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Vte pregnancy oct 2011
 

Vte pregnancy oct 2011

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  • James AH, Jamison MG, Brancazio LR, Myers ER. AJOG 2006 May;194(5):1311-5
  • The Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality for the years 2000 to 2001 was queried for all pregnancy-related discharges with a diagnosis of venous thromboembolism. 9,058,162 pregnancy admissions and 73,834 postpartum admissions. There were 3375 arterial thromboembolic events (2850 strokes and 525 myocardial infarctions) in addition to the 14,335 venous thromboembolic events. VTE were 4x more likely than arterial events.
  • During the period from 2000 to 2001, there were 9,058,162 pregnancy admissions and 73,834 postpartum admissions. Among the pregnancy admissions, there were 8,330,927 deliveries. Of these, 6,400,956 (77%) were vaginal and 1,929,971 (23%) were cesarean. There were 3375 arterial thromboembolic events (2850 strokes and 525 myocardial infarctions) in addition to the 14,335 venous thromboembolic events. Therefore, venous thromboembolic events were 4 times more common than arterial events.
  • ACOG PB # 124, September 2011
  • ACOG PB # 124, September 2011
  • ACOG PB # 124, September 2011
  • A personal history of venous thromboembolism that was associated with a nonrecurrent risk factor (eg, fractures, surgery, and prolonged immobilization). The recurrence risk among untreated pregnant women with such a history and a thrombophilia was 16% (odds ratio, 6.5; 95% confidence interval, 0.8-56.3) (53). A first-degree relative (eg, parent or sibling) with a history of high-risk thrombophilia or venous thromboembolism before age 50 years in the absence of other risk factors inasmuch as affected women should receive prophylaxis
  • ACOG PB # 124, September 2011

Vte pregnancy oct 2011 Vte pregnancy oct 2011 Presentation Transcript

  • VTE Pregnancy Kami M. Dixon, MD October 2011
  • References
    • Inherited Thrombophilias in Pregnancy
    • ACOG practice bulletin NUMBER 124, September 2011
    • Thromboembolism in Pregnancy
    • ACOG 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 2011
    • Douglas 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 1 st 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 FACTORS
    • Factor 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 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
  • 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
  • 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
  • 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 >99 th %TILE
    • INHERITED THROMBOPHILIAS
    • Antithrombin 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 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
  • 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
  • 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
  • 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
  • What to Use and Why?
    • Heparin Compounds
    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
  • WHAT ANTENATAL dosing?
    • Antenatal clinical surveillance
    • Prophylaxis LMWH 40mg SQ/24 hrs
        • Lovenox AntiXa 0.2-0.4
    • Intermediate LMWH 40mg SQ/12 hrs
    • Lovenox AntiXa 0.4-0.6
    • Adjusted dose LMWH 1mg/Kg/12hrs
    • Lovenox AntiXa 0.5-1.0
    • Draw Anti-Xa levels 4 hours after dose
  • IN CASE YOU ARE STUCK WITH HEPARIN
    • Antenatal clinical surveillance
    • Prophylaxis UFH 1 st tri : 5000-7500 Heparin units sq q 12 hrs
    • 2nd tri : 7500-10000
    • units sq q 12 hrs
    • 3 rd tri : 10000 units sq q 12 hrs
    • 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 1 st 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? 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
  • UNIVERSAL Post 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-Hyst
    • Go back to the AJOG Slide for OR/Risks!