Peripartum Thromboprophylaxis: A Scientific …. Thromboprophylaxis: A Scientific Approach. To The Issue. Leo R. Brancazio, MD. Department of Obstetrics & Gynecology. West …

PeripartumThromboprophylaxis:A Scientific Approach

To The IssueLeo R. Brancazio, MD

Department of Obstetrics & GynecologyWest Virginia University School of Medicine

Morgantown, West Virginia

Disclosures•None

Disclosures•Off-label or investigational drugs

•Low-molecular-weight heparins•Use peripartum not clearly defined

Review the changes in physiology during pregnancy that make peripartum thromboprohylaxis difficult to achieve

Objectives

Outline was authorities recommend concerning peripartum thromboprophylaxis

Objectives

Discuss the evidence for the various regimens and what data there are to support their use

Objectives

http://www.clinicalresearch.nl/epidemiology/wright/images/pe_ct.jpg. Accessed 9/13/05

Presenter

Presentation Notes

I am MAD

Cesarean delivery approximately doubles the risk of venous thromboembolism, but in the otherwise normal patient, this risk is still

low (approximately 1 per 1,000 patients). Given this increased risk, and based on extrapolation from perioperative data, placement of pneumatic compression devices before cesarean delivery is

recommended for all women not already receiving thromboprophylaxis.

Venous Thromboembolism Prevention Maternal Safety Bundle

Readiness• Every unit

• Use a standardized thromboembolism risk assessment tool during:

• Outpatient prenatal care

• Antepartum hospitalization

• Hospitalization after cesarean or vaginal birth

• Postpartum period (up to 6 weeks after birth)

D'Alton, Mary E., et al. "National partnership for maternal safety: consensus bundle on venous th


Recognition and Prevention• Every patient

• Apply standardized tool to all patients to assess venous thromboembolism risk at time points designated under Readiness

• Apply standardized tool to identify appropriate patients for thromboprophylaxis

• Provide patient education

• Provide all health care providers education regarding risk assessment tools and recommended thromboprophylaxis



Response• Every unit

• Use standardized recommendations for mechanical thromboprophylaxis

• Use standardized recommendations for dosing of prophylactic and therapeutic pharmacologic anticoagulation

• Use standardized recommendations for appropriate timing of pharmacologic prophylaxis with neuraxial anesthesia



Reporting and Systems Learning• Every unit

• Review all thromboembolism events for systems issues and compliance with protocols

• Monitor process metrics and outcomes in a standardized fashion

• Assess for complications of pharmacologic thromboprophylaxis

• Standardization of health care processes and reduced variation


NPMS Recommendations Vaginal Birth

• Low risk – No Prophylaxis

• If high risk based on scoring system –Consider LMWH or UFH

• H/O of VTE or thrombophilia – Pneumatic compression while in bed


NPMS Recommendations Cesarean Birth

• All women not receiving pharmacologic prophylaxis

• Perioperative pneumatic compression devices until ambulatory

• Pharmacologic prophylaxis if risk factors

• Hospitals may choose pharmacologic prophylaxis for all


NPMS Recommendations Cesarean Birth

• Timing

• Prophylactic UFH – when postcesarean patients otherwise meet criteria for postanesthesia care unit discharge

• Prophylactic LMWH – 4 hours after epidural catheter removal or spinal needle placement


Kakkar, Vijay. "The diagnosis of deep vein thrombosis using the 125I fibrinogen test." Archives of Surgery 104.2 (1972): 152-159.

3/100 In Obstetric Patients

Incidence

•VTE complicates 0.5% of all cesarean deliveries (95% CI; 0.1–2.8%)•Asymptomatic•Older literature supports this number•Asymptomatic DVT complicates 30-

50% of hip/knee patients•Symptomatic VTE complicates 0.1%

(0.05-0.3%)

Sia WW, Powrie RO, Cooper AB, et al. The incidence of deep vein thrombosis in women undergoing cesarean delivery. Thrombosis Research 2009;123:550-5.

Incidence

•DVT (DVT/PE) complicates 0.5% of all cesarean deliveries (95% CI; 0.1–2.8%)



Pharmacology & Complications of

Anticoagulants During Pregnancy

Nonpregnant

Pregnant

143 IU/kg10,000 IU / 70 kg

Brancazio et al, Am J Obstet Gynecol, 1995

Nonpregnant

Pregnant

143 IU/kg10,000 IU / 70 kg

Brancazio et al, Am J Obstet Gynecol, 1995

Stirrup CA, et al. Maternal anti-factor Xa activity following subcutaneous unfractionated heparin after Caesarean section. Anaesthesia, 2001;56

•8 women post C/S got 5000 units•Then 5 got 7500 units•Then 10 got 10,000 units

What About Postpartum?

Stirrup CA, et al. Maternal anti-factor Xa activity following subcutaneous unfractionated heparin after Caesarean section. Anaesthesia, 2001;56

•8 women post C/S got 5000 units•Then 5 got 7500 units•Then 10 got 10,000 units

What About Postpartum?

Blood Low Molecular Heparin Levels In Response to Enoxaparin 40 mg Injection

Casele HL, Laifer SA, Woelkers DA, Venkataramanan R. Changes in the pharmacokinetics of the low-molecular-weight heparin enoxaparin sodium during pregnancy. American journal of obstetrics and gynecology 1999;181:1113-7

Gibson JL, Ekevall K, Walker I, Greer IA. Puerperal thromboprophylaxis: comparison of the anti-Xa activity of enoxaparin and unfractionated heparin. British journal of obstetrics and gynaecology 1998;105:795-7.

Presenter

Presentation Notes

Randomized Trial Women at high risk UFH significant different the enoxaparin 20 mg no different than 40 mg

LMWH and Neuraxial Anesthesia

Relative Risk of Spinal Hematoma

Est. Incidence for Epidural Anesthesia

Est. Incidence for Spinal

Anesthesia

No Heparin

Atraumatic 1 1:220,000 1:320,000

Traumatic 11.2 1:20,00 1:29,000

With Aspirin 2.54 1:150,000 1:220,000

Heparin Anticoagulation PostNeuraxial Procedure

Atraumatic 3.16 1:70,000 1:100,000

Traumatic 112 1:2,000 1:2,900

Heparin > 1 hr post puncture 2.18 1:100,000 1:150,000

Heparin < 1 hr post puncture 25.2 1:8,700 1:13,000

With Aspirin 26 1:8,500 1:12,00

Horlocker T. Regional anesthesia in the anticoagulated patient: Defining the risks (the second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Regional Anesthesia and Pain Medicine 2003;28:172-97.

Risk Factors and Estimated Incidence for Spinal Hematoma and Central Neuraxial Anesthesia




Anesthesia

No Heparin

Atraumatic 1 1:220,000 1:320,000

Traumatic 11.2 1:20,00 1:29,000

With Aspirin 2.54 1:150,000 1:220,000


Atraumatic 3.16 1:70,000 1:100,000

Traumatic 112 1:2,000 1:2,900



With Aspirin 26 1:8,500 1:12,00






Anesthesia

No Heparin

Atraumatic 1 1:220,000 1:320,000

Traumatic 11.2 1:20,00 1:29,000

With Aspirin 2.54 1:150,000 1:220,000


Atraumatic 3.16 1:70,000 1:100,000

Traumatic 112 1:2,000 1:2,900



With Aspirin 26 1:8,500 1:12,00






Anesthesia

No Heparin

Atraumatic 1 1:220,000 1:320,000

Traumatic 11.2 1:20,00 1:29,000

With Aspirin 2.54 1:150,000 1:220,000


Atraumatic 3.16 1:70,000 1:100,000

Traumatic 112 1:2,000 1:2,900



With Aspirin 26 1:8,500 1:12,00






Anesthesia

No Heparin

Atraumatic 1 1:220,000 1:320,000

Traumatic 11.2 1:20,00 1:29,000

With Aspirin 2.54 1:150,000 1:220,000


Atraumatic 3.16 1:70,000 1:100,000

Traumatic 112 1:2,000 1:2,900



With Aspirin 26 1:8,500 1:12,00






Anesthesia

No Heparin

Atraumatic 1 1:220,000 1:320,000

Traumatic 11.2 1:20,00 1:29,000

With Aspirin 2.54 1:150,000 1:220,000


Atraumatic 3.16 1:70,000 1:100,000

Traumatic 112 1:2,000 1:2,900



With Aspirin 26 1:8,500 1:12,00



Selected Studies of Peripartum

Thromboprophylaxis

Snijder CA, Cornette JMW, Hop WCJ, Kruip MJHA, Duvekot JJ. Thromboprophylaxis and bleeding complications after cesarean section. Acta Obstetricia et Gynecologica Scandinavica 2012;91:560-5.

Venous Thromboembolic Events After Cesarean Delivery in Women Receiving Perioperative Low-Molecular-Weight Heparins

All events were DVT

Presenter

Presentation Notes

2 from each group suffer DVT (6 total) Blood loss at time of surgery no different (amount not stated)

Snijder CA, Cornette JMW, Hop WCJ, Kruip MJHA, Duvekot JJ. Thromboprophylaxis and bleeding complications after cesarean section. Acta Obstetricia et Gynecologica Scandinavica 2012;91:560-5.

Postoperative Bleeding Complications After Cesarean Delivery in Women Receiving Perioperative Low-Molecular-Weight Heparins

Presenter

Presentation Notes

2 from each group suffer DVT (6 total) Blood loss at time of surgery no different (amount not stated)

Ferres MA, Olivarez SA, Trinh V, Davidson C, Sangi-Haghpeykar H, Aagaard-Tillery KM. Rate of wound complications with enoxaparin use among women at high risk for postpartum thrombosis. Obstet Gynecol 2011;117:119-24.

Presenter

Presentation Notes

Retrospective Cohort 12/2007-10/2009 Protocol >35 and/or BMI >30 At-risk cohort who received prophylaxis vs. at-risk cohort who did not Enoxaparin 40 mg Start 6 hours postpop Continued daily until discharge

Outcome

ProtocolCompliant

Cases(n=653)

Protocol Noncompliant

Controls(n=1024) P

Deep Venous Thrombosis 0 1 (0.1) 0.99

Pulmonary Embolism 2 (0.3) 4 (0.4) 0.99

Incidence of Venous Thromboembolism in Protocol-Compliant Cases and Protocol-Noncompliant Controls

Ferres MA, Olivarez SA, Trinh V, Davidson C, Sangi-Haghpeykar H, Aagaard-Tillery KM. Rate of wound complications with enoxaparin use among women at high risk for postpartum thrombosis. Obstet Gynecol 2011;117:119-24.

Data are n (%) unless otherwise indicated.

Group Number VT EventsHemorrhagic

Complications

Unfractionated Heparin5000 IU 141 0 2

Enoxaparin 2000 IU (20 mg) 131 0 1

Incidence of Complications in Patients Using Unfractionated Heparin and

Low-Molecular-Weight Heparin

Watanabe T, Matsubara S, Usui R, Izumi A, Kuwata T, Suzuki M. No increase in hemorrhagic complications with thromboprophylaxis using low-molecular-weight heparin soon after cesarean section. The journal of obstetrics and gynaecology research 2011;37:1208-11.

Assumptions• VTE post C/S = 0.5%• OR of VTE post LMWH = 0.3• Major PPH with C/S LMWH = 2%

Blondon M. Thromboprophylaxis after cesarean section: decision analysis. Thrombosis Research 2011;127 Suppl 3:S9-S12.

How do SCDs Work?

• Forced Flow• Activation / Enhanced

Fibrinolysis1-3

1 Tarnay TJ, et al. Pneumatic calf compression, fibrinolysis, and the prevention of deep venous thrombosis. Surgery 1980; 88:489-496. 2 Salzman EW, et al. Effect of optimization on fibrinolytic activity and antithrombotic efficacy of external pneumatic calf compression. Ann Surg 1987; 206:636-641. 3 Jacobs DG, et al. Hemodynamic and fibrinolytic consequences of intermittent pneumatic compression: preliminary results. J Trauma 1996; 40:710-717.

Presenter

Presentation Notes

randomized trial in neurosurgical patients comparing sequential application of graded pressure with uniform pressure applied to either a segmented bladder or to a single bladder. Deep vein thrombosis was diagnosed by leg scanning and impedance plethysmography and confirmed by phlebography. Venous thrombosis developed in 3 of 45 patients with graded-sequential filling, 6 of 50 with uniform compressionmultiple compartments, and 3 of 41 with uniform pressure single bladder (differences not significant).

Salzman EW, et al. Effect of optimization on fibrinolytic activity and antithrombotic efficacy of external pneumatic calf compression. Ann Surg 1987; 206:636-641.

Presenter

Presentation Notes

Randomized trial in neurosurgical patients comparing sequential application of graded pressure with uniform pressure applied to either a segmented bladder or to a single bladder. Deep vein thrombosis was diagnosed by leg scanning and impedance plethysmography and confirmed by phlebography. Venous thrombosis developed in 3 of 45 patients with graded-sequential filling, 6 of 50 with uniform compressionmultiple compartments, and 3 of 41 with uniform pressure single bladder (differences not significant). Day1 -- 125 I-Fibrinogen scannning Day 2 -- impedence plethysmography Ascending phlebography in patients who had positive fibrinogen scans or IPGs.

Casele H, Grobman WA. Cost-effectiveness of thromboprophylaxis with intermittent pneumatic compression at cesarean delivery. Obstetrics & Gynecology 2006;108:535-40.

DVT post cesarean = 0.7%,with 75% of those asymptomatic


Reduction in DVT risk with ICDs = 70%


Casele H, Grobman WA. Cost-effectiveness of thromboprophylaxis with intermittent pneumatic compression at cesarean delivery. Obstet Gynecol 2006;108:535-40.




$37K

Reddick, Keisha LB, et al. "The Effects of Intermittent Pneumatic Compression during Cesarean Delivery on Fibrinolysis." Ame

Reddick, Keisha LB, et al. "The Effects of Intermittent Pneumatic Compression during Cesarean Delivery on Fibrinolysis." Ame

at Intermittent Pneumatic Compression During Cesarean Delivery Alte

Bottom line –Does any of this

work?

Clark, Steven L., et al. "Maternal mortality in the United States: predictability and the impact of protocols on fatal postcesarean pulmonary embolism and hypertension-related intracranial hemorrhage." American journal of obstetrics and gynecology (2014).

Kane, Eleanor V., et al. "A population-based study of venous thrombosis in pregnancy in Scotland 1980–200

ence Rates Of Pregnancy Related Venous Thromboembolism In S


Associations Between Postnatal Deep Venous Thrombosis and Mode of Delivery

by Year of Delivery.










Are We Trying To Interfere With Normal

Postpartum Physiology?

Rodger MA, Avruch LI, Howley HE, Olivier A, Walker MC. Pelvic magnetic resonance venography reveals high rate of pelvic vein thrombosis after cesarean section. American journal of obstetrics and gynecology 2006;194:436-7.

Rodger MA, Avruch LI, Howley HE, Olivier A, Walker MC. Pelvic magnetic resonance venography reveals high rate of pelvic vein thrombosis after cesarean section. American journal of obstetrics and gynecology 2006;194:436-7.

Khalil H, Avruch L, Olivier A, Walker M, Rodger M. The natural history of pelvic vein thrombosis on magnetic resonance venography after vaginal delivery. American journal of obstetrics and gynecology 2012;206:356.e1-4.

Khalil H, Avruch L, Olivier A, Walker M, Rodger M. The natural history of pelvic vein thrombosis on magnetic resonance venography after vaginal delivery. American journal of obstetrics and gynecology 2012;206:356.e1-4.

PeripartumThromboprophylaxis:A Scientific Approach

To The IssueLeo R. Brancazio, MD

Department of Obstetrics & GynecologyWest Virginia University School of Medicine

Morgantown, West Virginia

Documents

Peripartum Thromboprophylaxis: A Scientific …. Thromboprophylaxis: A Scientific Approach. To The Issue. Leo R. Brancazio, MD. Department of Obstetrics & Gynecology. West …