Esfhan Final

7/27/2019 Esfhan Final

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Fetal loss Due toFetal loss Due toThrombophiliaThrombophilia

GHOLAMREZA TOOGEH, M.D.GHOLAMREZA TOOGEH, M.D.

THROMBOSETHROMBOSE HEMOSTASIS RESEARCHHEMOSTASIS RESEARCH

CENTER(THRC)CENTER(THRC)oo

SCIENCESES(TUMS)SCIENCESES(TUMS)


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Introduction:Introduction:

InIn theirtheir lifetimes,lifetimes, womenwomen areare likelylikely toto faceface situationssituations associatedassociatedwithwith anan increasedincreased riskrisk ofof venousvenous thromboembolismthromboembolism (VTE),(VTE), bebe itit

..

,,miscarriage,miscarriage, intrauterineintrauterine fetalfetal growthgrowth retardation,retardation, intrauterineintrauterinedeathdeath andand possiblypossibly abortionabortion andand eclampsia,eclampsia, areare reportedreported toto bebe

moremore commoncommon nn womenwomen ww rom op crom op c e ec se ec s..

--latelate fetalfetal loss,loss, thisthis riskrisk maymay bebe significantlysignificantly greatergreater inin womenwomen

multiplemultiple thrombophillicthrombophillic defectsdefects..

FewFew smallsmall studiesstudies werewere showedshowed comparedcompared toto pastpast pregnanciespregnanciest eret ere waswas aa g er g er successsuccess raterate vsvs nn treatetreate womenwomen..


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DEFECTS CAUSING RECURRENT

CHROMOSOME

7% 15%

ANATOMICHORMONAL


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Mechanisms of Recurrent Miscarriage Due to BloodMechanisms of Recurrent Miscarriage Due to Blood

Factor XIII DeficiencyFactor XIII Deficiency Von Willebrand DiseaseVon Willebrand Disease

AntiphosphoIipid SyndromeAntiphosphoIipid Syndrome Stick Platelet S ndromeStick Platelet S ndrome

ee ng sor ers rom o c sor ers

Factor X DeficiencyFactor X Deficiency

Factor VII DeficiencyFactor VII Deficiency

Factor V DeficiencyFactor V Deficiency

MTHFR MutationsMTHFR Mutations

HyperhomocysteinemiaHyperhomocysteinemia

PAIPAI 11 EIevation/PoIymorphismsEIevation/PoIymorphisms

Factor II DeficiencyFactor II Deficiency HypofibrinogenemiaHypofibrinogenemia

DysfibrinogenemiaDysfibrinogenemia

Protein S DeficiencyProtein S Deficiency Factor V LeidenFactor V Leiden

Prothrombin GProthrombin G2021020210AA

Hemophilia A CarrierHemophilia A Carrier Protein c DeficiencyProtein c Deficiency

Antithrombin DeficiencyAntithrombin Deficiency

HeparinHeparin Cofactor II DeficiencyCofactor II Deficiency e c encye c ency

Elevated Lipoprotein (a)Elevated Lipoprotein (a)

Immune VascuIitisImmune VascuIitis


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DALLAS THROMBOSISDALLAS THROMBOSIS-- HEMOSTASIS CLINICALHEMOSTASIS CLINICAL

CENTER EXPERIENCECENTER EXPERIENCE

ThreeThree -- hundredhundred fiftyfifty--oneone womenwomen referredreferred forfor thrombosisthrombosis

andand hemostasishemostasis evaluationevaluation andand managementmanagement duringduring..

,,chromosomalchromosomal defectsdefects hadhad beenbeen ruledruled outout..

TheThe meanmean patientpatient ageage atat referralreferral waswas 3434 yearsyears andand thethe

meanmean numbernumber ofof miscarriagesmiscarriages waswas 22..99((22--99))..

TheseThese patientspatients werewere assessedassessed overover aa threethree yearyear periodperiod..


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DALLAS THROMBOSIS HEMOSTASIS CLINICALDALLAS THROMBOSIS HEMOSTASIS CLINICAL

322(92%)29(8%)

DEFFCT

NN=351


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DALLAS THROMBOSIS HEMOSTASIS CLINICALDALLAS THROMBOSIS HEMOSTASIS CLINICAL

CENTER EXPERIENCECENTER EXPERIENCE

200

150

100

Series1 7 195 64 38 23 12 12 3 3 3 6

BLE

EDI

APL

SSPS

MTH

FR

PAI -

poly

Prot

ein

F V

Leid

AT

defic

Hep

arin-

TPA

defic

Prot

ein


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DALLAS THROMBOSIS HEMOSTASISDALLAS THROMBOSIS HEMOSTASIS

CLINICAL CENTER EXPERIENCECLINICAL CENTER EXPERIENCE

94%

100%

60%

80%

40%

0%

20%

Live birth Abortion


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na yzena yze consecu veconsecu ve pregnanpregnan womenwomen meanmean

age=age=2424 years)years) withwith eithereither DVTDVT associatedassociated withwith

evaluationevaluation ofof thrombophilliathrombophillia andand subsequentsubsequent..

,,cytogenetic,cytogenetic, hormonal,hormonal, anatomical,anatomical, andand infectiveinfective

--mentionedmentioned causescauses..


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Mumbai Institute of Immunohematology experiencesMumbai Institute of Immunohematology experiences

Live bir th rates achieved b LMWH and UFH in cases with recurrent

,,

fetal loss(RFL) and deep vein thrombosis (DVT)l

12

14

16

6

810 TOTAL PATIENT

LIVE BIRTH7 8 8

65

0

2

4

+ + + +

1 1


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Tehran University ThrombosisTehran University Thrombosis-- HemostasisHemostasis

Research Center ExperiencesResearch Center Experiences

REFERRED SELF-REFERRED

OBSTETRICIAN/REPRODUCTIVE MEDICINE

ANATOMIC ENDOCRINE GENETIC/CHROMOSOME APL-S

WORK-UP WORK-UP WORK-UP WORK-UP

NEGATIVE

WORK-UP

ETIOLGICAL DIAGNOSIS

TREATMENT PROGRAM DESIGNED


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Tehran Universit ThrombosisTehran Universit Thrombosis-- HemostasisHemostasis


Anal zedAnal zed 4747 consecutiveconsecutive womenwomen meanmean a e=a e=3030..66 earsearswithwith eithereither badbad obstetricobstetric historyhistory oror aa historyhistory ofof recurrentrecurrent

fetalfetal lossloss inin themselvesthemselves oror herher familyfamily forfor evaluationevaluation ofofpregnancypregnancy..

n coagu a on eg men:n coagu a on eg men:AllAll patientspatients withwith thrombophilliathrombophillia werewere treatedtreated immediateimmediate postpost--conce tionconce tion withwith ASAASA atat 8080 m /dam /da withwith additionaddition ofof LMWHLMWH(Dalteparin)(Dalteparin) 55,,000000 IU/dayIU/day subcutaneouslysubcutaneously untiluntil delivery,delivery, thetheanticoagulationanticoagulation waswas continuedcontinued 66 weeksweeks inin postpartumpostpartum..

TheThe patientspatients withwith MTHFRMTHFR (hemocysteinemia)(hemocysteinemia) werewere alsoalsotreatedtreated withwith folatefolate atat 55 mg/daymg/day ++ pyridoxinepyridoxine 5050mg ay+mg ay+ mon ymon y..


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Tehran Universit ThrombosisTehran Universit Thrombosis-- HemostasisHemostasis


Laboratory Monitoring:Laboratory Monitoring:

-- -- v yv y ww u eu e

inin thethe casecase ofof womenwomen treatedtreated withwith LMWHLMWH..

DuringDuring eacheach visit,visit, aa detaileddetailed historyhistory ofof..

TheThe patientpatient hadhad routineroutine bloodblood countcountur ngur ng o owo ow--upup ,w,w spec aspec a re erencere erence oo

thrombocytopeniathrombocytopenia..


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Age

Mean; 30.6

40

45

50

25

30

35

Age

10

15

20

0

0 5 10 15 20 25 30 35 40 45 50


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Number of Abortion

Mean; 2.6

6

7

4

5

2

3

1

0 10 20 30 40 50


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reqency o oagu a on e ec

12, 26% Coagulation

35, 74%Negative


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12

8

109

7

5

3 34

Hcy

PSde

PCde

FVL

IIIMut

atio

Nega

tive

FXII

de

-1Mut

atio

.G20

210A

APL-

S

CREA

SE

F PA P

FVIII

I


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o ow up a us

57%

Follow up


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Result of Treatment

25%72

20

10%28

5

Abortion Live birth


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Comparison of results

300

350

200

250

Total patients

100

150 Live birth

0

50

Dallas ex . Tehran ex . Munbai ex .


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Comparison of results

100% %94

80% %72

%60

60% Total patients

20%

0%Dallas exp. Tehran exp. Mumbai exp.


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nn ourour exper ence,exper ence, rom op arom op a ss aa commoncommon

causecause ofof recurrentrecurrent miscarriagemiscarriage andand allall patientspatients,,defectdefect shouldshould bebe evaluatedevaluated forfor thrombophilliathrombophillia oror

..

thesethese 2727 patientspatients waswas %%7272 usingusing ASAASA ++

..

,, ..

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