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High prevalence of hemostatic abnormalities in women with a history of severe preeclampsia
Letters 989
Volume 182, Number 4 Am J Obstet Gynecol
Development Maternal-Fetal Medicine Units Network. We support such a trial. Shelley J. Chapman, MD Maternal-Fetal Medicine, Greenville Hospital System, 890 W Faris Rd, Suite 450/470, Box 32, Greenville, SC 29605 6/8/103769 doi:10.1067/mob.2000.103769
High prevalence of hemostatic abnormalities in women with a history of severe preeclampsia To the Editors: We congratulate van Pampus et al on their study of the association of severe preeclampsia with thrombophilia (van Pampus MG, Dekker GA, Wolf H, Huijgens PC, Koopman MM, von Blomberg BM. High prevalence of hemostatic abnormalities in women with a history of severe preeclampsia. Am J Obstet Gynecol 1999;180:1146-50), which is among the first of such studies to include a control group. However, we would like to make some comments. First, this case-control study suffers from selection bias in the choice of an unusually healthy control group. Control subjects had no fetal losses and had entirely uncomplicated pregnancies. In addition, 56% were parous, compared with 19% parous women in the patient group, and there was no matching for maternal age at delivery. On the other hand, if it is assumed that preeclampsia is indeed associated with thrombophilia, the exclusion of patients with preexisting vascular or renal disease caused a selection bias toward patients with thrombophilia. Second, ascertainment bias may have occurred because not all patients appear to have been tested for all the disorders studied (see Table I in the original article). Both selection bias and ascertainment bias most likely resulted in an increased contrast between patients and control subjects. Furthermore, we wonder why protein S deficiency, previously described by some of the authors of this study as showing a high prevalence among patients with preeclampsia (24.7%), was not investigated.1 Finally, the authors’ statement that thrombophilia was present in “…approximately 40% of the cases” cannot be concluded from Table I of the article. If only those patients who seem to have been tested for all the disorders studied are taken into account (Table III of the article), we calculate a prevalence of 35.2% (92/261), with a prevalence of 47.1% among patients at <28 weeks’ gestation. These figures are not 4 to 6 times higher than those observed in the control group (13.4%) but only 2.5 to 3.5 times higher. Although an extremely healthy control group was selected and although not all relevant types of thrombophilia were tested, the control group still showed a staggering 13.4% prevalence of thrombophilia. Therefore the authors’ recommendation that patients with preeclampsia should be evaluated for thrombotic disorders might as well be extended to the entire female population. In our view this high incidence of thrombophilic disorders in the control group does not lend support for a major role of thrombophilia in the pathogenesis of preeclampsia. The authors acknowledge that it remains
to be demonstrated whether anticoagulant treatment of these disorders will improve perinatal outcome. In any case the results of this study by no means justify prophylactic anticoagulant treatment to prevent preeclampsia in patients with thrombophilia but without a history of preeclampsia. Anjoke J.M. Huisjes, MD, Arie Franx, MD, PhD, and Hein W. Bruinse, MD, PhD Department of Obstetrics, Neonatology and Gynecology, University Medical Center Utrecht, Wilhelmina Children’s Hospital, PO Box 85090, 3508 AB, Utrecht, The Netherlands REFERENCE
1. Dekker GA, de Vries JI, Doelitzsch PM, Huijgens PC, von Blomberg BM, Jakobs C, et al. Underlying disorders associated with severe early-onset preeclampsia. Am J Obstet Gynecol 1995;173:1042-8.
6/8/103759 doi:10.1067/mob.2000.103759
Reply To the Editors: We appreciate the congratulations on our study from Huisjes et al. However, we do not share their concerns regarding the composition of the control group. Before undertaking the study we considered using a randomly selected control group, as Huisjes et al suggested. We rejected this idea, however, because truly random selection of women for testing appeared impossible. Control subjects had to be recruited by advertisement, and application could well be influenced by medical or obstetric complications (which indeed occurred; a substantial number of women who applied were rejected for this reason). We therefore preferred a small but extremely well-defined control group rather than a larger but potentially far more biased group. As described in the Comment section, our intention was to create an optimal contrast between the control group and the patient group. Because most thrombophilic disorders are genetic in origin, parity has no influence. Matching for parity was therefore not needed. Not all women in the study group were tested for all disorders. We intended to examine every woman who answered the inclusion criteria for all disorders. Unfortunately, in a small number of instances blood samples were misplaced or tests did not yield interpretable results. The opportunity for failure of a test result to be interpretable was influenced by chance and not by medical or obstetric factors. Protein S was examined in nearly all women because of earlier results by Dekker et al.1 We did not publish these data, however, because the reproducibility of the assay for protein S and its biologic significance are debated in the literature. The original hypothesis of the study was that if thrombophilia contributed to the origin of severe preeclampsia then (1) the prevalence of disorders would be extremely low in the control group and very high in the study group and (2) those women in whom preeclampsia developed during early pregnancy (<28 weeks’ gestation) would have the highest prevalence. The compositions of the
Volume 182, Number 4 Am J Obstet Gynecol
Development Maternal-Fetal Medicine Units Network. We support such a trial. Shelley J. Chapman, MD Maternal-Fetal Medicine, Greenville Hospital System, 890 W Faris Rd, Suite 450/470, Box 32, Greenville, SC 29605 6/8/103769 doi:10.1067/mob.2000.103769
High prevalence of hemostatic abnormalities in women with a history of severe preeclampsia To the Editors: We congratulate van Pampus et al on their study of the association of severe preeclampsia with thrombophilia (van Pampus MG, Dekker GA, Wolf H, Huijgens PC, Koopman MM, von Blomberg BM. High prevalence of hemostatic abnormalities in women with a history of severe preeclampsia. Am J Obstet Gynecol 1999;180:1146-50), which is among the first of such studies to include a control group. However, we would like to make some comments. First, this case-control study suffers from selection bias in the choice of an unusually healthy control group. Control subjects had no fetal losses and had entirely uncomplicated pregnancies. In addition, 56% were parous, compared with 19% parous women in the patient group, and there was no matching for maternal age at delivery. On the other hand, if it is assumed that preeclampsia is indeed associated with thrombophilia, the exclusion of patients with preexisting vascular or renal disease caused a selection bias toward patients with thrombophilia. Second, ascertainment bias may have occurred because not all patients appear to have been tested for all the disorders studied (see Table I in the original article). Both selection bias and ascertainment bias most likely resulted in an increased contrast between patients and control subjects. Furthermore, we wonder why protein S deficiency, previously described by some of the authors of this study as showing a high prevalence among patients with preeclampsia (24.7%), was not investigated.1 Finally, the authors’ statement that thrombophilia was present in “…approximately 40% of the cases” cannot be concluded from Table I of the article. If only those patients who seem to have been tested for all the disorders studied are taken into account (Table III of the article), we calculate a prevalence of 35.2% (92/261), with a prevalence of 47.1% among patients at <28 weeks’ gestation. These figures are not 4 to 6 times higher than those observed in the control group (13.4%) but only 2.5 to 3.5 times higher. Although an extremely healthy control group was selected and although not all relevant types of thrombophilia were tested, the control group still showed a staggering 13.4% prevalence of thrombophilia. Therefore the authors’ recommendation that patients with preeclampsia should be evaluated for thrombotic disorders might as well be extended to the entire female population. In our view this high incidence of thrombophilic disorders in the control group does not lend support for a major role of thrombophilia in the pathogenesis of preeclampsia. The authors acknowledge that it remains
to be demonstrated whether anticoagulant treatment of these disorders will improve perinatal outcome. In any case the results of this study by no means justify prophylactic anticoagulant treatment to prevent preeclampsia in patients with thrombophilia but without a history of preeclampsia. Anjoke J.M. Huisjes, MD, Arie Franx, MD, PhD, and Hein W. Bruinse, MD, PhD Department of Obstetrics, Neonatology and Gynecology, University Medical Center Utrecht, Wilhelmina Children’s Hospital, PO Box 85090, 3508 AB, Utrecht, The Netherlands REFERENCE
1. Dekker GA, de Vries JI, Doelitzsch PM, Huijgens PC, von Blomberg BM, Jakobs C, et al. Underlying disorders associated with severe early-onset preeclampsia. Am J Obstet Gynecol 1995;173:1042-8.
6/8/103759 doi:10.1067/mob.2000.103759
Reply To the Editors: We appreciate the congratulations on our study from Huisjes et al. However, we do not share their concerns regarding the composition of the control group. Before undertaking the study we considered using a randomly selected control group, as Huisjes et al suggested. We rejected this idea, however, because truly random selection of women for testing appeared impossible. Control subjects had to be recruited by advertisement, and application could well be influenced by medical or obstetric complications (which indeed occurred; a substantial number of women who applied were rejected for this reason). We therefore preferred a small but extremely well-defined control group rather than a larger but potentially far more biased group. As described in the Comment section, our intention was to create an optimal contrast between the control group and the patient group. Because most thrombophilic disorders are genetic in origin, parity has no influence. Matching for parity was therefore not needed. Not all women in the study group were tested for all disorders. We intended to examine every woman who answered the inclusion criteria for all disorders. Unfortunately, in a small number of instances blood samples were misplaced or tests did not yield interpretable results. The opportunity for failure of a test result to be interpretable was influenced by chance and not by medical or obstetric factors. Protein S was examined in nearly all women because of earlier results by Dekker et al.1 We did not publish these data, however, because the reproducibility of the assay for protein S and its biologic significance are debated in the literature. The original hypothesis of the study was that if thrombophilia contributed to the origin of severe preeclampsia then (1) the prevalence of disorders would be extremely low in the control group and very high in the study group and (2) those women in whom preeclampsia developed during early pregnancy (<28 weeks’ gestation) would have the highest prevalence. The compositions of the