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ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 3  |  Page : 1447-1452

Relationship between platelet indices and red blood cell indices and recurrent pregnancy loss


1 Department of Obstetrics and Gynecology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Obstetrics and Gynecology, Benha Teaching Hospital, Ministry of Health, Qaliobia, Egypt

Date of Submission26-Feb-2022
Date of Decision08-Apr-2022
Date of Acceptance10-Apr-2022
Date of Web Publication29-Oct-2022

Correspondence Address:
Asmaa M Khattab
Bata, Banha, Qalyubia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_68_22

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  Abstract 


Background
Recurrent pregnancy loss (RPL) is defined as the spontaneous loss of two or more clinical pregnancies as documented by ultrasonography or histopathologic examination, which occurs in up to 5% of women in the reproductive age.
Objectives
To evaluate the relationship between changes in blood indices and RPL.
Patients and methods
Our case–control study was conducted on 150 women attending Obstetrics and Gynecology Department, Faculty of Medicine, Menoufia University. They were divided into group A (100 women), who had a history of RPL, and group B (50 women), who had given birth at term (>37 weeks of gestation) to healthy infants.
Results
There were highly significant differences between the two groups regarding platelet distribution width. Receiver operating characteristic curve analysis showed that platelet distribution width could significantly predict repeated pregnancy loss (P < 0.05). Moreover, there were highly significant differences in red blood cell distribution width-standard deviation and red blood cell distribution width-coefficient of variation. Receiver operating characteristic curve analysis showed that red blood cell distribution width-standard deviation and red blood cell distribution width-coefficient of variation could significantly predict repeated pregnancy loss (P < 0.05).
Conclusion
Platelet indices and red blood cell indices can be used as predictors of RPL as they are of low cost and easily available tests.

Keywords: indices, platelets, pregnancy loss, recurrent, red cell


How to cite this article:
Anter ME, Dawood RM, Abd El-Gayed AM, Khattab AM, Salama HF. Relationship between platelet indices and red blood cell indices and recurrent pregnancy loss. Menoufia Med J 2022;35:1447-52

How to cite this URL:
Anter ME, Dawood RM, Abd El-Gayed AM, Khattab AM, Salama HF. Relationship between platelet indices and red blood cell indices and recurrent pregnancy loss. Menoufia Med J [serial online] 2022 [cited 2024 Mar 29];35:1447-52. Available from: http://www.mmj.eg.net/text.asp?2022/35/3/1447/359520




  Introduction Top


For married couples, recurrent pregnancy loss (RPL) is extremely disappointing. Unfortunately, the exact underlying pathogenesis of RPL is still unknown in many cases[1]. The American Society for Reproductive Medicine defined RPL as two or more miscarriages[2]. However, the European Society of Human Reproduction and Embryology defined it as three or more miscarriages[3]. Pregnancy loss is a traumatic occurrence in a couple's life, and the recurrent nature of RPL may exacerbate the distress. RPL has a significant psychological effect on couples who have experienced pregnancy loss; it is also a challenging and stressful field of reproductive medicine because the cause is unknown, resulting in limitation of management and therapy strategies[4]. The physical and psychological burden on the patient is often intolerable, and it is possible to state that the physical and psychological load on women worsens with each miscarriage they experience. According to a Japanese study, the live birth rate in women with RPL was the same in 2011–2018 (63.8%) as those in 1994–2010 (67.8%)[5], highlighting the fact that outcomes have not changed since the mid-1990s. So, it is essential that other methods for predicting and preventing recurrent miscarriages are developed[6]. Multifactorial causes such as uterine congenital anomalies, immunological disorders, endocrinological disorders, chromosomal abnormalities, infections, and autoimmune disorders have been reported, but till now, in 50–60% of all cases of RPL, the underlying etiology cannot be identified[6]. During the process of implantation and placental development, the hematological system plays a critical role. Compatible connection in between fetus, maternal circulation, and placenta is required for implantation of the embryo into the decidua of the uterus. During pregnancy, certain changes that lead to formation of the thrombus might cause pregnancy losses by disrupting the implantation stage[7]. Coagulation factor activation (e.g., thrombin–antithrombin complex and prothrombin fragment) and platelet activation (e.g., β-thromboglobulin or soluble platelet P-selectin) are both indicators of thrombophilia. However, those biomarkers consume a lot of time, are costly, and cannot be done as standard laboratory research[8],[9]. Platelet activation is caused by thrombophilia, which causes changes in platelet morphology, mean platelet volume (MPV), and platelet distribution width (PDW), and all of them could be utilized as platelet activation markers[10],[11]. Platelet indices and red blood cell indices are simple, cheap, and available biomarkers, so we aimed to study the relationship between platelet indices and RPL.


  Patients and methods Top


Our case–control study was conducted at the Department of Obstetrics and Gynecology, Faculty of Medicine, Menoufia University, Egypt, starting from September 2020 to September 2021. The study was registered with local ethics committee of the Faculty of Medicine, Menoufia University (19819OBSGN26). Moreover, the study protocol was registered on the clinical trial: NCT05190796. Written consent, discussion of the steps, aim of the study, and the information about abnormal results all were obtained and shared with each patient. Our study included 150 participants divided into two groups: group A (100 women), which has a history of RPL diagnosed by two or more miscarriages at or less than 20 weeks of gestation, and group B (50 healthy women), where women gave birth to a 37-week baby without any history of previous miscarriage. Patients whose age was between 18 and 40 years old were included. Our exclusion criteria were women with a history of RPL owing to uterine anomalies, thyroid disease, diabetes mellitus, hypertensive disorder, coagulation defects, deep venous thrombosis, pulmonary embolism, and also use of medications that affect the function of platelets such as aspirin, NSAIDS, oral contraceptives pills, anti-platelet, and anticoagulant drugs. All patients were subjected to proper full history, including personal history with focus on maternal age, gravidity, parity, and smoking habits; present history about any complaint or use of any medication; past obstetric history of all previous pregnancies with focus on gestational age and characteristics of pregnancy loss (e.g., anembryonic pregnancy, live embryo); past medical history such as diabetes, hypertension, and thyroid disorder; and detailed general examination, with special concern to weight, height, BMI, systolic blood pressure, and diastolic blood pressure. From each patient enrolled in the study, 3 ml of venous blood sample was drawn and placed into a vacutainer tube containing EDTA. Hematological parameters were demonstrated using Sysmex K × 21 automatized hematology analyzer (Sysmex Corporation, Kobe, Hyogo, Japan) within 1 h after collection of the blood sample and then the sample was mixed properly to avoid platelet aggregation. The blood sample was tested for evaluation of red blood cell indices such as hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), and erythrocyte count. There are two RDW measurements that can be used: the red cell distribution width-coefficient of variation (RDW-CV) and the red cell distribution width-standard deviation (RDW-SD)[12]. The calculation of RDW-CV depends on the mean cell size and the width of the distribution curve. The normal range of the RDW-CV is about 11.0–15.0%. The RDW-CV does not accurately reflect the variation of the red cell size[12]. The RDW-SD actually measures the width of the red cell distribution curve in femtoliters. The width of the distribution curve is calculated at a point of 20% above the baseline. The RDW-SD is an accurate measurement as it is unaffected by the MCV, so it accurately reflects the variation in red cell size. The average range of the RDW-SD is 40.0–55.0 fl[12]. Moreover, platelet indices were calculated, such as plateletcrit (PCT) values, which demonstrate the percentage of blood made up by platelets [it is calculated using the formula, PCT (%)=platelet count × MPV/10 000]; MPV; and PDW[13].

Sample size calculation

It was based on previous studies, such as Meena et al.[14], who reported that RDW-CV in cases (women with a history of RPL) was 16.33 ± 3.34, whereas RDW-CV in the control group (women without a history of pregnancy loss) was 14.86 ± 2.12. The minimum sample size calculated was 114 women, using the following formula:



Where n is the sample size, z1-α is z score for 95% confidence interval (CI) and equals 1.96; z1-β is the z score for power of the study 80% and equals 0.84, σ is the estimated SD, and μ is the estimated mean.

The total sample size was 114 women, which was increased to 150 women for drop-out rate and availability of cases and resources. They were divided into two groups (100 cases and 50 controls), with case to control ratio of 2: 1.

Statistical analysis

Data were collected, tabulated, and statistically analyzed by IBM personal computer and statistical package SPSS, version 22 (2013; IBM Corp., Armonk, New York, USA). Descriptive statistics included percentage, mean, and SD and analytic statistics included Student t test for two independent normally distributed groups. Linear association between variables was assessed by Pearson's correlation coefficients for parametric variables. Receiver operating characteristic (ROC) curves were constructed to assess the validity of the predictors. P value less than 0.05 was considered significant, and P value less than 0.001 was considered highly significant.

Outcome measures

MPV is the measurement of average size of the platelet, expressed in femtoliter. PCT is a measure of total platelet mass, expressed in percentage.PDW reflects variation of platelet size, which is expressed in femtoliter.


  Results Top


Our study revealed that there were no statistically significant differences between the two groups regarding demographic data (P > 0.05) [Table 1] and [Figure 1]. The number of miscarriages in patients with RPL ranged between three and eight times, with mean ± SD of 3.7 ± 1.08 [Table 2]. Analysis of data showed both RDW-CV and RDW-SD were significantly elevated in the cases with RPL than the control group (P < 0.05), whereas there were no significant correlations between the two groups regarding hemoglobin, hematocrit, red blood cell count, MCV, or MCH values (P > 0.05) [Table 3]. After analysis of the data, there was a positive significant correlation between the RDW-CV, RDW-SD, and PDW and the number of miscarriage among the study group [Figure 1],[Figure 2],[Figure 3]. According to PDW, there was a highly statistically significant difference, which was high in the study group than in the control group (P < 0.05). However, there were no differences in other platelet parameters such as platelet count, MPV, and PCT (P > 0.05) [Table 4]. ROC curve analysis for RDW-SD can be a significant predictor of RPL at a cutoff value of more than or equal to 47.8 with 93% sensitivity, 94% specificity, 96.9% positive predictive value (PPV), and 87% negative predictive value (NPV). The area under the ROC curve (AUC) [95% CI was 0.954 (0.91–0.99)]. RDW-CV can also be another significant predictor of RPL at a cutoff value of more than or equal to 13.9 with 94% sensitivity, 82% specificity, 91.3% PPV, and 87.2% NPV. The AUC (95% CI) was 0.965 (0.94–0.99). PDW can significantly predict RPL at a cutoff value of more than or equal to 16.6, with 99% sensitivity, 96% specificity, 98% PPV, and 97.9% NPV. The AUC (95% CI) was 0.994 (0.98–1.0) [Table 5] and [Figure 4].
Figure 1: Scatter graph showing positive significant correlation between RDW-SD and number of miscarriage. RDW-SD, red blood cell distribution width-standard deviation.

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Figure 2: Scatter graph showing positive significant correlation between RDW-CV and number of miscarriage; the regression equation is also shown. RDW-CV, red blood cell distribution width-coefficient of variation.

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Figure 3: Scatter graph showing positive significant correlation between PDW and number of miscarriage. PDW, platelet distribution width.

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Figure 4: ROC curve for the performance of RDW-SD, RDW-CV, and PDW in early diagnosis of recurrent pregnancy loss. PDW, platelet distribution width; RDW-CV, red blood cell distribution width-coefficient of variation; RDW-SD, red blood cell distribution width-standard deviation; ROC, receiver operating characteristic.

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Table 1: The demographic data of the women enrolled in the study

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Table 2: Descriptive statistics of number of miscarriage among cases group

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Table 3: Red blood cells indices differences between women with recurrent pregnancy loss and normal healthy women

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Table 4: Platelet indices changes among the two groups

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Table 5: Area under the curve for red blood cell distribution width-standard deviation, red blood cell distribution width-coefficient of variation and platelet distribution width

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  Discussion Top


Unfortunately, our results found no relation or changes in MCHC between women with RPL and normal heathy women. This was in contrast to Zeynep et al.[15], who concluded that low MCHC level was associated with recurrent miscarriage. More future research studies are needed to make sure or deny these results by serial measurements before and during the pregnancy throughout the different trimesters. The RDW is a measure of anisocytosis, which reflects the variation and changes in erythrocyte size. It constitutes a routine component of hematology laboratory tests[16]. Different research studies on the correlation between RPL and RDW were published, and all concluded that there is high RDW in all women with previous RPL than healthy women without any history of miscarriage[17]. Our study was in agreement with all of these previous studies as our study revealed that women who had a history of recurrent miscarriages had higher RDW values than the other healthy group; not only this but also there is a strong relation between the RDW and number of miscarriages, with a significantly predictor cutoff value of more than or equal to 47.8 for RDW-SD and cutoff value of more than or equal to 13.9 for RDW-CV. Platelets become more spherical and have a larger surface area after activation. Platelet volume is measured by hematology analyzers using an electrical field deformation, which is dependent on the vertical diameter of platelet[18]. Platelet volume is measured in relation to the cross-diameter of the platelet by laser optical technology, so activated platelets appear larger[19]. Many previous studies concluded that women with RPLs owing to unknown cause had higher PDW values than healthy women. According to the findings of that study, the elevation of PDW values might be more predictive of miscarriage than MPV values[20]. In cases that were susceptible for thromboembolic events, studies have shown that accompanying PDW elevation was more beneficial than MPV elevation alone[21]. All of these results were in accordance with our results, and also, we found a high significant correlation between the PDW and the number of miscarriages with positive predictor cutoff value of more than or equal to 16.6. Conversely, other study found that there was no difference between women who had recurrent miscarriage and healthy controls regarding PDW values. They observed elevated level of PCT in the case group[16]. Another study found that neither platelet count nor platelet indices were useful as predictor of cases with recurrent miscarriage[22]. So, further future studies are required to study the relation between PDW, other platelet biomarkers, and recurrent miscarriage. To rectify the limitations of the study, further prospective trials are required including pregnant female with history of RPL and other healthy women pregnant at the same gestational weeks to evaluate the changes during pregnancy and its reflection on the red blood cell indices and platelet indices.


  Conclusion Top


Complete blood count parameters such as high RDW and PDW may be used as predictors of RPL. Moreover, this test is simple, available, and commercially cheap.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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