Presentation on theme: "Venous Thromboembolism: Risk Assessment and Prophylaxis"— Presentation transcript:
1 Venous Thromboembolism: Risk Assessment and Prophylaxis
2 VTE ProphylaxisVenous thromboembolism (VTE) is a leading cause of maternal mortality and severe morbidityMaternal death from VTE is amenable to preventionProphylaxis is the most readily implementable means of systematically reducing the maternal death rateProtocols in the UK has led to significant reduction in maternal death from VTEStrategies for preventing VTE require minimal resources and are easily implementableSee Slide.
3 Key Elements in VTE Prophylaxis Bundles Risk assessment tools Protocols for antenatal and postpartum prophylaxis Suggested dosing scheduleAnesthesia recommendationsKey referencesInternational GuidelinesKey papersThis maternal safety bundle provides strategies for venous thromboembolism risk assessment and prophylaxis.The key elements in this bundle include management recommendations that apply to all obstetric patients including risk assessment tools, protocols for prophylaxis, dosage recommendations and recommendations for administration of anesthesia.For information on how to further implement and incorporate this bundle within the obstetric unit, please refer to the introductory section of this toolkit for an overview of important clinical considerations.
4 Risk AssessmentAll patients should be assessed for VTE risk multiple times in pregnancy including during:Presentation for prenatal careHospitalization for an antepartum indicationDelivery hospitalization (in-house postpartum)Discharge from a delivery hospitalizationProphylaxis can be based on risk factors or can be empiricThe core concept of this set of management recommendations is that all obstetric patients should be assessed at multiple time points during pregnancy for thromboembolism risk.Appropriate prophylaxis of patients at risk for thromboembolism is the strategy most likely to reduce severe morbidity and mortality from this cause.
5 Risk AssessmentThromboembolism prophylaxis is a Joint Commission quality measuresThe Joint Commission states that all patients should receive VTE prophylaxis OR have documentation why no VTE prophylaxis was givenWithin a day of hospital admissionWithin a day of surgeryThe Joint Commission Specifications Manual for National Hospital Inpatient SafetyThromboembolism risk assessment and prophylaxis are important quality measures for all hospitalized patients including patients hospitalized for obstetric indications.
6 Risk Assessment ToolsTo aid clinicians and hospitals in providing prophylaxis, risk assessment tools have been developed.
7 Risk Assessment Tools Sources: Risk assessment tools were based on recommendations from major society guidelinesPrenatal outpatient and postpartum discharge thromboprophylaxis are based primarily on American College of Chest Physicans and ACOG recommendationsInpatient prophylaxis is based primarily on RCOG recommendationsPharmacologic prophylaxis may be with unfractionated heparin (UFH) or low-molecular weight heparin (LMWH)Chest, Feb 2012; 141ACOG Practice Bulletin No 123, 2011See Slide.
8 Initial Assessment During Pregnancy Clinical historyAnticoagulationMultiple VTE episodesVTE with high-risk (HR) thrombophiliaVTE with acquired thrombophiliaTreatment doseLMWH or UFHIdiopathic VTEVTE with pregnancy or oral contraceptiveVTE with low risk (LR) thrombophiliaFamily history of VTE with HR thrombophiliaHR thrombophiliaProphylacticLMWH or UFH• At the initial assessment during pregnancy (during the first prenatal care visit), the patient’s clinical history should be reviewed and if the patient has a history of prior VTE events and/or thrombophilias, anticoagulation with low molecular weight or unfractionated heparin should be considered.• For patients with multiple prior events or who have high-risk thrombophilias, treatment dose heparin may be indicated.• For patients with a less concerning history, prophylactic heparin may be indicated.• Lastly, patients with low-risk thrombophilia or a prior provoked event may not require prophylaxis.1st VTE provokedFamily history of VTE with LR thrombophiliaLR thrombophilia (including acquired)No treatmentChest, Feb 2012; 141, ACOG Practice Bulletin No 123, 2011
9 Risk Assessment High-risk thrombophilias are defined as: Factor V Leiden or prothrombin gene mutation homozygousAntithrombin III deficiencyCompound heterozygote disorders (FVL and prothrombin)Low-risk thrombophiliaFactor V Leiden or prothrombin gene mutation heterozygousProtein C or S deficiencyAcquired thrombophiliaHigh-risk thrombophilias are defined as:• Factor V Leiden or prothrombin gene mutation homozygous• Antithrombin III deficiency• Compound heterozygote disorders (factor V Leiden and the prothrombin gene mutation)Low-risk thrombophilias are defined as:• Factor V Leiden or prothrombin gene mutation heterozygotes• Protein C or S deficiencyThe main acquired thrombophilia is antiphospholipid antibody syndrome.Antiphospholipid antibody syndromeACOG Practice Bulletin No 123, 2011
10 Prevalence and Risks of VTE with Thrombophilias Prev in Gen Pop%Lifetime ↑ VTE Risk% of all VTEVTE Risk/Preg (No hx)VTE Risk/Preg (Prior VTE)Low-risk thrombophiliasFVL heterozygote1-153-840< 0.310PTG heterozygote2-5317< 0.5>10Protein C activity (<50%)10-15144-17Protein S free Ag (<55%)**20.10-22High-risk thrombophiliasFVL homozygote< 11.5PTG homozygote0.52.8> 17FVL/PTG compound0.011-34.7> 20Antithrombin III def (<60%)0.0225-5013-7• This table demonstrates that patients with a history of thromboembolism and a thrombophilia are at high-risk for an event during pregnancy, particularly in comparison to the nonpregnant state.• The column on the far right demonstrates the probability of an event with a thrombophilia in the setting of a prior event.** Should not be tested in pregnancy or high-estrogen states.If necessary, levels < 24% in pregnancy in 1 series: Paidas MJ, et al. J Thromb Haemost 2005.
11 Initial Assessment During Pregnancy Provoked VTE is defined as an event occurring in the setting of a temporary risk factor that increases risk such as:Orthopedic surgeryIndwelling lineImmobilizationUnprovoked VTE occurs in the absence of temporary risk factors.*AN EXCEPTION: VTE provoked by estrogen (OCP, prior pregnancy) should be treated as being at higher risk for recurrence and guidelines for “unprovoked VTE” should be followed for patients with this clinical historySee Slide.
12 Antepartum Hospitalization All patientsMechanical prophylaxisANDAll patients:Should be given pharmacologic prophylaxis if risk factors are present (next slide)ORMay be given pharmacologic prophylaxis empirically• During antepartum hospitalization, all patients should receive sequential compression devices.• Additionally, pharmacologic prophylaxis in the form of low molecular weight heparin or unfractionated heparin should be added, either empirically OR if patients were receiving prophylaxis as outpatients or have risk factors including medical and obstetrical complications.These recommendations have been adopted primarily from RCOG guidelines
13 Antepartum Hospitalization Risk-Factor Based Prophylaxis Recommend heparin if at least 1 of the factors below is present:MedicalconditionsAlready receiving LMWH orUFH as outpatientPre-pregnancy Morbid Obesity(BMI > 40)Any history of VTEHeart diseaseLupusRenal diseaseSickle cellMajor infectionOther major medical conditionsProphylacticLMWH or UFHOR 2 or more risk factors below are present:PregnancycomplicationsAge>40 or <15 yearsPre-pregnancy obesity (BMI > 30)Bed restAny thrombophiliaMedical conditionsPregnancy complicationsThe guidance outlined here lists risk factors associated with increased risk for VTE and justify pharmacologic prophylaxis during an antepartum hospitalization.IUGRPreeclampsiaMultiple gestationARTRCOG, 2009 Green Top 37a
14 Delivery Hospitalization Early mobilizationAvoid dehydrationChemoprophylaxis based on risk factorsAll patientsWomen undergoing cesarean delivery should:Receive sequential compression devices perioperatively and postpartumReceive chemoprophylaxis (LMWH or UFH) either empirically OR based on risk factorsDuring delivery hospitalizations all patients should receive early mobilization, avoid dehydration, and receive chemoprophyalxis based on risk factors.Women undergoing cesarean delivery should receive sequential compression devices perioperatively and postpartum and should receive chemoprophylaxis either empirically or be assessed for risk factors and, if risk factors are present, receive chemoprophylaxis on that basis.
15 Delivery Hospitalization Recommend heparin if at least 1 of the factors below is presentAlready receiving heparin as outpatientPre-pregnancy class 3 obesity (BMI > 40)Any history of VTEThrombophilia and family history of VTEOR 2 or more risk factors below are present:ProphylacticLMWH or UFHuntil discharge2 or more risk factors:Cesarean deliveryHemorrhage (if stable after hours)HysterectomyGeneral anesthesiaPostpartum infectionAge>40 or <15 yearsPre-pregnancy obesity (BMI > 30)Bed restAny ThrombophiliaMedical or pregnancy complications• Risk factors are listed that would justify pharmacologic prophylaxis.• Patients who have one or more major risk factors OR two or more minor risk factors should receive pharmacologic prophylaxis.RCOG, 2009 Green Top 37a
16 Assessment During Postpartum Discharge Clinical historyAnticoagulationMultiple VTE episodesVTE with high-risk (HR) thrombophiliaVTE with acquired thrombophilia6 Weeks TreatmentLMWH/UFHIdiopathic VTEVTE with pregnancy or oral contraceptiveVTE with low risk (LR) thrombophiliaFamily history of VTE with HR thrombophiliaHR thrombophilia (including acquired)VTE provoked*LR thrombophilia and family history of VTE*6 WeeksProphylacticLMWH/UFH• On discharge home, patients should also be assessed.• The management algorithm is the same as for prenatal outpatient management EXCEPT that for postpartum patients with a history of provoked VTE or a family history of VTE with a low-risk thrombophilia, prophylaxis is recommended.* (two changes from initial assessment)LR thrombophiliaNo treatmentChest, Feb 2012; 141 ACOG Practice Bulletin No 123, 2011
17 Anticoagulation - LMWH Advantages of LMWH compared to UFHFewer bleeding episodesLower risk of heparin induced thrombocytopenia (HIT)Lower incidence of osteoporosisMore predictable pharmacokineticsAnti-Xa activity measurement not required for LMWH except forExtremes of body weightRenal impairmentLMWH has longer half life than UFHMay be an advantage or a disadvantageIn terms of a choice of agent, low molecular weight heparin has certain advantages over unfractionated heparin.With low molecular weight heparin, there are fewer bleeding episodes, lower risk of HIT, lower incidence of osteoporosis, and more predictable pharmacokinetics.Anti-Xa activity measurement is not required for LMWH except for extremes of body weight and renal impairment.LMWH has a longer half life than UFH which may be an advantage or disadvantage.Greer et al. Blood. 2005;106(2):401–407Ni Ainle F et al. Blood Coagul Fibrinolysis. 2008;19 (7):689–692Nelson-Piercy C et al, Eur J Obstet Gynecol Reprod Biol. 2011, Dec;159(2):293-9.
18 Contraindications to LMWH Therapy Hemophilia or other known bleeding disorderActive or threatened antenatal bleeding (e.g. placenta previa, placental abruption) based on clinical judgment of balancing risks/benefits (consider holding LMWH/UFH hours after cessation of bleeding)Thrombocytopenia (platelet count <75 x109)Recent stroke (hemorrhagic/ischemic)Severe renal disease (GFR <30ml/min)Severe liver disease (prolonged PT)Uncontrolled hypertension (BP >200mmHg systolic or >120mmHg diastolic)Unfractionated heparin should be used if there is a specific contraindication to LMWHContraindications to LMWH therapy include:• Hemophilia or other known bleeding disorder• Active or threatened antenatal bleeding based on clinical judgment of balancing risks/benefits• Thrombocytopenia• Recent stroke• Severe renal disease• Severe liver disease• Uncontrolled hypertensionUnfractionated heparin should be used if there is a specific contraindication to LMWH
19 Screening for Heparin Induced Thrombocytopenia (HIT) For patients expected to be on either UFH or LMWH for greater than >7 days a complete blood count should be sent to assess for HIT 7-10 days after initiation of therapyA platelet count of <150,000/microL or acute drop to<50% of baseline require further evaluation and immediate consultation with a hematologist or maternal-fetal medicine specialistA preceding diagnosis of gestational thrombocytopenia or idiopathic thrombocytopenic purpura may confound screening for HIT, and consultation with a hematologist or maternal fetal medicine specialist may be required for patients with these conditionsHeparin induced thrombocytopenia is a rare but serious complication of heparin therapyHIT is more common with unfractionated heparin than low molecular weight heparinFor patients who will undergo an extended course of heparin prophylaxis either inpatient or outpatient (> 7 days), screening for HIT with a CBC 7-10 days after initiation of treatment is recommendedA platelet count of <150,000/microL or acute drop to less than <50% of baseline require further evaluation and immediate consultation with a hematologist or maternal-fetal medicine specialist
20 Prophylaxis and Spontaneous Labor For patients on LMWH prenatally, consideration should be made to switch to UFH at weeks gestational age to facilitate administration of regional anesthesiaWhen patients are transitioned from LMWH to UFH, HIT should also be screened for with a CBC 7-10 after UFH is initiatedSee Slide.
21 Protocols for Prophylaxis AgentLMWHEnoxaparinDalteparinTinzaparinUFHUnfractionated heparinWeight basedGestational age-based<50kg20mg daily2500 units daily3500 units dailyFirst trimesterunitsTwice daily50-90kg40mg daily5000 units daily4500 units dailySecond trimesterunits91-130kg60mg daily*7500 units daily*7000 units daily*Third trimester10000 unitskg80mg daily*10000 units daily*9000 units daily Postpartum 5000 units twice daily>170kg0.6mg/kg/day*75 units/kg/day• For prophylaxis, low molecular weight heparin dosing during pregnancy differs based on which agent is being used and the patient’s weight.• For unfractionated heparin, dosing depends on the trimester.• For antepartum patients it is reasonable to administer a dose of 5000 units UFH twice daily during hospitalization for prophylaxis to facilitate regional anesthesia.Hospitalized antepartum patients may receive units UFH twice daily for prophylaxis to facilitate regional anesthesia*=may be given in two divided dosesAdapted from ACOG Practice Bulletin 123, ACCP Recommendations , RCOG Green Top Guideline 37a
22 Protocols for Therapeutic Dosing LMWHEnoxaparinDalteparinTinzaparinUnfractionated heparinWarfarin (postpartum)Dosing:Antepartum or Postpartum1mg/kg twice daily200 units/kg/day175 units/kg/day10000 units or more twice daily adjusted to mid interval target aPTT ( )INR(postpartum only)• Protocols for therapeutic dosing are based on patient weight for LMWH and achieving a therapeutic PTT for heparin.• Warfarin is not used during pregnancy except in extremely rare conditions such as mechanical heart valves.• Warfarin postpartum is dosed based on INR testing.Adapted from ACOG Practice Bulletin 123
23 Timing of Neuroaxial Anesthesia Antepartum/IntrapartumUFH prophylaxis(≤10,000IU/day)No contraindications to timing of heparin dose and performance of neuraxial blockadeUFH therapeuticWait 6 hours post last dose prior to neuraxial blockadeLMWH prophylaxisWait 12 hours post last dose prior to neuraxial blockadeLMWH therapeuticWait 24 hours post last dose prior to neuraxial blockadePostpartum Wait ≥1 hour after epidural catheter removal or spinal needle placementWait ≥4 hours after epidural catheter removal or spinal needle placementAvoid therapeutic dosing with epidural catheter in situ. Wait at least 24 hours after catheter removal or spinal needleThis table demonstrates recommendations for timing of neuroaxial anesthesia in relation to pharmacological anticoagulation.• Twice daily UFH at a dose of 5000 units is typically not a contraindication to neuraxial anesthesia• For therapeutic UFH neuraxial anesthesia should be deferred 6 hours after the last dose• For prophylactic and therapeutic LMWH neuraxial anesthesia should be deferred 12 and 24 hours after the last dose respectively• Postpartum UFH may be given 1 hour after spinal or epidural catheter removal• Postpartum LMWH may be given 4 hours after spinal or epidural catheter removal• Therapeutic LMWH may be given 24 hours after spinal or epidural catheter removalSources: FDA Drug Safety Communication Nov, 2013; NYP protocol
24 Post-Cesarean Prophylaxis Unfractionated heparin (UFH)The patient should receive the first dose of UFH on meeting criteria for PACU discharge, but no sooner than one hour after epidural catheter removalStandard order 5000 units SC every 12 hoursIf an epidural catheter remains in situ for pain control, it should not be removed until 3 hours after last dose of UFHIntraoperative UFH (infrequent) should be given no sooner than 30 minutes after spinal or epiduralSee Slide.NYP protocol
25 Post-Cesarean Prophylaxis Low-molecular-weight heparin (LMWH)The patient should receive the first dose of LMWH no sooner than 6 hours postoperatively regardless of anesthesia techniqueIf an epidural catheter remains in situ for pain control, it should not be removed until 12 hours after last dose of LMWHIf the epidural catheter is to be removed prior to a dose of LMWH, the LMWH may not be given until 4 hours after removalSee Slide.Sources: FDA Drug Safety Communication Nov, 2013; NYP protocol
26 Therapeutic Postpartum Prophylaxis For patients who have therapeutic LMWH postpartum anticoagulation planned:LMWH should be deferred until at least 24 hours after spinal needle placement or epidural catheter removalProphylactic UFH dosing should be considered during the 24 hours postpartum after regional anesthesia for these patientsFor patients with major risk factors for hemorrhage precluding therapeutic LMWH (recent postpartum hemorrhage, wound hematoma, coagulopathy) prophylactic UFH and/or SCDs should be consideredSee Slide.
27 ConclusionAll patients require VTE risk assessment at multiple time points in pregnancy and postpartumAll patients undergoing cesarean delivery require mechanical prophylaxis, early ambulation, and adequate hydrationWomen with additional risk factors for VTE after delivery will benefit from pharmacologic prophylaxisEmpiric pharmacologic prophylaxis for all women undergoing cesarean delivery and for all antepartum hospital admissions is a reasonable clinical strategyKey papers include major society guidelines, an overview of the role of VTE in maternal morbidity and mortality, and evidence that VTE prophylaxis is suboptimal in the United States.