Relationship between hypertensive disease stages of pregnancy and plateletcrit values: A retrospective cohort study.

Mustafa Can Sivas: Writing – review & editing, Writing – original draft, Validation, Methodology, Formal analysis, Data curation, Conceptualization. Reyhan Aslancan: Writing – review & editing, Validation, Formal analysis, Data curation. Taha Yasin Bayram: Writing – review & editing, Investigation, Formal analysis, Data curation.

The written informed consent in accordance with national legislation and institutional requirements was obtained from all patients for each procedure and publication.

This study was performed in line with the principles of the Declaration of Helsinki. This study was reviewed and approved by the Ethics Committee of the Basaksehir Cam and Sakura City Hospital with the approval number: 2022.10.341, dated October 26, 2022.

This research did not receive any specific funding.

There were no statistically significant differences among the four groups in terms of age, gravidity or parity (p > 0.05) ( Table 1 ). Table 1 Comparison of the age, gravida, parity values between the groups. Table 1 Groups [C] (n = 36) [GHT] (n = 36) [PE + P] (n = 36) [sPE + P] (n = 36) p value Age 28.17 ± 4.32 31.53 ± 6.34 30.28 ± 5.64 28.78 ± 5.95 0.054∗ Gravida 2.50 ± 0.77 3.06 ± 1.41 2.25 ± 1.40 2.58 ± 1.94 0.124∗ Parity 1.36 ± 0.59 1.58 ± 1.15 0.92 ± 1.02 1.22 ± 1.51 0.087∗ [C], control group; [GHT], gestational hypertension group; [PE + P], preeclampsia + proteinuria group; [sPE + P], severe preeclampsia + proteinuria group. Values given as mean (±standart deviation), ∗One-way ANOVA test was used for comparison of variables among groups. p value < 0.05 is determined as significant. Comparison of the age, gravida, parity values between the groups. [C], control group; [GHT], gestational hypertension group; [PE + P], preeclampsia + proteinuria group; [sPE + P], severe preeclampsia + proteinuria group. Values given as mean (±standart deviation), ∗One-way ANOVA test was used for comparison of variables among groups. p value < 0.05 is determined as significant. The group data were normally distributed. The mean platelet count ranged from 219,250/mm 3 to 241,310/mm 3 in the groups. There were no significant differences among the groups in terms of platelet counts or PCT values (p > 0.05) ( Table 2 ). Table 2 Analysis of PCT and platelet values during termination between groups. Table 2 Groups [C] (n = 36) [GHT] (n = 36) [PE + P] (n = 36) [sPE + P] (n = 36) p value PCT 0.26 ± 0.05 0.27 ± 0.05 0.26 ± 0.07 0.25 ± 0.06 0.641∗ PLT 240,110 ± 59,120 234,690 ± 59,890 241,310 ± 74,800 219,250 ± 53,330 0.416∗ [C], control group; [GHT], gestational hypertension group; [PE + P], preeclampsia + proteinuria group; [sPE + P], severe preeclampsia + proteinuria group; PCT, plateletcrit; PLT, platelet (/mm 3 ). Values given as mean (±standart deviation), ∗One-way ANOVA test was used for comparison of variables among groups. p value < 0.05 is determined as significant. Analysis of PCT and platelet values during termination between groups. [C], control group; [GHT], gestational hypertension group; [PE + P], preeclampsia + proteinuria group; [sPE + P], severe preeclampsia + proteinuria group; PCT, plateletcrit; PLT, platelet (/mm 3 ). Values given as mean (±standart deviation), ∗One-way ANOVA test was used for comparison of variables among groups. p value < 0.05 is determined as significant. The mean platelet count ranged from 232,080/mm 3 to 251,580/mm 3 in the groups. There were no significant differences among the groups in terms of platelet counts or PCT values (p > 0.05) ( Table 3 ). Table 3 Analysis of PCT and platelet counts in early stage of pregnancy between groups. Table 3 [C] (n = 36) [GHT] (n = 36) [PE + P] (n = 36) [sPE + P] (n = 36) p value PCT 0.26 ± 0.05 0.27 ± 0.05 0.27 ± 0.05 0.26 ± 0.06 0.692∗ PLT 251,580 ± 55,390 249,140 ± 53,750 249,390 ± 58,830 232,080 ± 57,510 0.430∗ [C], control group; [GHT], gestational hypertension group; [PE + P], preeclampsia + proteinuria group; [sPE + P], severe preeclampsia + proteinuria group; PCT, plateletcrit; PLT, platelet (/mm 3 ). Values given as mean (±standart deviation), ∗One-way ANOVA test was used for comparison of variables among groups. p value < 0.05 is determined as significant. Analysis of PCT and platelet counts in early stage of pregnancy between groups. [C], control group; [GHT], gestational hypertension group; [PE + P], preeclampsia + proteinuria group; [sPE + P], severe preeclampsia + proteinuria group; PCT, plateletcrit; PLT, platelet (/mm 3 ). Values given as mean (±standart deviation), ∗One-way ANOVA test was used for comparison of variables among groups. p value < 0.05 is determined as significant.

The study was planned and completed as a retrospective cohort study. This study was performed in accordance with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Basaksehir Cam and Sakura City Hospital (date: October 26, 2022, number: 2022.10.341/protocol no: 341). Pregnant women between the ages of 17–42 with gestational ages ≥36 weeks who were admitted to Basaksehir Cam and Sakura City Hospital with a complaint of hypertension with no thrombocytopenia between August 2020 and August 2022 and were hospitalized were analyzed. Considering the inclusion/exclusion criteria and group criteria, pregnant women were included in the study respectively towards the past until each group contained 36 patients. When a group contained 36 subjects, that group was considered complete. Patient groups: Group [C] (control, n = 36): This group consisted of healthy pregnant women who were hospitalized in the delivery room for labor and did not have any additional diseases. Group [GHT] (gestational hypertension, n = 36): This group included patients whose blood pressure was >140/90 mmHg and was regulated and who did not have proteinuria. The diagnosis of gestational hypertension was based on the onset of high blood pressure after the 20th week of pregnancy and its normalization before the 12th week after delivery. Group [PE + P] (preeclampsia + proteinuria, n = 36): This group included only patients with a PE diagnosis. High blood pressure (>140/90 mmHg) and the presence of proteinuria (300 mg/24 h) were used as the basis for the diagnosis of PE. Group [sPE + P] (severe preeclampsia + proteinuria, n = 36): This group included patients with sPE. For the diagnosis of sPE, in addition to the presence of high blood pressure and proteinuria, the patient had to exhibit one of the HELLP syndrome parameters (hemolysis LDH >600 IU/L, increased liver enzymes ALT/AST >65 IU/L), one of the prodromal symptoms (headache, blurred vision, epigastric tenderness) or evidence of end-organ damage (hematuria). PCT values were determined from the blood samples taken during hospitalization from all pregnant women. Additionally, the PCT and platelet values of these groups at 17–30 weeks of pregnancy were determined and compared ( Fig. 1 ) (please refer to supplementary information “PCT late week data” and “PCT early week data”). Fig. 1 Research flow chart. Fig. 1 Research flow chart. The limit for defining thrombocytopenia was 140 mm/Hg and/or a diastolic pressure >90 mmHg. The limit for defining proteinuria was ≥300 mg/24 h. Patients with chronic diseases such as diabetes mellitus, chronic hypertension or malignancy were excluded to minimize the effect of chronic conditions on PCT. All the patients who were included in the study had delivered within 36 h after hospitalization ( Fig. 1 ). When determining the sample size, the calculation was performed in accordance with the protocol for GPower 3.1 software [ 10 , 11 ], with a power value of 0.80, a margin of error of 0.05 and an effect size of 0.6. For statistical analysis, SPSS Version 20.00 (IBM Corporation Armonk, NY: USA. Released 2011) was used. To evaluate the distribution of the data, the Shapiro‒Wilk test was used. Variables with a normal distribution are presented as the mean ± standard deviation, and one-way ANOVA was used to define the differences among groups. A p value of 0.05 was taken as the threshold level for statistical significance.

In our study, while the mean platelet count was similar between the [GHT] group and the [PE + P] or [sPE + P] groups, proteinuria was not associated with higher or lower PCT. There were no differences between the group with healthy pregnancies and the [PE + P] or [sPE + P] groups in terms of PCT values. Similarly, no differences were observed between the [GHT] group and the [PE + P] or [sPE + P] groups in terms of PCT values. The PCT value was not successful in diagnosing or predicting sPE in patients whose platelet counts were not reduced. Additionally, PCT values were not affected by the presence of proteinuria in PE or sPE patients. When the PCT and platelet values in the groups in the early stage of pregnancy were compared, the PCT value was not successful in diagnosing or predicting sPE early in pregnancy in patients whose platelet counts were not reduced. PCT values have a specific course in many different diseases. Studies have reported that the PCT value is elevated, especially in patients with malignant diseases. Among those studies, some have suggested that the platelet count and PCT are elevated and the MPV is reduced in patients with gynecologic tumors [ 12 ]. PCT, the MPV and the platelet distribution width (PDW) have been shown to be elevated in patients with endometrial cancer [ 13 ]. An elevated PCT and reduced MPV and PDW have been observed in endometriosis patients [ 14 ]. Studies show that the PCT value, the importance of which has begun to be demonstrated in many areas, may be a marker of sPE have been examined under the title of PCT and PE relationship. Although few studies on this topic exist, it is noteworthy that in most of them, severely preeclamptic patients and normotensive patients were compared [ 5 , 8 ]. In the study by Freitas et al., in which severely preeclamptic patients were compared with nonpregnant women and normotensive pregnant women, lower PCT values were detected in the sPE group [ 5 ]. Umezuluike et al. reported similar results [ 6 ]. Thalor et al. compared preeclamptic patients with healthy pregnant controls and reported that there was no significant relationship between PCT values and PE [ 7 ]. A few studies support the findings of Thalor et al. [ 8 , 15 ]. Additionally, in our study, similar to in Taylor et al., there was no difference in the PCT value between the healthy pregnant control group and the PE group. In addition, our study revealed that there was no significant difference in PCT between the sPE group and the healthy control group. PCT is calculated with the formula “PCT = platelet count × MPV/10,000” [ [2] , [3] , [4] ]. According to this formula, PCT is directly affected by the platelet count. And a low platelet count directly decreases the PCT value. It is understood that the amount of decrease in platelet count may play a role as an important factor in whether statistical significance is obtained or not by affecting the amount of decrease in the PCT value. A decrease in the platelet count is observed in the majority of patients with sPE [ 1 ]. The fact that the PCT value was lower in patients with sPE than in normal pregnant women in some studies can be explained by this factor. Similarly, in preeclamptic patients or patients diagnosed with sPE due to HELLP syndrome or prodromal symptoms, the platelet count may have not yet decreased, which may explain the reason to detect non-decreased PCT values in some studies. Singh et al. reported that 75 % of non-severe preeclamptic patients with normal platelet counts did not have decreased PCT values [ 16 ]. In contrast, it is important to highlight the study by Ates et al., which focused on the relationship between PCT and proteinuria. This study revealed that in the presence of proteinuria in both male and female patients with a history of chronic hypertension, the PCT value was greater than that in those without proteinuria [ 9 ]. Although there are no other studies in the literature on the relationship between proteinuria and PCT, this study provides a different perspective. The presence of proteinuria may increase PCT in severely preeclamptic patients. Unlike in previous studies, the GHT (proteinuria-), PE (proteinuria+) and sPE (proteinuria+) groups were compared together in our study. Thus, the stages of gestational hypertension with and without proteinuria were evaluated. It was determined that there was no difference in PCT values in the presence of proteinuria. In chronic hypertension, endothelial damage occurs due to shear stress. Long-term endothelial damage initiates platelet activation, and thrombotic activity results in hypertension-related proteinuria. In addition, the renin‒angiotensin‒aldosterone system is activated, and the level of catecholamines increases. As a result, a high MPV and an increase in the platelet count are observed due to the newly produced platelets with large volume. Both factors act in to increase the PCT value [ 9 ]. In PE, endothelial damage occurs due to trophoblastic mediators [ 1 , 17 ]. However, in PE, unlike in chronic hypertension, there is a decrease in renin-angiotensin-aldosterone activity. In addition, changes in platelet aggregation and a decrease in platelet count are observed [ 17 ]. The PCT value in PE may be affected by more than one pathophysiological factor, such as the duration of endothelial damage, platelet-activating factor level, platelet behavior patterns, and decrease in the renin‒angiotensin‒aldosterone system activity. However, further studies are needed. Wu et al. reported that the PCT values between 13 and 32 weeks of gestation in pregnant women who were diagnosed with PE during the final stage of pregnancy were higher than those in normal pregnant women [ 18 ]. Similarly, Chen et al. reported higher PCT values in the early gestational weeks blood samples of preeclamptic pregnant women [ 19 ]. In our study, no difference was found in either PCT values or platelet values between the late and early stages of pregnancy. In addition, the mean values were very similar. There are no studies in the literature examining PCT changes in patients with GHT. Additionally, there are no studies in the literature examining the relationship between proteinuria and PCT in patients with GHT/PE/sPE. All stages of hypertensive condition in pregnancy were analyzed in a single study by including the GHT (proteinuria-) group in addition to the groups with PE (proteinuria +), sPE (proteinuria +) and healthy pregnancies. Unlike in other studies, in this study, patients who did not have thrombocytopenia and were diagnosed with sPE with other parameters (HELLP, etc.) were included. Therefore, our study provides a standardized study model that also takes into account platelet values and the presence of proteinuria. In this study, all pregnant women were ≥36 weeks pregnant. Thus, possible unknown effects during different trimesters of pregnancy that may influence the PCT value were excluded from the study. In addition, the differences in PCT values between late and early stage of pregnancy were analyzed. Trying to diagnose with PCT values in patients with sPE whose platelet counts have not decreased can lead to errors in the diagnosis of the majority of patients. A normal PCT value should not be interpreted as the absence of progression to sPE. While a normal PCT value does not have diagnostic significance, a decrease in PCT may give an idea of progression to sPE. However, platelet values lower than 100,000/mm 3 already indicate sPE. Analyzing the PCT value at this stage is not useful. In this context, the use of PCT values in the diagnosis or prediction of sPE at pregnancies past 36 weeks or in the early stage may not be appropriate. During the intergroup comparisons, the MPV, which is the second important PCT parameter, was not considered. How MPV values change in this process should be examined. Patients were included in the study according to the order of admission to the hospital respectively towards the past. A randomized patient selection method in studies with larger patient populations will increase the power of the study by eliminating unknown factors that may affect the study results. In the literature, studies on hypertensive diseases of pregnancy and PCT values have not investigated the potential effects of antihypertensive drugs on platelet counts or PCT values. Antihypertensive drug treatments, especially methyldopa, may rarely cause side effects such as bone marrow depression and thrombocytopenia [ 20 , 21 ]. Although the lack of a significant difference in platelet counts between the groups in our study minimized the possible unknown effects (especially thrombocytopenia) of the drugs, standardization of the drug factor in subsequent studies should be taken into consideration.

The PCT value may not be appropriate to use for the diagnosis or prediction of sPE in patients whose platelet counts have not decreased. A normal PCT value should not be interpreted as the absence of progression to sPE. There is a need for new PCT and PE studies that take platelet counts into account and include women in the early weeks of pregnancy.

Gestational hypertension (GHT) is a progressive condition that emerges after the 20th week of pregnancy and is mediated by placental trophoblasts. GHT is described as preeclampsia (PE) when proteinuria occurs (>300 mg/24 h). GHT is described as severe preeclampsia (sPE) when end-organ damage or hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome or prodromal symptoms such as occipital headache, visual symptoms, and epigastric pain appear [ 1 ]. The plateletcrit (PCT) value, which is a platelet index, has recently become prominent. PCT is the volume occupied by platelets in the blood as a percentage and is calculated according to the formula “PCT = platelet count × mean platelet volume (MPV)/10,000” [ [2] , [3] , [4] ]. Some published studies have shown that PCT increases or decreases in various diseases. In some studies, the PCT value was relatively lower in patients who were diagnosed with sPE [ 5 , 6 ]. Some studies reported that the PCT value was not different in those with sPE [ 7 , 8 ]. Additionally, one study reported higher PCT values in male or nonpregnant female patients with chronic hypertension and proteinuria [ 9 ]. PE is a disease with different stages in which proteinuria is added to GHT, which can progress to sPE. Even if proteinuria is not present, patients with GHT may be defined as having sPE in the presence of other parameters, such as prodromal symptoms and HELLP syndrome. When the studies are considered; it is understood that the PCT value in PE patients can be affected by the presence of thrombocytopenia and/or proteinuria. Additionally, studies are needed to standardize these two parameters to elucidate the reason different results have been obtained regarding the PCT value in previous works. We predicted that the PCT value would not be lower in the absence of thrombocytopenia in preeclamptic or severely preeclamptic patients with proteinuria. The objective of this study was to investigate the correlation between PCT and stages of hypertensive disease of pregnancy by comparing values in groups with healthy pregnancies, GHT, PE with proteinuria and sPE with proteinuria.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data will be made available on request.