C. Anandakumar

Plasminogen Activators, Plasminogen Activator Inhibitors and Markers of Intravascular Coagulation in Pre-Eclampsia

In pre-eclampsia (PE), reduced levels of plasma urokinase-like plasminogen activator (u-PA) and plasminogen activator inhibitor-2 (PAI-2), and increased levels of plasma tissue-type plasminogen activator (t-PA) antigen were seen. The majority of moderate and severe pre-eclamptic women (7 out of 10) ended up with pre-term delivery as compared with 2 out of 11 who went on to term. Patients with moderate and severe PE had significantly lower levels (mean +/- SD, ng/ml) of PAI-2 (58.4 +/- 34.9) and u-PA antigen (1.61 +/- 0.62) as compared to those with mild PE (95.6 +/- 39.3 and 1.61 +/- 0.62 and 2.12 +/- 0.61, respectively). Significantly raised t-PA antigen (14.6 +/- 5.7 ng/ml) was seen in moderate and severe PE as compared with mild PE (9.9 +/- 3.4 ng/ml). PAI-1 activity was significantly raised only in moderate and severe PE as compared with normal pregnancy. There were no significant differences in thrombin-antithrombin-III complexes, D-dimer and beta-thromboglobulin levels between the PE group and normal pregnancy, although these parameters were above the non-pregnant levels. Platelets in PE were within the range found in normal pregnancy. It appears that measurements of plasma u-PA and PAI-2 levels in patients with PE may have prognostic value in determining the outcome of pregnancy in this pregnancy disorder.

Randomised controlled trial of methyldopa and isradipine in preeclampsia : effects on uteroplacental and fetal hemodynamics

This is a prospective randomised controlled study in 21 women admitted with preeclampsia in the third trimester. The mean arterial blood pressure decreased by 11.1 mmHg (95% confidence interval -14.9 to -7.3 mmHg) in the methyldopa group, and by 9.3 mmHG (95% confidence interval-14.4 to -4.2 mmHG) in the isradipine group. The maternal heart rate decreased by 6.9 beats per min (95% confidence interval -11.6 to -2.2 bpm) during methyldopa treatment, and by 2.5 beats per min (95% confidence interval -9.2 to 4.3) during isradipine treatment. Pulsatility index in maternal and fetal vessels was not affected by either of the two drugs. The birth weight and placental weight and neonatal outcome were similar and uneventful. The hypotensive effect was similar for methyldopa and isradipine. Except reduced maternal heart rate on methyldopa, fetal and uteroplacental hemodynamics were not altered during treatment of preeclampsia with methyldopa or isradipine.

Coagulation and fibrinolysis in viable mid-trimester pregnancies of normal, intrauterine growth retardation, chromosomal anomalies and hydrops fetalis and their eventual obstetric outcome

Abstract A total of 71 pregnant women diagnosed by ultrasound to have viable fetus in late mid-trimester pregnancies of normal, IUGR, hydrops fetalis and chromosomal anomalies were studied for their coagulation, fibrinolytic and inhibitor levels with association on eventual obstetrics outcome. A hypercoagulable state was observed in all the pregnancies studied. However, higher hypercoagulation evidenced by significantly raised prothrombin formation and clot elasticity together with higher levels of D-dimer, uPA antigen and PAI-1 than observed in normal pregnancy suggests a hyperfibrinolytic/inhibitor state in hydrops fetalis pregnancy associated with bad obstetric outcome. In IUGR pregnancy associated with good outcome further enhanced clot elasticity was seen whilst no significant differences were observed in pregnancy with chromosomal anomalies when compared to uncomplicated normal pregnancy. Our study suggests that in hydrops fetalis pregnancy, further enhanced prothrombin formation and hyperfibrinolysis/inhibitor at late mid-trimester is associated with a poor obstetric outcome.

Analysis of cystic hygroma, ascitic, and pleural fluids by conventional lymphocyte culture and fluorescent in situ hybridization

Serous fluids from cystic hygromas, pleural effusions, and ascites are an easily accessible and plentiful source of lymphocytes. The feasibility and reliability of using these as alternative sources to conventional amniotic fluid or fetal blood cultures have been studied here. In some cases of prenatal diagnosis, especially in pregnancies complicated by the presence of cystic hygromas and fetal hydrops, obtaining amniotic fluid or fetal blood can be difficult due to obstruction by the cyst or oligohydramnios. A total of 14 cases with fetal hydrops detected ultrasonigraphically between 15 and 33 weeks of pregnancy over a period of 1 year have been subjected to conventional amniotic fluid or fetal blood karyotyping, along with samples of fluids from cystic hygromas, ascites or pleural effusions as obtained. Pleural fluids (n=4), cystic hygroma fluids (n=5), and ascitic fluids (n=6) were obtained. The culture failure rate was low, 2/14. Karyotypically, two of the fluids, both from cystic hygromas, were 45,X; the rest were normal. A rapid 1‐day additional test of fluorescent in situ hybridization (FISH) was carried out on uncultured cells of the alternative fluids using probes for the most commonly occurring aneuploidies, 13, 18, 21, X and Y, with good results.

Early Asymmetric IUGR and Aneuploidy

Objective: To determine the incidence of chromosomal abnormalities in fetuses with asymmetric growth retardation in the second and early third trimesters of pregnancy.

Amniotic fluid plasminogen activators and inhibitors and TAT-complex levels during 2nd trimester pregnancy and labour

The levels of haemostatic variables in amniotic fluids of normal 2nd trimester of pregnancy and during labour were determined. t-PA antigen and PAI-1 levels were significantly increased during labour in comparison to 2nd trimester. t-PA/inhibitor complexes and single-chain urokinase plasminogen activator (scu-PA) were present with free t-PA seen only during labour but not during 2nd trimester pregnancy. PAI-1 activity was not detectable during 2nd trimester but a mean value of 23.2 ± 14 AU/ml was observed during the labour. PAI-2 antigen levels remained elevated whilst fibrinogen, Factor X and plasminogen were not detectable in the amniotic fluids studied. Functional ATIII was not detected during labour but low activity (mean 21.3 ± 8.9%) was seen in 21 of the 25 amniotic fluid samples collected in 2nd trimester of pregnancy. ATIII antigen levels of mean 0.015 ± 0.005 g/L and 0.012 ± 0.003 g/L were found during the 2nd trimester and labour respectively. Significant increase in t-PA activity in maternal plasma as compared to amniotic fluid was observed during labour although no significant differences in u-PA, PAI-2 and PAI-1 activity levels were observed. The increased fibrinolytic activity in the plasma during labour and an overwhelming inhibitory capacity of the amniotic fluid prepare the subject for the haemostatic challenge of delivery.

Management trend and safety of vaginal delivery for term breech fetuses in a tertiary care hospital of Karachi, Pakistan

Abstract Aim: To investigate the safety of vaginal delivery for term breech fetuses in a tertiary-care hospital of Pakistan. Methods: We reviewed the medical records of all live singleton breech deliveries at or beyond 37 weeks of gestation, at the Aga Khan University Hospital, Karachi, from January 1988 to December 1995. Results: Rate of cesarean section increased from 48% (1988) to 74% (1995). Out of 287 subjects, 158 underwent elective cesarean section while 129 received a trial of labor, 77% of which delivered vaginally. There was no neonatal or maternal death. Compared to babies delivered by emergency or elective cesarean section, those delivered vaginally had significantly more neonatal intensive-care unit admissions (none and 5% versus 13 %) and higher rates of birth trauma (none and 0.6% versus 7%). However, there was no significant difference in the Apgar score at 5 minutes and the risk of maternal complications by delivery mode. Conclusion: Allowing trial of labor to carefully selected mothers can result in vaginal delivery in 77% of the cases. However, the risk of trauma and neonatal intensive-care unit admissions, among vaginal births may favor the decision of elective cesarean section, unless rigorous pre-delivery assessment and conduct of delivery by adequately trained obstetricians is performed.

Fetal and neonatal haemodilution associated with multiple placental chorioangioma: case report.

A pregnancy with polyhydramnios and abnormal antepartum fetal heart rate pattern was found to have multiple placental haemangiomas. Multiple placental haemangiomas can give rise to fetal cardiac failure due to a hyperdynamic circulation or fetal anaemia either due to haemodilution or possibly destruction of blood cells in the chorioangioma. Whether fluid restriction with or without diuretics or blood transfusion is the correct form of treatment of neonatal cardiac failure in such a case is discussed.

Early fetal blood sampling--another available option for early prenatal diagnosis.

Fourteen cases had early fetal blood sampling (FBS) performed between 13 and 18 weeks gestation in the Antenatal Diagnostic Centre, National University Hospital, Singapore from Jan 1988 to December 1994. The indications were: a) ultrasound abnormality (n = 6), b) hydrops (n = 1), c) screening for blood disorders (n = 2), d) amnio results inconclusive or to confirm abnormal amnio results (n = 5). This article analyses retrospectively the early FBS procedure and its outcome. There were no procedure related fetal losses in this study. The reliable rapid results obtained following the procedure enabled the obstetrician to counsel the couple regarding the current pregnancy and advise them accordingly for the subsequent pregnancy. Thus we found it useful not only in our patients but also for patients from overseas who get their results within a week to plan their stay.

Discrepancy between Cytogenetic and FISH Results on an Amniotic Fluid Sample of 45,X/46,X,idic(Y)(p11)

The presence of abnormal ultrasound markers showing a thick nuchal fold with short middle phalanx of the fifth finger in an otherwise normal-appearing female fetus led to the sampling of amniotic fluid at 16 weeks gestation. Cytogenetic analysis with routine G-banding showed a 45,X karyotype in all 20 cells analysed from two flasks. However, fluorescent in situ hybridization on uncultured cells showed presence of a Y signal in 9 cells, 11 cells showing a single signal for the X. A cytogenetic analysis of the fetal blood at 23 weeks confirmed the presence of two cell lines, 45,X and 46,X,idic(Y)(p11). The couple opted to have the pregnancy terminated. However, the fetus was not available to carry out confirmatory tests.