Conditions that increase the risk of cesarean-related blood transfusions: a single-center cohort study

Objective

This study aimed to define the conditions that increase the possibility of receiving a blood transfusion in patients who had a cesarean section.

Methods

This study was conducted between January 2016-May 2020 in a university hospital located in Konya, Turkey. Pregnant women undergoing cesarean section were included. Of 4303 eligible patients, 188 women were the transfused group and 4115 women were the non-transfused group. Logistic regression analysis was performed for potential confounding factors.

Results

A total of 4303 eligible patients were evaluated in this study. There were 4115 patients (95.6%) in the Non-transfused Group. The Transfused Group consisted of 188 patients (4.4%). The probability of transfusion was higher in pregnant women with placenta previa, placenta accreta spectrum, thrombocytopenia, preoperative anemia, macrosomia above 4500 g, and multiple gestations (Adjusted OR values (95% CI); 10.58(4.75-23.57), 7.75(3.22-18.61), 7.85(3.46-17.79), 5.71(4.21-7.74), 4.22(1.21-14.67) and 2.10(1.18-3.72), respectively). There was no increase in the possibility of transfusion in 4000-4500 gram macrosomia, uterine fibroids, preeclampsia, premature rupture of membranes, previous cesarean sections and gestational diabetes mellitus.

Conclusion

Placenta previa, placenta accreta spectrum, thrombocytopenia, preoperative anemia, macrosomia above 4500 g and multiple gestations increase the possibility of transfusion. Perioperative blood preparation is vital in such patients. Prevention of anemia during pregnancy is critical in reducing transfusions.

Keywords

blood transfusion, cesarean section, peripartum hemorrhage, postpartum hemorrhage

Introduction

Obstetric hemorrhage is still one of the most important causes of morbidity and mortality in women of reproductive age (1). Cesarean section alone is considered an important reason for this (2). Cesarean rates are increasing all over the world (3). In peripartum hemorrhage, the condition of the mother can deteriorate rapidly, and many complications, including maternal death, may occur if blood products are not available at the time of need. Some studies have shown that conditions such as placental anomalies and preoperative maternal anemia increase the possibility of blood transfusion in cesarean operations (4-7). There is inconsistent information in the literature as to whether conditions such as the number of previous cesarean sections, multiple pregnancies, macrosomia and uterine fibroids increase the possibility of transfusion. However, there are a limited number of studies evaluating blood transfusion risk in cesarean operations.
There is still no consensus on which patients should be prepared for a blood transfusion. Preoperative blood transfusion preparation is done for all patients scheduled for cesarean surgery in many centers (8, 9). However, there are still some difficulties in obtaining blood and blood products in many parts of the world. On the other hand, when the increasing cesarean rates are taken into account, unnecessary blood preparation will lead to both a decrease in blood stocks and an increase in costs.
The aim in this study was to evaluate the conditions that increase the possibility of receiving a blood transfusion in patients who had a cesarean section in a tertiary center. The evaluation of factors that are not known preoperatively were excluded from the scope of this study (adhesion, atony, T-shaped incision, etc).

Methods

This study was conducted in the province of Konya, Turkey at a University hospital, where the complicated cases out of 5,000 births per year were collected. The study was approved by the University Ethics Committee (Decision no: 2020/2808) and conducted according to Helsinki Declaration and good clinical practice. All births between January 2016 and May 2020 were analyzed in the electronic database. All patients who gave birth before 24 weeks, those who gave birth vaginally and those whose data was incomplete were excluded. In addition, 3 patients pregnant with twins one of which was a normal vaginal delivery and the other by cesarean section were excluded from the study.
Gestational age was calculated based on the last menstrual date and confirmed by an early stage ultrasound at less than 12 weeks. Information such as age, body mass index (BMI), gestational week, obstetric history, preoperative and postoperative hemoglobin values and whether or not they received perioperative blood transfusion were recorded for all patients with complete blood count done at most seven days before the operation. Patients who decided to have a cesarean section at least eight hours in advance were defined as ‘elective cesarean’. All other cesareans were defined as "emergency cesarean". If more than one complete blood test was performed preoperative, the values closest to the time of delivery were recorded. Anemia was defined as a hemoglobin value below 11 g / dL (10, 11). Thrombocytopenia was defined as a platelet value below 100 k / µL. Only pregnant women with uterine fibroids larger than 5 cm were included for the uterine fibroids criterion. The diagnosis of preeclampsia was made according to the criteria in the latest American College of Obstetricians and Gynecologists (ACOG) bulletin (12).
Pregnant women with new-onset hypertension and proteinuria after 20 weeks of gestation were defined as preeclampsia. In addition, pregnant women with new-onset hypertension and end-organ damage, even without proteinuria, were also included in this group. Gestational diabetes mellitus (GDM) was diagnosed according to the criteria of the American Diabetes Association (13). Accordingly, the diagnosis was made with one-step 75 OGTT or two-step 100-gr OGTT tests between 24-28 weeks.
Placenta previa, placenta accreta spectrum (PAS) and polyhydramnios were diagnosed with Samsung H70 (Hampshire, UK) or Voluson E8 (General electric) ultrasound devices. Placenta previa was defined as the placenta covering the entire internal os. The diagnosis of PAS was based on ultrasound showing multiple placental lacunaes, disruption of the bladder line, loss of the clear zone, myometrial thinning, abnormal vascularity and placental bulge. These diagnoses were confirmed either perioperatively or pathologically (14). Polyhydramnios was defined as the measurement of the single deepest pocket ≥8 cm.
Control hemoglobin values were measured approximately 24 hours after the cesarean section in the clinic where the study was conducted. The blood transfusion decision was made according to the patient's vital signs, perioperative estimated bleeding amount and intraoperative hemoglobin levels, or postoperative hemoglobulin level below 7 g / dL. Transfusion indications were set by an anesthesiologist during the operation or by obstetricians during the postoperative period. Women who received a blood transfusion during the cesarean section or up to 24 hours postoperatively were defined as the ‘transfused group’. All other patients were defined as the ‘non-transfused group’.
Statistical analysis
All data were analyzed by the Statistical Package for the Social Sciences, version 23, SPSS Inc., Chicago, IL (SPSS). The normal distribution of the data was evaluated with the Kolmogorov-Smirnov test. The Chi-Square test was used for the analysis of categorical data and the Student T or the Mann Whitney U tests were used for continuous variables. Adjusted odds ratios and 95% confidence intervals were calculated with the logistic regression for potential confounding factors. A P value of 0.05 was considered statistically significant.
The G * Power 3.1 program (Düsseldorf, Germany) was used for posthoc power analysis. The α error probability, effect size and power of the study were 0.05, 0.5, and 0.99, respectively.
 

Results

A total of 4303 eligible patients were evaluated in this study. There were 4115 patients (95.6%) in the Non-transfused Group. The Transfused Group consisted of 188 patients (4.4%) (Figure 1). The amount of transfused blood ranged from 1-6 bags. The highest frequency of blood transfused was 2 (60.6%) (Figure 2).
The transfused Group had a lower average age (29.0 ± 6.0 vs 27.9 ± 6.0, p = 0.007). In addition, multiple gestation rates were higher in the Transfused Group (3.7% vs %7.4, p = 0.010). Preoperative hemoglobin and hematocrit values were lower in the Transfused Group (p values <0.001, <0.001, respectively). The groups were homogeneously distributed in terms of BMI, gravida, parity, number of previous cesarean sections and indications (Table 1).
There was no significant difference between the two groups in terms of GDM, preeclampsia, PROM, emergency cesarean, general anesthesia and birth weight. In the Transfused Group, the rates of placenta previa, PAS, ablatio placenta and babies over 4500g were higher (p values <0.001, <0.001, <0.001, 0.043, respectively). Pregnant women in the Transfused Group gave birth in an earlier week of gestation (median value was 38.0 vs 37.6, p <0.001) (Table 2).
In the logistic regression analysis, the possibility of transfusion was found to be higher in placenta previa, PAS, thrombocytopenia, preoperative anemia, macrosomia over 4500 grams and multiple gestations (Adjusted OR values (95% CI); 10.58(4.75-23.57), 7.75(3.22-18.61), 7.85(3.46-17.79), 5.71(4.21-7.74), 4.22(1.21-14.67) and 2.10(1.18-3.72), respectively). There was no increase in the possibility of transfusion in macrosomia over 4000 grams, uterine fibroids, preeclampsia, PROM, previous cesarean sections and GDM. (Table 3).
 

Discussion

This study clearly determines some of the conditions that increase the possibility to receive a blood transfusion. Preoperative anemia, placenta previa, PAS, thrombocytopenia, macrosomia more than 4500 gram and multiple gestations are indications in which we identified patients with a high risk of receiving a blood transfusion.
Cesarean-related transfusion rates vary greatly from 0.53% to 20% in different studies (6, 7, 9, 15). The reason for this may be factors such as the socioeconomic status of the countries where the study was conducted, anemia rates or the different orientations of physicians regarding transfusion. Transfusion attitude has been shown to vary widely among clinicians (16). In the present study, transfusion rates were determined as 4.4%. Preoperative anemia is one of the most important factors that increase the risk of blood transfusion and shows how important it is to combat anemia during pregnancy. In the present study, the possibility of blood transfusion increased 5.7 times in pregnant women with preoperative anemia. The Royal College of Obstetricians and Gynecologists (UK) and the French College of Gynecologists and Obstetricians recommend that the hemoglobin level in pregnant women should be 8 g / dl and above (17).  Treating preoperative anemia is one of the most important measures to reduce transfusion during cesarean operations.
It is known that platelet counts below 100 k / µL (70 k / µL according to some studies) before surgical procedures increase the risk of hemorrhage (18, 19). As expected, in the present study, the possibility of transfusion was found to be 7.8 times higher in patients with thrombocytopenia.
Multiple pregnancies are thought to be a risk factor for postpartum hemorrhage, as this is one cause for enlargement of the entire uterus (4, 5). In the present study, it was determined that the possibility of transfusion is higher in multiple pregnancies (adjusted OR = 2.10; %95 CI 1.18-3.72). Since the size of the placental bed is larger in multiple pregnancies, it will not be surprising to have more bleeding even if there is no atony. However, Akinlusi et al. stated in their study that multiple gestations do not increase the possibility of receiving a blood transfusion in cesarean operations (crude OR = 1.25; 95% CI 1.25–4622.06) (9). Polyhydroamniosis, another reason for increased uterine volume, is also a risk factor for atony. However, in the present study, an increase in the possibility of blood transfusion was not detected in pregnant women with polyhydramnios.
Another reason why uterine volume increases is macrosomia, defined as birth weight over 4000 or 4500 g, regardless of gestational age (20). In a study, an increase in the risk of postpartum hemorrhage was found in pregnant women carrying macrosomic fetuses (OR 3.18; 95% CI 2.47–4.10)  (21), so the risk of transfusion was found to be higher in cesarean deliveries of babies over 4500 grams. However, there was no increase in transfusion risk in pregnant women carrying macrosomic babies of 4000-4500g.
There are inconsistent studies in the literature regarding the increase in the number of previous cesarean sections on blood transfusion. In a study conducted by Rouse et al. in 2006, it was found that as the number of cesarean sections increased, the risk of transfusion increased (6). In a study by Abdelazim et al., the risk of blood transfusion was found to be 4.7 times higher in pregnant women with a third cesarean section compared to pregnant women with a second cesarean section (2). In some studies, it has been found that the increase in the number of previous cesarean sections does not increase the risk of postpartum bleeding (15, 22). In the present study, there was no evidence that the number of cesarean sections had increased the risk of transfusion. In countries with a high number of previous cesarean sections, the experience of obstetricians and the clinic's transfusion habits may be effective in these differences.
In a multicentric study, it was determined that uterine fibroids increased the risk of cesarean delivery and postpartum hemorrhage in pregnant women (23). In some studies, an increase in the possibility of blood transfusion was found in uterine fibroids above 5 cm, where the size and location of the fibroids are determinants (24). In the present study, there was no increase in the possibility of receiving blood transfusion when cesareans were performed on pregnant women with uterine fibroids of 5 cm or more. It is difficult to determine the risk of bleeding in pregnant women with fibroids due to many confounder factors such as the location, number of fibroids, and the distance to the incision site.
In a study in which cesarean and normal vaginal deliveries were evaluated together, the risk of peripartum blood transfusion was found to be higher in the presence of hypertension (OR=2.41; 95% CI 2.29-2.53). (25). In the current study, the transfusion rate was not increased in patients with preeclampsia. The reason for this may be that only women who gave birth by cesarean section were evaluated in the current study.
Although the fasting glucose levels of the patients who received transfusions were found to be high, there are not enough studies on this subject. (25). In our current study, it was determined that GDM did not increase the risk of blood transfusion.
The strength of this study is that it evaluated the patients who received a cesarean-related transfusion in a sufficient number of cases in terms of the many confounder factors (polyhydramnios, PROM, myoma uteri, macrosomia, etc.) in a tertiary center.
This study also has limitations. The limitations of the study are that it is single-centered, retrospective, and the patients who underwent transfusion are not subgrouped and analyzed according to the amount transfused. It is also known that the experience of the surgeon plays a role in bleeding. Therefore, the possible confounder effect of surgeries performed by different teams can be considered among the limitations (26).

 

Conclusion

In conclusion, the risk of blood transfusion in cesarean operations varies greatly between different countries. Pregnant women with placenta previa, PAS, thrombocytopenia, preoperative anemia,> 4500 g of macrosomia and multiple gestations should be prepared for blood transfusion before a cesarean operation. Tackling anemia during pregnancy will decrease cesarean-related transfusion rates.

1.         Practice Bulletin No. 183: Postpartum Hemorrhage. Obstetrics & Gynecology. 2017;130(4):e168-e86.

2.         Abdelazim I, Alanwar A, Shikanova S, Kanshaiym S, Farghali M, Mohamed M, et al. Complications associated with higher order compared to lower order cesarean sections. J Matern Fetal Neonatal Med. 2020;33(14):2395-402.

3.         Boerma T, Ronsmans C, Melesse DY, Barros AJ, Barros FC, Juan L, et al. Global epidemiology of use of and disparities in caesarean sections. The Lancet. 2018;392(10155):1341-8.

4.         Blitz MJ, Yukhayev A, Pachtman S, Reisner J, Moses D, Greenberg M, et al. 230: Factors associated with postpartum hemorrhage requiring blood transfusion in twin gestations. American Journal of Obstetrics & Gynecology. 2018;218(1):S150-S1.

5.         Blitz MJ, Yukhayev A, Pachtman SL, Reisner J, Moses D, Sison CP, et al. Twin pregnancy and risk of postpartum hemorrhage. The Journal of Maternal-Fetal & Neonatal Medicine. 2020;33(22):3740-5.

6.         Rouse DJ, MacPherson C, Landon M, Varner MW, Leveno KJ, Moawad AH, et al. Blood transfusion and cesarean delivery. Obstet Gynecol. 2006;108(4):891-7.

7.         Bao Y, Xu C, Qu X, Quan S, Dong Y, Ying H. Risk factors for transfusion in cesarean section deliveries at a tertiary hospital. Transfusion (Paris). 2016;56(8):2062-8.

8.         Anorlu RI, Orakwe CO, Abudu OO, Akanmu AS. Uses and misuse of blood transfusion in obstetrics in Lagos, Nigeria. West Afr J Med. 2003;22(2):124-7.

9.         Akinlusi FM, Rabiu KA, Durojaiye IA, Adewunmi AA, Ottun TA, Oshodi YA. Caesarean delivery-related blood transfusion: correlates in a tertiary hospital in Southwest Nigeria. BMC Pregnancy and Childbirth. 2018;18(1):24.

10.       Pavord S, Daru J, Prasannan N, Robinson S, Stanworth S, Girling J. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2020;188(6):819-30.

11.       ACOG Practice Bulletin No. 95: anemia in pregnancy. Obstet Gynecol. 2008;112(1):201-7.

12.       ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol. 2019;133(1):e1-e25.

13.       Association AD. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020. Diabetes care. 2020;43(Supplement 1):S14-S31.

14.       Comstock CH. Antenatal diagnosis of placenta accreta: a review. Ultrasound Obstet Gynecol. 2005;26(1):89-96.

15.       Abbas S, Mughal S, Hussain SNF, Hossain N. Blood transfusion and high-order cesarean delivery; Report from a developing country. Pak J Med Sci. 2019;35(6):1520-5.

16.       Matot I, Einav S, Goodman S, Zeldin A, Weissman C, Elchalal U. A survey of physicians' attitudes toward blood transfusion in patients undergoing cesarean section. Am J Obstet Gynecol. 2004;190(2):462-7.

17.       Shaylor R, Weiniger CF, Austin N, Tzabazis A, Shander A, Goodnough LT, et al. National and International Guidelines for Patient Blood Management in Obstetrics: A Qualitative Review. Anesth Analg. 2017;124(1):216-32.

18.       Fogerty AE. Thrombocytopenia in Pregnancy: Mechanisms and Management. Transfus Med Rev. 2018;32(4):225-9.

19.       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(1):29-33.

20.       Macrosomia: ACOG Practice Bulletin, Number 216. Obstet Gynecol. 2020;135(1):e18-e35.

21.       King JR, Korst LM, Miller DA, Ouzounian JG. Increased composite maternal and neonatal morbidity associated with ultrasonographically suspected fetal macrosomia. The Journal of Maternal-Fetal & Neonatal Medicine. 2012;25(10):1953-9.

22.       Butwick AJ, Ramachandran B, Hegde P, Riley ET, El-Sayed YY, Nelson LM. Risk Factors for Severe Postpartum Hemorrhage After Cesarean Delivery: Case-Control Studies. Anesth Analg. 2017;125(2):523-32.

23.       Zhao R, Wang X, Zou L, Li G, Chen Y, Li C, et al. Adverse obstetric outcomes in pregnant women with uterine fibroids in China: A multicenter survey involving 112,403 deliveries. PLoS ONE. 2017;12(11):e0187821.

24.       Shavell VI, Thakur M, Sawant A, Kruger ML, Jones TB, Singh M, et al. Adverse obstetric outcomes associated with sonographically identified large uterine fibroids. Fertil Steril. 2012;97(1):107-10.

25.       Ouh Y-T, Lee K-M, Ahn KH, Hong S-C, Oh M-J, Kim H-J, et al. Predicting peripartum blood transfusion: focusing on pre-pregnancy characteristics. BMC Pregnancy and Childbirth. 2019;19(1):477.

26.       Dairo MD, Lawoyin TO, Onadeko MO, Asekun-Olarinmoye EO, Adeniji AO. HIV as an additional risk factors for anaemia in pregnancy: evidence from primary care level in Ibadan, Southwestern Nigeria. Afr J Med Med Sci. 2005;34(3):275-9.

	File/Dsecription
	Table-1 Baseline characteristics of the groups
	Table-2 Comparison of the groups in terms of obstetric outcomes
	Table-3 Odds ratios for blood transfusion
	figure1 Subject selection
	Figure2 Distribution of transfused blood packs. pRBC, packed red blood cell.
	manuscript manuscript
	revision notes point by point