Severe thrombocytopenia in pregnancy: a cross-sectional analysis of perinatal and neonatal outcomes across different platelet count categories

Introduction

Thrombocytopenia is defined as a decrease in platelet count below 150 × 10⁹/L due to increased platelet consumption and/or decreased bone marrow megakaryocyte production and is observed at a rate of 7–11 % during pregnancy [1], [2], [3]. A situation where the platelet count is lower than 50 × 10⁹/L is defined as severe thrombocytopenia, and its incidence is less than 1 % [4], 5]. The causes of thrombocytopenia during pregnancy can differ significantly based on several factors, including the specific week of gestation at which the condition is diagnosed, the overall clinical status of the patient, and the degree of severity of the thrombocytopenia itself [6], 7]. Severe thrombocytopenia during pregnancy poses significant risks to both the mother and fetus, including urgent delivery decisions, as maternal thrombocytopenia may signify a life-threatening condition, postpartum hemorrhage due to delivery-related hemostatic challenges, and thrombocytopenia in the neonate [8]. Guidelines emphasize that adults with platelet counts <30 × 10⁹/L have the highest risk of fatal bleeding and should be treated for this condition [8], 9]. This study aims to compare the perinatal and neonatal outcomes of women with severe thrombocytopenia during pregnancy according to different platelet levels (0–30 × 10⁹/L and 30–50 × 10⁹/L).

Materials and methods

This study cross-sectional evaluated the perinatal records of pregnant women with platelet counts below 50 × 10⁹/L during pregnancy. These patients were followed at the Gynecology and Obstetrics Clinic of Necmettin Erbakan University Faculty of Medicine Hospital between January 2015 and May 2024, and those meeting the study criteria were incorporated into the research. The research was granted ethical approval by the Ethics Committee of Necmettin Erbakan University Faculty of Medicine, with decision number 2024/5016 (ID 19820), and was conducted in compliance with national standards, institutional regulations, and the Declaration of Helsinki.

We conducted our study in a tertiary university hospital. During pregnancy, cases of severe thrombocytopenia with platelet counts <50 × 10⁹/L according to complete blood count (CBC) were diagnosed by reviewing hospital medical records. Consultative opinions from hematologists were obtained for all pregnancy complications due to severe thrombocytopenia.

The following are the inclusion criteria for the study: Pregnant women aged 17–46 who were followed up and delivered at the clinic. The study excluded pregnant women who gave birth at different facilities, those who ceased follow-up after being diagnosed at our clinic, as well as those with significant fetal abnormalities, chromosomal disorders, and genetic syndromes. The analysis in this study was conducted using the lowest platelet count that was recorded during pregnancy. We divided all included pregnancies into two thrombocytopenia groups based on their lowest platelet count during pregnancy: Group A (platelet counts 0–30 × 10⁹/L) and Group B (platelet counts 30–50 × 10⁹/L).

Hematologists made the Immune thrombocytopenic purpura (ITP) diagnosis using international consensus criteria [6], 10]. The diagnosis of preeclampsia and HELLP syndrome (co-occurrence of microangiopathic hemolytic anemia, elevated liver function tests, and low platelet count) was determined according to the 2019 criteria of the American College of Obstetricians and Gynecologists [11]. We determined other causes of thrombocytopenia using the appropriate diagnostic criteria. Postpartum hemorrhage (PPH) was diagnosed using the 2017 ACOG revised criteria (cumulative blood loss ≥1,000 mL or bleeding associated with signs/symptoms of hypovolemia within 24 h of labor) [12]. Maternal platelet counts were analyzed using an automatic cell counter, with venous blood samples collected in ethylene diamine tetraacetate (EDTA) tubes. All participants had peripheral blood smears performed to rule out pseudothrombocytopenia, and hematologists conducted evaluations. Information was systematically recorded on various factors, including age, pregnancy status, parity, number of abortions, method of conception, causes of severe thrombocytopenia, treatments received during pregnancy, mode of delivery, type of anesthesia for cesarean sections, maternal complications, gestational age, birth weight, neonatal platelet counts, APGAR scores, and parameters for NICU admissions.

We evaluated the normality of the data using the Kolmogorov-Smirnov and Shapiro-Wilk tests, along with histograms. For continuous variables, we performed an independent t-test based on the distribution’s normality, reporting the scale data as median (minimum-maximum) and mean. When scale data showed a non-normal distribution, we applied the Mann-Whitney U test, with results expressed as median (minimum-maximum). To identify significant differences in categorical variables, we utilized appropriate chi-square tests or Fisher’s exact tests. All statistical analyses were performed using a two-tailed approach, considering statistical significance at p≤0.05. The analyses were carried out with SPSS version 20.0 (IBM Corp., Armonk, NY, USA).

Results

This study included 195 pregnant women with severe thrombocytopenia. We divided the pregnant women with severe thrombocytopenia into two groups: group A (platelet counts 0–30 × 10⁹/L) (n=72) and group B (platelet counts 30–50 × 10⁹/L) (n=123). The study evaluated all cases with severe thrombocytopenia and found that the median age of the patients ranged from 17 to 46 years, with a median age of 30 years. The number of pregnancies was 3 (1–8), parity was 1 (0–5), and abortion history was 1 (0–5). Of the patients, 10.8 % (n=21) had assisted reproductive treatment (ART) pregnancies. The most common cause of severe thrombocytopenia was ITP, found in 56.6 % of cases (n=111). Other causes were PE (preeclampsia) in 14.8 % (n=29), HELLP in 8.7 % (n=17), thrombotic thrombocytopenic purpura (TTP) in 3.1 % (n=6), disseminated intravascular coagulation in 3.6 % (n=7), uterine atony in 6.7 % (n=13), sepsis in 2.6 % (n=5), platelet dysfunction in 6.7 % (n=13), and liver cirrhosis in one patient. We observed no pregnant women with systemic lupus erythematosus. 67.3 % (n=132) did not receive treatment for thrombocytopenia.

For treatment of thrombocytopenia, 21.4 % (n=42) of cases received platelet concentrates; 3.1 % (n=6) received steroids; one received steroids + platelet concentrates; one received steroids + intravenous immunoglobulin (IVIG); one received steroids + IVIG + platelet concentrates; 2 % (n=4) received IVIG; two received IVIG + platelet concentrates; and 3.1 % (n=6) received plasma exchange. A total of 85.1 % (n=166) of the deliveries were by cesarean section. During the cesarean section, 62 (37.3 %) received spinal anesthesia and 104 (62.7 %) received general anesthesia. Postpartum hemorrhage occurred in 27 (13.8 %) cases. In our study, the cause of all postpartum hemorrhages was uterine atony. Six (3.07 %) patients underwent postpartum hysterectomy. 42.6 % of the births were premature at less than 37 weeks, and 29.2 % were premature at less than 34 weeks. There was stillbirth in 8.7 %. The NICU admitted 47 (24.1 %) of the newborns (Table 1).

Upon dividing patients with severe thrombocytopenia into two groups based on their platelet levels and evaluating them, we observed significant differences in maternal outcomes related to gravida, parity, and abortion history. We observed no significant differences in maternal age, type of conception, diabetes mellitus (DM), preterm premature rupture of membranes (PPROM), etiology of thrombocytopenia, treatment methods, type of delivery, type of anesthesia, preop hemoglobin, postop hemoglobin, postpartum hysterectomy, delivery week, delivery week below 37 weeks, birth weight, stillbirth, and 5th minute APGAR score. However, there was a significant difference between the groups for delivery under 34 weeks (p=0.035) and NICU admission (p=0.05) (Table 2).

Discussion

In our study, we found a significant increase in the risk of premature birth before the 34th week of gestation and admission to the neonatal intensive care unit in pregnancies complicated by severe thrombocytopenia with a platelet count below 30 × 10⁹/L compared to the group with 30 × 10⁹/L–50 × 10⁹/L.

In the study conducted by Zou et al., significant differences were observed between different platelet groups in terms of age in pregnant women with severe thrombocytopenia, but no difference was observed between the groups in terms of gravity and parity [13]. In our study, when the demographic characteristics of the patients were examined and the group below 30 × 10⁹/L was compared with the other group, it was found that although there was no significant age difference between them, the severity, parity and number of miscarriages were significantly lower than the other group.

The causes of severe thrombocytopenia during pregnancy vary according to the stage of pregnancy, the severity of thrombocytopenia, and the clinical condition of the patient and include diseases such as preeclampsia, HELLP, and ITP, as well as serious diseases such as TTP, DIC, platelet dysfunction, placental abruption, and sepsis [6], 7], [14], [15], [16]. In our study, the most common cause of severe thrombocytopenia was ITP (56.6 %). Although previous studies showed hypertensive disorders during pregnancy as the most common cause [7], 17], 18], Zhou et al.’s research found that ITP was the most common cause of severe thrombocytopenia during pregnancy [13]. The reason why more ITP patients were followed in our clinic in cases of severe thrombocytopenia may be that it is a tertiary center that accepts referrals because patients can be followed together by hematology and gynecology clinics.

The aim of treatment for ITP during pregnancy is not to normalize the platelet count but to reduce the risk of bleeding. In ITP, no additional treatment is required unless the platelet count falls below 20–30 × 10⁹/L in the first two trimesters or is complicated by bleeding regardless of the platelet count [1]. If pregnant women with ITP require treatment to increase their platelet count, they can receive glucocorticoids or intravenous immune globulin (IVIG) without a platelet transfusion, provided there is sufficient time before the planned delivery [19], 20]. However, if there is insufficient time, platelet transfusions are taken into consideration [3]. In patients with preeclampsia and HELLP syndrome, the mainstay of treatment is the management of the underlying condition and delivery of the fetus [21]. Plasmapheresis should be started promptly for TTP [22]. The primary goal in the treatment of DIC is to treat the underlying cause [23]. As can be seen, the follow-up and treatment of each cause of severe thrombocytopenia are different from each other. However, regardless of the cause of thrombocytopenia, a pregnant woman with severe thrombocytopenia should undergo platelet transfusion immediately if she has active bleeding or if surgery and/or delivery are imminent. For a pregnant woman who is not bleeding and is preparing for delivery or a cesarean section, the platelet count threshold is 30 × 10⁹/L for vaginal delivery and 50 × 10⁹/L for cesarean delivery [8]. According to estimates, PPH affects 6–11 % of all births worldwide [24]. In another recent multicenter study, this rate was observed as 15 % [25]. A study in West China found a 3.8 % rate of postpartum hemorrhage in a group of patients with severe thrombocytopenia [13]. The UK conducted a national cohort study that included cases with severe thrombocytopenia and reported a 51 % PPH rate [26]. In our study group, the PPH rate for all patients with severe thrombocytopenia was 13.8 %, which is consistent with a recent multicentre study [25]. However, our findings of different result from the aforementioned studies conducted in Western China and the UK may be related to different study populations, management strategies, and therapeutic effects during pregnancy. We observed no significant difference in the frequency of PPH between the groups with severe thrombocytopenia. No significant difference in PPH was observed among pregnant women with severe thrombocytopenia, who were previously divided into three groups based on different platelet counts, and our findings are consistent with this study [13]. Although thrombocytopenia may increase the severity of bleeding, obstetric causes such as uterine atony, genital traumas, and retained placenta also play an important role in the etiology of postpartum bleeding [27]. Uterine atony was present in all postpartum bleeding observed in our study. This explains the lack of a significant difference between different platelet levels and postpartum bleeding rates. In patients with uterine atony, uterotonic drugs were applied together with bimanual massage, and in cases where adequate control could not be achieved with these, uterine compression sutures were used. Simultaneous adequate intravenous access was provided, and blood, blood products, and crystalloids were administered. However, hysterectomy was performed in cases of massive bleeding that could not be controlled with these approaches.

General anesthesia was performed 62.7 % of cesarean sections, while spinal anesthesia was performed in the remaining 37.3 %. Although the exact platelet count required for safe spinal anesthesia is not known in many randomized controlled and non-randomized trials, general anesthesia seems to be safer because of the risk of spinal epidural hematoma in severe thrombocytopenia [28], [29], [30]. In our study, we found no differences in the type of anesthesia between the two groups, and we did not observe spinal hematoma in any of the cases that underwent spinal anesthesia. The reason why spinal hematoma was not observed may be that obstetric patients have more compatible epidural spaces due to the physiological changes of pregnancy, and the cases are managed appropriately by maternal-fetal medicine specialists, hematologists, and anesthetists [31].

We studied the platelet counts of 39 newborns from pregnant women who were following up for severe thrombocytopenia. While neonatal mild thrombocytopenia (plt: 100 × 10⁹/L and <150 × 10⁹/L) was detected in the majority of them, moderate (plt: 50 × 10⁹/L–99 × 10⁹/L) and severe thrombocytopenia (plt: <50 × 10⁹/L) were not detected in any of them. In contrast to the previous study [13], no neonates with severe thrombocytopenia were found in our study and no neonates had major hemorrhage such as neonatal intracranial hemorrhage.

In a study done in West China by Zhou and colleagues, pregnant women with severe thrombocytopenia were split into three groups based on their platelet counts: 30–50 × 10/⁹L, 10–30 × 10⁹/L, and <10 × 10⁹/L. The study found that the risk of giving birth before 37 weeks was significantly higher in the group with platelet counts below 10 × 10⁹/L compared to the other groups. However, there was no difference in the risk of giving birth before 34 weeks between the groups [13]. In our study, no difference was observed in the rates of preterm birth below 37 weeks among different platelet groups, and it was observed that the rate of preterm birth below 34 weeks was higher in cases with a platelet count below 30 × 10⁹/L (p=0.035). Although the severity of thrombocytopenia is not an indicator of pregnancy termination or delivery, the optimal delivery time is determined according to the etiology of thrombocytopenia and obstetric conditions [8]. The reason for premature birth under 34 weeks more in the group below 30 × 10⁹/L may be that the reasons leading to low platelet levels and/or other concurrent complications may cause the severity of the disease to increase, and therefore iatrogenic premature birth may be performed. And accordingly, newborn admissions may have been observed more in the group below 30 × 10⁹/L (p=0.05).

Conclusions

Our study demonstrates that pregnancies complicated by severe thrombocytopenia with platelet count <30 × 10⁹/L are associated with an increased risk of preterm birth and NICU admission before 34 weeks. Although the underlying causes of thrombocytopenia did not differ significantly between groups, appropriate management strategies tailored to the severity of the condition are vital. These findings highlight the importance of close monitoring and individualized care for pregnant women with severe thrombocytopenia to improve maternal and neonatal health outcomes. Future prospective studies are needed to further investigate the impact of thrombocytopenia on pregnancy outcomes and to develop standard management guidelines.