Philip Samuels

Estimation of the Risk of Thrombocytopenia in the Offspring of Pregnant Women with Presumed Immune Thrombocytopenic Purpura

Abstract Background and Methods. The optimal management of immune thrombocytopenic purpura during pregnancy remains controversial because the risk of severe neonatal thrombocytopenia remains uncertain. We studied the outcome of the index pregnancy in 162 women with a presumptive diagnosis of immune thrombocytopenic purpura to determine the frequency of neonatal thrombocytopenia and to determine whether neonatal risk could be predicted antenatally by history or platelet-antibody testing. Results. Two maternal characteristics were identified as predicting a low risk of severe neonatal thrombocytopenia: the absence of a history of immune thrombocytopenic purpura before pregnancy, and the absence of circulating platelet antibodies in the women who did have a history of the condition. Eighteen of 88 neonates (20 percent; 95 percent confidence interval, 13 to 30 percent) born to women with a history of immune thrombocytopenic purpura had severe thrombocytopenia (platelet count <50×109 per liter at birth), as co...

Detection of endothelial cell-reactive immunoglobulin in patients with anti-phospholipid antibodies

Individuals with anti‐phospholipid antibodies are at increased risk for the development of thrombosis and fetal loss. The pathogenesis of these syndromes is unknown, but may involve antibody‐mediated alterations in endothelial cell coagulant activity. To address this possibility, we determined the incidence of endothelial cell‐reactive antibodies in 76 patients whose plasma contained anti‐phospholipid antibodies, but who had no clinically‐evident immune disorder. Plasma from 47 patients deposited significantly more immunoglobulin on cultured endothelial cells than control plasma. Positive tests were more frequent in patients with a history of thrombosis than in those without (17/19 v 23/48; P=0.004). However, we observed no correlation between immunoglobulin deposition on cardiolipin and endothelial cells by individual plasmas. Furthermore, endothelial cell reactivity was not diminished by adsorption of anti‐cardiolipin antibodies from patient sera using liposomes. Immunoglobulin fractions prepared from 5/6 patient sera immuno‐precipitated a ≈ 70 kDa endothelial cell surface protein; 4/5 of these fractions also induced the release of von Willebrand factor from endothelial cells. These results demonstrate that plasma from many patients with anti‐phospholipid antibodies, but no clinically‐evident autoimmune disease, also contains endothelial cell‐reactive antibodies. Detection of such antibodies might help identify individuals in this patient population at greatest risk for thrombosis.

Antiplatelet antibody testing in thrombocytopenic pregnant women.

OBJECTIVEnThe purpose of the study was to attempt to distinguish pregnant women with gestational thrombocytopenia from those with idiopathic immune thrombocytopenia by eight different platelet antibody assays.nnnSTUDY DESIGNnSera from pregnant women with presumed gestational thrombocytopenia (n = 160) and idiopathic immune thrombocytopenia (n=90) were prospectively tested for indirect and platelet-associated immunoglobulins G and M and complement C3, as well as for serotonin release. After the results were analyzed, a subset of patients were subsequently analyzed for circulating antiplatelet antibody directed against platelet membrane glycoprotein GPIIb/IIIa.nnnRESULTSnIndirect immunoglobulin G was significantly greater in the 85 women with idiopathic immune thrombocytopenia than in the 129 women with gestational thrombocytopenia (p<0.001). Platelet-associated immunoglobulin G was elevated in the majority of women, both those with gestational thrombocytopenia and those with idiopathic immune thrombocytopenia. There were also no statistically significant difference in the values for platelet-associated C3 or indirect immunoglobulin M and C3. Levels of platelet-associated immunoglobulin M showed a tendency to be higher in women with gestational thrombocytopenia (p=0.04), as did the values in the serotonin release assay (p=0.06).nnnCONCLUSIONnOur data demonstrate that patients with gestational thrombocytopenia had surprisingly high levels of platelet-associated immunoglobulin despite mild thrombocytopenia. Comparison of a relatively large number of patients with idiopathic immune thrombocytopenia and gestational thrombocytopenia indicates that women with idiopathic immune thrombocytopenia cannot be distinguished from those with gestational thrombocytopenia by means of one or more of the prototypic platelet antiglobulin tests currently in use. Our preliminary data with glycoprotein-specific assays indicate that they may be more useful.

Prenatal detection of fetal anomalies in pregnancies complicated by insulin-dependent diabetes mellitus ☆ ☆☆ ★

Abstract OBJECTIVES: We evaluated the clinical utility of a comprehensive program of prenatal diagnostic testing for congenital anomalies in pregnancies complicated by insulin-dependent diabetes mellitus. STUDY DESIGN: Data were retrospectively analyzed from 289 diabetic women and their newborns from August 1987 to July 1993. Our protocol included initial hemoglobin A1 and maternal serum α-fetoprotein determinations and comprehensive fetal ultrasonography inclusive of a standard four-chamber view of the heart and detailed multiimage fetal echocardiography. RESULTS: Anomalies were identified in 29 of 289 (10%) fetuses and neonates: 12 cardiac only, 14 noncardiac, and 3 combined. In 21 of the 29 (72%) neonates the anomalies were detected prenatally. Twelve of 15 (80%) cardiac and 10 of 17 (59%) noncardiac lesions were identified prenatally. Cardiac lesions, especially of the cardiac septum and great vessels, accounted for 50% of all fetal defects. Malformations of the neuroaxis, skeleton, and genitourinary system were also detected. There were six neonatal deaths and four therapeutic pregnancy terminations associated with congenital anomalies. Although the hemoglobin A1 level was statistically significantly increased in 22 mothers of anomalous fetuses (p = 0.017), the actual difference between affected and nonaffected pregnancies was not clinically meaningful and much overlap occurred. Although 96% of women with a normal hemoglobin A1 level were delivered of normal infants, only 14% of those with an elevated value had a malformed fetus. Similarly, although 89% of gravid women with a normal maternal serum α-fetoprotein level were delivered of nonaffected fetuses, only 7.3% of patients with an elevated value had a malformed fetus. For the detection of cardiac defects, the sensitivity of the four-chamber view compared with detailed multiimage fetal echocardiography was 33% and 92%, respectively. CONCLUSIONS: This study demonstrates the utility of a comprehensive program to detect fetal anomalies in pregnancies complicated by diabetes mellitus. (A M J O BSTET G YNECOL 1996;174:1424-8.)

Management of the diethylstilbestrol-exposed pregnant patient: A prospective study

Over a 5-year period we have managed 63 diethylstilbestrol-exposed pregnant patients with a standardized protocol requiring weekly cervical examination and decreased physical activity of the patient. Twenty-six patients (42%) underwent a prophylactic cerclage for a history of second-trimester loss or a hypoplastic cervix on initial clinical examination (group I). Thirty-six patients (58%) were followed expectantly (group II). Sixteen patients (44%) in group II demonstrated cervical change and required an emergency cerclage. Twenty-one patients were managed expectantly with no cerclage. The gestational age at delivery for group I was 37.7 +/- 2.80 versus 34.5 +/- 6.9 weeks for patients without a cerclage (p = 0.04). There were no perinatal deaths if a cerclage was performed, whereas there were five deaths (24%) in the group without cerclage. The five deaths occurred at a mean gestational age of 24.40 +/- 4.0 weeks and a mean birth weight of 614.00 +/- 441.73 gm. Patients with a hypoplastic cervix or prior reproductive loss had a better outcome with early cerclage than patients with a normal cervix followed expectantly. We presently lack a reliable method to detect the diethylstilbestrol-exposed patient at greatest risk for perinatal loss. Based on our experience we believe that placement of a cerclage early in pregnancy should be a strong consideration.

Abnormalities in platelet antiglobulin tests in preeclamptic mothers and their neonates

We prospectively studied 40 women with preeclampsia and 26 women with normal pregnancy for the presence of platelet-bound and circulating platelet-bindable immunoglobulin and complement. Although only 12 patients with preeclampsia had a platelet count less than 150,000/mm3, 36 of 40 demonstrated an abnormal direct antiglobulin test, compared with only three of 26 control subjects (p less than 10(-8]. An abnormal indirect test was also detected in 30 of 40 patients with preeclampsia compared with five of 26 healthy pregnant control women (p = 9.3 X 10(-6]. Abnormal antiglobulin tests persisted for 2 to 6 weeks after delivery. Although each neonate had a platelet count greater than 200,000/mm3 at the time of delivery, 10 of 18 had an abnormal direct antiglobulin test compared with one of 14 control subjects (p = 0.0049). The high frequency of abnormal platelet antiglobulin tests in women with preeclampsia and their neonates may indicate an immune cause of certain aspects of the syndrome or may reflect the extent of platelet activation.

The origin of increased serum iron in pregnancy- induced hypertension

Serum iron was measured in 30 patients with pregnancy-induced hypertension and 24 normal pregnant women. The mean iron concentration was significantly higher in the group with pregnancy-induced hypertension (111 ± 26 μg/ml) than in the controls (69 ± 17 μg/ml) (p

Evaluation of maternal fluid dynamics during tocolytic therapy with ritodrine hydrochloride and magnesium sulfate

OBJECTIVEnThe purpose of the study was to observe and compare the effects of ritodrine hydrochloride and magnesium sulfate on maternal fluid dynamics.nnnSTUDY DESIGNnFourteen women in preterm labor were prospectively studied during tocolytic therapy with either ritodrine hydrochloride or magnesium sulfate. The cardiovascular and renal effects of a pretreatment crystalloid infusion were compared with those observed during tocolytic therapy. Profile analysis and repeated measures of variance were used to analyze the data.nnnRESULTSnRitodrine hydrochloride was associated with decreased colloid osmotic pressure, hematocrit, and serum proteins and increased maternal and fetal heart rates. Arginine vasopressin levels increased during the first 2 hours of therapy, then returned to baseline. Sodium excretion was reduced and there was marked fluid retention. Intravenous magnesium sulfate also resulted in a reduction of colloid osmotic pressure, but hematocrit, serum protein concentration, arginine vasopressin, maternal and fetal heart rates, and mean arterial pressure were minimally affected. Sodium excretion increased to a maximum at 6 to 8 hours of treatment, then returned to baseline. A positive fluid balance was also noted in magnesium sulfate-treated patients but to a lesser degree than with ritodrine.nnnCONCLUSIONSnSodium retention appears to be the primary cause of plasma volume expansion in ritodrine-treated patients, whereas volume expansion during magnesium sulfate therapy is probably related to intravenous overhydration. In the absence of risk factors for pulmonary capillary membrane injury, available evidence supports volume overload as the principal mechanism for pulmonary edema during tocolytic therapy.

Plasma concentration of endothelin-1 in women with cocaine-associated pregnancy complications

OBJECTIVEnThe purpose of this study was to determine if the plasma concentration of endothelin-1 is elevated in pregnant women abusing cocaine and to determine how these levels differ from those in patients with preeclampsia and in women with uncomplicated pregnancies.nnnSTUDY DESIGNnPlasma endothelin-1 levels were measured in 30 women with acute cocaine intoxication, 32 women with preeclampsia, 14 pregnant women with chronic hypertension, 26 women with uncomplicated pregnancies, and 16 nonpregnant individuals. Serial samples after delivery were obtained in 12 women with preeclampsia, 10 with cocaine abuse, 4 with chronic hypertension, and 7 with uncomplicated pregnancies.nnnRESULTSnThe mean endothelin-1 concentration in those with cocaine abuse was 18.2 +/- 8.1 pg/ml (95% confidence interval 15.2 to 21.2). This was similar to that in women with preeclampsia (21.1 +/- 5.9 pg/ml, 95% confidence interval 19 to 23.3) (p = 0.2) but significantly different from that in women with chronic hypertension (11.5 +/- 3.6 pg/ml, 95% confidence interval 9.4 to 13.6) (p < 0.001) and women with uncomplicated pregnancies (6.7 +/- 3.9 pg/ml, 95% confidence interval 5.1 to 8.2) (p < 0.001).nnnCONCLUSIONSnEndothelin-1 levels in women abusing cocaine are comparable to those in women with preeclampsia and are significantly higher than those in gravid women with chronic hypertension and women with uncomplicated pregnancies. Elevated levels of endothelin-1 may contribute to some of the pregnancy-related complications in women abusing cocaine.

Maternal glucose intolerance and the subcutaneous terbutaline pump

OBJECTIVEnOur hypothesis was that use of the subcutaneous terbutaline pump does not affect maternal glucose tolerance.nnnSTUDY DESIGNnWith the 1-hour glucose tolerance test, we examined the incidence of glucose intolerance in 37 patients using the pump compared with that of 54 patients receiving oral terbutaline and 634 control subjects without risk factors for gestational diabetes. The frequency of gestational diabetes and the need for insulin to maintain glycemic control were subjected to chi 2 analysis.nnnRESULTSnThe incidence of gestational diabetes was 6% in the control subjects, 5% in patients using the pump (p = 0.8), and 11% in those on the oral therapy regimen (p = 0.4). A total of 8% of controls who had gestational diabetes required both insulin and diet, compared with 100% using the pump (p less than 0.01) and 50% on the oral terbutaline regimen (p = 0.03).nnnCONCLUSIONnThe incidence of gestational diabetes is not increased in patients receiving terbutaline via the subcutaneous pump. The use of terbutaline by any route significantly increases the need for insulin to achieve glycemic control.