Preoperative moderate thrombocytopenia is not associated with increased blood loss for low-risk cesarean section: a retrospective cohort study

It has been recommended by guidelines that a preoperative platelet (PLT) count of 50× 10⁹/L or greater is safe for elective major surgery except neurosurgery or ophthalmic surgery involving the posterior segment of the eye [1, 2]. However, the strength of such recommendation is weak due to the very low quality of evidence. Since the bleeding risk may vary enormously among different types of surgery, it is more reliable to evaluate the tolerance of thrombocytopenia for each specific surgery type. To the best of our knowledge, there is scarce convincing evidence indicating the impact of preoperative moderate thrombocytopenia (PLT 50–100 × 10⁹/L) on blood loss for cesarean section (CS).

The occurrence of thrombocytopenia (PLT less than 150 × 10⁹/L) is as high as 7–12% in pregnancy [3]. Excessive blood loss at delivery is one of the leading causes for maternal mortality [4]. As a consequence, there has been considerable concern over the safety of thrombocytopenic patients undergoing CS in the past years. Recent publications indicate that delivery could be uneventful for most patients with idiopathic thrombocytopenic purpura (ITP) and gestational thrombocytopenia (GT) [5, 6]. On the contrary, patients with HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome are at high risk for the sudden development of disseminated intravascular coagulation (DIC) and associated massive hemorrhage [7]. Given the heterogeneous etiology of thrombocytopenia, it is difficult to determine the indication for specific therapy to raise PLT count before CS. Actually, the minimum PLT count acceptable for CS differs greatly among medical centers, ranging from to 50–80 × 10⁹/L [6, 8, 9]. That is where the controversies arose and continued.

In this work, we designed this retrospective noninferior cohort study to evaluate the association of moderate thrombocytopenia with the calculated blood loss during and after CS. We hypothesized that moderate thrombocytopenia does not have clinically significant effect on blood loss.

In the present study, we respectively reviewed the calculated blood loss, visually estimated blood loss, blood transfusion, invasive hemostatic intervention, postoperative adverse events, ICU stay, hospital stay and all-cause mortality in low-risk CS patients with preoperative PLT 50–100 × 10⁹/L over a period of 6 years in a tertiary medical center. We found that preoperative moderate thrombocytopenia is not associated with increased blood loss, requirement for blood transfusion, or incidence of adverse events.

It has been reported that the leading causes for thrombocytopenia are GT, pre-eclampsia and ITP [12], which are consistent with our data. GT is resulted from hemodilution and increased platelet turnover during pregnancy [13], and requires no treatment as it is not associated with increased bleeding risk or altered delivery mode [10]. Studies in ITP complicating pregnancy demonstrated that severe morbidity or mortality was uncommon, despite the moderate drop of PLT [14, 15]. Hence, there has been a trend towards a more conservative management [16, 17], even without much information about the blood loss at delivery in thrombocytopenic pregnant patients.

Guidelines recommend a PLT threshold of 50 × 10⁹/L prior to major surgery and 100 × 10⁹/L for neurosurgery and ophthalmic surgery [1, 2, 18, 19]. However, it has been found that a preoperative platelet count of 50–100 × 10⁹/L is associated with increased requirement for blood transfusion and 30-day mortality after non-cardiac surgery [20]. Since the minimum PLT count safe for CS remains unclear, decisions on whether to raise PLT count before CS are often based on physicians’ clinical experience rather than high-quality evidence. Thromboelastography has been indicated to be a good predictor of bleeding risk in patients with severe thrombocytopenia (PLT<10 × 10⁹/L) caused by hematologic malignancies [21]. Nevertheless, its predictive value in patients with PLT 50–100 × 10⁹/L is still open to doubt, and the high cost may limit its use.

Our findings elucidate that patients with preoperative moderate thrombocytopenia had no more blood loss, blood product transfusion, or postoperative adverse events than the ones with normal PLT count. Based on these findings, we could cautiously speculate that raising PLT count to above 100 × 10⁹/L before low-risk CS might bring little obvious benefits to patients without massive hemorrhage. Preoperative PLT transfusion is commonly used to rapidly raise PLT count in thrombocytopenic patients. However, such prophylactic transfusion might be unnecessary for CS patients with PLT 50–100 × 10⁹/L in absence of additional bleeding risk. In this way, a series of transfusion-associated risks could be reduced, including febrile, allergic reactions, arrhythmia, transmissible infections, hemolysis, auto-antibody production, transfusion related acute lung injury and immunomodulation [2, 22].

The blood loss was calculated based on pre- and post-operative HCT. Its inaccuracy mainly results from the change of circulating blood volume [23], which could be minimized in our study by applying comparable infusion strategy to each patient if there was no massive hemorrhage. The data of postoperative HCT was acquired from the results of CBC test performed 24–36 h after surgery, thus there was enough time for fluid shift and volume balance [24]. Based on the recommendations by World Health Organization (WHO), primary PPH is defined as blood loss more than 500 ml within 24 h after delivery [25]. Since most peripartum hemorrhage occurs during or within the first 4 h posterior to delivery [26], the calculated blood loss measured 24–36 h postoperatively in this study is reflective of the above high-risk period. Although other methods could also be used in blood loss estimation, their limitations cannot be ignored. In our study, the visually estimated blood loss is less than the calculated value in both groups. This is consistent with the data in previous publications, indicating that the blood loss could be highly underestimated by visual estimation [27‐29]. Gravimetric method has also been demonstrated low accuracy because of the invisible interference of the weight of amniotic fluid [30, 31]. A novel mobile application, photographic colorimetric system, has been proven to be more reliable, but it cannot be accessed in most countries [32, 33].

There were significantly more patients admitted to ICU in the thrombocytopenic group than in the control group. However, only two (16.7%) of them went to ICU for massive hemorrhage. In fact, most (9/12, 75%) of them had severe autoimmune disease with multi-organ involvement prior to surgery. It has been widely accepted that pregnancy could be a trigger for an increase in SLE activity [34]. Furthermore, thrombocytopenia in SLE patients during pregnancy is also a predictor for severe organ damage and poor prognosis [35]. Patients in the thrombocytopenic group also spent statistically more days in hospital after surgery, whereas the mean difference between groups was 0.40 day, which could be considered as clinically insignificant.

According to prior publications, well-recognized risk factors for excessive hemorrhage or blood transfusion of CS are: low BMI, prolonged operation duration, emergency, abnormal placentation, previous uterine scar, multiple pregnancies, neonatal macrosomia, placenta previa, placental abruption, preoperative anemia and general anesthesia [36‐42]. In our study, we tried to control the confounders in three ways. First, we excluded patients with coagulopathy, platelet dysfunction, bleeding tendency, history of PPH, abnormal placentation and preoperative anemia. Second, the two groups were well-balanced in age and surgery timing (emergency or elective) at baseline by using matching approach. Third, there was significantly higher general anesthesia rate in the thrombocytopenia group than control group (22.6% vs 2.6%). In view of the possible association of general anesthesia with uterine atony and increased hemorrhage [43], anesthesia method may represent a significant confounder. Therefore, we included anesthesia method, along with BMI, operation duration and gestational weeks in the mixed-effect model. As a result, the upper bound of the two-side 95% CI of the calculated blood loss was still no greater than the pre-defined noninferiority delta.

Being observational and retrospective by nature, we cannot draw causal relationships and there could be inaccuracy in medical records. Furthermore, our study was subject to the following aspects of limitations. First, the calculated blood loss and transfusion rate is slightly lower than that reported previously [6, 13, 16], possibly due to the exclusion of patients with risk factors for excessive hemorrhage in our study. Consequently, the conclusion could not be hastily applied to patients at higher risk of massive blood loss. Additionally, since the average blood loss was within normal range in both groups, the potential effects of preoperative thrombocytopenia in patients who experienced primary PPH might be masked. To address this possibility, we conducted an exploratory subgroup analysis in patients with calculated blood loss > 500 ml. In this subgroup, the calculated blood loss was 679.7 ± 228.0 ml and 644.5 ± 175.7 ml in thrombocytopenic group (n = 34, 21.9%) and control group (n = 79, 25.5%), respectively. No significant difference was observed between groups (Student t-test p = 0.375). Second, considering a small sample size, the incidence of adverse event is very low and no hemostatic intervention or mortality was observed. Although we found no statistical differences between groups, perhaps there is still insufficient evidence to determine the impact of thrombocytopenia on these secondary outcomes. Third, our data was collected from a tertiary hospital, where patients were carefully evaluated during pregnancy, and the obstetrician team were experienced and skilled. Therefore, it is unknown whether our findings could also be instructive in primary medical settings with limited resources. Finally, we did not assess the clinical outcomes of neonates. Thus, the impact of maternal thrombocytopenia on infants’ PLT count at birth needs to be further explored.

In conclusion, preoperative moderate thrombocytopenia (PLT 50–100 × 10⁹/L) does not increase the risk of blood loss, the requirement for blood transfusion, or the occurrence of adverse events in patients undergoing CS in absence of other risk factors for excessive hemorrhage. A restrictive preoperative PLT threshold might optimize blood utilization without worsening maternal outcomes. Prospective observational studies with larger sample size and randomized controlled trials are required to better refine the preoperative prophylactic platelet transfusion strategy.