Pregnancy outcome in homozygous sickle cell disease: observations from the Jamaican Birth Cohort.

OBJECTIVE: To document pregnancy outcome in homozygous sickle cell (SS) disease and in age-matched controls with a normal haemoglobin genotype followed from birth for up to 45 years. METHODS: A total of 100 000 consecutive non-operative deliveries screened for sickle cell disease at the main Government maternity hospital in Kingston, Jamaica between 1973 and 1981 detected 311 (149 female) babies with SS disease who were matched by age and gender with 250 (129 female) controls with an AA haemoglobin phenotype. These individuals have been followed from birth with prospective assessment of menarche and detailed documentation of all pregnancies. RESULTS: There were 177 pregnancies in 71 SS patients and 226 pregnancies in 74 AA controls. Mothers with SS disease had more spontaneous abortions (adjusted relative risk [aRR] 3.2, 95% CI 1.6-6.1), fewer live births (aRR 0.7, 95% CI 0.6-0.9) and their offspring were more likely to have a gestational age <37 weeks (aRR 2.1, 95% CI 1.1-3.7) and low birthweight <2.5 kg (aRR 3.0, 95% CI 1.6-5.3). They were more prone to acute chest syndrome (aRR 13.7, 95% CI 4.1-45.5), urinary tract infection (aRR 12.8, 95% CI 1.3-125.9), pre-eclampsia/eclampsia (aRR 3.1, 95% CI 1.1-8.8), retained placenta (aRR 10.1, 95% CI 1.1-90.3), sepsis (Fisher's Exact test 0.04) and pregnancy-related deaths (Fisher's Exact test 0.02). Four of five deaths were attributable to acute chest syndrome. There was no genotypic difference in pregnancy-induced hypertension or postpartum haemorrhage. CONCLUSION: Pregnancy in SS disease carries risks for both mother and child. The variable characteristics of pregnancy-related deaths complicate their prevention. TWEETABLE ABSTRACT: Pregnancy in SS disease compared with controls showed increased abortions and stillbirths, fewer live births and maternal deaths in 7% patients.

Maternal and Perinatal Morbidity and Mortality Associated With Anemia in Pregnancy.

OBJECTIVE: To estimate the incidence of anemia in pregnancy and compare the maternal and perinatal outcomes of women with and without anemia. METHODS: We conducted a population-based retrospective cohort study on all pregnant women in British Columbia who had a live birth or stillbirth at or after 20 weeks of gestation between 2004 and 2016. Women were diagnosed with anemia based on two criteria: third-trimester hemoglobin value or a delivery admission diagnosis of anemia (made before delivery). Anemia was categorized into no anemia (hemoglobin 11 g/dL or greater), mild (9-10.9 g/dL), moderate (7-8.9 g/dL), severe (less than 7 g/dL), or anemia of unspecified severity (with diagnosis made before delivery). Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% CIs expressing the association between anemia and maternal and perinatal outcomes. RESULTS: Of 515,270 women in the study population, 65,906 (12.8%) had anemia: 11.8%, 0.43%, and 0.02% had mild, moderate, and severe anemia, respectively, and 0.58% had anemia of unspecified severity. Anemic women had longer hospitalization duration and more antenatal admissions, and rates of preeclampsia, placenta previa and cesarean delivery were higher among women with anemia. The intrapartum-postpartum blood transfusion rate was 5.1 per 1,000 among women without anemia, and higher among women with anemia (aOR 2.45, 95% CI 1.74-3.45 for mild anemia; 21.3, 95% CI 12.2-37.3 for moderate anemia; not analyzable for severe anemia; and 48.3, 95% CI 6.60-353.9 for anemia of unspecified severity). Anemia was associated with preterm birth (mild anemia, aOR 1.09, 95% CI 1.05-1.12; moderate anemia, aOR 2.26, 95% CI 2.02-2.54; anemia of unspecified severity, aOR 2.27, 95% CI 2.06-2.50), small-for-gestational-age live birth, low 5-minute Apgar score, neonatal death, and perinatal death. CONCLUSION: Maternal anemia in pregnancy represents a common and potentially reversible risk factor associated with antepartum, intrapartum, and postpartum maternal morbidity and perinatal morbidity and mortality.

Quality Improvement Opportunities Identified Through Case Review of Pregnancy-Related Deaths From Obstetric Hemorrhage.

OBJECTIVE: To analyze quality improvement opportunities (QIOs) identified through review of cases of maternal death from obstetric hemorrhage by the California Pregnancy-Associated Mortality Review Committee. DESIGN: Qualitative descriptive using thematic analysis. SAMPLE: A total of 159 QIOs identified from 33 cases of pregnancy-related deaths from obstetric hemorrhage in California from 2002 to 2007. METHODS: We coded and thematically organized the 159 QIOs using three of the four domains commonly applied in quality improvement initiatives for maternal health care: Readiness, Recognition, and Response. Data did not include reporting issues, so the Reporting domain was excluded from the analysis. RESULTS: Thematic findings indicated that facility Readiness would be improved through practice standardization, better organization of equipment to treat hemorrhage, and planning for care of women with risk factors for hemorrhage. Recognition of hemorrhage by health care providers could be improved through accurate assessment of blood loss, risk factors, and early clinical signs of deterioration. Provider Response could be improved through reducing delays in administering blood, seeking consultations, transferring women to higher levels of care within or outside of the facility, and moving on to other treatments if a woman does not respond to current treatment. CONCLUSION: Hemorrhage is the most preventable cause of maternal death in California. Morbidity and mortality from hemorrhage can be prevented if birth facilities and maternity care clinicians align local practices with national safety guidelines.

Towards zero mortality in sickle cell pregnancy: A prospective study comparing haemoglobin SS and AA women in Lagos, Nigeria.

INTRODUCTION: Sickle cell disease in pregnancy carries increased risk of maternal and perinatal morbidity and mortality. Past studies on pregnancy complications in sickle cell disease women were limited by relatively small sample sizes, and use of retrospective and hospital discharge data. STUDY DESIGN: This prospective case-control study compared booked pregnant Haemoglobin (Hb) SS women with AA controls from two tertiary centres in Lagos, in order to precisely identify their complication and mortality rates and identify associated factors. Eligible pregnant HbSS and HbAA women were recruited from antenatal clinics at booking and follow-up visits. Information was collected on a proforma and data was analyzed using IBM SPSS version 20. RESULTS: We found higher complication rate in HbSS group, commonest complications being vaso-occlusive crisis (RR 1.47, 95% CI 1.22 - 1.78), pregnancy induced hypertension (RR 1.31, 95% CI 1.08 - 1.57), urinary tract infection (RR 1.32, 95% CI 1.12 - 1.57), and intrauterine growth restriction (RR 1.2, 95% CI 1.05 - 1.34). HbSS group had higher systolic and mean arterial blood pressure values in early puerperium compared to HbAA group (p = 0.014 and 0.024 respectively). No maternal death recorded in both group. Incidence of low birth weight <2.5Kg was 38% in HbSS and 4% in HbAA subjects, p = 0.001. However, overall maternal and perinatal outcomes were comparable in both groups (p = 1.000). CONCLUSION: Although sickle cell disease poses higher obstetric risk in pregnancy, maternal and perinatal outcome can be as good as in the non-sickle cell pregnant women if adequate and prompt individualized care is given to this group of women.

Management of high risk cardiac conditions in pregnancy: Anticoagulation, severe stenotic valvular disease and cardiomyopathy.

Cardiovascular disease contributes to approximately one third of all maternal mortality and remains a significant source of peri­ and postpartum morbidity. As more women at risk for and with cardiovascular disease are desiring pregnancy, it is imperative that general cardiologists and obstetricians participate collaboratively in preconception counseling and are more facile with management of these lesions during peri­ and postpartum periods. This review aims to address this growing need and highlights the management strategies for some of the major high risk cardiac conditions encountered during pregnancy including anticoagulation, cardiomyopathies as well as severe mitral and aortic stenosis; aortopathy, pulmonary hypertension, and severe congenital heart lesions will not be addressed.

Multidisciplinary care results in similar maternal and perinatal mortality rates for women with and without SCD in a low-resource setting.

In Africa, the maternal mortality rate in sickle cell disease (SCD) is ~10%. Our team previously demonstrated an 89% decrease in mortality rate in a before-and-after feasibility study among women with SCD living in low-resource setting in Ghana. In the same cohort including additional participants with and without SCD, we used a prospective cohort design to test the hypothesis that implementing a multidisciplinary care team for pregnant women with SCD in low-resource setting will result in similar maternal and perinatal mortality rates compared to women without SCD. We prospectively enrolled pregnant women with and without SCD or trait and followed them up for 6-week postpartum. We tested the newborns of mothers with SCD for SCD. We recruited age and parity matched pregnant women without SCD or trait as the comparison group. Maternal and perinatal mortality rates were the primary outcomes. A total of 149 pregnant women with SCD (HbSS, 54; HbSC, 95) and 117 pregnant women without SCD or trait were included in the analysis. Post-intervention, maternal mortality rates were 1.3% and 0.9% in women with and without SCD, respectively (P = 1.00); the perinatal mortality rates were 7.4% and 3.4% for women with and without SCD, respectively (P = 0.164). Among the mothers with SCD, ~15% of newborns had SCD. Multidisciplinary care of pregnant women with SCD may reduce maternal and perinatal mortality rates to similar levels in pregnant women without SCD in low-resource settings. Newborns of mothers with SCD have a high rate of SCD.

TTP: long-term outcomes following recovery.

Although risk for relapse may be the greatest concern following recovery from acquired, autoimmune thrombotic thrombocytopenic purpura (TTP), there are multiple other major health issues that must be recognized and appropriately addressed. Depression may be the most common disorder following recovery from TTP and may be the most important issue for the patient's quality of life. Severe or moderate depression has occurred in 44% of Oklahoma Registry patients. Recognition of depression by routine screening evaluations is essential; treatment of depression is effective. Minor cognitive impairment is also common. The recognition that cognitive impairment is related to the preceding TTP can provide substantial emotional support for both the patient and her family. Because TTP commonly occurs in young black women, the frequency of systemic lupus erythematosus, as well as other autoimmune disorders, is increased. Because there is a recognized association of TTP with pregnancy, there is always concern for subsequent pregnancies. In the Oklahoma Registry experience, relapse has occurred in only 2 of 22 pregnancies (2 of 13 women). The frequency of new-onset hypertension is increased. The most striking evidence for the impact of morbidities following recovery from TTP is decreased survival. Among the 77 patients who survived their initial episode of TTP (1995-2017), 16 (21%) have subsequently died, all before their expected age of death (median difference, 22 years; range 4-55 years). The conclusion from these observations is clear. Following recovery from TTP, multiple health problems occur and survival is shortened. Therefore, careful continuing follow-up is essential.

Risk of maternal mortality in women with severe anaemia during pregnancy and post partum: a multilevel analysis.

BACKGROUND: Anaemia affects as many as half of all pregnant women in low-income and middle-income countries, but the burden of disease and associated maternal mortality are not robustly quantified. We aimed to assess the association between severe anaemia and maternal death with data from the WHO Multicountry Survey on maternal and newborn health. METHODS: We used multilevel and propensity score regression analyses to establish the relation between severe anaemia and maternal death in 359 health facilities in 29 countries across Latin America, Africa, the Western Pacific, eastern Mediterranean, and southeast Asia. Severe anaemia was defined as antenatal or postnatal haemoglobin concentrations of less than 70 g/L in a blood sample obtained before death. Maternal death was defined as death any time after admission until the seventh day post partum or discharge. In regression analyses, we adjusted for post-partum haemorrhage, general anaesthesia, admission to intensive care, sepsis, pre-eclampsia or eclampsia, thrombocytopenia, shock, massive transfusion, severe oliguria, failure to form clots, and severe acidosis as confounding variables. These variables were used to develop the propensity score. FINDINGS: 312 281 women admitted in labour or with ectopic pregnancies were included in the adjusted multilevel logistic analysis, and 12 470 were included in the propensity score regression analysis. The adjusted odds ratio for maternal death in women with severe anaemia compared with those without severe anaemia was 2·36 (95% CI 1·60-3·48). In the propensity score analysis, severe anaemia was also associated with maternal death (adjusted odds ratio 1·86 [95% CI 1·39-2·49]). INTERPRETATION: Prevention and treatment of anaemia during pregnancy and post partum should remain a global public health and research priority. FUNDING: Barts and the London Charity.

Perinatal Maternal Mortality in Sickle Cell Anemia: Two Case Reports and Review of the Literature.

As outcomes of patients with sickle cell anemia improve and survival into adulthood with good quality of life and expectation of long-term survival becomes more common, challenges have developed, including issues related to reproduction. Pregnancy is frequently complicated in patients with sickle cell anemia with mortality up to 4.0%. Here we report maternal perinatal mortality in two women with sickle cell anemia who died post-partum due to acute chest syndrome (ACS), caused by bone marrow fat embolism and review the literature pertinent to this subject. Patient A was a 28-year-old woman with sickle cell anemia with multiple complications. At 30 weeks' gestation she developed hemolysis associated with poor placental function necessitating delivery by C-section. The fetus was delivered successfully but she died due to multi organ failure after delivery. Autopsy showed pulmonary and amniotic fluid embolization. Patient B was a 37-year-old woman with uncomplicated sickle cell anemia who presented with pre term labor and crisis, then ACS and fetal distress. The infant was delivered successfully but the patient died after cardiovascular collapse. Autopsy results showed fat and bone marrow embolization as the cause of death. Pregnancy continues to be high risk for patients with sickle cell anemia including those with mild disease. Maternal perinatal mortality could be unpredictable due to serious complications of sickle cell disease. More studies to assess maternal perinatal mortality are needed.

Clinical dissection of thrombotic microangiopathy.

Differential treatment strategies are applied in thrombotic microangiopathy (TMA) according to the sub-classifications. Hence, it is worthwhile to overview clinical manifestations and outcomes of overall TMA patients according to sub-classifications. We analyzed TMA patients whose serum lactate dehydrogenase levels >250 IU/L, with the presence of schistocytes in their peripheral blood smear, or with typical vascular pathologic abnormalities in their renal biopsy. We compared clinical manifestations including overall survival (OS) and renal survival according to TMA causes. A total of 117 TMA patients (57 primary and 60 secondary TMA) were analyzed. Renal symptom was the most common manifestation in whole patients, while renal function at diagnosis was worst in pregnancy-related TMA group. Primary TMA patients had more frequent CNS symptom and hematologic manifestation compared to secondary TMAs. Among secondary TMAs, pregnancy- and HSCT-related TMA patients showed prevalent hemolytic features. During 150.2 months of follow-up, 5-year OS rate was 64.8%. Poor prognostic factors included older age, combined hematologic and solid organ malignancies, lower hemoglobin levels, and lower serum albumin levels. There was no significant difference in OS between primary and secondary TMAs. Seventy-eight percent of patients experienced AKI during TMA. Five-year death-censored renal survival rate was poor with only 69.2%. However, excellent renal outcome was observed in pregnancy-associated TMA. TMA showed various clinical manifestations according to their etiology. Notably, both OS and renal survival were poor regardless of their etiologies except pregnancy-associated TMA. Physicians should differentiate a variety of TMA categories and properly manage this complex disease entity.

Implementation of multidisciplinary care reduces maternal mortality in women with sickle cell disease living in low-resource setting.

Sickle cell disease (SCD) is associated with adverse pregnancy outcome. In women with SCD living in low-resource settings, pregnancy is associated with significantly increased maternal and perinatal mortality rates. We tested the hypothesis that implementing a multidisciplinary obstetric and hematology care team in a low-resource setting would significantly reduce maternal and perinatal mortality rates. We conducted a before-and-after study, at the Korle-Bu Teaching Hospital in Accra, Ghana, to evaluate the effect of a multidisciplinary obstetric-hematology care team for women with SCD in a combined SCD-Obstetric Clinic. The pre-intervention period was assessed through a retrospective chart review to identify every death and the post-intervention period was assessed prospectively. Interventions consisted of joint obstetrician and hematologist outpatient and acute inpatient reviews, close maternal and fetal surveillance, and simple protocols for management of acute chest syndrome and acute pain episodes. Primary outcomes included maternal and perinatal mortality rates before and after the study period. A total of 158 and 90 pregnant women with SCD were evaluated in the pre- and post- intervention periods, respectively. The maternal mortality rate decreased from 10 791 per 100 000 live births at pre-intervention to 1176 per 100 000 at post-intervention, representing a risk reduction of 89.1% (P = 0.007). Perinatal mortality decreased from 60.8 per 1000 total births at pre-intervention to 23.0 per 1000 at post-intervention, representing a risk reduction of 62.2% (P = 0.20). A multidisciplinary obstetric and hematology team approach can dramatically reduce maternal and perinatal mortality in a low-resource setting.

Implementing at-scale, community-based distribution of misoprostol tablets to mothers in the third stage of labor for the prevention of postpartum haemorrhage in Sokoto State, Nigeria: Early results and lessons learned.

BACKGROUND: Postpartum haemorrhage (PPH) is a leading cause of maternal death in Sokoto State, Nigeria, where 95% of women give birth outside of a health facility. Although pilot schemes have demonstrated the value of community-based distribution of misoprostol for the prevention of PPH, none have provided practical insight on taking such programs to scale. METHODS: A community-based system for the distribution of misoprostol tablets (in 600ug) and chlorhexidine digluconate gel 7.1% to mother-newborn dyads was introduced by state government officials and community leaders throughout Sokoto State in April 2013, with the potential to reach an estimated 190,467 annual births. A simple outcome form that collected distribution and consumption data was used to assess the percentage of mothers that received misoprostol at labor through December 2014. Mothers' conditions were tracked through 6 weeks postpartum. Verbal autopsies were conducted on associated maternal deaths. RESULTS: Misoprostol distribution was successfully introduced and reached mothers in labor in all 244 wards in Sokoto State. Community data collection systems were successfully operational in all 244 wards with reliable capacity to record maternal deaths. 70,982 women or 22% of expected births received misoprostol from April 2013 to December 2014. Between April and December 2013, 33 women (< 1%) reported that heavy bleeding persisted after misoprostol use and were promptly referred. There were a total of 11 deaths in the 2013 cohort which were confirmed as maternal deaths by verbal autopsies. Between January and December of 2014, a total 434 women (1.25%) that ingested misoprostol reported associated side effects. CONCLUSION: It is feasible and safe to utilize government guidelines on results-based primary health care to successfully introduce community distribution of life saving misoprostol at scale to reduce PPH and improve maternal outcomes. Lessons from Sokoto State's at-scale program implementation, to assure every mother's right to uterotonics, can inform scale-up elsewhere in Nigeria.

Shedding Light on Inherited Thrombophilias: The Impact on Pregnancy.

Physiologic changes of pregnancy result in a hypercoagulable state, placing the risk for venous thromboembolic events at 1 in 1600 births. Venous thromboembolic events are one of the leading causes of maternal mortality. A correlation among venous thromboembolic events, pregnancy complications, and inherited thrombophilia continues to be investigated. This article primarily focuses on the impact of inherited thrombophilias on pregnancy, labor, and birth and yet also addresses acquired thrombophilia. Prophylactic and therapeutic perinatal anticoagulation are lifesaving and pregnancy-sparing interventions. Interprofessional management of these high-risk pregnancies allows for increased surveillance to reduce perinatal morbidity and mortality.

Evaluation of obstetrical patients with disseminated intravascular coagulopathy - tertiary center experience.

OBJECTIVE: The purpose of the present study is twofold: (a) to investigate the etiology of disseminated intravascular coagulopathy (DIC) caused by obstetrical conditions and (b) to present parameters that can be used in predicting DIC-related mortality in obstetrical patients. MATERIAL AND METHOD: Obstetrical patients who had a delivery at or were referred (after delivery) to Obstetrics and Gynecology Clinic of Dicle University between July 2006 and December 2013 were retrospectively analyzed in this study. Those patients diagnosed with DIC were included in the study. RESULTS: Fifty-six obstetrical patients carrying the diagnosis of DIC were included in this study. The overall mortality rate was 25% among these patients. More specifically, the mortality rate was 10.7% among patients with a DIC score ≤5 and 40.7% among those with a DIC score > 5. Multiple logistic regression analysis resulted in the finding that international normalized ratio (INR) and urea were among those factors affecting mortality in obstetrical DIC [OR: 8.44 (CI: 1.9-36.8), OR: 1.05 (CI: 1.0-1.1), respectively]. CONCLUSION: DIC is a syndrome that might be caused by obstetrical conditions. It is associated with high mortality and morbidity rates. In obstetrical DIC, urea is the most important factor affecting mortality. In addition, we are of the opinion that DIC score might guide mortality predictions as a determinant of prognosis.

Prophylactic transfusion for pregnant women with sickle cell disease: a systematic review and meta-analysis.

Pregnancy in women with sickle cell disease is associated with adverse maternal and neonatal outcomes. Studies assessing the effects of prophylactic red blood cell transfusions on these outcomes have drawn inconsistent conclusions. The objective of this systematic review was to assess the effect of prophylactic compared with on-demand red blood cell transfusions on maternal and neonatal outcomes in women with sickle cell disease. A systematic search of several medical literature databases was conducted. Twelve studies involving 1291 participants met inclusion criteria. The studies had moderate to high risk of bias. Meta-analysis demonstrated that prophylactic transfusion was associated with a reduction in maternal mortality (7 studies, 955 participants; odds ratio [OR], 0.23; 95% confidence interval [CI], 0.06-0.91), vaso-occlusive pain episodes (11 studies, 1219 participants; OR, 0.26; 95% CI, 0.09-0.76), pulmonary complications (9 studies, 1019 participants; OR, 0.25; 95% CI, 0.09-0.72), pulmonary embolism (3 studies, 237 participants; OR, 0.07; 95% CI, 0.01-0.41), pyelonephritis (6 studies, 455 participants; OR, 0.19; 95% CI, 0.07-0.51), perinatal mortality (8 studies, 1140 participants; OR, 0.43; 95% CI, 0.19-0.99), neonatal death (5 studies, 374 participants; OR, 0.26; 95% CI, 0.07-0.93), and preterm birth (9 studies, 1123 participants; OR, 0.59; 95% CI, 0.37-0.96). Event rates for most of the results were low. Prophylactic transfusions may positively impact several adverse maternal and neonatal outcomes in women with sickle cell disease; however, the evidence stems from a relatively small number of studies with methodologic limitations. A prospective, multicenter, randomized trial is needed to determine whether the potential benefits balance the risks of prophylactic transfusions.

Life after acquired thrombotic thrombocytopenic purpura: morbidity, mortality, and risks during pregnancy.

Patients who have recovered from their acute episode of acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura (TTP) were once thought to have complete recovery except for risk of relapse. Data from previous publications from the Oklahoma TTP-hemolytic uremic syndrome (HUS) Registry are summarized. Patients have decreased cognitive function and increased prevalence of hypertension, systemic lupus erythematosus, major depression, and albuminuria as compared to the expected values from the US population. The proportion of patients that died during the follow-up period was greater than expected based on the US population reference population. Among women who had a pregnancy following recovery from TTP, relapse during pregnancy or postpartum is uncommon, but the occurrence of preeclampsia may be increased. Thirteen of 16 pregnancies in these women resulted in healthy children. Increased morbidity and mortality in TTP patients following recovery suggest that TTP may be more of a chronic disorder than a disorder with acute episodes and complete recovery.

Prophylactic red blood cell exchange may be beneficial in the management of sickle cell disease in pregnancy.

BACKGROUND: Sickle cell disease (SCD) is associated with chronic hemolysis and painful episodes. Pregnancy accelerates sickle cell complications, including prepartum and postpartum vasoocclusive crisis, pulmonary complications, and preeclampsia or eclampsia. Fetal complications include preterm birth and its associated risks, intrauterine growth restriction, and a high rate of perinatal mortality. The purpose of this study was to evaluate pregnancy outcomes in patients with SCD who underwent planned preventive red blood cell exchange (RBCX). STUDY DESIGN AND METHODS: We retrospectively evaluated the complications of SCD in 37 pregnant patients. Patients with SCD who had undergone prophylactic RBCX were compared with a control group who had not undergone RBCX during pregnancy. RESULTS: Forty-three exchange procedures were performed in 24 patients. The control group comprised 13 patients with a mean age of 27.4 ± 3.3 years who had not undergone RBCX during pregnancy. Four of the five patients who developed a vasoocclusive crisis died. There was a significant difference in maternal mortality between the study and control groups (p = 0.011). There was also a significant difference in the incidence of vasoocclusive crisis between the study and control groups. One fetal death occurred in the 20th gestational week in a patient in the control group, although there were no postpartum complications in either the babies or the mothers in the control group. CONCLUSION: This study has demonstrated that prophylactic RBCX during pregnancy is a feasible and safe procedure for prevention of complications. Given the decrease in the risks of transfusion, RBCX warrants further study.