><li>Low Risk Thrombophilia & NSVD : </li></ul><ul><li>1-6 weeks prophyl (Lovenox 40 mg qd) </li></ul><ul><li>Low Risk Thrombophilia & C/S : </li></ul><ul><li>6 weeks Lovenox 40 mg bid </li></ul><ul><li>More than 2 risk factors w/o Thrombophilia: 6 weeks postpartum Lovenox 40 mg daily </li></ul>
  26. 26. ACUTE VTE IN PREGNANCY <ul><li>Lovenox 1-1.2 mg /Kg q 12 hrs in hospital 3-7 days </li></ul><ul><li>After 3 rd dose check AntiXa levels </li></ul><ul><li>Peak AntiXa 4 hrs after sq ( 0.5-1.0) </li></ul><ul><li>Trough AntiXa for PE or large proximal DVT 1 hr before sq ( >/= 0.5 ) </li></ul><ul><li>Consider temporary Vena-Cava filter for patients @high risk for PE </li></ul>
  27. 27. PE OR PROXIMAL DVT WITHIN 4 WEEKS FROM DELIVERY <ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>Total length of anticoagulation should be 6 months , with at least 6 weeks of PP anticoagulation </li></ul>
  28. 28. But I want an Epidural…. <ul><li>MAINTAIN patients on Lovenox even after 36 weeks UNLESS at risk for PTD </li></ul><ul><li>D/C Full dose Lovenox at least 24 hours prior to procedure </li></ul><ul><li>Start Heparin 5000 units BID and take last dose > 1 hour prior to procedure </li></ul><ul><li>Eg Monday 8 am C/S: </li></ul>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
  29. 29. Dr. Can I have an Epidural? 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 2010 Thanks Dr. LaValle 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
  30. 30. UNIVERSAL Post C/S VTE Prevention <ul><li>All women recommended to use graduated elastic compression stockings. </li></ul><ul><li>SCD here @ Riverside before ambulation </li></ul><ul><li>(place and have working prior to and during placement of intrathecal medication) </li></ul><ul><li>PLUS </li></ul><ul><li>Consider Postoperative Lovenox 40 Q day for at least 7 days but up to 6 weeks if 2 additional risk factors present </li></ul>
  31. 31. SOME of the Risk Factors <ul><li>Age >35 yr </li></ul><ul><li>Obesity (BMI >30) </li></ul><ul><li>Parity >3 </li></ul><ul><li>Smoker </li></ul><ul><li>Gross varicose veins </li></ul><ul><li>Current infection </li></ul><ul><li>Preeclampsia </li></ul><ul><li>Immobility for >4 days before operation </li></ul><ul><li>Multiple gestation </li></ul><ul><li>Emergency cesarean section during labor or difficult prolonged surgery </li></ul><ul><li>C-Hyst </li></ul><ul><li>Go back to the AJOG Slide for OR/Risks! </li></ul>

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