VTE Prophylaxis South Dakota Perinatal Association Conference Annie Siewert, MD, MS, FACOG South Dakota Perinatal Association Conference 9/21/2018

VTE and the Obstetrical Patient Objectives Describe Incidence of VTE in the United States Discuss risk stratification and assessment of VTE in obstetrical patients.  Discuss current recommendations for VTE prophylaxis in antepartum and postpartum patients.   VTE and the Obstetrical Patient

Maternal Mortality is on the Rise U.S Maternal Mortality Rate 1987: 7.2 deaths per 100,000 births 2011: 17.8 deaths per 100,000 births One of only 8 countries to have an increase in maternal mortality CDC: Pregnancy Mortality Surveillance System

VTE and Pregnancy: How big is this problem?

Causes of Maternal Mortality in the United States CDC: Pregnancy Mortality Surveillance System

VTE and Pregnancy: Epidemiology Pregnant women are 4-5X higher risk 0.5-2.0/1000 pregnant women 1.1 deaths per 100,000 deliveries WHO Systemic Review of maternal mortality reports VTE cause of 14.9% of deaths in developed countries One of leading causes of maternal death in U.S 9% of all maternal deaths in the U.S. ACOG Practice Bulletin #196.2018

VTE and Pregnancy: Epidemiology Pregnancy-Associated VTE 75-80% are caused by DVT 20-25% are caused by Pulmonary Embolism ACOG Practice Bulletin #196.2018

VTE and Pregnancy: Epidemiology Risk of VTE increased 72% between 1998-2009 Increasing BMI Increased c-section rates AMA Increased rate of medical co-morbidities ACOG Practice Bulletin #196.2018

VTE: Prevention Alliance for Innovation (AIM) on Maternal Health National alliance to promote consistent and safe maternity care Reduce maternal mortality by 1,000 and severe maternal morbidity by 100,000 instances over the course of four years, 2014 – 2018. Funded through the federal Maternal and Child Health Bureau.

VTE and Pregnancy: Recognition

Symptoms of VTE in Pregnancy Pregnancy causes the Perfect Storm for VTE Hypercoagulable state Venous Stasis Decreased venous outflow Compression of IVC and pelvic veins by uterus Decreased mobility ACOG Practice Bulletin 196. 2018

Symptoms of VTE in Pregnancy Two most common symptoms Pain Swelling Circumference difference of 2cm or more Homan’s sign is poor diagnostic tool Obstetrical population is unique More likely in LLE More likely proximal involving iliac and iliofemoral veins UpToDate: Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis. RCOG. April 2015

Timing of VTE in Pregnancy 50% occur in during pregnancy 50% occur in postpartum period UpToDate: Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis. RCOG. April 2015

Timing of VTE in Pregnancy Antepartum: 0.1-0.2% Equal distribution of VTE over each trimester Postpartum: 0.3-0.4% 2-5X higher risk Highest risk in the first 6 weeks postpartum Highest overall risk in first week TEG parameters abnormal at one week Risk of VTE after C-section similar over weeks 1, 2, and 3 Normalizes 12-13W postpartum UpToDate: Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis. RCOG. April 2015

VTE and Pregnancy: Where do we go from here?

Prevention of VTE United Kingdom and the Royal Collage of Obstetricians and Gynaecologists (RCOG) has developed robust comprehensive strategy for VTE prevention in the obstetric population Decreased death from VTE by almost half 2003-2005: 1.94 per 100,000 deliveries 2006-2008: 0.79 per 100,000 deliveries

Prevention of VTE Thromboprophylaxis is underutilized in the U.S Typically SCDs Ordered for only 25% of patients undergoing c-section Estimated that 75% of woman receive no prophylaxis following C-section

VTE: Prevention Lack of Use and Noncompliance with Mechanical Prophylaxis Systemic review of >2500 patients 25% were noncompliant with mechanical prophylaxis Observation study demonstrated noncompliance in 21% of patients after C-section Endorse Survey Evaluated prophylaxis rates in 17,084 major surgery patients 38% of patients at risk for VTE did not receive prophylaxis

Prevention VTE and Pregnancy Nationwide movement for the prevention of VTE focusing on: Establishing guidelines Risk identification National society recommendations ACOG ACCP Maternal Safety Bundles National Partnership for Maternal Safety VTE and Pregnancy

VTE and Pregnancy: Prevention “The single cause of death most amenable to reduction by systemic change in practice.” Clark, SL. Semin. Perinatol 2012; 36 (1):42-47

VTE and Pregnancy: Risk Assessment and Stratification

VTE and Pregnancy: Risk Factors Postpartum Cesarean Delivery Medical Comorbidities BMI>25 Preterm Delivery<36W Obstetric Hemorrhage Stillbirth AMA>35yo HTN Smoking Pre-eclampsia or Eclampsia Postpartum Infection Antepartum Multiple gestation Varicose Veins Inflammatory Bowel Disease UTI Diabetes Hospitalization>3 Days BMI>30 AMA>35yo UpToDate: Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis

VTE Risk Factors: What are the odds? Previous VTE Thrombophilia APA Syndrome SLE Heart Disease BMI>40 Cesarean Section Elective Cesarean Section Emergency Cesarean Section Blood Transfusion Postpartum Infection IUGR Antepartum Hemorrhage Smoking>10 cigs/day Multiple gestation Age>35 CHTN PreE Odds Ratio 24.8 51.8 15.8 8.7 7.1 4.0** 3.7** 2.3 3.6 7.6** 4.1** 1.7-2.2 1.6 1.4-1.7 1.87 0.9 VTE Risk Factors: What are the odds?

VTE: Risk Stratification Goal is to have an effective tool for risk assessment and use it for every patient Recommendations from National Societies ACOG ACCP RCOG

VTE Prevention: Cesarean Delivery SCD’s preoperatively and postpartum Pharmacologic prophylaxis based on risk factors Opt out strategy All patients undergoing C-section would receive pharmacologic prophylaxis unless there is a contraindication New York Presbyterian Hospital

VTE: Risk Stratification ACOG Previously recommended pharmacologic prophylaxis for small group of women Prior VTE Thrombophilias SCDs for all c-section patients No further recommendations ACOG Practice Bulletin #196.2018

“Current evidence is insufficient to recommend universal adoption of pharmacologic prophylaxis for VTE, and thromboprophylaxis should be individualized according to patient risk factors.” “…Other candidates for anticoagulation during pregnancy include women with a history of thrombosis or those who are at significant risk of VTE during pregnancy or the postpartum period.”

Pregnancy

The California Maternal Quality Care Collaborative is a multi- stakeholder organization committed to ending preventable morbidity, mortality and racial disparities in California maternity care. CMQCC uses research, quality improvement toolkits, state- wide outreach collaboratives and its innovative Maternal Data Center to improve health outcomes for mothers and infants.   CMQCC was founded in 2006 at Stanford University School of Medicine together with the State of California in response to rising maternal mortality and morbidity rates. Since CMQCC’s inception, California has seen maternal mortality decline by 55 percent between 2006 to 2013, while the national maternal mortality rate continued to rise. 

https://www.cmqcc.org/resource/improving-health-care-response-maternal-venous-thromboembolism-pregnancy-slide-set

https://www.cmqcc.org/resource/improving-health-care-response-maternal-venous-thromboembolism-pregnancy-slide-set

https://www.cmqcc.org/resource/improving-health-care-response-maternal-venous-thromboembolism-pregnancy-slide-set

https://www.cmqcc.org/resource/improving-health-care-response-maternal-venous-thromboembolism-pregnancy-slide-set

https://www.cmqcc.org/resource/improving-health-care-response-maternal-venous-thromboembolism-pregnancy-slide-set

VTE Risk Factors Major Risk Factors Odds Ratio Minor Risk Factors Previous VTE 24.8 BMI>40* 4 Thrombophilia 51.8 Cesarean Section** 3.7 APA Syndrome 15.8 Elective Cesarean Section 2.3 SLE 8.7 Emergency Cesarean Section 3.6 Heart Disease 7.1 Blood Transfusion** 7.6** Postpartum Infection** 4.1 IUGR Antepartum hemorrhage Smoking >10 cigs/day 1.7-2.2 Multiple Gestation 1.6 Age >35 1.4-1.7 CHTN 1.87 PreE 0.9 VTE Risk Factors

VTE and Pregnancy: Thromboprophylaxis Implementation

Avera Obstetric VTE Risk Assessment Tool Major Risk Factors Consider anticoagulation if 1 present Previous VTE Thrombophilia Antithrombin Deficiency Factor V Leiden Prothrombin Gene Mutation Anti-phosholipid Antibody Syndrome Lupus Heart Disease Minor Risk Factors Consider anticoagulation if 2 or more present Cesarean section BMI>40 Age >35 Hemorrhage (if stable 12-24 hrs) Postpartum Infection Multiple gestation Smoking General anesthesia IUGR Preeclampsia Chronic hypertension Blood Transfusion (if stable 12-24 hrs)

Prophylactic Anticoagulation Dosing Regimens Unfractionated heparin Weight Enoxaparin <50kg 20mg Daily 50-90kg 40mg Daily 91-130kg 60mg Daily 131-170kg 80mg Daily >170kg 0.6mg/kg/Day   Unfractionated heparin Any weight 5000 units twice daily

Timing of Anticoagulation After Regional Anesthesia

Risk of Bleeding with Prophylactic Anticoagulation Safety of prophylactic anticoagulation in patients undergoing c-section at Duke University No differences in EBL at delivery No change in postpartum hematocrit No difference in blood product administration Limmer et al. Thrombosis Research 132 (2013) e19-23

Contraindications to LMWH Administration Hemophilia or other known bleeding disorder Active or threatened antenatal bleeding (consider holding LMWH/UFH 12–24h after cessation of bleeding) Thrombocytopenia (platelet count <75K) Recent stroke (hemorrhagic/ischemic) Severe renal disease (GFR < 30ml/min) Severe liver disease (prolonged PT) Uncontrolled hypertension (BP > 200mmHg systolic or >120mmHg diastolic) Limmer et al. Thrombosis Research 132 (2013) e19-23

THANK YOU!!

References Limmer et al. Postpartum wound and bleeding complications in Women who received peripartum anticoagulation. Thrombosis Research 132 (2013) e19-23 Bates SM., Greer IA., Middeldorp S., Veenstra DL., Prabulos AM., Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(Suppl): e691S–736S  James AH , Jamison MG , Brancazio LR , Myers ER . Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol. 2006;194(5):1311-1315. Jacobsen AF, Skjeldestad FE , Sandset PM . Ante- and post- natal risk factors of venous thrombosis: a hospital-based case-control study. J Thromb Haemost. 2008;6(6):905-912. ACOG Practice Bulletin #196. Thromboembolism in Pregnancy. July 2018. CDC: Pregnancy Mortality Surveillance System. http://www.cdc.gov/reproductivehealth/maternalinfanthealth/pmss.html UpToDate: Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis. April 14, 2016. Council on Patient Safety in Women’s Health Care. Safety Action Series: Maternal Venous Thromboembolism Prevention Patient Safety Bundle. December 2015 ACOG District II. Safe Motherhood Initiative: Maternal Safety Bundle for Venous Thromboembolism. November 2015 RCOG. Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium. Green-top Guideline No. 37a; April 2015 https://www.cmqcc.org/resource/improving-health-care-response-maternal-venous-thromboembolism-pregnancy-slide-set