Thrombophilia and unexplained pregnancy loss in Indian patients.
BACKGROUND
The role of acquired and congenital thrombophilias in the aetiology of unexplained pregnancy loss in the Indian population has not been studied in detail. We studied the association of acquired and inherited markers of thrombophilia in a large group of patients with unexplained pregnancy loss.


METHODS
A total of 602 women with pregnancy loss were referred to us for evaluation of thrombophilia between April 2000 and June 2005. After investigations to rule out cytogenetic, hormonal, anatomical and microbiological causes, no cause was ascertained in 430 women for the pregnancy loss. Of these, 49 women, who had a history of only one pregnancy loss, were excluded. The remaining 381 women comprised the study group. These patients and 100 age-matched women who did not have any obstetric complication and had at least one normal healthy child (controls) underwent detailed investigations for the presence of thrombophilia markers. These included screening coagulations tests, tests for lupus anticoagulant (LA), IgG and IgM antibodies to anticardiolipin antibodies (ACA), beta2 glycoprotein 1 (beta2GP1) and annexin V. The genetic markers studied included protein C (PC), protein 5 (PS), antithrombin III (AT III), factor V Leiden (FVL), PT gene G20210A, MTHFR C677T, EPCR 23 bp insertion and PAI 4G/5G polymorphisms.


RESULTS
Of the 381 women with pregnancy loss, 183 had 2 and 198 had > or = 3 pregnancy losses. Early pregnancy loss occurred in 136 patients, late pregnancy loss in 119, and both early and late pregnancy losses in 126. The strongest association was observed with ACA (OR 32.5, 95% CI: 8.6-21.8, p < 0.001) followed by annexin V (OR 17.1, 95% CI: 2.9-99.4, p < 0.001), LA (OR 8.2, 95% CI: 1.4-47.7, p = 0.01) and anti-beta2GP1 (OR 5.8, 95% CI: 1.6-22.1, p = 0.007). No association of antiphospholipid antibodies with the time of pregnancy loss was found except LA which was significantly associated with early pregnancy loss compared with late pregnancy loss (p < 0.05). The risk of pregnancy loss with PS deficiency (OR 17.8, 95% CI: 3.1-102.9, p < 0.001) was the highest observed for any heritable thrombophilia followed by PC deficiency (OR 5.8, 95% CI: 1-34, p = 0.06). There were no statistically significant differences in the frequency of any of the genetic thrombophilias studied between women with early and late pregnancy loss. A combination of > or = 2 genetic factors was observed in 41 (10.8%) while that of genetic and acquired risk factors were observed in 79 (20.7%) patients. No more than one risk factor was observed in any of the controls. In all, 176 (46.2%) patients had at least one acquired thrombophilia while 143 (37.5%) had at least one genetic thrombophilia marker. Overall, 288 patients (75.6%) had either an acquired, genetic or both markers of thrombophilia.


CONCLUSIONS
Thrombophilia is an important factor in both early and late pregnancy losses. Women with unexplained pregnancy loss should be screened for the presence of thrombophilias.
Vora
Sonal
S
National Institute of Immunohaematology (ICMR), K.E.M. Hospital, Parel, Mumbai 400012, Maharashtra, India.
Shetty
Shrimati
S
Salvi
Vinita
V
Satoskar
Purnima
P
Ghosh
Kanjaksha
K
D000022:Abortion, Spontaneous / Q000453:epidemiology* / Q000209:etiology* / Q000517:prevention & control; D000293:Adolescent; D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001780:Blood Coagulation Tests; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007194:India / Q000453:epidemiology; D008403:Mass Screening; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic; D011256:Pregnancy Outcome; D012307:Risk Factors; D019851:Thrombophilia / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D055815:Young Adult
D017153:Antibodies, Anticardiolipin; D015415:Biomarkers; D005819:Genetic Markers