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Wednesday, April 20

11:30 a.m. EasternDial In: 888.863.0985

Conference ID: 88305603

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Speakers

Michael Paidas, MD, FACOG

Professor & Vice Chair, Obstetrics

Director, MFM Fellowship

Director, Yale Women and Children’s Center for Blood Disorders and

Preeclampsia Advancement

Department of Obstetrics, Gynecology & Reproductive Sciences, Yale Medical

School

Liyana Winchell, RN, BSN

Labor and Birth and Maternal Special Care Units, Yale-New Haven

Hospital

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Disclosures

Michael Paidas, MD has no real or perceived conflicts of interest to disclose.

Liyana Winchell, RN, BSN has no real or perceived conflicts of interest to disclose.

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Objectives

Describe the need for antenatal VTE prevention in hospitalized women.

Discuss the importance of conducting effective antenatal VTE risk assessment.

Review patient factors associated with increased risk of VTE during antenatal hospitalization.

Provide a summary of VTE prevention measures that can be modified for use within your institution.

Identify issues that may arise from use of antenatal chemoprophylaxis.

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Epidemiology of VTE & Pregnancy

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Risk of VTE is correlated with age

Annual incidence of all venous thromboembolism, deep vein thrombosis (DVT) alone, and pulmonary embolism (PE) with or without deep vein thrombosis (PE ± DVT) by age.

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Rate of VTE in pregnancy

1. The incidence of VTE increases exponentially with age, from 5/100,000/year among children to 6/1000/year among 80 year olds.

2. Among reproductive age women (< 40 years) the risk of VTE is 1/10,000.

3. A retrospective cohort study of 268,525 patients over a 19 year period reported a prevalence of VTE of 1 per 1627 births.

4. Thus the risk of VTE is increased 6-fold during pregnancy.

Cushman. Semin Hematol. 2007; 44:62-9. Gherman et al. ObstetGynecol. 1999; 94:730-4.

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VTE & GA: Danish National Cohort

Adjusted incidence rate ratios (IRR) of thromboembolism in pregnant & puerperal women vs

non pregnant women not using oral contraceptives, adjusted for age, calendar yr &

education.

Venous thromboembolism in pregnant and puerperal women in Denmark 1995-2005. A national cohort study. Virkus RA, Løkkegaard EC, Bergholt T, Mogensen U, Langhoff-Roos J, Lidegaard Ø. Thromb Haemost. 2011 Aug;106(2):304-9.

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Risk of VTE Postpartum:Systematic Review

1. VTE risk is 21.5 to 84-fold higher in postpartum women compared to non-pregnant women

2. VTE risk postpartum is highest immediately after delivery (standardized incidence ratio for DVT 115.1 [95% CI 96.4-137.0] and for PE 80.7 [95% CI 53.9-117.9].

3. Between four and six weeks postpartum, VTE risk declined but is still five times to seven times that of nonpregnant, nonpostpartum women.

Jackson E et al Obstet Gynecol 2011;117:691-703.

Slide 12Friedman. Vaginal delivery and thromboprophylaxis AM Am J Obstet Gynecol 2015

Thromboembolism EventsA

A, Rate of thromboembolism events per 100,000 hospitalizations. B, Change in the rate of thromboembolic events since 2006.DVT, deep vein thrombosis; PE, pulmonary embolism; VTE, venous thromboembolism

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Risk Factors of VTE & Pregnancy

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Anatomic Changes During Pregnancy

• ↑venous

capacitance

• ↑mechanical

obstruction by

the uterus

• ↓ venous

outflow

• ↓mobility

• ↑vascular injury

Courtesy of Andra James, MD

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Clotting Factor Changes in Pregnancy

Coagulation Factors: • Marked Increase in Pregnancy:

– Fibrinogen, FVII, von Willebrand factor & ristocetincofactor, FX, FXII, F XIII

• Slight Increase or No Change:– F II, FV & IX

• Decrease: – FXI

Decrease in Anticoagulant & Fibrinolytic Activity:• Protein S levels (free and total) decrease by 40%

– PAI-1 levels increase two to three-fold in pregnancy– PAI-2 present due to placental production

Practice bulletin no. 123: thromboembolism in pregnancy.Obstet Gynecol. 2011 Sep;118(3):718-29.

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The Risk of Venous Thromboembolism in Pregnant

Patient with Selected ThrombophiliasCondition Prevelance in

European populations

Prevelance in Patients with VTE

in Pregnancy

Risk of VTEwithout prior

history

Risk of VTE with prior history

Factor V Leiden (FVL)HeterozygousHomozygous

5.3%0.07%

44<1

0.26%1.50%

>10%>10%

Prothrombin mutation (PGM)

HeterozygousHomozygous

2.90%0.02%

17<1

0.37-0.5%2.8

>10%>10%

Compound FVL/PGM 0.17% <1 4.70%

Protein C deficiency 0.2-0.3% <14 0.8-1.7%

Protein S deficiency 0.03%-0.13% 12 <1-6.6%

Antithrombin deficiency 0.02-1.1% 1 11.6%* 11-40%

Hendrix PW and Paidas MJ, Ch Thrombophilia in Pregnancy, Textbook: Management and Therapy of Early Pregnancy Complications, In Press 2016

*Rheaume M. Pregnancy- related Venous Thromboembolism in Asymptomatic Women with Antithrombin Deficiency Obstet Gynecol 2016; 127 (4): 649.

Slide 17Modified from: Bourjeily G, Paidas M, Khalil H, Rosene-Montella K, Rodger

M.Lancet. 2010 Feb 6;375(9713):500-12.

Virchow’s triad

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Risk Factors for VTE Associated with Pregnancy

Antepartum & Postpartum VTE

Odds ratio (95% CI)

Thrombophilia 51.8 (38.7-69.2)

Previous VTE 24.8 (17.1-36.0)

Family history of VTE 3.9

Superficial venous thrombosis

10.0 (1.3-78.1)

BMI >25 kg/m2 1.8 (1.3-2.4)

Antepartumimmobilization

7.7 (3.2-19.0)

BMI > 25 kg/m2 ^ & antepartum immobilization

62.3 (11.5-337.6)

Postpartum VTE Odds ratio(95% CI)

Infection (vaginal) 20.2 (6.4-63.5)

Infection (Cesarean) 6.2 (2.4-26.3)

Pre-eclampsia &IUGR 5.8 (2.1-16.0)

Emergency Cesarean 2.7 (1.8-4.1)

Hemorrhage (w/o surg.) 4.1 (2.3-7.3

Hemorrhage (w/ surg.) 12.1 (3.9-36.9)

Modified from Bourjeily G, Paidas M, Khalil H, Rosene-Montella K, Rodger M.Lancet. 2010 Feb 6;375(9713):500-12.

Antepartum VTE Odds ratio(95% CI)

Assisted Reproduction 4.3 (1.3-3.4)

Smoking 2.1 (17.1-36.0)

Other possible Risk factors

Odds ratio(95% CI)

Cesarean 2.1 (1.8-2.4),1.3 (0.7-2.2)

Age 2.1 (2.0-2.3),0.8 (0.6-1.1)

Parity 1.1 (0.9-1.4)1.7 (1.2-2.4)

^ BMI at first prenatal visit

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Prevention of VTE associated with Pregnancy:

The Controversies

before we address antepartum prophylaxis in the hospital….

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ACOG Practice Bulletin Thromboembolism in Pregnancy Number 123, September 2011

• Pneumatic compression devices recommended prior to Cesarean delivery for all women not already receiving thromboprophylaxis

• Studies of routine thromboprophylaxis for Cesarean delivery are too small & underpowered.

• For patients with undergoing Cesarean delivery with additional risk factors for thromboembolism, individual risk assessment may require thromboprophylaxis with both pneumatic compression devices & UFH or LMWH.

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Table 1. Summary of major society guideline recommendations for obstetric thromboprophylaxis for patients who have undergone caesarean delivery

ACOG

Perioperative mechanical thromboprophylaxis recommended for all patients undergoing caesarean delivery

Pharmacologic prophylaxis (LMWH or UFH) recommended for

High-risk thrombophilias

Any prior VTE event

A family history of VTE and a thrombophilia

Chest

Pharmacologic prophylaxis (LMWH) recommended for one major or two or more minor risk factors

Mechanical prophylaxis recommended for those with contraindications to pharmacologic prophylaxis

Major risk factors (one needed for prophylaxis)

Immobility (strict bed rest ≥1 week in the antepartum period)

Postpartum haemorrhage ≥1000 mL with surgery

Previous VTE

Pre-eclampsia with fetal growth restriction

Thrombophilia

Antithrombin deficiency

Factor V Leiden (homozygous or heterozygous)

Prothrombin G20210A (homozygous or heterozygous)

Medical conditions

Systemic Lupus erythematosus

Heart disease

Sickle cell disease

Blood transfusion

Postpartum infection

Minor risk factors (two needed for prophylaxis)

BMI >30 kg/m2

Multiple pregnancy

Emergency caesarean

Smoking >10 cigarettes/day

Fetal growth restriction

Thrombophilia

Protein C deficiency

Protein S deficiency

Pre-eclampsia

RCOG

Risk factors (LMWH recommended for any of the following risk factors)

Previous VTE

Antenatal anticoagulation

Caesarean in labour

Asymptomatic thrombophilia

Prolonged admission

Major medical co-morbidities (e.g. heart or lung disease, systemic Lupus erythematosus, cancer, inflammatory conditions, nephrotic syndrome, sickle cell disease, intravenous drug user

Age >35

BMI >30 kg/m2

Parity ≥3

Smoker

Any surgical procedure

Gross varicose veins

Current systemic infection

Immobility

Pre-eclampsia

Mid-cavity rotational operative delivery

Labour >24 hours

PPH >1 litre or transfusion

BMI, body mass index; PPH, postpartum haemorrhage; VTE, venous thromboembolism.

Palmerola KL, D’Alton ME, Brock CO, Friedman AM BJOG 2015

VTE prevention after Cesarean Delivery

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Calculated Rates of Pharmacologic Prophylaxis Post Cesarean Delivery for using Major Societal Guidelines in a tertiary care center

Society Percent (95% CI)

ACOG 1 (0.3-3.0)

CHEST 34.8 (29.6-40.4)

RCOG 85.0 (80.5-88.6)

Palmerola KL, D’Alton ME, Brock CO, Friedman AM BJOG 2015

BMI ≥ 30kg/m2

38.6%

BMI ≥ 40kg/m2

9.0%

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VTE Prevention: Initial Assessment

Friedman AM and D’Alton ME Sem Perinatology 2016

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Antepartum Hospitalization (not for delivery) & VTE Risk in Pregnancy

• Associated with an increased risk of VTE incidence rate ratio 17.5, 95% CI 7.69 to 40.0) compared with time outside hospital.

• Greatest risk factors for VTE:

• BMI >30 kg/m2

• maternal age >35 years

• Admission during third trimester

• Hospital stay >3 days.

Sultan AA et al. BMJ 2013;347:f6099

Slide 25 Friedman AM and D’Alton ME Sem Perinatology 2016

VTE Prevention: Antepartum Hospitalization

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Yale Approach to Postpartum VTE Prophylaxis

Pre Pregnancy

BMI (kg/m2)

Enoxaparin UFH

<40 40mg daily(CrCl < 30 ml/min)

5,000 U q8 hr

≥40 40mg q 12 hr(CrCl < 30 ml/min)

7,500 U q8 hr

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VTE Prevention: Postpartum (in hospital)

Friedman AM and D’Alton ME Sem Perinatology 2016

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VTE Prevention: After Discharge

Friedman AM and D’Alton ME Sem Perinatology 2016

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Contraindications to low-molecular weight heparin administration

• Hemophilia or other known bleeding disorder

• Active or threatened antenatal bleeding (e.g., previa, abruption). Balance risks/benefits

• Thrombocytopenia (platelet count <75 x 109)

• Recent stroke (hemorrhagic/ischemic)

• Severe renal disease (GFR < 30 ml/min)

• Severe liver disease (prolonged PT)

• Uncontrolled hypertension (BP > 200 mmHg systolic or >120 mmHg diastolic)

Friedman AM and D’Alton ME Sem Perinatology 2016

Slide 30Hendrix PW and Paidas MJ, Ch Thrombophilia in Pregnancy, Textbook:

Management and Therapy of Early Pregnancy Complications, In Press 2016

Suggested Anticoagulation Doses

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Neuraxial Anesthesia & Anticoagulation

Friedman AM and D’Alton ME Sem Perinatology 2016

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Nursing Perspective

• Nursing Handoff: Discussion of antepartum or postpartum VTE risk factors & prophylactic interventions.

• Nursing Interventions: – Pharmacologic prophylaxis – Sequential Compression Devices and/or compression stockings– Encourage ambulation – Passive and active ROM– Physical therapy – Intravenous hydration – Encourage smoking cessation (i.e. Nicotine patch), etc.

• Documentation: Electronic Health Records “Peripheral Neurovascular” flowsheet to document any assessed VTE issues & prophylactic interventions.

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Take Home Points

• Venous thromboembolism (DVT & PE) rates associated with pregnancy are rising in the USA.

• Reducing the rate of VTE will lower maternal mortality and morbidity.

• Pregnant patients and women considering pregnancy should have a VTE risk assessment and a plan established for each time period.

• Every hospital should evaluate and adopt workable guidelines, by consensus involving all stakeholders, for VTE prevention in the antepartum and postpartum periods.

• Reevaluate protocols as new data is gathered.

• Clinical studies are required to identify optimal strategies for VTE prevention in the hospital setting.

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Q&A Session Press *1 to ask a question

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A recording of this presentation will be made available on our website:

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Next Safety Action SeriesMaternal Mental Health: Enhancing Screening

and Better PracticesThursday, May 5, 2016 | 11:00 a.m. Eastern

Tiffany Moore Simas, MD, MPH, MEd,

FACOG

Director, Research Division & Associate Director,

Residency Program, Dept Ob/Gyn

University of Massachusetts Medical School/UMass

Memorial Health Care

Christena Raines, RN, MSN, APRN-BC

Perinatal Psychiatric Nurse Practitioner

University of North Carolina Perinatal Mood Disorder

Clinic, UNC Hospitals

Click Here to Register