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Obstetrics & Gynecology 2000;95:29-33
© 2000 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Platelet Count at Term Pregnancy: A Reappraisal of the Threshold

FRANÇOISE BOEHLEN, MD, PATRICK HOHLFELD, MD, PHILIPPE EXTERMANN, MD, THOMAS V. PERNEGER, MD and PHILIPPE DE MOERLOOSE, MD

From the Division of Angiology and Haemostasis, Department of Internal Medicine, University Hospital, Geneva; the Department of Gynecology and Obstetrics, University Hospital, Lausanne; the Department of Gynecology and Obstetrics, University Hospital, Geneva; and the Institute of Social and Preventive Medicine and Quality of Care Unit, Geneva, Switzerland.

Address reprint requests to: Philippe de Moerloose, MD, Haemostasis Unit. University Hospital of Geneva Geneva, 1211 14, Switzerland E-mail: philippe.demoerloose{at}hcuge.ch


   Abstract
Top
Abstract
Patients and Methods
 Results
 Discussion
 References
 
Objective: To assess the safety of a new platelet count threshold for the definition of maternal thrombocytopenia late in pregnancy.

Methods: A platelet count was performed in 6770 pregnant women late in pregnancy and in 6103 of their newborns as well as in a control group of 287 age-matched nonpregnant healthy women.

Results: The prevalence of maternal thrombocytopenia (platelet count less than 150 x 109/L) was 11.6%. The mean platelet counts (248 compared with 213 x 109/L) and 2.5th percentile (164 compared with 116 x 109/L) were significantly higher in healthy nonpregnant women than in pregnant women. Among thrombocytopenic pregnant women, 621 (79%) had platelet counts between 116 and 149 x 109/L; none (0%; 95% confidence interval 0, 0.6) had complications related to thrombocytopenia, and none of their newborns had severe thrombocytopenia (platelet count less than 20 x 109/L).

Conclusion: In healthy pregnant women, a platelet count over 115 x 109/L late in pregnancy does not require further investigation during pregnancy and may be considered a safe threshold.

Thrombocytopenia in pregnant women is a relatively common finding. The causes and mechanisms of such thrombocytopenia are still a matter of controversy.1–3 There are several well-established causes of thrombocytopenia such as preeclampsia and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, disseminated intravascular coagulation, autoimmune diseases, infections, and many other infrequent causes.4–8 However, the majority of thrombocytopenic pregnant women are healthy, have no history of thrombocytopenia, and are incidentally detected by routine blood testing. This condition, called incidental or gestational thrombocytopenia, usually has no influence either on the evolution of pregnancy and delivery or on the newborn, particularly on the risk of neonatal thrombocytopenia.9–14 Several mechanisms have been advocated, such as a compensated state of subclinical coagulopathy,1,2,15–17 hemodilution,18,19 endothelial cell injury,20 and undiagnosed immune thrombocytopenic purpura (ITP).21,22

Studies of platelet count variation during pregnancy were generally performed on a limited number of pregnancies and showed either a decrease or no change of the platelet count2,3,6,9,23 ( Verdy E, Bessous V, Dreyfus M, Kaplan C, Tchernia G, Uzan S. Longitudinal analysis of platelet count and volume in normal pregnancy [letter]. Thromb Haemost 1997;77:806–7[Medline]). Furthermore, the reported prevalence of maternal thrombocytopenia is variable. In a recent survey, we analyzed 6770 pregnant women near term and found a prevalence of thrombocytopenia of 11.6%.14 Other studies reported values between 6.6%11 and 15%.24 When only platelet counts below 100 x 109/L were considered, the prevalence of thrombocytopenia was similar, around 1%.11,14

The detection of a mild maternal thrombocytopenia during pregnancy may lead to complementary examinations. To avoid unnecessary investigations, our study aimed to determine a safe threshold value for the definition of maternal thrombocytopenia at the end of pregnancy.


   Patients and Methods
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Abstract
 Patients and Methods
Results
 Discussion
 References
 
Six thousand seven hundred seventy pregnant women were consecutively included in this 18-month study performed in two university hospitals of Switzerland, Lausanne and Geneva. The study received the approval of both hospitals’ ethics committees. A platelet count was performed with a cell counter Sysmex K-1000 (Toa Medical Electronics, Kobe, Japan) on admission to the labor ward or during a prenatal visit during the last month of pregnancy. At birth, 6103 neonates (90.1% of all newborns) had a cord platelet count; for technical reasons, samples were not collected or processed in the remaining 9.9% of infants. Particular aspects of this study have been reported.13,14 No exclusion criteria were used.

The control group consisted of 287 consecutive samples of all women aged 18–47 years who presented for the first time to give blood at the transfusion blood center of Geneva during the 18-month enrollment period.

Mostly descriptive statistics (means, percentiles, and proportions) are presented. Confidence intervals (CIs) on proportions were obtained using exact estimation for a binomial parameter. To compare proportions across groups, we computed odds ratios (OR), along with exact CIs based on permutations (analogous to Fisher exact test). Confidence intervals on percentiles were computed using a binomial-based method.25 This method relies on finding observations corresponding to quantiles 2.5% and 97.5% of a binomial distribution with parameters n and q/100 (where n is the total number of observations and q the percentile of interest); their ranks define the lower and upper limit of the CI for the percentile. Between-group tests on percentiles, including medians, were derived from the CIs. Means were compared using Mann-Whitney tests. P < .05 was considered statistically significant. Routine analyses were performed on Stata software (Stata Corp., College Station, TX); exact procedures were performed on StatXact and LogXact software (Cytel Software Corp., Cambridge, MA).


   Results
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Abstract
 Patients and Methods
 Results
Discussion
 References
 
As shown in Table 1Go, the mean platelet count of pregnant women was significantly lower compared with control women. The 2.5th percentile was also very different in pregnant and control women. The histogram of platelet count indicates a left shift during pregnancy (Figure 1Go). In this study, platelet counts of 150 x 109/L represent the first percentile in the control group and the 11.5th percentile in pregnant women.


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  		Table 1. Mean Platelet Counts of Women and Controls
 


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  		Figure 1. Histogram of platelet count of pregnant women compared with nonpregnant women.

 
Among the 6770 pregnant women included, 786 (11.6%; 95% CI 10.8, 12.4) had a platelet count less than 150 x 109/L. This thrombocytopenia was of unknown origin, ie, gestational for 738 women (94%) (Table 2Go). Among the 48 remaining women, the most common diagnoses were preeclampsia and HELLP syndrome, which represented 75% (36 of 48) of thrombocytopenia of known origin. Immune thrombocytopenic purpura was infrequent, occurring in only four pregnant women (incidence of one in 1700 pregnancies). Other diagnoses, such as disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, severe pernicious anemia, or antepartum hemorrhage, were rare. The proportion of thrombocytopenia of unknown origin decreased with the severity of thrombocytopenia (Table 2Go). None of the 621 women with platelet counts between 116 and 149 x 109/L had complications related to thrombocytopenia and none of their newborns had severe thrombocytopenia.


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  		Table 2. Diagnosis and Incidence of Maternal and Neonatal Thrombocytopenia According to Maternal Platelet Count
 
Only 165 of 786 thrombocytopenic women (21% of the thrombocytopenic women and 2.4% of all pregnant women) had a platelet count below the 2.5th percentile for pregnant women (less than 116 x 109/L). The origin of thrombocytopenia was known in 29 women, and in the remaining 136 women with a platelet count less than 116 x 109/L of unknown origin, no maternal complication was observed. When considering the 621 women with a platelet count between 116 and 149 x 109/L, 602 (97%) had gestational thrombocytopenia. Among the 19 remaining women (3%), 17 had either preeclampsia or HELLP syndrome, one associated with ITP, one antepartum hemorrhage, and one severe pernicious anemia (Table 2Go). The diagnosis was suspected for all of these women before the results of the platelet count were received.

Among the 6103 tested newborns, 33 (0.5%) had a platelet count below 150 x 109/L (Table 2Go). Twenty-three (0.4%) were born to nonthrombocytopenic mothers, six (1.0%; OR 2.4; 95% CI 0.8, 6.2) to mothers with mild thrombocytopenia (platelet count between 116 and 149 x 109/L), and four (2.8%; OR 6.3; 95% CI 1.6, 18.8) to mothers with a platelet count less than 116 x 109/L. Only four of these 33 newborns had severe thrombocytopenia (platelet count less than 20 x 109/L) and only one of the four mothers was thrombocytopenic (platelet count 106 x 109/L) and was treated for ITP with corticosteroids. Among the four newborns, the first died of severe bleeding due to anti-HPA-1a alloimmunization, the second was born to the mother with known ITP, and the third died of neonatal acute myeloid leukemia M7 with cytomegalovirus infection. The last was healthy, as was his mother, and the cause of the thrombocytopenia remained unclear; the platelet count was at 71 x 109/L at day 1 and 302 x 109/L at day 4.

We looked for the 2.5th percentile according to nationality (available for 96.5% of the pregnant women), and for the six groups considered, similar results were obtained: 118 x 109/L for the women from northern Europe (n = 2883), 109 x 109/L for southern Europe (n = 1889), 116 for eastern Europe (n = 640), 111 x 109/L for Africa (n = 473), 117 x 109/L for Asia (n = 361), and 123 x 109/L for America (n = 286; 85.4% from South America).


   Discussion
Top
Abstract
 Patients and Methods
 Results
 Discussion
References
 
Thrombocytopenia is usually defined as a platelet count under 150 x 109/L; this value represents the 2.5th percentile of the distribution in a healthy population of men and nonpregnant women. In our study, the control group of nonpregnant women had a 2.5th percentile at 164 x 109/L, with a CI including 150 x 109/L, and so confirmed that the usual threshold of 150 x 109/L is appropriate for nonpregnant women of childbearing age in the general population.

The 2.5th percentile for the platelet count at the end of pregnancy (116 x 109/L) is significantly lower than the value usually accepted in a general population. This difference could be explained by a two-mode distribution of platelet counts in pregnant women: one group of women with severe thrombocytopenia and another group with a normal distribution. However, the histogram of platelet number shows a significant left shift for the whole distribution of platelet counts in pregnant compared with nonpregnant women. Thus, the use of the conventional threshold leads to a high prevalence of maternal thrombocytopenia (11.6%) in our study population.

The question is therefore: Is it appropriate to define a lower safety threshold for the platelet count during pregnancy to avoid unnecessary maternal investigations, without risk to the mother and her infant? Indeed, it does not seem reasonable to perform detailed investigations in all cases of mild maternal thrombocytopenia during the third trimester, as a specific diagnosis is rarely found. This may be because some investigations cannot be performed during pregnancy (platelet life span), because of the present lack of specific tests to identify autoimmune thrombocytopenia, because mild maternal thrombocytopenia is usually not associated with maternal or neonatal morbidity,26 or because there is no relationship between maternal and neonatal platelet counts. Although the risk of neonatal thrombocytopenia is greater in newborns of mothers with autoimmune thrombocytopenia, only a small percentage of infants born to mothers with ITP present with severe neonatal thrombocytopenia (platelet count less than 20 x 109/L), with exceptional case reports of intracranial hemorrhage often associated with other risk factors.10,12,27–30 In our study, we did observe no maternal or neonatal bleeding complications or death in the group of 621 pregnant women with mild thrombocytopenia late in pregnancy. For these reasons, in the absence of an underlying disease, we propose to follow the clinical course of these pregnant women and to refrain from detailed investigations in the presence of a platelet count above 115 x 109/L late in pregnancy. The clinical history (prior history of autoimmune disease, specifically splenectomy in the case of ITP, prior history of maternal or neonatal thrombocytopenia, bleeding disorder, drug ingestion, infection, etc) and clinical examination (bruises, hypertension, icterus, hepatosplenomegalia, etc) must be taken into account.30,31

Our study does not allow us to define a clear protocol for pregnant women with thrombocytopenia below 115 x 109/L, but based on previous reports7,27,32 ( Bussel J, Druzin M, Cines DG, Samuels P. Thrombocytopenia in pregnancy [letter]. Lancet 1991;337:251), it seems reasonable to consider investigations in this group of women. Between 75 and 115 x 109/L, when clinical history and examination are normal, limited investigations such as complete blood count and smear and hepatic function tests as well as human immunodeficiency virus (HIV) and hepatitis C virus serologies may be considered. Other investigations may be indicated in specific cases. It seems reasonable to investigate thrombocytopenia below 75 x 109/L, a threshold beneath which the diagnosis of gestational thrombocytopenia is generally not considered32 ( Bussel J, Druzin M, Cines DG, Samuels P. Thrombocytopenia in pregnancy [letter]. Lancet 1991;337:251). Our results are in agreement with this protocol of investigation. Indeed, 10% of pregnant women with a platelet count between 75 and 115 x 109/L had thrombocytopenia of known origin. All these 15 women would have been detected by either examination (including blood pressure) or a blood test (complete blood count and hepatic function). None of these women had HIV or hepatitis C virus infections. In the group of pregnant women with a platelet count less than 75 x 109/L, several important conditions (Table 2Go) were diagnosed, confirming the fact that investigations are essential in this group of thrombocytopenic pregnant women.

This attitude does not imply that thrombocytopenia late in pregnancy should be neglected. Indeed, in such cases, it seems important to obtain a postpartum platelet count that can assist in determining the cause of pregnancy-associated thrombocytopenia and differentiate this from other potential causes.22 As pointed out in other studies, the best predictor of neonatal thrombocytopenia is the history of a decreased platelet count in a previous sibling.

It would have been interesting to know platelet counts before or at the beginning of pregnancy, but in our settings, platelet counts are routinely performed only at the end of pregnancy. Therefore, it is not possible to correlate the platelet counts observed at the end of pregnancy with previous platelet counts for the majority of the women.


   Footnotes
 
This collaborative work was partly funded by a grant from the Henri Dubois-Ferrière Dinu Lipatti Foundation.

PII S0029-7844(99)00537-2

Received May 10, 1999. Received in revised form July 13, 1999. Accepted July 22, 1999.


   References
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Abstract
 Patients and Methods
 Results
 Discussion
 References
 
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2. Tygart SG, McRoyan DK, Spinnato JA, McRoyan CJ, Kitay DZ. Longitudinal study of platelets indices during normal pregnancy. Am J Obstet Gynecol 1986;154:883–7.[Medline]

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5. Starkie CM, Harding LK, Fletcher DJ, Stuart J. Intravascular coagulation and abnormal lung scans in preeclampsia and eclampsia. Lancet 1971;ii:889–91.

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8. Kaplan C, Forestier F, Dreyfus M, Morel-Kopp MC, Tchernia G. Maternal thrombocytopenia during pregnancy: Diagnosis and etiology. Semin Thromb Hemost 1995;21:85–94.[Medline]

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14. Boehlen F, Hohlfeld P, Extermann P, de Moerloose P. Maternal antiplatelet antibodies in predicting the risk of neonatal thrombocytopenia. Obstet Gynecol 1999;93:169–73.[Abstract/Free Full Text]

15. Rakoczi I, Tallian F, Bagdany S, Gati I. Platelet life-span in normal pregnancy and preeclampsia as determined by a non-radioisotope technique. Thromb Res 1979;15:553–6.[Medline]

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18. Rinder HM, Bonan JL, Anandan S, Rinder CS, Rodrigues PA, Smith BR. Noninvasive measurement of platelet kinetics in normal and hypertensive pregnancies. Am J Obstet Gynecol 1994;170:117–22.[Medline]

19. Lurie S. Changes in platelet volume and count during pregnancy: A longitudinal study. Gynecol Obstet Invest 1995;40:71–2.[Medline]

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21. Tchernia G, Morel-Kopp MC, Yvart J, Kaplan C. Neonatal thrombocytopenia and hidden maternal autoimmunity. Br J Haematol 1993;84:457–63.[Medline]

22. Ajzenberg N, Dreyfus M, Kaplan C, Yvart J, Weill B, Tchernia G. Pregnancy-associated thrombocytopenia revisited: Assessment and follow-up of 50 cases. Blood 1998;92:4573–80.[Abstract/Free Full Text]

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25. Conover WJ. Practical nonparametric statistics. 2nd ed. New York: Wiley, 1980:111–6.

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