Torri Metz, MD Assistant Professor Maternal-Fetal Medicine ...steamboatperinatalconference.com/wp-content/...Maternal-Fetal Medicine. January 12, 2017. Torri Metz, MD. Assistant Professor

Torri Metz, MDAssistant Professor

Maternal-Fetal MedicineJanuary 12, 2017

Torri Metz, MDAssistant Professor

Maternal-Fetal MedicineJanuary 12, 2017

I have no relevant financial relationships to disclose or conflicts of interest to resolve.

NOT discussing how to treat an active VTE NOT discussing how to use prophylaxis in

women with a history of VTE NOT discussing how to use prophylaxis in

women with thrombophilias NOT discussing use of prophylaxis in the

antepartum period WILL discuss the use of prophylaxis in all

other postpartum women

…found his wife unconscious at their home on November 26. A blood clot in her lungs had killed her. She hadn't been breathing for about an hour. At the time, she was 14 weeks pregnant with the couple's second child.

Fort Worth Texas News Nov 2013 …The diagnosis was crushing and irrevocable. At

33, … was brain-dead after collapsing on her kitchen floor in November from what appeared to be a blood clot in her lungs.

New York Times Nov 2013

Slide courtesy of Sandy Sedgley

Maternal mortality rate in United States 1900: 850 women per 100,000 live births

Maternal mortality rate in United States in 1986: 7.4 per 100,000 live births

Doubled over past 20 years: 14.5 per 100,000 live births

Call to action from multiple organizations including ACOG, AWHONN, CDC, SMFM, ACNM, and othersNational Partnership for Maternal

Safety

Obstetric Hemorrhage

Severe Hypertension in Pregnancy

Venous Thromboembolism in Pregnancy Recommended bundles released over

next 2 years

Dalton et al Obstet Gynecol 2014

VTE (DVT or PE) incidence 0.5-2.2 per 1000 deliveries

Daily risk of VTE in postpartum period increased 15- to 35-fold compared to age-matched non-pregnant women

Greatest risk for 3-6 weeks postpartum Small residual increased risk up to 12 weeks

postpartum

Bates et al J Thromb Thrombolysis 2016

By preventing venous stasis and/or by thinning the bloodAmbulation Sequential compression devices

(SCDs) Low molecular weight heparin

(LMWH) or unfractionated heparin (UFH)

ACOG recommends SCDs for all women with a cesarean until fully ambulatory

RCOG recommends risk-based scoring system

Chest recommends different risk-based scoring system

Dosing for prophylaxis not delineated

Aim: To assess the effects of thromboprophylaxis in women who are pregnant or who have recently given birth and are at increased risk of VTE on the incidence of VTE and adverse effects of treatment

Randomised trials comparing one method of prophylaxis to placebo or two different methods of prophylaxis 16 randomized trials

9 trials assessed prophylaxis after cesarean

Conclusion: Current available information is insufficient to make firm recommendations for prophylaxis

TRIAL TYPE N RR for VTE (95% CI)

4 trials LMWH/UFH vs placebo 840 1.30 (0.39-4.27)

3 trials LMWH vs UFH 217 0.33 (0.01-7.99)

1 trial 5-day vs 10-day LMWH 646 0.36 (0.01-8.78)

1 trial UFH vs no heparin 210 0.16 (0.02-1.36)

Cochrane Database Cyst Review 2010

SCDs for all cesarean deliveries

Clark et al Retrospective cohort study HCA deliveries Compared 2007-12 (after protocol for

universal SCDs at c/s) to 2000-2006 births Decrease from 7 post-op PE deaths per

458,097 cesareans to 1 post-op PE death per 465,880 cesareans (p=0.038)

Clark et al 2014 Am J Obstet Gynecol

Following implementation of a risk-based VTE prophylaxis guideline there was a reduction in maternal death due to VTE

Implementation of VTE protocol associated with a reduction in maternal deaths 1.94 deaths per 100,000 births (2003-5) 0.79 deaths per 100,000 births (2006-8) 1.01 deaths per 100,000 births (2011-13) All lower than all triennial periods 1985-2005

Cantwell R, et al BJOG 2011

41 women died from VTE 2003-5 compared to 18 women 2006-8

Mostly observed decrease in antenatal deaths and deaths after vaginal delivery

Of 18 deaths: 16 had risk factors 56% substandard care (no risk assessment, no

prophylaxis, failure to investigate symptoms or failure to ensure multidisciplinary care)

Friedman et al Sem Perinatol 2016

Consider heparin for 7 days in women with BMI ≥ 30 and 1 or more other risk factors

Consider heparin for 6 weeks in women with BMI ≥ 30 and 2 or more other risk factors

Consider heparin for 7 days in women with BMI ≥ 40 and no other risk factors

RCOG Green-top Guideline 2009

RISK FACTORS FOR VTE

Age > 35 years Parity ≥ 3 Operative procedures such as cesarean, D&C, tubal ligation, hysterectomy

Obesity with BMI > 30 mg/kg2 Smoker

Prolonged labor in the hospital (>24 hours)

Long distance travel (> 4 hrs) Varicose veins Pregnancy arising from assisted reproductive technology

Medical comorbidities(lupus, cardiac disease, etc)or current systemic infection

Blood transfusion Preeclampsia

Immobility (including bedrest or labor >24 hrs)

Multiple gestation Dehydration/hyperemesis

RCOG Green-top Guideline 2009

Consider heparin in women with one major or two minor risk factors

Consider extended duration (6 weeks) of therapy in women at very high risk

Bates Chest 2012

MAJOR MINOR

Immobility (>1 wk) BMI > 30 kg/m2

PPH > 1000 with operation Multiple gestation

Previous VTE PPH > 1000 cc

Preeclampsia with FGR Smoking > 10 cigs/day

Thrombophilia (ATIII, Factor V, Prothrombin)

FGR (<25 %ile)

Medical conditions Thrombophilia (Prot C/S)

Blood transfusion Preeclampsia

Postpartum infection

Evidence-based guidance for VTE prevention Threshold for prophylaxis based on author

consensus Risk threshold 3% or greater For risk factors with only case-control data RR of

60-fold postpartum needed to reach threshold (assuming baseline risk of 0.05%) Of note, based on majority opinion, but not

consensusBates et al J Thromb Thrombolysis 2016

Prevention of VTE in women with clinical risk factors: Postpartum prophylaxis while in hospital to

women with a history of antepartum immobilization for at least 7 days and to those immobilized postpartum with known thrombophilia or significant medical comorbidity


Prophylaxis for prevention of VTE in women after cesarean delivery should be provided with any of the following risk factors: One or more prior VTE History of antepartum immobilization (BR x 1 wk) Significant postpartum infection PPH >1000cc with re-operation Preeclampsia with FGR Significant medical co-morbidities Known thrombophilia Bates et al J Thromb Thrombolysis 2016

Prophylaxis for prevention of VTE in women after cesarean delivery should be provided with any TWO of the following risk factors: PPH >1000cc with no re-operation BMI > 30 kg/m2

Fetal growth restriction Preeclampsia Multiple gestation Tobacco use

Emergency cesarean Bates et al J Thromb Thrombolysis 2016

Low molecular weight heparin to prevent postpartum venous thromboembolism: a pilot randomised placebo-controlled trial

Multinational, double blind pilot RCT Randomized “high risk” postpartum women

to 21 days of LMWH or placebo 1,346 potentially eligible 968 ineligible,

378 (31.5%) eligible 25 randomized (0.7 per center per month)

Rodger MA et al Thromb Haemost 2015

D’Alton ME, et al Obstet Gynecol 2016



For women with a history of VTE or known thrombophilia SCDs intrapartum Postpartum prophylaxis with UFH or

LMWH

Women with multiple risk factors for VTE can be considered for pharmacologic prophylaxis


Risk Factor Points

Age 41-60 yrs 1

Minor surgery (<45 mins) 1

Visible varicose veins 1

Swollen legs 1

BMI > 25 mg/kg2 1

Currently on bedrest 1

Serious lung disease 1

Pregnancy or postpartum 1

Hx of stillbirth, recurrent SAB, PT delivery for preE or FGR 1

Other risk factors (smoking, DM, BMI > 40 kg/m2, blood transfusion)

1


Risk Factor Points

Central venous access 2

Major surgery (>45 minutes) 2

Patient confined to bed (>72 hrs) 2

Family history of thrombosis 3

History of DVT/PE 3

Prothrombin gene mutation or Factor V Leiden 3

Lupus anticoagulant or elevated anticardiolipin antibodies 3

Elevated serum homocysteine 3

Other congenital or acquired thrombophilia 3

Risk Factors Points

Previous VTE 3

Reduced mobility 3

Thrombophilia 3

Acute infection and/or rheumatologic disorder

1

BMI > 25 kg/m2 1

Pregnancy 1


All women undergoing cesarean should use SCDs until fully ambulatory Continue until fully ambulatory

Pharmacologic prophylaxis should be used in women with risk factors

Available scoring systems can be used to assess risk

Consider giving all women with a cesarean delivery post-op prophylaxis (UFH/LMWH)


All women should be assessed for VTE risk Use modified Caprini or Padua score, or RCOG

Expanded use of prophylaxis (both mechanical and pharmacologic) Most women with c/s pharmacologic ppx

Does not make specific recommendations for ongoing lovenox administration outside of the hospital based on risk factors


Does not make a recommendation for dose of prophylaxis

Gives hospitals the ability to create a protocol that meets the needs of the patients and providers but states there must be a protocol

Encourages evaluation of the instituted protocol for both efficacy and complications


No Level I evidence to support using tools to assess VTE risk in all women

1.2 million cesareans per year in U.S. Over half meet RCOG criteria From HCA: 1 death/500,000 If lovenox reduced by half

1 death/ 1 million 4-day course is $52 which means

$52 million to prevent 1 deathWordpress.com

Compares LMWH ppx for 7 days with no ppx after cesarean in healthy women with no history of VTE

Baseline case 30 yr-old women with a normal pregnancy

Decision tree: No events, DVT, PE, major non-GYN bleeding, PPH,

HIT, recurrent VTE Treatments for VTE and HIT are modeled for 3 mos

Blondon et al Thromb Haemost 2010

Assumptions: 0.5% VTE rate, reduction in VTE with LMWH (OR 0.3), PE mortality 10%

NNT=40 to prevent VTE in highest risk group Net gain 1.5 days/pt QALEs at 3 mos LMWH

SIMULATED GROUP THROMBOTIC EVENTS

BLEEDING EVENTS

1 million low risk 1359 983

Emergency c/s 2869 954

Smoking, overweight 11,000 800

Smoking, overweight, emergency c/s 23,000 ----

Blondon et al Thromb Haemost 2010

Cross-sectional survey of fellows of ACOG re VTE ppx for cesareans

400 invited to participate, 209 responded (52.3%), 157 provided prenatal care

92.4% used pneumatic compression devices 17.8% used UFH and LMWH routinely 19.1% routinely use combination prophylaxis 38.2% had local hospital guidelines

Donnelly et al J Matern Fetal Neonatal Med 2014

High rate of VTE in our population compared to reported incidence at the national level May be a result of our relatively closed system

with the ability to follow women through PP

We do not take care of women with VTE in the postpartum period Seen in ED and/or admitted to medicine

Already were using SCDs universally for cesarean deliveries

Needed a thromboprophylaxis policy in place to improve quality of care

Limited and highly variable guidance from organizations and experts

Full implementation of RCOG would result in the majority of our patients receiving prophylaxis “RCOG-lite” One more risk factor needed to meet criteria

Easier administration with prefilled syringes Once daily dosing for normal weight women on

prophylaxis Less side effect Bone loss associated with UFH Heparin-induced thrombocytopenia with UFH▪ Need for additional monitoring with platelet counts

Does not cross the placenta Oral anticoagulants (warfarin) do cross

Enoxaparin (lovenox) preferred agent at DH Therapeutic▪ 1 mg/kg subcu BID

Prophylactic▪ ≤ 40 kg/m2: 40 mg once daily▪ > 40 kg/m2: 40 mg BID

Medication Dose for Prophylaxis

Dalteparin 5000 units daily

Tinzaparin 4500 units daily

Enoxaparin 40 mg daily

Nadroparin 2850 units daily


RCT to compare fixed dose (40 mg enoxaparin daily) to weight-based dosing (0.5 mg/kg BID) for post-cesarean prophylaxis in obese women (BMI ≥ 35 mg/kg2)

Primary outcome: proportion of subjects with anti-Xa levels in prophylactic range (0.2-0.6)

88% (37/42) wt-based vs 14% (6/42) fixed dose reached prophylactic levels (OR 44.4, 95% CI 12.4-158.5)

Stephenson et al J Perinatol 2016

28 year-old G4 P4 who presented in labor Pregnancy significant for a history of cesarean

delivery x 2, desires repeat with tubal

Obese with a BMI of 33 mg/k2

Repeat cesarean delivery performed with no complications

Deck doc or midwife ready to write the postpartum orders

Do we need to make changes to

our VTE prophylaxis

policy at DH?

Women with VTEs identified with billing codes over a 3 year period from pre-policy implementation through policy implementation with an order set

Also assessed rate of readmission, ED visits and wound complications

All complications (VTE and wound) confirmed with a detailed chart review

Outcome 2013(before

implement)N=3157

2014(after

implement, no order set)

N=3217

2015(after

implement with order set)

N=3393

P value

VTE 5 (0.2) 4 (0.1) 5 (0.1) 0.9120PE 3 (0.1) 4 (0.1) 5 (0.1) 0.5462DVT 2 (0.1) 0 (0.0) 1 (0.0) 0.4493Wound complication 23 (0.7) 35 (1.1) 29 (0.9) 0.6081

ED visit 259 (8.2) 250 (7.8) 281 (8.3) 0.8950Readmission 25 (0.8) 41 (1.3) 48 (1.4) 0.0198

9 women had VTE events after implementation of protocol in 2014 4 received prophylaxis▪ All only qualified for 7 days▪ 1 had a VTE on day 5, and all others between days 29-51

3 did not meet criteria for prophylaxis 2 met criteria but did not receive LMWH

Is this a failure of the protocol? Would these have been prevented with full RCOG?

Detailed chart abstraction from May 2013 (pre-protocol) May 2014 (protocol but no order set) May 2015 (protocol with order set)

31.13% (95% CI 25.43-36.83%) of women received LMWH prophylaxis postpartum in May 2015

89.5% provider adherence to protocol

What can we conclude? Current policy appears to be safe for our

patients▪ No increase in wound complications/ED visits

Current policy may need to be expanded given the delayed diagnosis of VTE in our population Need to evaluate cost with high rate of

lovenox administration

No modifications to the protocol now

Will present at SMFM and discuss with other institutions that have implemented similar policies

More data are needed 2016 data available now

VTE prophylaxis is intended to prevent one of the most common causes of maternal death

All institutions need policy for prophylaxis

Denver Health has instituted a risk-based prophylaxis policy given that our patients are at high risk for VTE

Ongoing collection of safety and efficacy data will help guide modifications of policy

American College of Obstetricians and Gynecologists Practice Bulletin #84. Prevention of Deep Vein Thrombosis and Pulmonary Embolism. August 2007.

American College of Obstetricians and Gynecologists Practice Bulletin #138. Inherited thrombophilias in pregnancy. September 2013.

American College of Chest Physicians. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practical Guidelines. Chest 2012.

Bain E, Wilson A, Tooher R, et al. Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period. Cochrane Database Syst Review. 2014 Feb 11; 2: CD001689,

Bates SM, Middeldorp S, Rodger M, et al. Guidance for the treatment and preentionof obstetric-associated venous thromboembolism, J ThrombThrombolysis 2016; 41: 92-128.

Blondon M. Thromboprophylaxis after cesarean section: decision analysis. Thrombosis Research 2011; 127 Supp 3 S9-12.

Clark SL, Christmas JT, Frye DR, et al. Maternal mortality in the United States: predictability and the impact of protocols on fatal postcesarean pulmonary embolism and hypertension-related intracranial hemorrhage. Am J Obstet Gynecol 2014; 211:32.e1-9..

D’Alton ME, Friedman AM, Smiley RM, et al. National Partnership for Maternal Safety: Consensus Bundle on Venous Thromboembolism, Obstet Gynecol 2016.

Donnelly JC, Raglan GB, Bonanno C, et al. Practice patterns and preferences of obstetricians and gynecologists regarding thromboprophylaxis at the time of Cesarean section. J Matern Fetal Neonatal Med 2014; 27(18): 1870-3.

Friedman AM and Ananth CV. Obstetrical venous thromboembolism: Epidemiology and strategies for prophylaxis. Sem Perinatol 2016; 40:81-6.

Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (3rd Edition). Regional Anesthesia and Pain Medicine 2010, 35(1): 64-101

Rodger MA, Phillips P, Kahn SR, et al. Low-molecular-weigh-heparin to prevent postpartum venous thromboembolism: A pilot randomised placebo-controlled trial. Thromb Haemost 2015; 113(1): 212-6.

Royal College of Obstetricians and Gynaecologists. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium. Green-top Guideline, No. 37a, Nov 2009.

Stephenson ML, Serra AE, Neeper JM, et al. A randomized controlled trial of differing doses of post-cesarean enoxaparin thromboprophylaxis in obese women. J Perinatol 2016; 36:95-9.

Documents

Torri Metz, MD Assistant Professor Maternal-Fetal Medicine ...steamboatperinatalconference.com/wp-content/...Maternal-Fetal Medicine. January 12, 2017. Torri Metz, MD. Assistant Professor