Post on 02-Apr-2018
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
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
Venous Thromboembolism Prevention Maternal Safety Bundle
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
D'Alton, Mary E., et al. "National partnership for maternal safety: consensus bundle on venous th
Venous Thromboembolism Prevention Maternal Safety Bundle
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
D'Alton, Mary E., et al. "National partnership for maternal safety: consensus bundle on venous th
Venous Thromboembolism Prevention Maternal Safety Bundle
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
D'Alton, Mary E., et al. "National partnership for maternal safety: consensus bundle on venous th
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
D'Alton, Mary E., et al. "National partnership for maternal safety: consensus bundle on venous th
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
D'Alton, Mary E., et al. "National partnership for maternal safety: consensus bundle on venous th
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
D'Alton, Mary E., et al. "National partnership for maternal safety: consensus bundle on venous th
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%)
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.
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.
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.
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
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
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
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
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
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
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
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
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.
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.
Salzman EW, et al. Effect of optimization on fibrinolytic activity and antithrombotic efficacy of external pneumatic calf compression. Ann Surg 1987; 206:636-641.
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
Casele H, Grobman WA. Cost-effectiveness of thromboprophylaxis with intermittent pneumatic compression at cesarean delivery. Obstetrics & Gynecology 2006;108:535-40.
Reduction in DVT risk with ICDs = 70%
Casele H, Grobman WA. Cost-effectiveness of thromboprophylaxis with intermittent pneumatic compression at cesarean delivery. Obstetrics & Gynecology 2006;108:535-40.
Casele H, Grobman WA. Cost-effectiveness of thromboprophylaxis with intermittent pneumatic compression at cesarean delivery. Obstet Gynecol 2006;108:535-40.
Casele H, Grobman WA. Cost-effectiveness of thromboprophylaxis with intermittent pneumatic compression at cesarean delivery. Obstet Gynecol 2006;108:535-40.
Casele H, Grobman WA. Cost-effectiveness of thromboprophylaxis with intermittent pneumatic compression at cesarean delivery. Obstet Gynecol 2006;108:535-40.
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
Kane, Eleanor V., et al. "A population-based study of venous thrombosis in pregnancy in Scotland 1980–200
Associations Between Postnatal Deep Venous Thrombosis and Mode of Delivery
by Year of Delivery.
Kane, Eleanor V., et al. "A population-based study of venous thrombosis in pregnancy in Scotland 1980–200
Associations Between Postnatal Deep Venous Thrombosis and Mode of Delivery
by Year of Delivery.
Kane, Eleanor V., et al. "A population-based study of venous thrombosis in pregnancy in Scotland 1980–200
Associations Between Postnatal Deep Venous Thrombosis and Mode of Delivery
by Year of Delivery.
Kane, Eleanor V., et al. "A population-based study of venous thrombosis in pregnancy in Scotland 1980–200
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