Prosthetic Heart Valves and Anticoagulation use during

Pregnancy

WaelWael AlAl--HusamiHusami MD, FACCMD, FACCInterventional Cardiology and Vascular MedicineInterventional Cardiology and Vascular Medicine

LaheyLahey Clinic Medical CenterClinic Medical Center

Tufts University School of MedicineTufts University School of Medicine

BostonBoston

OverviewOverview1.1. Historical Perspective.Historical Perspective.2. Bioprostheses (Tissue valves).3. Mechanical prostheses.4. Selection of PHV in women of childbearing age

who desire to become pregnant.5. Maternal and fetal risks associated with

pregnancy in patients with PHV.6. Management of patients with PHV during

pregnancy.

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Historical PerspectiveHistorical Perspective1953: Development of the heart/lung machine (cardiopulmonary bypass) allowed intra-cardiac procedures to beperformed.Later, improvements (cardio-plegia) led to asystolic arrest.1960: First Cardiac Valve Replacement.1968: Coronary Artery Bypass Surgery.

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Classification of Prosthetic Heart Valves

1- Biological or tissue valves, with flexible leaflet occluders of animal or human origin.

2- Mechanical prostheses, with rigid, manufactured occluders.

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DefinitionsDefinitionsAutograft valve refers to a translocation within the same individual, eg, of the pulmonary valve into the aortic valve position. Autologous (or autogenous) tissue valve involves fabricating a valve from the patient’s own nonvalvular tissue, eg, pericardium.

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DefinitionsDefinitions Cont.Cont.

Homograft (or allograft) valve refers to transplantation from a donor of the same species; eg, a donor’s aortic or pulmonary valve into a recipient’s aortic or pulmonary position.

Heterograft (or xenograft) valve is a transplant from another species, either an intact valve, eg, a porcine aortic valve, or a valve fashioned from heterologous tissue, eg, bovine pericardium.

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DefinitionsDefinitionsComplications of Prosthetic Heart ValvesComplications of Prosthetic Heart ValvesStructural Structural valvularvalvular deterioration (SVD)deterioration (SVD):: any change in any change in function of an operated valve resulting from an function of an operated valve resulting from an intrinsic intrinsic abnormality causing abnormality causing stenosisstenosis or regurgitation.or regurgitation.

Nonstructural dysfunction :Nonstructural dysfunction : any abnormality resulting in any abnormality resulting in stenosisstenosis or regurgitation of the operated valve that or regurgitation of the operated valve that is not is not intrinsicintrinsic to the valve itself exclusive of thrombosis and to the valve itself exclusive of thrombosis and infection. This includes infection. This includes inappropriate inappropriate sizing, also called sizing, also called valve prosthesisvalve prosthesis––patient mismatch.patient mismatch.

the American Association for Thoracic Surgery (AATS) and the Socthe American Association for Thoracic Surgery (AATS) and the Society of Thoracic Surgeons iety of Thoracic Surgeons (STS) Guidelines for Clinical Reporting. In 1988(STS) Guidelines for Clinical Reporting. In 1988

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DefinitionsDefinitionsComplications of Prosthetic Heart ValvesComplications of Prosthetic Heart Valves Cont.Cont.

Valve thrombosis:Valve thrombosis: any thrombus, in the absence of any thrombus, in the absence of infection, attached to or near an operated valve that infection, attached to or near an operated valve that occludes part of the blood flow path or interferes occludes part of the blood flow path or interferes with function of the valve.with function of the valve.EmbolismEmbolism is any embolic event that occurs in the is any embolic event that occurs in the absence of infection after the immediate absence of infection after the immediate perioperativeperioperative period. This includes any new, period. This includes any new, temporary or permanent, focal or global temporary or permanent, focal or global neurological deficit and peripheral embolic event.neurological deficit and peripheral embolic event.

the American Association for Thoracic Surgery (AATS) and the Socthe American Association for Thoracic Surgery (AATS) and the Society of Thoracic Surgeons iety of Thoracic Surgeons (STS) Guidelines for Clinical Reporting. In 1988(STS) Guidelines for Clinical Reporting. In 1988

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Choice of ProsthesisChoice of Prosthesis

Durability of Prosthesis.Necessity for anticoagulationanticoagulation.Risk of Thrombo-embolism & Bleeding.Re-operation rate .Hemodynamic Performance.Possible future pregnancy.

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Tissue Valves1.1. Porcine Porcine HeterograftsHeterografts..2.2. StentlessStentless Porcine Porcine XenograftsXenografts..3.3. Pericardial (Pericardial (XenograftXenograft) Aortic valves.) Aortic valves.4.4. Homograft ( Allograft) Aortic Valves.Homograft ( Allograft) Aortic Valves.5.5. Pericardial Pericardial AutograftAutograft Valves.Valves.6.6. Pulmonary Pulmonary AutograftsAutografts /The Ross procedure./The Ross procedure.

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11-- StentedStented Porcine aortic Porcine aortic HeterograftsHeterografts

Widely used for the Widely used for the mitralmitral & the aortic & the aortic positions.positions.Mounted on rigid or flexible stents to which the leaflets and sewing ring are attached.Most of the information regarding pregnancy in women with bioprostheticvalves has been obtained in women with porcine heterografts.

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Porcine Porcine HeterograftsHeterografts

Hancock valveHancock valve Medtronic Intact valveMedtronic Intact valve

CarpenterCarpenter--Edwards valvesEdwards valves

Braunwald E, Heart Disease. 7th edition. 2005;1553– 621AlAl--HusamiHusami

Ann Ann ThoracThorac SurgSurg 1995;60: S2211995;60: S221--88

Durability of the Hancock Bioprosthesis Compared With Standard Aortic Valve Bioprostheses

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Ann Ann ThoracThorac SurgSurg 1995;60: S2211995;60: S221--88AlAl--HusamiHusami

22-- StentlessStentless Porcine Porcine XenograftsXenografts::

Since the Since the stentstent adds to the obstruction & increase adds to the obstruction & increase stress on the leaflets, stress on the leaflets, stentlessstentless valves have been valves have been developed for the aortic developed for the aortic postionpostion..More physiological flow& low More physiological flow& low transvalvulartransvalvulargradients than gradients than stentedstented porcine valves.porcine valves.Provide superior hemodynamic profile compared to stented porcine aortic heterografts especially in patients with small aortic root *

*Hvass et al. J Thorac Cardiovasc Surg 1999;117:267–72AlAl--HusamiHusami

StentlessStentless Porcine Porcine XenograftsXenografts::

St. Jude Medical St. Jude Medical stentlessstentless valvevalve Edwards Edwards stentlessstentless valvevalve

Medtronic Freestyle valveMedtronic Freestyle valve

Braunwald E, Heart Disease. 7th edition. 2005;1553– 621AlAl--HusamiHusami

33-- Pericardial (Pericardial (XenograftXenograft) ) Aortic valvesAortic valves

Bovine pericardial valves are fabricated rather Bovine pericardial valves are fabricated rather than harvested directly.than harvested directly.Good longGood long--term durability that appears to be term durability that appears to be equivalent or better than that of the equivalent or better than that of the procineprocinebioprosthesisbioprosthesisGreater risk to develop MS.Greater risk to develop MS.

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CarpenterCarpenter--EdwardsEdwardsBovine Pericardial ValveBovine Pericardial Valve

LaheyLahey Clinic Clinic CathCath Lab. 2006Lab. 2006AlAl--HusamiHusami

Figure 5. Freedom from structural valve deterioration (SVD) Figure 5. Freedom from structural valve deterioration (SVD)

for porcine and pericardial aortic valve replacement patients.for porcine and pericardial aortic valve replacement patients.

Gao et al. J Am Coll Cardiol 2004;44:384–8AlAl--HusamiHusami

Gao et al. Concluded Concluded

Freedom from structural deterioration and Freedom from structural deterioration and reoperationreoperation makes pericardial valves makes pericardial valves bioprosthesisbioprosthesis of choice for aortic valve of choice for aortic valve replacement. replacement. The 10The 10--year results for the pericardial valve year results for the pericardial valve continue to demonstrate a strong performance, continue to demonstrate a strong performance, which may broaden its indication to younger which may broaden its indication to younger patients with aortic valve disease. patients with aortic valve disease.

Gao et al. J Am Coll Cardiol 2004;44:384–8AlAl--HusamiHusami

44-- Homograft ( Allograft) Aortic Homograft ( Allograft) Aortic Valves:Valves:

First tissue valve to be used in 1960.First tissue valve to be used in 1960.Harvested from cadavers within 24 hrs of donor death.Harvested from cadavers within 24 hrs of donor death.Advantages:HemodynamicsHemodynamics are superior to are superior to stentedstented porcine valves and porcine valves and similar to similar to stentlessstentless porcine valves.porcine valves.Low Low ThrombogenicityThrombogenicityExtremely low rate of infection and are indicated for Extremely low rate of infection and are indicated for patients with native or prosthetic valve patients with native or prosthetic valve endocarditisendocarditis..Preferable substitute for AVR in younger patients.

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Disadvantages:Not on shelf.Re-operation difficult.

Homograft ( Allograft) Aortic ValvesHomograft ( Allograft) Aortic Valves

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Homograft Aortic Valve Homograft Aortic Valve Durability

M.OM.O’’BrienBrien et al J. Heart V. et al J. Heart V. DisDis 2001;10:3342001;10:334--345345

1,022 patients mean age 47yrs: Actuarial Survival1,022 patients mean age 47yrs: Actuarial Survival

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55-- Pericardial Pericardial AutograftAutograftValves:Valves:

PatientPatient’’s own pericardium is inserted into s own pericardium is inserted into a frame, then used into either the aortic or a frame, then used into either the aortic or the the mitralmitral position position LongLong--term durability appears to be term durability appears to be excellent excellent

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66-- Pulmonary Pulmonary AutograftsAutografts(The Ross procedure)(The Ross procedure)

The patientThe patient’’s own Pulmonary valve is removed s own Pulmonary valve is removed and used to replace the Aortic valve, then the and used to replace the Aortic valve, then the aortic homograft valve is then inserted into aortic homograft valve is then inserted into Pulmonary position.Pulmonary position.

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The Ross procedure The Ross procedure cont.cont.

AdvantagesAdvantagesViable aortic valveNonthrombogenicNonthrombogenicRisk of Risk of endocarditisendocarditis is low.is low.No anticoagulation.anticoagulation.LongLong--term durability appears to be term durability appears to be excellent. excellent. It can be used in children, adolescents, and It can be used in children, adolescents, and young women who wish to be a pregnant.young women who wish to be a pregnant.

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The Ross procedure The Ross procedure cont.cont.

DisadvantagesDisadvantages

Longer operation.High incidence of Pulmonary homograft High incidence of Pulmonary homograft stenosisstenosis..High re-operation in this group of patients because of progression of aortic regurgitation.Concomitant severe mitral valve regurgitation.

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The Ross procedure The Ross procedure cont.cont.

Contraindications:Contraindications:Bicuspid valves and dilated aortic roots, Bicuspid valves and dilated aortic roots, because the implanted pulmonary artery tissue because the implanted pulmonary artery tissue exposed to higher aortic pressures leading to exposed to higher aortic pressures leading to significant dilation of the significant dilation of the autograftautograft..Marfans Syndrome.Some connective tissue disease (R.arthritis/ SLE).Active rheumatic heart disease.Triple vessel CAD/ Mitral v. dis..

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Does pregnancy accelerate the rate of bioprosthetic

SVD?AlAl--HusamiHusami

SVD bioprostheses

Hanania et al. 7 74Kadri et al. 4 14Sbarouni et al. 17 49Born et al. 33 20Lee et al. 44 5757 graft survival rate 17% in two

pregnancy vs 55% in one pregnancy.

Badduke et al. 88 17 37 pregnancies.10 SVD per 70 Non-pregnant

Does pregnancy accelerate the rate of bioprosthetic SVD?

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Reports Failed to Support the Reports Failed to Support the previous studiesprevious studies

Preg. Non-Preg

SVDPregPreg..

SVDNonNon

Avila et al. 48 37 27% 30% Re-operation(8% in both groups)

Jamieson et al. 53 202 51% 41%

Salazar et al. 58 107 3.5%Perpatient-year

3.4%Perpatient-year

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Freedom from Structural Valve Freedom from Structural Valve DeteriorationDeterioration

Jamieson et al. Ann Jamieson et al. Ann ThTh Surg.1995Surg.1995

PregnantPregnant NonNon--PregnantPregnant

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Early Mortality for reEarly Mortality for re--operationoperation

Ann Thorac Surg Jamieson et al. 1995;60:S282-7AlAl--HusamiHusami

In Summary

Deterioration of bioprosthetic heart valves during pregnancy has been reported in several studies, but could not be confirmed by others.Although most available data might support an accelerated SVD of bioprosthetic valves during pregnancy, this could simply reflect the well-established deterioration of tissue valves in young individuals.

Elkayam et al. JACC Vol. 46, No. 3, 2005AlAl--HusamiHusami

Choice of ProsthesisChoice of Prosthesis

Durability of Prosthesis.Necessity for anticoagulationanticoagulation.Risk of Thrombo-embolism & Bleeding.Re-operation rate .Hemodynamic Performance.Possible future pregnancy.

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ThromboembolicThromboembolic EventEvent

Circulation North et al.1999;99;2669-2676AlAl--HusamiHusami

Tissue ValvesFirst 3 First 3 postoppostop. Months, the . Months, the thromboembolicthromboembolic rate is high for that rate is high for that anticoagulation is required while anticoagulation is required while sewing ring becomes sewing ring becomes endothelializedendothelialized..ThromboembolicThromboembolic event is 1event is 1--2/ 100 2/ 100 patientspatients--years.years.

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Early Mortality for Early Mortality for rere--operationoperation

Because women of childbearing age who receive bioprosthetic valves are likely to need re-operation, the risk associated with a second surgery has to be considered when a PHV is being selected. Early mortality for re-operation in such patient populations has been reported to be 3.8% in one study (1) and 8.7% in another (2).

(1) Jamieson et al. Ann Thorac Surg 1995;60 S282–7 (2) Badduke J ThoracCardiovasc Surg 1991;102:179–86

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Hemodynamic Profile

HemodynamicHemodynamic profiles are similar to profiles are similar to those of comparable sized.those of comparable sized.The hemodynamic profile of the stentedporcine heterografts is, in general, inferior to that of low profile mechanical prostheses of comparable size.

Vongpatanasin et al. N Engl J Med 1996;335:407–16AlAl--HusamiHusami

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Mechanical ProsthesesMechanical Prostheses

CagedCaged--ballballTiltingTilting--discdiscBileafletBileaflet valvesvalves

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StarrStarr--Edwards Edwards CagedCaged--ballball

The oldest prosthetic valve in continuous The oldest prosthetic valve in continuous use.use.Has the longest record of predictable Has the longest record of predictable performance of any artificial valve.performance of any artificial valve.Were extensively used in women of Were extensively used in women of childchild--bearing age & during pregnancy.bearing age & during pregnancy.

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CagedCaged--ball Disadvantagesball Disadvantages

Bulky, therefore, it is not suitable for:Bulky, therefore, it is not suitable for:11-- MitralMitral position in patient with small LV position in patient with small LV cavity.cavity.22-- Aortic Aortic postionpostion in patient with a small aortic in patient with a small aortic annulus, or those requiring a valveannulus, or those requiring a valve--aortic arch aortic arch composite graft.composite graft.The incidence of The incidence of theromboembolismtheromboembolism is is slightly higher than other mechanical slightly higher than other mechanical prostheses valves.prostheses valves.

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CagedCaged--ballball

LaheyLahey Clinic Clinic CathCath Lab. 2006Lab. 2006AlAl--HusamiHusami

BileafletBileaflet valvesvalves

St. Jude St. Jude BileafletBileaflet valves are the most widely valves are the most widely used.used.Less bulky Less bulky Lower profile than cagedLower profile than caged--ball, and are therefore ball, and are therefore has superior has superior hemodynamicshemodynamics. . Favorable flow characteristics especially in the Favorable flow characteristics especially in the smaller sizes and causes a lower smaller sizes and causes a lower transvalvulartransvalvularpressure gradient & cardiac output. Therefore, it pressure gradient & cardiac output. Therefore, it is useful in children. is useful in children.

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BileafletBileaflet Valves Valves Cont.Cont.

ThrombogenicityThrombogenicity in in MitralMitralposition is < other prosthetics.position is < other prosthetics.The leaflets swing apart during opening, creating 3 flow areas, 1 central and 2 peripheral.

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St. Jude St. Jude BileafletBileaflet valvevalve

LaheyLahey Clinic EP Lab. 2006Clinic EP Lab. 2006AlAl--HusamiHusami

TiltingTilting--discdisc

11--Omniscience valve :Omniscience valve :The disc swings to an 80 degreeThe disc swings to an 80 degreeangle, providing a large centralangle, providing a large centralflow orifice.flow orifice.

22--MedtronicMedtronic--Hall valve:Hall valve:Has a central perforation to Has a central perforation to improve the improve the HemodynamicsHemodynamics..

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Mechanical PHVs Problems during Pregnancy

Risk of thromboembolism and maternal bleeding. On Fetal, increased risk of :1- Fetal loss.2- Prematurity.3- Low birth weight.4- Birth defects.5- Mortality.

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Summary & Recommendations

The selection of PHV for women of childbearing The selection of PHV for women of childbearing age remains difficult and needs to be age remains difficult and needs to be individualized.individualized.Bileaflet mechanical valves provide a superb record of durability, excellent hemodynamic profile, and relatively small risk of thromboembolic and bleeding complications with careful anticoagulation.

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Summary and RecommendationsCont.

In women who are not interested in anticoagulation or for whom close follow-up is not possible, a tissue valve is preferred.In the aortic position, homografts, pericardial valves, and stentless porcine xenografts have not been extensively used in pregnancy.(Ross procedure) is associated with higher rateof SVD and need for re-operation compared with the new-generation mechanical prostheses.

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Preconception evaluation and consultation

Careful history & physical examination.Echo-Doppler study to evaluate cardiac and valvularfunction. Exercise testing with maximum oxygen consumption, can provide an objective estimation of functional capacity.The patient and her family should be advised onpotential complications that might occur during pregnancy.Marked impairment of LV function, symptomatic (class III and IV) should be advised against pregnancy.

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MANAGEMENT OF COMPLICATIONS

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Effect of Effect of ValvularValvular Heart Disease Heart Disease (VHD) on Maternal Outcome of (VHD) on Maternal Outcome of

PregnancyPregnancy

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Safe Drugs

1- Digoxin2- Diuretics3- Nitrates4- Hydralazine5- beta blockers.

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Contraindicated Drugs:1- ACE inhibitors: neonatal anuria, renal failure, limb deformities, cranial ossification deficits, and lung hypoplasia, renal tubular renal tubular dysplasiadysplasia, prolonged neonatal , prolonged neonatal hypotension, and patent hypotension, and patent ductusductus arteriosusarteriosus..2- Angiotensin receptor antagonist.3- Amiodarone: changes in fetal thyroid function, Congenital hypothyroidism, Mental Retardation.4- Sodium Nitroprusside: animal study showed adverse fetal effect.

55-- StatinsStatins:: Sever CNS defects and limb deformities. Sever CNS defects and limb deformities. AlAl--HusamiHusami

Anticoagulant use During Anticoagulant use During Pregnancy in Women with Pregnancy in Women with

ValvularValvular Heart DiseaseHeart Disease

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HematologicHematologic Changes During Changes During PregnancyPregnancy

↑↑ Clotting factor concentration Clotting factor concentration (Fibrinogen, Von (Fibrinogen, Von WillebrandWillebrand Factor, Factor, Factor VIII)Factor VIII)↑↑ Platelet adhesiveness.Platelet adhesiveness.↓↓ FibrinolysisFibrinolysis..↓↓ Protein S activity.Protein S activity.Stasis throughout vascular bed.Stasis throughout vascular bed.↑↑ risk thrombosis & embolism.risk thrombosis & embolism.

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Prosthetic Valve ThrombosisProsthetic Valve Thrombosis

Pregnancy is associated with an increasedincidence of thromboembolism due to a hypercoagulable state.Thromboembolic events occur in 7%-23% of patients, one-half of them with valve thrombosis.1-4% maternal mortality.

Chan WS, Arch Chan WS, Arch IntInt Med 2000; 160(2): 191Med 2000; 160(2): 191--66AlAl--HusamiHusami

Prosthetic Valve ThrombosisProsthetic Valve ThrombosisCont.Cont.

Patients at high risk:Patients at high risk:11-- Older generation valve in the Older generation valve in the mitralmitralposition.position.

22-- Multiple prosthetic valves.Multiple prosthetic valves.Most effective anticoagulant has the Most effective anticoagulant has the highest risk of fetal complications.highest risk of fetal complications.

Chan WS, Arch Chan WS, Arch IntInt Med 2000; 160(2): 191Med 2000; 160(2): 191--66AlAl--HusamiHusami

Prosthetic Valve Thrombosis Prosthetic Valve Thrombosis Cont.Cont.

S&S: S&S: Sudden Sudden dyspneadyspnea, Muffled sounds & New , Muffled sounds & New murmurs.murmurs.

Complications: peripheral embolization and bleeding, were reported in 18% and death in 5.6%.

DxDx:: TEE.TEE.Rx:Rx: ThrombolyticThrombolytic agent for 24agent for 24--72 hrs, heparin & 72 hrs, heparin & Aspirin.Aspirin.Surgery Surgery is required for is required for nonrespondersnonresponders & mobile & mobile thrombi & thrombi & in whom thrombolysis is contraindicated.

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WarfarinWarfarin AnticoagulationAnticoagulationLow molecular weightLow molecular weight-- Crosses placenta.Crosses placenta.Effect greater in the fetus than the mother, Effect greater in the fetus than the mother, ↓↓ VitVit K K dependent factors in fetal liver.dependent factors in fetal liver.Fetal Complications: spontaneous abortions, stillbirths, Fetal Complications: spontaneous abortions, stillbirths, hemorrhage, hemorrhage, warfarinwarfarin embryopathiesembryopathies ((chondromalaciachondromalaciapunctatapunctata, stippled epiphyses and nasal and limb , stippled epiphyses and nasal and limb hypoplasiahypoplasia, CNS abnormalities, optic atrophy, , CNS abnormalities, optic atrophy, microcephalymicrocephaly, mental retardation, , mental retardation, spasticityspasticity, , hypotoniahypotonia, , and Low IQ).and Low IQ).RetroplacentalRetroplacental hemorrhage.hemorrhage.

William William GaaschGaasch ( ( LaheyLahey Clinic), Clinic), Jess MandelJess MandelAlAl--HusamiHusami

WarfarinWarfarin EmbryopathiesEmbryopathies

Exposure 6Exposure 6--12 weeks gestation.12 weeks gestation.Past reported 30% risk.Past reported 30% risk.Incidence 4Incidence 4--10%10%Oakley et al: Br Heart J 1995Oakley et al: Br Heart J 1995

Dose related, low risk with< 5 mg/dayDose related, low risk with< 5 mg/dayVitale et al: J Am Vitale et al: J Am CollColl Cardio 1999Cardio 1999

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UF Heparin in PregnancyUF Heparin in Pregnancy

High molecular weight, dose not High molecular weight, dose not cross placenta.cross placenta.Short half life.Short half life.Variable responseVariable response-- dose adjusted, dose adjusted, Close PTT monitoring.Close PTT monitoring.Treatment of choiceTreatment of choice-- late pregnancy, late pregnancy, delivery.delivery.

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UF Heparin in Pregnancy UF Heparin in Pregnancy Cont.Cont.

↑↑ risk of prosthetic valve thrombosisrisk of prosthetic valve thrombosis→→ thrombothrombo--embolic events, embolic events, ↑↑ maternal & maternal & fetal mortality.fetal mortality.Long term use not recommendedLong term use not recommendedOsteoporosis= 30%, sterile abscesses.Osteoporosis= 30%, sterile abscesses.↑↑ risk of maternal hemorrhage bleeding at risk of maternal hemorrhage bleeding at utroplacentalutroplacental junction.junction.

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Uncertainty Regarding Uncertainty Regarding LMWHLMWH

Dose not cross the placenta, no Dose not cross the placenta, no teratogenicteratogeniceffects.effects.AntithromboticAntithrombotic protection.protection.Potential advantages.Potential advantages.↑↑ Bioavailability, administration ease.Bioavailability, administration ease.↓↓ Osteoporosis & Thrombocytopenia.Osteoporosis & Thrombocytopenia.

MelissariMelissari E; E; ThrombThromb& & HemostHemost 19921992AlAl--HusamiHusami

Uncertainty Regarding Uncertainty Regarding LMWH LMWH Cont.Cont.

Weight based administration inadequate in Weight based administration inadequate in pregnancy.pregnancy.* * Measurement of antiMeasurement of anti--XaXa activity necessary activity necessary to ensure adequate anticoagulation in to ensure adequate anticoagulation in pregnancy.pregnancy.Peak( 4 hr post) antiPeak( 4 hr post) anti--XaXa level= 1.0 U/ml.level= 1.0 U/ml.Avoid excessive AC, antiAvoid excessive AC, anti--XaXa level>1.5 level>1.5 U/ml.U/ml.

Barbour L: Am J Barbour L: Am J ObstetObstet GynecolGynecol 2004.2004.AlAl--HusamiHusami

Complications of Complications of EnoxaparinEnoxaparinUse During Pregnancy.Use During Pregnancy.

Pregnancies 624 Pregnancies 624 Hemorrhagic events 72(10.4%)Hemorrhagic events 72(10.4%)Serious Hemorrhage 11(1.6%)Serious Hemorrhage 11(1.6%)Neonatal hemorrhage 14(2.0%)Neonatal hemorrhage 14(2.0%)Major Congenital abnormalities 17(2.5%)Major Congenital abnormalities 17(2.5%)

LepercqLepercq j, Br J j, Br J ObstetObstet GynecGynec 2001; 108(11): 11342001; 108(11): 1134--4040AlAl--HusamiHusami

Congenital Anomalies with use Congenital Anomalies with use of of LovenoxLovenox in Pregnant Womenin Pregnant Women

2002:2002:““There have been reports of congenital anomalies in infants There have been reports of congenital anomalies in infants born to women who received born to women who received enoxaparinenoxaparin during pregnancy during pregnancy including cerebral anomalies, limb anomalies, including cerebral anomalies, limb anomalies, hypospadiashypospadias, , peripheral vascular malformation, peripheral vascular malformation, fibroticfibrotic dysplasiadysplasia, and , and cardiac defect. A cause and effect relationship has not been cardiac defect. A cause and effect relationship has not been established nor has the incidence been shown to be higher than established nor has the incidence been shown to be higher than in the general population.in the general population.””July 2003: July 2003: ““Pregnant women with Pregnant women with thromboembolicthromboembolic disease, including disease, including those with mechanical prosthetic heart valves, and those with those with mechanical prosthetic heart valves, and those with inherited or acquired inherited or acquired thrombophiliasthrombophilias, also have increased risk , also have increased risk of other maternal complications and fetal loss regardless of theof other maternal complications and fetal loss regardless of thetype of anticoagulant used.type of anticoagulant used.””

FDA Precautions for use of FDA Precautions for use of LovenoxLovenox in Pregnant Womenin Pregnant WomenAlAl--HusamiHusami

FDA Precautions for use of FDA Precautions for use of LovenoxLovenox in Pregnant Womenin Pregnant Women

20022002““ The use of The use of lovenoxlovenox injection is not injection is not recommended for recommended for thromboprophylaxisthromboprophylaxis in in patients with prosthetic heart valves.patients with prosthetic heart valves.””

July 2003July 2003““The use of The use of LovenoxLovenox injection for injection for

thromboprophylaxisthromboprophylaxis in pregnant women in pregnant women with mechanical prosthetic heart valves has with mechanical prosthetic heart valves has not been adequately studiednot been adequately studied””

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2003 2003 AHA/ACCScientific Statement on Scientific Statement on WarfarinWarfarin

UFH/LMWH throughout pregnancy.UFH/LMWH throughout pregnancy.WarfarinWarfarin throughout pregnancy switch to throughout pregnancy switch to UFH/LMWH at wk 38.UFH/LMWH at wk 38.UFH/LMWH first trimester, UFH/LMWH first trimester, warfarinwarfarin 22ndnd

trimester, UFH/LMWH at wk 38.trimester, UFH/LMWH at wk 38.* Premature labor common, recommendation * Premature labor common, recommendation to switch at week 36.to switch at week 36.

Hirsh et al Circulation April 1, 2003AlAl--HusamiHusami

American College of Chest Physicians recommendations,

published in 2004

Ginsberg JS, Chest 2001;119:122SGinsberg JS, Chest 2001;119:122S--131S131SAlAl--HusamiHusami

Anticoagulation Prophylaxis in Anticoagulation Prophylaxis in Pregnant Women With a Prosthetic Pregnant Women With a Prosthetic

Heart ValveHeart Valve

Elkayam et al. et al. JACC Aug.,2005AlAl--HusamiHusami

Anticoagulation in PregnancyAnticoagulation in PregnancySummary and ConclusionsSummary and Conclusions

Decision regarding AC for PHV in pregnancy Decision regarding AC for PHV in pregnancy requires detailed discussion.requires detailed discussion.Insufficient data to predict efficacy & safety of Insufficient data to predict efficacy & safety of any regimen.any regimen.Risk of AC in pregnant pt was PHV related to Risk of AC in pregnant pt was PHV related to inadequate dosing & monitoring.inadequate dosing & monitoring.Meticulous monitoring must be emphasized.Meticulous monitoring must be emphasized.

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Summary and Conclusions Summary and Conclusions Cont.Cont.

Low dose Aspirin:Low dose Aspirin:11-- SafeSafe-- antithromboticantithrombotic effect has not proven.effect has not proven.22-- Recommended for pt with shunts, Recommended for pt with shunts, cynosiscynosis & & biological valves.biological valves.33--Possible Possible ↓↓ incidence of incidence of preeclampsiapreeclampsia..LMWHLMWHNot enough information available in 2008.Not enough information available in 2008.ThrombolyticThrombolytic therapytherapyEmergency use only.Emergency use only.

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