Bad Obstetric History and Fetal loss Due to Thrombophilia

GHOLAMREZA TOOGEH, M.D. THROMBOSE HEMOSTASIS RESEARCH CENTER(THRC) TEHRAN UNIVERSITY of f MEDICAL SCIENCESES(TUMS)

Introduction:

In their lifetimes, women are likely to face situations associated with an increased risk of venous thromboembolism (VTE), be it through hormonal therapy or pregnancy pregnancy. . Several pregnancy complications complications, including recurrent miscarriage, intrauterine fetal growth retardation, intrauterine death and possibly abortion and eclampsia, are reported to be more common in i women with ith thrombophillic th b hilli defects d f t. defects. Women with thrombophillia have a 2-3 fold increased risk of late fetal loss, this risk may be significantly greater in women multiple thrombophillic defects. defects. Few small studies were showed compared to past pregnancies there h was a higher hi h success rate (84 84% % vs 20 20% %) in i treated d women women. .

DEFECTS CAUSING RECURRENT MISCARRIAGE

7% 63%

15%
CHROMOSOME

15%

ANATOMIC HORMONAL COAGULATION

Mechanisms of Recurrent Miscarriage Due to Blood Coagulation Protein/Platelet Defects

Bl di Disorders Bleeding Di d

Th Thrombotic b ti Di Disorders d

Factor XIII Deficiency Von Willebrand Disease Factor X Deficiency Factor VII Deficiency Factor V Deficiency Factor II Deficiency Hypofibrinogenemia Dysfibrinogenemia Hemophilia A Carrier

AntiphosphoIipid Syndrome Sticky y Platelet Syndrome y MTHFR Mutations Hyperhomocysteinemia PAI 1 EIevation/PoIymorphisms Protein S Deficiency Factor V Leiden Prothrombin G20210 G20210A A Protein c Deficiency Antithrombin Deficiency Heparin Cofactor II Deficiency TPA D Deficiency fi i Elevated Lipoprotein (a) Immune VascuIitis

DALLAS THROMBOSISTHROMBOSIS- HEMOSTASIS CLINICAL CENTER EXPERIENCE

Three - hundred fifty fifty-one women referred for thrombosis and hemostasis evaluation and management during pregnancy after suffering recurrent miscarriages miscarriages. . All patients were referred after anatomic ,hormonal hormonal or chromosomal defects had been ruled out out. . The mean patient age at referral was 34 years and the mean number of miscarriages was 2.9(2-9). These patients were assessed over a three year period. period.

DALLAS THROMBOSIS HEMOSTASIS CLINICAL CENTER EXPERIENCE

29(8%) 322(92%)

NO DEFFECT DEFFCT

N=351

DALLAS THROMBOSIS HEMOSTASIS CLINICAL CENTER EXPERIENCE

200

150

100

50

MTH PAI - Prot F V AT Hep TPA Prot BLE APL SPS FR poly ein Leid defic arin- defic ein EDI S 7 195 64 38 23 12 12 3 3 3 6

Series1

DALLAS THROMBOSIS HEMOSTASIS CLINICAL CENTER EXPERIENCE

Result of Treatment

94% 100% 80% 60% 40% 20% 0% Live birth Abortion 6%

Mumbai Institute of Immunohematology experiences

Analyzed A l d 32 consecutive ti pregnant t women (mean ( age=24 age= 24 years) with either DVT associated with pregnancy or a history of recurrent fetal loss for evaluation of thrombophillia and subsequent management during pregnancy pregnancy. . All the women had a thorough investigation (ie, (ie cytogenetic, hormonal, anatomical, and infective causes for fetal loss) and were negative for above abovementioned causes causes. .

Mumbai Institute of Immunohematology experiences (Kanjaksha Ghosh,etal) Ghosh etal)

Live birth rates achieved by LMWH and UFH in cases with recurrent fetal loss(RFL) and deep vein thrombosis (DVT)l
18 16 14 12 10 8 6 4 2 0

17

8 6 5 1 1

TOTAL PATIENT LIVE BIRTH

RFL+UFH RFL UFH

RFL+LMWH RFL LMWH

DVT+UFH DVT UFH

DVT+LMWH DVT LMWH

Tehran University Thrombosis Thrombosis- Hemostasis Research Center Experiences

REFERRED SELF-REFERRED

OBSTETRICIAN/REPRODUCTIVE MEDICINE

ANATOMIC WORK-UP

ENDOCRINE WORK-UP

GENETIC/CHROMOSOME WORK-UP

APL-S WORK-UP

COAGULATION/IMMUNOLOGIC WORK-UP

NEGATIVE

ETIOLGICAL DIAGNOSIS TREATMENT PROGRAM DESIGNED

Tehran University y ThrombosisThrombosis- Hemostasis Research Center Experiences

Analyzed 47 consecutive women (mean age age=30 age= 30. 30 .6 years) with either bad obstetric history or a history of recurrent fetal loss in themselves or her family for evaluation of thrombophillia and subsequent management during pregnancy. pregnancy . A ti Anticoagulation l ti R Regimen: i All patients with thrombophillia were treated immediate post postconception p with ASA at 80 mg/day g y with addition of LMWH (Dalteparin) 5,000 IU/day subcutaneously until delivery, the anticoagulation was continued 6 weeks in postpartum postpartum. . The patients with MTHFR (hemocysteinemia) were also treated with folate at 5 mg/day + pyridoxine 50 mg/day+B12 mg/day+B /d +B12 +B12/monthly 12/ / /monthly. thl .

Tehran University y ThrombosisThrombosis- Hemostasis Research Center Experiences

Laboratory

Monitoring: No anti anti-Xa or anti anti-IIa activity was studied in the case of women treated with LMWH LMWH. . During each visit, a detailed history of bleeding was taken from each patient patient. . The patient had routine blood count d i during f ll -up ,with followfollow ith special i l reference f t to thrombocytopenia. thrombocytopenia .

Tehran University ThrombosisThrombosis- Hemostasis Research Center Experiences

Age

Mean; ; 30.6y y
50 45 40 35 30 25 20 15 10 5 0 0 5 10 15 20 25 30 35 40 45 50

Age

Tehran University ThrombosisThrombosis- Hemostasis Research Center Experiences

Number of Abortion
Mean; 2.6

7 6 5 4 Series1 3 2 1 0 0 10 20 30 40 50

Tehran University ThrombosisThrombosis- Hemostasis Research Center Experiences

F Freqency of f Coagulation C l ti Defect D f t

12, 26% 35, 74%

Coagulation defect Negative

Tehran University ThrombosisThrombosis- Hemostasis Research Center Experiences

Etiology of Coagulation Defects
12 10 8 9 7 5 2 2 3 3 4

H PS cy de PC f de f FX II I FV M L ut N ati o eg n at PA F ive I-1 XII d Pr Mu ef o. ta G ti o 20 n FV 21 0A II I IN AP C LR EA S SE D

Tehran University ThrombosisThrombosis- Hemostasis Research Center Experiences

F ll Follow up Status St t

43% 57%

No Follow up Follow up

Tehran University ThrombosisThrombosis- Hemostasis Research Center Experiences

Result of Treatment
%72

25 20 15 10 5 0 Abortion
%28

Live birth

Conclusion
Comparison of results
350 300 250 200 150 100 50 0 Dallas exp. p Tehran exp. p Munbai exp. p Total patients Live birth

Conclusion
Comparison p of results
100% 80% 60% Total patients 40% 20% 0% Dallas exp. Tehran exp. Mumbai exp. Live birth
%94 %72 %60

Conclusion

I our experience, In i th thrombophillia b hilli i is a common cause of recurrent miscarriage and all patients with no anatomical, anatomical hormonal or chromosomal defect should be evaluated for thrombophillia or bleeding disorder disorder. . The success rate of normal term delivery in these 27 patients was %72 using ASA + Daltaparin. Daltaparin . In addition, addition side effects of therapy were minimal minimal. .