Platelets

ISSN: 0953-7104 (Print) 1369-1635 (Online) Journal homepage: http://www.tandfonline.com/loi/iplt20

Immature platelet fraction in hypertensive

pregnancy

Daniela Moraes, Terezinha Paz Munhoz, Bartira E. Pinheiro da Costa, Marta

Ribeiro Hentschke, Fernando Sontag, Luiza Silveira Lucas, Giovani Gadonski,
Ivan Carlos Antonello & Carlos E. Poli-de-Figueiredo

To cite this article: Daniela Moraes, Terezinha Paz Munhoz, Bartira E. Pinheiro da Costa,
Marta Ribeiro Hentschke, Fernando Sontag, Luiza Silveira Lucas, Giovani Gadonski, Ivan Carlos
Antonello & Carlos E. Poli-de-Figueiredo (2015): Immature platelet fraction in hypertensive
pregnancy, Platelets, DOI: 10.3109/09537104.2015.1101060

To link to this article: http://dx.doi.org/10.3109/09537104.2015.1101060

Published online: 20 Nov 2015.

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ISSN: 0953-7104 (print), 1369-1635 (electronic)

Platelets, Early Online: 1–5

© 2015 Taylor & Francis Group, LLC. DOI: 10.3109/09537104.2015.1101060

ORIGINAL ARTICLE

Immature platelet fraction in hypertensive pregnancy

Daniela Moraes1,2, Terezinha Paz Munhoz2, Bartira E. Pinheiro da Costa1, Marta Ribeiro Hentschke1, Fernando Sontag1,
Luiza Silveira Lucas 1, Giovani Gadonski1, Ivan Carlos Antonello1, & Carlos E. Poli-de-Figueiredo 1
1
Programa de Pos-Graduaçao em Medicina e Ciencias da Saude (Nefrologia), Faculdade de Medicina, Instituto de Pesquisas Biomedicas, Hospital São Lucas
– Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil and 2Laboratorio de Patologia Clinica –Hospital São Lucas Hospital
/Faculdade de Farmácia Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil

Abstract Keywords
Downloaded by [Tufts University] at 11:39 06 December 2015

Background: Imbalance in hemostatic mechanisms can occur during pregnancy with a Blood platelets, mean platelet volume,
tendency for hypercoagulability and increased thrombosis risk. Pregnant women with preeclampsia, pregnancy induced
hypertensive disorder, especially preeclampsia, show alterations in platelet indexes. hypertension
Immature platelet fraction (IPF) has been suggested as a sensitive index for monitoring
changes in platelet production and destruction. Objectives: To evaluate the IPF in patients History
diagnosed with a gestational hypertensive disorder (GHD). Patients and methods: A cross-
Received 31 December 2014
sectional study was conducted at an University Hospital to estimate maternal blood IPF
Accepted 22 September 2015
index in 99 pregnant women, divided into three groups: normotensive pregnancy (NP),
Published online 20 November 2015
preeclampsia syndrome (PES), and non-proteinuric hypertensive pregnancy (nPHP).
Following ethical approval and written informed consent, samples were collected from 33
NP, 34 PES, and 32 nPHP women. Platelet indexes were measured by fluorescent flow
cytometry. Results: IPF and mean platelet volume (MPV) counts in GHD were significantly
higher than in NP (IPF: 3.8, 2.4–5.1%; 8.6, 5.8–10.6%; 7.3, 4.2–10.2%; p < 0.001 and MPV:
10.6 ± 0.9 fL; 12.1 ± 1.0 fL; 11.6 ± 1.0 fL; p < 0.001 for NP, PES, and nPHP, respectively). No
difference was detected between PES and nPHP groups. The distribution of patients with
an IPF above 6.1%for NP, PES, and nPHP was 9%, 65%, and 43.8%, respectively (p < 0.001).
IPF as a test to differentiate GHD from the controls achieved an area under the curve of
0.83 on a receiver operating characteristics curve. Conclusion: A distinct profile in platelet
indexes was detected in hypertensive pregnancies. It suggests that these markers could be
used in daily routine as an additional tool in the management of pregnant women.

Introduction larger and more reactive than mature ones [10]. Immature
platelet fraction (IPF) corresponds to the level of platelet
Gestational hypertensive disorders (GHDs) are one of the lead-
production in the bone marrow. It reflects the stage of throm-
ing causes of maternal–fetal morbidity and mortality [1–3].
bopoiesis and can be used to distinguish the causes of throm-
According to the National High Blood Pressure Education
bocytopenia [11], with it being a more stable parameter than
Program Working Group Report on High Blood Pressure,
mean platelet volume (MPV).
(NHBPEPWG), GHD in pregnancy are divided into preeclamp-
Increased MPV and decreased erythrocyte numbers in GHD
sia (PE), superimposed preeclampsia (SPE), gestational hyper-
have been suggested as auxiliary indexes for the diagnosis and
tension (GH), and chronic hypertension (CH) [4]. The etiology
classification of disease severity [10]. We therefore hypothesized
of preeclampsia is unknown, and its pathophysiological
that IPF and MPV would be increased and total platelet numbers
mechanisms are related to placental ischemia, endothelial dys-
reduced in hypertensive pregnancies in comparison to normoten-
function, inflammation, and coagulation alterations among
sive ones. The aim of the present study was to evaluate platelet
others [5–7].
indexes in hypertensive pregnancies with preeclampsia syndrome
Hemostatic changes occur during gestation and are exacer-
(PES), non-proteinuric hypertensive pregnancies (nPHP), and
bated in preeclampsia. Thrombocytopenia is a relatively com-
normotensive pregnancies (NPs).
mon finding in pregnancy [8, 9], with approximately 12% of
pregnant women presenting a platelet count of less than 150 ×
Methods
109/L and 1% having a count lower than 100 × 109/L [8, 9].
Immature platelets, also known as reticulated platelets, are Subjects and selection criteria
A cross-sectional study was conducted enrolling 99 pregnant
women. Patients were divided into three groups: normotensive
Correspondence: C. E. Poli-de-Figueiredo, Programa de Pos-Graduaçao
controls (NP, n = 33), PES (n = 34), and nPHPs (n = 32). Women
em Medicina e Ciencias da Saude (Nefrologia), Instituto de Pesquisas
Biomedicas, Hospital São Lucas – Pontifícia Universidade Católica do were recruited at the Hospital São Lucas (HSL) of the Pontifical
Rio Grande do Sul (PUCRS), Centro Clinico PUCRS C414, Av. Ipiranga, Catholic University of Rio Grande do Sul (PUCRS), Porto
6690, Porto Alegre, RS, Brazil 90610-000. E-mail: cepolif@pucrs.br Alegre, Brazil, and all participants signed an informed consent
 2 D. Moraes et al. Platelets, Early Online: 1–5

form. The protocol was approved by the Research and Ethics
Committee of PUCRS (Document # 105.164).
Using the VI Brazilian Hypertension Guidelines and the
NHBPEPWG, preeclampsia was defined as blood pressure
≥140 mmHg systolic and/or ≥90 mmHg diastolic, accompanied
by new proteinuria ≥0.3 g/24 h after 20 weeks of gestation [4, 12,
13]. A urine protein:creatinine (UPC) ratio equal to or greater
than 0.3 was considered to be equivalent to a 24-h proteinuria
≥0.3 g/24 h for the diagnosis of PES. The term PES was
employed to describe women with either preeclampsia or super-
imposed preeclampsia. Women with gestational hypertension or
with chronic hypertension without proteinuria were considered to
have nPHP. Pregnant women with a history of venous or arterial
thrombosis, renal disease, infections, or or hemolysis, elevated
liver enzymes and low platelets (HELLP) syndrome were
excluded. Normotensive pregnant women with a proteinuria dip-
stick reading of 1+ were not included.
Sample collection and blood analysis
Vacutainer® tubes containing EDTA (ethylenediaminetetraa-
cetic acid) were used to collect 4 mL of blood from all
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as percentages. Variance analysis (ANOVA) was performed for
the quantitative variables and with log-transformation for the
asymmetric quantitative variables, and differences identified
with Tukey test. A Chi-square test was used for the categorical
variables, and ANOVA and Chi-square to compare the three
groups. The null hypothesis was rejected when p < 0.05.
Sample size was calculated considering alpha = 0.05, effect
size of 0.8 SD, and 90% power (β = 0.10), resulting in 34
patients per group.
Results
Subjects
The demographic and clinical data are shown in Table I. Maternal
and gestational age were no different between the groups at the
time of collection; however, there was a significant difference in
gestational age at delivery, as well as in blood pressure levels and
neonatal birth weight.
Biochemical measurements

patients from the twentieth week of gestation. Inclusion of
the pregnant controls sought to maintain similarity of age and
gestational age among the groups, seeking greater homogene-
ity between them. All samples were analyzed at the
Laboratory of Clinical Pathology/HSL/PUCRS, within 4 h of
collection, using the XE-5000® (Sysmex Corporation, Kobe,
Japan) automated hematology system. The platelets and plate-
let index counts were conducted using the impedance method,
which also provided MPV, platelet distribution width (PDW),
and plaquetocrit (PCT) readings. IPF was quantified using the
optical fluorescence method conducted in the reticulocyte/
optical platelet channel of the same equipment. In this
approach, a polymethine fluorescent dye is used to stain the
RNA/DNA of the reticulated cells, platelet membranes, and
granules. This method allows the simultaneous counting of
reticulocytes, erythrocytes, and fluorescent platelets.
Statistical analysis
Data were analyzed using the SPSS Statistics Package for
Windows software, Version 21.0. (IBM, Armonk, NY) and pre-
sented as mean ± standard deviation (SD) or median (interquar-
tile range), as appropriate. Categorical variables were expressed
Hemoglobin and red blood cell, white blood cell, and platelet
counts were not significantly different between the women with
NP, PES, and nPHP.
IPF, MPV, and PDW platelet indexes were statistically differ-
ent between NP and both PES and nPHP groups. Data are pre-
sented in Table II and Figure 1a and b.
The distribution of patients with an IPF above the cutoff point
considered normal (6.1%) [14] was 65% for the PES group, 43.8%
for the nPHP, and only 9% for patients in the NP group. Data
relating to MPV show that 34.4% of PES patients have results
above the 12.5 fL cutoff point [15], with only 18.8% in nPHP
patients and no patients in the NP group. IPF and MPV above
cutoff points are shown in Figure 2a and b.
IPF was also plotted on a ROC curve (receiver operating
characteristics) to assess its value as a test to differentiate GHD
from the controls (Figure 3). The area under the curve was 0.83.
Discussion
The findings of the present study demonstrate that patients
with hypertension in pregnancy, PES, or nPHP have increased
immature platelet count when compared to the normotensive
group. The same was demonstrated for the MPV and PDW.
On the other hand, the groups did not present a significant

Table I. Demographic and clinical data.

NP PES nPHP
(n = 33) (n = 34) (n = 32) p

Age, years (mean ± SD) 24.7 ± 6.6 27.5 ± 7.7 27.8 ± 7.3 0.167
Caucasian, n (%) 24 (72.7) 20 (58.8) 15 (46.9) 0.155
Nulliparous, n (%) 13 (39.4) 20 (58.8) 15 (46.9) 0.116
Previous abortions, n (%) 9 (28.1)a 6 (18.2) b 3 (10) b 0.047
Gestational age, weeks 36.3 ± 3.1 35.8 ± 3.6 36.4 ± 3.4 0.762
(mean ± SD) at sampling
Gestational age, weeks (mean ± SD) at delivery 39.3 ± 1.6a 36.6 ± 2.9b 37.6 ± 2.2b <0.001
Systolic blood pressure, mmHg (mean ± SD) 114.1 ± 11.2a 156.7 ± 13.5b 157.1 ± 11.3b <0.001
Diastolic blood pressure, mmHg (mean ± SD) 72.4 ± 11.1a 101.4 ± 8.8b 100.3 ± 12.26b <0.001
Urine protein:creatinine ratio * 2.15(0.41–2.80)a 0.14(0.081–0.19)b <0.001
Normal vaginal delivery, 13(65) 8 (24.2) 19(61.3) 0.007
n (%)
Birth weight, kg 3325 ± 466.3a 2737 ± 779.4b 2948 ± 736.7b 0.006
(mean ± SD)

NP: normotensive pregnancy; PES: preeclampsia syndrome; nPHP: non-proteinuric hypertensive pregnancy; *NP group checked by negative dipstick
test for urinary protein. p: ANOVA or Chi-square. Distinct index letters indicate the differences between groups.
 DOI: 10.3109/09537104.2015.1101060 Hypertension in pregnancy and immature platelet fraction 3
Table II. Hematological profile of patients.

Blood indexes NP (n = 33) PES (n = 34) n PHP(n = 32) p

Red cells 4.0 ± 0.4 4.15 ± 0.4 4.1 ± 0.4 0.091

(106/uL)
White cells (/uL) 10 402.3 ± 2062.8 11 209.3 ± 2930.2 10 750.6 ± 2072.9 0.389
Hematocrit (%) 35.4 ± 2.8 36.1 ± 3.0 35.9 ± 2.9 0.538
Hemoglobin (g/dL) 11.8 ± 0.91 12.3 ± 1.16 12,2 ± 1.0 0.127
Platelet (/uL) 235 758 ± 53,007 209 206 ± 65 785 213 844 ± 57 931 0.155
Mature platelets (/uL) 227 095 ± 52 911a 192 255 ± 64 201b 200 039 ± 60 517b 0.047
IPF (%) 3.8 (2.4–5.1)a 8.6 (5.8–10.6)b 7.3 (4.2–10.2)b <0.001
IPF absolute (/uL) 8662 ± 3,908a 16 951 ± 7424b 13 805 ± 5097b <0.001
MPV (fL) 10.6 ± 0.9a 12.1 ± 1.0b 11.6 ± 1.0b <0.001
PDW (fL) 12.80 ± 1.7a 15.96 ± 2.7b 15.26 ± 2.9b <0.001
PCT (%) 0.25 ± 0.05 0.25 ± 0.08 0.24 ± 0.05 0.940

IPF: immature platelets fraction; MPV: mean platelet volume; PDW: platelet distribution width; PCT: plaquetocrit. Distinct index letters indicate the
differences between groups.
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Figure 2. (a). Percentage distribution of patients with immature platelet

Figure 1. (a). Patient distribution according to IPF result. (b). Patient
fraction exceeding 6.1%. (b). Percentage distribution of patients with
distribution according to the MPV result. (PES = preeclampsia syndrome;
mean platelet volume exceeding 12.5 fL. (PES = preeclampsia syndrome;
NP = normotensive controls; nPHP = non-proteinuric hypertensive
NP = normotensive controls; nPHP = non-proteinuric hypertensive
pregnancy).
pregnancy).

reduction in the total platelet count, when compared either
between groups or with reference values. This can be
explained by the continuous production of platelets by the
bone marrow due to increased peripheral platelet consump-
tion, made evident by a higher immature platelet fraction.
Despite the number of mature platelets being statistically
different between the PE and NP groups, the change in the
count was not considered clinically relevant.
There are still some conflicting results in the published litera-
ture in relation to the total platelet count and the MPV during
normal and preeclamptic pregnancies. Some authors have found
no differences in either the total number of platelets or the MPV
 4 D. Moraes et al.
Figure 3. ROC (receiver operating characteristics) curve of the gestational
Downloaded by [Tufts University] at 11:39 06 December 2015
hypertension disorder and normotensive pregnancy for immature platelet
fraction.
in normotensive and hypertensive pregnant patients [16, 17],
whilst other studies, including this one, have shown significant
differences in the MPV but not in the total platelet count between
these two groups of women. It is possible that these discrepancies
can be explained by the differences in methods applied and the
anticoagulants used. Although EDTA is the anticoagulant of
choice for the test, MPV increases significantly in dependence
on the temperature and time of collection [18, 19].
Several researchers have shown a decrease in the platelet count
and an increase in the MPV in women with PE [20, 21, 11,
22–25], but data regarding immature platelets are rare [26].
Only one study was found in the literature with evidence of
increased reticulated platelets in patients with PE, using a slightly
different method [27]. Other platelet alterations have also been
previously reported in pregnancy [28–32].
The present study investigated the presence of immature plate-
lets in preeclampsia syndrome. Strict exclusion criteria were
adopted to reject patients with any hematological or associated
disease. The statistical impossibility of distinguishing pure pre-
eclampsia from superimposed PE due to the sample size limits
analysis of the clinical importance of the IPF in separating them.
On the other hand, there are few studies in the literature discuss-
ing similar findings. The importance of this study is the provision
of new information related to the relevance of platelets in this
syndrome. The area under the ROC curve (0.83) suggests that
immature platelets can be a useful biomarker in GHD and can be
relevant in the routine of health care attention.
The method applied for obtaining the platelet data is simple,
accessible with low-cost, and the blood collection required is
already a standard procedure in all hospitals. Therefore, the cap-
ability of the majority of laboratories to obtain the IPF can be
useful in the evaluation of pregnant women with gestational
hypertensive disorders.
Finally, platelet indexes are altered in hypertensive disor-
ders during pregnancy with an increase in mean platelet
volume and, particularly, in the immature platelet index.
Both can easily be introduced into the health care assistance
for pregnant women. Further studies are required before the
use of these markers can be recommended for inclusion in
clinical routine, especially in the evaluation of
platelet alterations with maternal and fetal consequences.
Platelets, Early Online: 1–5
Acknowledgments
We thank Professor Mario Wagner for the statistical analysis, and to
Roche Diagnóstica Brasil Ltda, São Paulo (Brazil), for providing reagents
to the measurements.
Poli-de-Figueiredo is a CNPq researcher.
Declaration of interest
Reagents for IPF assays were provided by Roche Diagnóstica Brasil Ltda,
São Paulo, Brazil.
Funding
Grant support was received from the Conselho Nacional de
Desenvolvimento Científico e Tecnológico (CNPq; National Council for
Scientific and Technological Development), Fundação de Amparo à
Pesquisa do Rio Grande do Sul (FAPERGS; Foundation for the Support
of Research in the State of Rio Grande do Sul), and Coordenação de
Aperfeiçoamento de Pessoal de Nível Superior (CAPES; Coordination for
the Improvement of Higher Education Personnel Foundation).
ORCID
Carlos E. Poli-de-Figueiredo http://orcid.org/0000-0002-7333-8884
Luiza Silveira Lucas http://orcid.org/0000-0001-6587-7661
References
1. Redman CWG. Preeclampsia: A multi-stress disorder. Rev Med
Internet 2011;32:41–44.
2. Duley L. The global impact of pre-eclampsia and eclâmpsia. Semin
Perinatol 2009;33:130–137.
3. Victora CG, Black RE, Boerma JT, Bryce J. Measuring impact in
the millennium development goal era and beyond: A new approach
to large-scale effectiveness evaluations. Lancet 2011;377:85–95.
4. National High Blood Pressure Education Program Working Group
on High Blood Pressure in Pregnancy. Report of the national high
blood pressure education program working group on high blood
pressure in pregnancy. Am J Obstet Gynecol 2000;183:S1–S22.
5. Redman CW, Sargent IL. Latest advances in understanding pree-
clampsia. Science 2005;308:1592–1594.
6. Roberts JM, Hubel CA. The two stage of preeclampsia: Variations
on the theme. Placenta 2009;30:32–37.
7. Rana S, Karumanchi SA, Levine RJ, Venkatesha SM, Rauh-Hain
JA, Tamez H, Thadhani R. Sequential changes in antiangiogenic
factors in early pregnancy and risk of developing preeclampsia.
Hypertension 2007;50:137–142.
8. Boehlen F, Hohlfeld P, Extermann P, Perneger TV, de Moerloose P.
Platelet count at term pregnancy: A reappraisal of the threshold.
Obstet Gynecol 2000;95:29–32.
9. Valera MC, Parant O, Vayssiere C, Arnal JF, Payrastre B.
Physiologic and pathologic changes of platelets in pregnancy.
Platelets 2010;21:587–595.
10. Jaremo P, Lindahl TL, Lennmarken C, Forsgren, H. The use of
platelet density and volume measurements to estimate the severity
of pre-eclampsia. Eur J Clin Invest 2000;30:1113–1118.
11. Jung H, Jeon H, Kim HJ, Kim SH. Immature platelet fraction:
establishment of a reference interval and diagnostic measure for
thrombocytopenia. Korean J Lab Med 2010;30:451–459.
12. VI Diretrizes Brasileiras de Hipertensão. Arq Bras Cardiol
2010;95:1–51.
13. Poli-de-Figueiredo CE, Tavares A, Freitas EV, Burdmann EDA,
Oliveira IL, Magalhães LC, Sass N, Bresolin NL, Bezerra R,
Koch V, et al. Hipertensão em situações especiais. J Bras Nefrol
2010;32:54–59.
14. Briggs C, Kunka S, Hart D, Oguni S, Machin SJ. Assessment of an
immature platelet fraction (IPF) in peripheral thrombocytopenia. Br
J Haematol 2004;126:93–99.
15. Fuzer S, Patzer C, Pinto M, Pereira O, Rode J, Pagnussatti V,
Perrenoud M, Munhoz TP. Avaliação do VPM e P-LCR em
pacientes com dislipidemia [abstract]. In: Annals of the 28°
Congresso da Sociedade Brasileira de Hematologia e Hemoterapia,
Rev Bras Hematol Hemoter 2005;27:350–351.
16. Makuyana D, Mahomed K, Shukusho FD, Majoko F. Liver and
kidney function tests in normal and pre-eclamptic gestation-a
 DOI: 10.3109/09537104.2015.1101060
comparison with non-gestational reference values. Cent Afr J Med
2002;48:55–59.
17. Ceyhan T, Beyan C, Baser I, Kaptan K, Güngör S, Ifran A. The
effect of pre-eclampsia on complete blood count, platelet count and
mean platelet volume. Ann Hematol 2006;85:320–322.
18. Bath PM, Butterworth RJ. Platelet size: Measurement, physiology
and vascular disease. Blood Coagul Fibrinolysis 1996;7:157–161.
19. Dastjerdi MS, Emami, T, Najafian A, Amini M. 2006 Mean platelet
volume measurement, EDTA or citrate? Hematology 2006;11:317–319.
20. Ahmed Y, Iddekinge BV, Paul C, Sullivan HF, Elder MG.
Retrospective analysis of platelet numbers and volumes in normal
pregnancy and in pre-eclampsia. Br J Obstet Gynaecol
1993;100:216–220.
21. Annam V, Srinivasa K, Santhosh K, Suresh DR. Evaluation of
platelet indices and platelet counts and their significance in Pre
eclampsia and eclampsia. Int J Biol Med Res 2011;2:425–428.
22. Howarth S, Marshall R, Barr AL, Evans S, Pontre M, Ryan N.
Platelet indices during normal pregnancy and pre-eclampsia. Br J
Biomed Sci 1999;56:20–22.
23. Dundar O, Yoruk P, Tutuncu L, Erikci AA, Muhcu M, Ergur AR,
Atay V, Mungen E. Longitudinal study of platelet size changes in
gestation and predictive power of elevated MPV in development of
pre-eclampsia. Prenat Diagn 2008;28:1052–1056.
24. Freitas LG, Alpoim PN, Komatsuzaki F, Carvalho MD, Dusse LM.
Preeclampsia: Are platelet count and índices useful for its prognos-
Downloaded by [Tufts University] at 11:39 06 December 2015
tic? Hematology 2013;18:360–364.
25. Yang SW, Cho SH, Kwon HS, Sohn IS, Hwang HS. Significance of
the platelet distribution width as a severity marker for the
Hypertension in pregnancy and immature platelet fraction 5
development of preeclampsia. Eur J Obstet Gynecol Reprod Biol
2014;175:107–111.
26. Everett TR, Garner SF, Lees CC, Goodall AH. Immature platelet
fraction analysis demonstrates a difference in thrombopoiesis
between normotensive and preeclamptic pregnancies. Thromb
Haemost 2014;111:1177–1179.
27. 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–
122.
28. Kazmi RS, Cooper A, Lwalleed BA. Platelet function in Pre-
eclampsia. Semin Thromb Hemost 2011;37:131–136.
29. Rabini RA, Salvolini E, Staffolani R, Pugnaloni A, Simonelli L,
Biagini G, Cester N, Garzetti GG, Mazzanti L. Biochemical-
morphological modifications of platelet membranes during
pregnancy-induced hypertension. Exp Mol Pathol 1995;63:
175–185.
30. Holthe MR, Staff AC, Berge LN, Lyberg T. Different levels of
platelet activation in preeclamptic, normotensive pregnant, and non-
pregnant women. Am J Obstet Gynecol 2004;190:1128–1134.
31. Konijnenberg A, Stokkers EW, van der Post JA, Schaap MC,
Boer K, Bleker OP, Sturk A. Extensive platelet activation in
preeclampsia compared with normal pregnancy: Enhanced
expression of cell adhesion molecules. Am J Obstet Gynecol
1996;176:461–469.
32. Hutt R, Ogunniyi SO, Sullivan MHF, Elder MG. Increased platelet
volume and aggregation precede the onset of preeclampsia. Obstet
Gynecol 1994;83:146–149.