AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 9, NUMBER 5/6
Sept/Nov 1992
PREECLAMPSIA EFFECT O N PLATELET COUNT Ran Neiger, M.D., Stephen A. Contag, M.D., and Donald R. Coustan, M.D.
Thrombocytopenia is well recognized when preeclampsia is complicated by the hemolysis, elevated liver tests, low platelet count (HELLP) syndrome. We studied the effect of preeclampsia on the platelets of women whose platelet count and liver function were within normal range. We prospectively evaluated 67 preeclamptic women, gestational age 30 to 42 weeks, with disease of variable severity. The platelet counts of these patients, obtained within 24 hours preceding delivery, were significantly lower than the platelet counts of 71 control subjects. The platelet counts did not differ significantly between patients with mild and severe preeclampsia. Our findings suggest the existence of subclinical thrombocytopenia in preeclamptic women whose platelet values are within normal range.
There is conflicting information regarding changes in the platelet count during normal pregnancy, with most studies reporting a decrease in the mean concentration of circulating platelets in pregnant women, when compared with nonpregnant control subjects.1-3 This decrease is related to the physiologic increase in plasma volume and to an increased platelet consumption.3 Concomitantly, circulating platelet volume and distribution width are increased45 due to an accelerated platelet production by the bone marrow, with the release of larger, younger platelets. Patients who develop preeclampsia have lower platelet counts,6"8 as well as a greater increase in the platelet volume, 78 when compared with pregnant control subjects. When a large number of studies are combined, this phenomenon apparently occurs in approximately 18% of preeclamptic pregnancies.9 However, the majority of studies documenting such a decrease in platelet concentrations in preeclamptic women included patients with significant thrombocytopenia, with platelet counts of less than 100,000/ mm3. The purpose of our study was to assess the effect of preeclampsia on the platelet counts of patients without clinically detectable thrombocytopenia who had no liver involvement, and to compare platelet counts of mild and severely preeclamptic patients, looking for a possible relationship between the severity of the disease and its effect on platelets' concentration.
MATERIALS AND METHODS Our study population included 67 consecutive preeclamptic patients, gestational age 30 to 42 weeks (average, 37.7 ± 3), with disease of variable severity, delivered at Memorial Medical Center, Savannah, Georgia, between January 1988 and June 1989. Forty-seven patients were managed by the house staff and 20 were treated by private obstetricians. The diagnosis of preeclampsia was based on criteria established by the American College of Obstetricians and Gynecologists.10 The preeclampsia was considered severe when one of the following conditions was met: systolic blood pressure values of 160 mmHg or above, or diastolic of 110 mmHg or above, on at least two occasions, 6 hours apart; proteinuria of 5 gm or greater in 24 hours, urine output of less than 30 ml/hour over a 2-hour period in a well-hydrated patient, or visual disturbances including scotomata and blurred vision. All patients had a laboratory workup that included a complete blood count, platelet count, blood urea nitrogen, uric acid, creatinine, bilirubin, and liver enzymes. Exclusion criteria included platelet value below 150,000/mm3, elevated liver enzymes, and the presence of a chronic underlying disease. We compared the platelet values of these patients, obtained within the 24 hours preceding delivery, to platelet counts of 71 healthy pregnant controls who delivered at the same
Memorial Medical Center, Department of Obstetrics and Gynecology, Savannah, Georgia, and Brown University/Women & Infants' Hospital, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Providence, Rhode Island Reprint requests: Dr. Neiger, Department of Obstetrics and Gynecology, University of Tennessee Medical Center-Knoxville, 1924 Alcoa Highway, Knoxville, TN 37920
378
Copyright © 1992 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
Downloaded by: National University of Singapore. Copyrighted material.
ABSTRACT
PREECLAMPSIA EFFECT O N PLATELETS/Neiger, Contag, Coustan
hospital over the corresponding period, at similar gestational ages (average, 37 ± 3 weeks), obtained during the 24 hours prior to delivery. Statistical analysis consisted of Student's t test for the comparison of means of independent samples.
400 -i
RESULTS
COMMENT The exact pathophysiologic mechanisms responsible for the decrease in platelet count in preeclamptic patients is not known. One proposed mechanism is an increased consumption due to platelet adherence to damaged vascular endothelium.1112 Vasospasm and endothelial lesions are associated with an increase in the ratio of thromboxane to prostacyclin, causing platelet adherence and aggregation.13 Platelet-bound and circulating platelet-bindable immunoglobulin and complement were demonstrated in the plasma of preeclamptic patients, suggesting that immune mechanisms may contribute to the decrease in platelet counts seen in these patients.1415 Some cases of severe preeclampsia are complicated by disseminated intravascular coagulation (DIC),1617 but it is unlikely that DIC is the cause of thrombocytopenia in the majority of patients, since most preeclamptic women have normal plasma fibrinogen and only a minimal elevation of fibrin split products. Although most studies report that thrombocytopenia occurs more commonly in patients with eclampsia than in
Table 1.
Demographic Data
Preeclampsia
Control
67
71 23, ,5 ± 5. 8 2 ± 1. 5 2,,1 ± 1. 4 38 37, .7 ± 3
Number Age (yr) Gravidity Parity Caucasians (%) Gestational age at delivery (weeks) *NS: not significant.
22 ± 6 .2 2.5 ± 1 .4 1.6 ± 1 .2 30
37 ± 3
p Va/ue
NS* NS
Sept/Nov 1992
PREECLAMPSIA EFFECT O N PLATELET COUNT Ran Neiger, M.D., Stephen A. Contag, M.D., and Donald R. Coustan, M.D.
Thrombocytopenia is well recognized when preeclampsia is complicated by the hemolysis, elevated liver tests, low platelet count (HELLP) syndrome. We studied the effect of preeclampsia on the platelets of women whose platelet count and liver function were within normal range. We prospectively evaluated 67 preeclamptic women, gestational age 30 to 42 weeks, with disease of variable severity. The platelet counts of these patients, obtained within 24 hours preceding delivery, were significantly lower than the platelet counts of 71 control subjects. The platelet counts did not differ significantly between patients with mild and severe preeclampsia. Our findings suggest the existence of subclinical thrombocytopenia in preeclamptic women whose platelet values are within normal range.
There is conflicting information regarding changes in the platelet count during normal pregnancy, with most studies reporting a decrease in the mean concentration of circulating platelets in pregnant women, when compared with nonpregnant control subjects.1-3 This decrease is related to the physiologic increase in plasma volume and to an increased platelet consumption.3 Concomitantly, circulating platelet volume and distribution width are increased45 due to an accelerated platelet production by the bone marrow, with the release of larger, younger platelets. Patients who develop preeclampsia have lower platelet counts,6"8 as well as a greater increase in the platelet volume, 78 when compared with pregnant control subjects. When a large number of studies are combined, this phenomenon apparently occurs in approximately 18% of preeclamptic pregnancies.9 However, the majority of studies documenting such a decrease in platelet concentrations in preeclamptic women included patients with significant thrombocytopenia, with platelet counts of less than 100,000/ mm3. The purpose of our study was to assess the effect of preeclampsia on the platelet counts of patients without clinically detectable thrombocytopenia who had no liver involvement, and to compare platelet counts of mild and severely preeclamptic patients, looking for a possible relationship between the severity of the disease and its effect on platelets' concentration.
MATERIALS AND METHODS Our study population included 67 consecutive preeclamptic patients, gestational age 30 to 42 weeks (average, 37.7 ± 3), with disease of variable severity, delivered at Memorial Medical Center, Savannah, Georgia, between January 1988 and June 1989. Forty-seven patients were managed by the house staff and 20 were treated by private obstetricians. The diagnosis of preeclampsia was based on criteria established by the American College of Obstetricians and Gynecologists.10 The preeclampsia was considered severe when one of the following conditions was met: systolic blood pressure values of 160 mmHg or above, or diastolic of 110 mmHg or above, on at least two occasions, 6 hours apart; proteinuria of 5 gm or greater in 24 hours, urine output of less than 30 ml/hour over a 2-hour period in a well-hydrated patient, or visual disturbances including scotomata and blurred vision. All patients had a laboratory workup that included a complete blood count, platelet count, blood urea nitrogen, uric acid, creatinine, bilirubin, and liver enzymes. Exclusion criteria included platelet value below 150,000/mm3, elevated liver enzymes, and the presence of a chronic underlying disease. We compared the platelet values of these patients, obtained within the 24 hours preceding delivery, to platelet counts of 71 healthy pregnant controls who delivered at the same
Memorial Medical Center, Department of Obstetrics and Gynecology, Savannah, Georgia, and Brown University/Women & Infants' Hospital, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Providence, Rhode Island Reprint requests: Dr. Neiger, Department of Obstetrics and Gynecology, University of Tennessee Medical Center-Knoxville, 1924 Alcoa Highway, Knoxville, TN 37920
378
Copyright © 1992 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
Downloaded by: National University of Singapore. Copyrighted material.
ABSTRACT
PREECLAMPSIA EFFECT O N PLATELETS/Neiger, Contag, Coustan
hospital over the corresponding period, at similar gestational ages (average, 37 ± 3 weeks), obtained during the 24 hours prior to delivery. Statistical analysis consisted of Student's t test for the comparison of means of independent samples.
400 -i
RESULTS
COMMENT The exact pathophysiologic mechanisms responsible for the decrease in platelet count in preeclamptic patients is not known. One proposed mechanism is an increased consumption due to platelet adherence to damaged vascular endothelium.1112 Vasospasm and endothelial lesions are associated with an increase in the ratio of thromboxane to prostacyclin, causing platelet adherence and aggregation.13 Platelet-bound and circulating platelet-bindable immunoglobulin and complement were demonstrated in the plasma of preeclamptic patients, suggesting that immune mechanisms may contribute to the decrease in platelet counts seen in these patients.1415 Some cases of severe preeclampsia are complicated by disseminated intravascular coagulation (DIC),1617 but it is unlikely that DIC is the cause of thrombocytopenia in the majority of patients, since most preeclamptic women have normal plasma fibrinogen and only a minimal elevation of fibrin split products. Although most studies report that thrombocytopenia occurs more commonly in patients with eclampsia than in
Table 1.
Demographic Data
Preeclampsia
Control
67
71 23, ,5 ± 5. 8 2 ± 1. 5 2,,1 ± 1. 4 38 37, .7 ± 3
Number Age (yr) Gravidity Parity Caucasians (%) Gestational age at delivery (weeks) *NS: not significant.
22 ± 6 .2 2.5 ± 1 .4 1.6 ± 1 .2 30
37 ± 3
p Va/ue
NS* NS
