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Human Cytomegalovirus (HCMV) infection is associated with bad obstetric history (BOH) and adverse pregnancy outcomes (APO). Here, we characterized antiviral humoral profiles, systemic and virus specific cellular immune responses concurrently in pregnant women (n = 67) with complications including BOH and associated these signatures with pregnancy outcomes. Infection status was determined using nested blood PCR, seropositivity and IgG avidity by ELISA. Systemic and HCMV specific (pp65) cellular immune responses were evaluated by flow cytometry. Seropositivity was determined for other TORCH pathogens (n = 33) on samples with recorded pregnancy outcomes. This approach was more sensitive in detecting HCMV infection. Blood PCR positive participants, irrespective of their IgG avidity status, had higher cytotoxic potential in circulating CD8+ T cells (p < 0.05) suggesting that infection associated cellular dysfunction was uncoupled with avidity maturation of antiviral humoral responses. Also, impaired anamnestic degranulation of HCMV-pp65-specific T cells compared to HCMV blood PCR negative participants (p < 0.05) was observed. APO correlated with HCMV blood PCR positivity but not serostatus (p = 0.0039). Most HCMV IgM positive participants (5/6) were HCMV blood PCR positive with APO. None were found to be IgM positive for other TORCH pathogens. Multiple TORCH seropositivity however was significantly enriched in the APO group (p = 0.024). Generation of HCMV specific high avidity IgG antibodies had no bearing on APO (p = 0.9999). Our study highlights the utility of an integrated screening approach for antenatal HCMV infection in the context of BOH, where infection is associated with systemic and virus specific cellular immune dysfunction as well as APO.
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Infecciones por Citomegalovirus , Complicaciones Infecciosas del Embarazo , Embarazo , Humanos , Femenino , Resultado del Embarazo , Mujeres Embarazadas , Infecciones por Citomegalovirus/diagnóstico , Linfocitos T CD8-positivos , Monitorización Inmunológica , Citomegalovirus , Anticuerpos Antivirales , Inmunoglobulina G , Inmunoglobulina MRESUMEN
Background & objectives: Accurate diagnosis of immunodeficiencies requires a critical comparison of values with age-matched controls. In India, the existing reference values for rare lymphocyte subsets are currently not available and we rely on the data originating from other countries for the interpretation of the results. Furthermore, there is limited information on normal variation for these rare-subset parameters in Indian children. So, this study aimed to establish normative values for clinically important lymphocyte subsets in Indian children at different age groups. Methods: 148 children aged ≥16 yr were enrolled in this study. The study population included 61 per cent males and 39 per cent females and was divided into the following groups: cord blood (n=18), 0-6 months (n=9), 6-12 months (n=13), 1-2 yr (n=19), 2-5 yr (n=27), 5-10 yr (n=25) and 10-16 yr (n=37). The absolute and relative percentage of lymphocytes, T, B, natural killer cell, along with activated, naïve and memory subsets, was determined by flow cytometry. Results: Median values and the 10th and 90th percentiles were obtained for 34 lymphocyte sub-populations. The T and B naïve compartments showed a decreasing trend, whereas memory cells showed an increase with age. The activated T cell subset shows an increasing pattern up to one year and then declines gradually. Double negative T cells are relatively stable. TCRgd+T cell percentage increases with age. Interpretation & conclusions: This single-centre pilot study provides preliminary data that justifies the need for future large-scale multi centric studies to generate a reference range for interpreting extended immunophenotyping profiles in the paediatric age group, making it possible for clinicians to assess the immunological status in inborn errors of immunity, infectious and autoimmune diseases.
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Subgrupos Linfocitarios , Subgrupos de Linfocitos T , Masculino , Femenino , Niño , Humanos , Proyectos Piloto , Recuento de Linfocitos , Inmunofenotipificación , Citometría de Flujo , India/epidemiología , Valores de ReferenciaRESUMEN
BACKGROUND: Immunoskeletal dysplasia with neurodevelopmental abnormalities (ISDNA) is an ultra-rare genetic condition that belongs to the group of spondyloepimetaphyseal dysplasias. It is caused due to presence of biallelic variants in the EXTL3 gene. The encoded exostosin like glycosyltransferase 3 (EXTL3) protein plays a key role in heparan sulfate synthesis. The skeletal and nervous systems are prominently affected in ISDNA with variability in immunological manifestations. Here, we report the 15th case of ISDNA (third patient of an Indian ancestry) in the world, along with a review of literature. CASE PRESENTATION: A 15-month-old female child with clinical indications of global developmental delay, short stature, coarse facial features, and hypotonia was referred to our clinic. Spondyloepimetaphyseal dysplasias associated with extra-skeletal manifestations was suspected based on clinic-radiological correlation. Whole exome sequencing analysis revealed the presence of a homozygous known pathogenic variant c.953C > T (p. Pro318Leu) in exon 3 of the EXTL3 gene, thereby confirming diagnosis of ISDNA. CONCLUSION: We present an ultra-rare case of ISDNA- third patient of Indian ancestry and only the 15th reported case in the literature. On review of all cases in the literature, we find that the affected individuals show abnormalities primarily in three systems namely- skeletal, nervous and immune system. Notably, patients harbouring the same variant in EXTL3 gene show phenotypic variability especially with respect to presence or absence of immunological manifestations, suggesting a role of unknown modifiers. Hence, it is currently not possible to correlate the variant position in the EXTL3 gene with disease severity.
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Enanismo , Anomalías Musculoesqueléticas , Osteocondrodisplasias , Enanismo/genética , Femenino , Homocigoto , Humanos , Lactante , Hipotonía Muscular , N-Acetilglucosaminiltransferasas/genética , Osteocondrodisplasias/genéticaRESUMEN
Examination of a survivor of sexual assault should be performed meticulously. The aim is to confirm whether penetration occurred, document injuries and collect evidence to bring perpetrators to justice. First aid, contraception, preventive measures for Sexually Transmitted diseases and psychological support should be given to the survivor.
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BACKGROUND/PURPOSE OF THE STUDY: Foetal urinary tract dilation (UTD) abnormalities affect 1-5% of all pregnancies. However, exact incidence is difficult to estimate because of different terminologies used to define the condition and different grading systems to define its severity antenatally as well as postnatally worldwide. In order to overcome this problem, the new UTD classification system has been introduced in the year 2014 so as to have universal approach for diagnosis and management of UTD globally. Indian data about clinical utility of the UTD classification system and its role in prenatal prediction of severity of renal disease are lacking. The present study aims to investigate clinical utility of new UTD classification system in foetal UTD abnormalities and to evaluate the role of UTD classification system in antenatal prediction/prognostication of severity of UTD abnormalities. METHODS: We conducted a single-centre retrospective study between April 2014 and January 2017, which included 70 infants with antenatally diagnosed UTD delivered in our hospital and managed in our paediatric unit postnatally. Pre- and postnatal ultrasound findings were noted, and UTD-A and UTD-P classification were applied retrospectively in all cases as per criteria defined in the new UTD classification. Postnatal outcome in all cases was evaluated in terms of need for immediate postnatal urosurgical intervention, presence of persistent UTD pathology and severity of renal impairment in relation to their pre- and postnatal UTD A and P risk categories. RESULTS: None from UTD A1 risk group in the last prenatal scan showed significant postnatal UTD abnormality. In contrast to this, UTD A2-3 risk group in the last prenatal scan had persistent postnatal UTD pathology in 70% cases. All infants with abnormal postnatal UTD diagnosis were identified prenatally as UTD A2-3 (high risk). Nine infants (12.8%, n = 70) who needed urosurgical intervention postnatally were categorised as UTD A2-3 prenatally and UTD P3 postnatally. CONCLUSION: We found increased frequency of complications and urosurgical interventions in all infants with antenatal UTD A2-3 grades in the last prenatal scan in comparison with those with UTD A1 grades who showed complete resolution (100%) postnatally. Antenatal UTD classification may be useful in antenatal prediction and prognostication of postnatal severity, especially in high-risk cases (i.e. UTD A2-3).
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Aborto Habitual/etiología , Anticoagulantes/uso terapéutico , Micropartículas Derivadas de Células/metabolismo , Adulto , Aspirina/uso terapéutico , Estudios de Casos y Controles , Femenino , Heparina/uso terapéutico , Humanos , Embarazo , Complicaciones Hematológicas del Embarazo/tratamiento farmacológico , Resultado del Embarazo , Trombofilia/tratamiento farmacológico , Adulto JovenRESUMEN
OBJECTIVE: The objective of the study was to assess the fetal outcome after receiving intrauterine transfusion (IUT) in Rh-isoimmunized pregnancy in a tertiary care center. STUDY DESIGN: This was a retrospective observational descriptive study in which all Rh-negative gravidas with isoimmunization warranting IUTs (40 patients) were analyzed during the period from January 1, 2010 to October 31, 2015. Primary outcome variables were fetal outcomes and procedural-related factors. RESULTS: Forty pregnancies (13-hydropic, 27-non-hydropic) required 74 IUTs. IUT was performed at gestational age of 15.4-33 weeks when indicated. The amount of blood transfused ranged from 4 to 110 ml. There were two sudden intrauterine fetal deaths during the procedure, four post-procedure intrauterine fetal deaths in fetuses with severe hydrops, and three neonatal deaths. The overall survival rate was found to be 77.5%. CONCLUSION: IUT was found to be an effective therapy in correcting anemia in fetuses of Rh isoimmunized mothers. Early diagnosis of fetal anemia and intrauterine blood transfusion by an experienced fetal medicine specialist is very important for the perinatal outcome.
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OBJECTIVE: To evaluate the combination of plasma activated endothelial microparticles (CD62e), serum Copeptin (CPP) and placental growth factor (PlGF) levels at 18-23â¯weeks of gestation for prediction of preeclampsia (PE) in primigravid women. METHODS: This was a nested case-control study from a prospective cohort of 1115 primigravid women attending antenatal care clinic. Plasma levels of CD62e and serum Copeptin, PlGF levels were measured by flow cytometry and ELISA, respectively. Data were presented as median (Interquartile range) and biomarker levels were compared between patients and controls using Mann-Whitney Test. Using binary logistic regression, predictive potential of a combination of biomarkers for PE prediction was determined. RESULTS: Women who developed PE 41 (3.97%) showed significantly increased levels of plasma CD62e [799.33 (546.86-1249.29) versus 384.08 (245.03-576.00), pâ¯<â¯0.0001], serum Copeptin [303.42 (226.01-484.18) versus 207.24 (169.73-276.46), pâ¯<â¯0.0001] and reduced level of PlGF [238.38 (161.36-312.62) versus 947.21 (466.7-1428.56), pâ¯<â¯0.0001] compared to controls at 18-23â¯weeks of gestation. None of the marker showed statistically significant alteration in levels in fetal growth restriction (FGR) group 68 (6.58%) compared to controls. Using binary logistic regression analysis, AUC, Sensitivity, specificity, PLR, NLR, PPV, and NPV of combination of CD62e, Copeptin and PlGF for prediction of PE at 18-23â¯weeks of gestation was 0.969, 92.3%, 90.3%, 9.73, 0.08, 79.17%, and 96.94%, respectively. CONCLUSION: At 18-23â¯weeks, Combination of CD62e microparticles, copeptin, and PlGF levels can effectively identify women at risk of developing PE later in gestation.
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Biomarcadores/sangre , Preeclampsia/diagnóstico , Diagnóstico Prenatal , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Selectina E/sangre , Femenino , Edad Gestacional , Glicopéptidos/sangre , Humanos , Factor de Crecimiento Placentario/sangre , Preeclampsia/sangre , Valor Predictivo de las Pruebas , Embarazo , Segundo Trimestre del Embarazo , Estudios ProspectivosRESUMEN
OBJECTIVE: The present study was aimed at a comprehensive analysis of acquired thrombophilia in a large series of Indian women with fetal loss. STUDY DESIGN: Four hundred and thirty women (median age 26 years, range 18-39 years) with unexplained fetal loss (median number of abortions 3, range 1-13) were screened for the presence of antiphospholipid antibodies (APA), i.e. lupus anticoagulant (LA), IgG/M antibodies for cardiolipin (ACA), beta 2 glycoprotein 1 (beta2 GP1) and annexin V. We also studied 100 normal healthy women (median age 24 years, range 18-30 years) who had at least one healthy child and did not have any miscarriage or other obstetric complications. RESULTS: The prevalence of persistently positive LA was 8.1% and 1% in the patients and controls, respectively (OR 8.7; 95% CI, 1.4-51; P<0.05). The overall prevalence of IgG and/or IgM antibodies for cardiolipin, beta 2 GP1 and annexin V were as follows-ACA 27.9% (OR 18.9; 95% CI, 5-70; P<0.05), beta 2 GP1 12.2% (OR 6.8; 95% CI, 1.8-25; P<0.05) and annexin V 14.6% (OR 17; 95% CI, 2.9-98; P<0.05). The conventional LA and ACA tests were positive 23.2% of the cases as against 1% in the controls (OR 14.8; 95% CI, 3.9-55; P<0.05). The prevalence of LA, ACA, beta 2 GP1 and annexin V antibodies as independent risk factors were observed in 0.5%, 16.5%, 5.4% and 7.8% in the patients as against 1% each in the controls. The overall positivity for any one of the APA studied was 42.6% (OR 10.2; 95% CI, 4.5-23; P<0.05). CONCLUSION: The present study thus indicates the importance of APA in women experiencing fetal loss where all the conventional causes of miscarriages have been ruled out. It also suggests that conventional APA assays (LA and ACA) are effective in the detection of a majority of APA positive cases and by the addition of other cofactor-dependent (beta 2 GP1 and annexin V) APA assays, there is a considerable increase in the diagnostic efficiency in the detection of APA.
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Aborto Espontáneo/inmunología , Anticuerpos Antifosfolípidos/sangre , Tamizaje Masivo/métodos , Aborto Espontáneo/sangre , Aborto Espontáneo/etiología , Adolescente , Adulto , Anexina A5/inmunología , Anticuerpos/sangre , Cardiolipinas/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Inhibidor de Coagulación del Lupus/sangre , Embarazo , Trombofilia/inmunología , beta 2 Glicoproteína I/inmunologíaRESUMEN
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. CONCLUSION: 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.
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Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Complicaciones Hematológicas del Embarazo , Trombofilia/complicaciones , Trombofilia/epidemiología , Aborto Espontáneo/prevención & control , Adolescente , Adulto , Anticuerpos Anticardiolipina/análisis , Biomarcadores/análisis , Pruebas de Coagulación Sanguínea , Femenino , Marcadores Genéticos , Humanos , India/epidemiología , Tamizaje Masivo , Embarazo , Resultado del Embarazo , Factores de Riesgo , Trombofilia/diagnóstico , Trombofilia/genética , Adulto JovenRESUMEN
BACKGROUND: Deep venous thrombosis (DVT) is an important complication in the peripartal and postpartal period. METHODS: We followed up prospectively the prevalence of DVT in 34720 prenatal mothers between June 2002 and July 2006 attending the antenatal clinics of two major hospitals in Mumbai, India. Thirty two women (0.1%) presented for the first time with symptomatic DVT i.e. 17 in the first trimester, 6 in the second and 9 in the third trimester of pregnancy. Nine had history of fetal loss while in the remaining twenty three there was no history of fetal loss. RESULTS: The evaluation of both acquired and heritable thrombophilia showed a conglomeration of thrombophilia in this group when compared to 100 normal pregnant women who have given birth to at least one healthy baby with no history of fetal death, DVT or other obstetrical complications. The relative risks for all the antiphospholipid antibodies (APA) studied i.e lupus anticoagulant (LA), IgG/IgM antibodies for cardiolipin (ACA), beta2 glycoprotein 1 (beta2 GP 1) and annexin V were significantly higher in women with pregnancy associated DVT (RR 7.4 95% CI 4.3-11.3 P < 0.05). Among the genetic thrombophilia markers studied, Protein S (PS) deficiency was the strongest risk factor (RR 5.00 95% CI 3.02-5.00 P < 0.05) followed by factor V Leiden (FVL) mutation (RR 4.57 95% CI 2.23-4.57 P < 0.05) and PAI 4G/4G homozygosity (RR 3.24 95% CI 1.85-5.12 P < 0.05). Protein C (PC) and endothelial protein C receptor (EPCR) 23 bp insertion polymorphism was also increased in the patient group as compared to controls but the difference was not statistically significant. The MTHFR C677T, fibrinogen gene beta448 Arg/Lys polymorphisms were not significantly different from the normal controls, while antithrombin III (AT III) deficiency and PT G20210A polymorphism were absent in both controls and patients. Two or more risk factors were present in 22 out of 32 cases (68.75%). CONCLUSION: We conclude that the prevalence of DVT in India is more or less similar to other reports published and both acquired and heritable thrombophilia show strong association with DVT associated with pregnancy.
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INTRODUCTION: Preeclampsia (PE) remains to be an enigmatic puzzle for clinicians and researchers perplexing them for decades. As delivery remains only choice of treatment, early prediction of PE will offer timely therapeutic invention and hence extensive research efforts have been put in identification of biomarkers which will facilitate early prediction of PE. METHODS: Serum levels of CPP, PlGF and plasma total annexin V MPs were assessed in women who subsequently developed PE (n = 33), IUGR (n = 81) and normal pregnancy outcome (n = 112) at 10-14 weeks of gestation. Comparison of biomarker levels between patients and control group was done using Mann Whitney test. Receiver operating curve (ROC) analysis and binary logistic regression analysis were used to evaluate predictive utility of combination of CPP, PlGF and total annexin V MPs for prediction of PE. RESULTS: Women who subsequently developed PE showed significantly elevated levels of total annexin V MPs [2766.04 (2086.88-3794) versus 1090.74 (631.91-2197.16)] and CPP [440.98 (365.12-488.92) versus 217.8 (171.13-308.98)] compared to controls. Serum PlGF levels were significantly reduced in women with PE 17.68 (12.66-22.32) compared to controls 105.22 (35.02-255.1). Using logistic regression analysis, the combination of CPP, PlGF and total annexin V MPs gave high predictive value with AUC of 0.970, 93.1% sensitivity, 90.7% specificity, 77.50% Positive predictive value, 98.10% Negative predictive value, 11.69 Positive likelihood ratio and 0.07 Negative likelihood ratio for PE prediction at 10-14 weeks. CONCLUSION: The combination of serum markers and plasma microparticles can be used for 10-14 weeks prediction and discrimination of PE from other pregnancy complications.
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Anexina A5/sangre , Glicopéptidos/sangre , Factor de Crecimiento Placentario/sangre , Preeclampsia/diagnóstico , Adulto , Biomarcadores/sangre , Micropartículas Derivadas de Células , Femenino , Humanos , Preeclampsia/sangre , Valor Predictivo de las Pruebas , Embarazo , Resultado del Embarazo , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Preeclampsia is a pregnancy related condition identified by hypertension and either proteinuria or end-organ dysfunction after 20(th) week of gestation and complicates 2-8% pregnancies worldwide. Enigmatic pathophysiology and multi-system involvement hinder accurate identification and clinical management of patients. Inadequate trophoblast invasion and subsequent inflammatory response have been implicated in the onset of PE. In absence of effective treatment of preeclampsia except delivery, recent research has been focused on identification of specific and sensitive biomarkers for early prediction of PE. Several angiogenic, anti-angiogenic, inflammatory, biophysical (mean arterial pressure and uterine artery Doppler) biomarkers, alone and in combination, have been proposed for prediction but limited predictive values have hindered their use in clinical settings. Current review summarizes some of relatively new biomarkers such as corin, copeptin, microparticles and miRNA, the prognostic efficiency of which are either analyzed in associated disorders or recently discovered.
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Preeclampsia/fisiopatología , Femenino , Humanos , Preeclampsia/mortalidad , Embarazo , PronósticoRESUMEN
The objective of this study was to evaluate whether the global reference curves adapted on the basis of WHO data for India and the Hadlock reference curves fit the population in India and to validate the reference curves. The data were retrieved retrospectively from the records of women registration for antenatal care at a charitable maternity hospital in Mumbai, India. All pregnancies were dated on CRL obtained before 14 weeks. Births before 34(th) week were excluded. The expected frequencies of birth weights below the 1(st), 5(th), 10(th), 50(th), 90(th), 95(th) and 99(th) centiles from three reference ranges were compared with observed frequencies. It was found that the WHO generic reference adapted to India significantly underpredicted the birth weights and that the Hadlock reference ranges significantly overpredicted the birth weights. The use of generic reference adapted to Sri Lanka showed a better fit to the observed data. We concluded that global reference curves adapted on the basis of WHO data for India and the Hadlock reference ranges do not fit all the population in India and the charts need validation. Reference charts modified on the basis of data for Sri Lankan population show a better fit to the observed data, and therefore are more appropriate for use in clinical practice in South India.
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BACKGROUND: 15% of reproducing couples suffer from pregnancy loss(PL) and recurs in 2-3%. One of the most frequently hypothesized causes of unexplained PL refers to a defective maternal haemostatic response leading to uteroplacental thrombosis. Hereditary thrombophilia and antiphospholipid antibodies have been extensively described as risk factors for PL in women with unknown aetiology. Recently, a new marker has emerged: the cell-derived procoagulant circulating microparticles(MPs) which have been reported to have a major role in many thrombosis complicated diseases. This study aims to analyze the significance of procoagulant MPs in women suffering from unexplained recurrent pregnancy loss(RPL), and characterize their cellular origin. METHOD AND FINDINGS: 115 women with RPL were analyzed for common thrombophilia markers and different cell derived MPs-total annexinV, platelet(CD41a), endothelial(CD146,CD62e), leukocyte(CD45), erythrocyte(CD235a) and tissue factor(CD142)(TF) expressing MPs and were compared with 20 healthy non-pregnant women. Methodology for MP analysis was standardized by participating in the "Vascular Biology Scientific and Standardization Committee workshop". RESULTS: Total annexinV, TF and endothelial MPs were found significantly increased(p<0.05, 95% confidence interval) in women with RPL. The procoagulant activity of MPs measured by STA-PPL clotting time assay was found in correspondence with annexinV MP levels, wherein the clot time was shortened in samples with increased MP levels. Differences in platelet, leukocyte and erythrocyte derived MPs were not significant. Thirty seven of 115 women were found to carry any of the acquired or hereditary thrombophilia markers. No significant differences were seen in the MP profile of women with and without thrombophilia marker. CONCLUSION: The presence of elevated endothelial, TF and phosphatidylserine expressing MPs at a distance (at least 3 months) from the PL suggests a continued chronic endothelial damage/activation which may get exaggerated at the onset of pregnancy. The data suggests that MPs may contribute to uteroplacental thrombosis and are associated with the pathogenesis of RPL.