Red Cell Exchange Transfusion Research Articles

The enigma of sickle cell hepatopathy: Pathophysiology, clinical manifestations and therapy.

Sickle cell disease (SCD) is one of the most common genetic disorders in the world predominantly affecting economically disadvantaged populations. There is a notable discrepancy between the growing adult SCD population and available diagnostic and therapeutic interventions for SCD. Sickle cell hepatopathy (SCH) is an all-inclusive term to describe the acute and chronic liver manifestations of SCD. The pathophysiology of SCH follows no defined pattern or sequence that poses challenges to clinicians and researchers alike. Evidence is lacking for this underreported disease at various levels from diagnostic to therapeutic options. This paper reviews the basic pathophysiology, clinical features, biochemical and radiological findings of various SCH manifestations and outlines the management of each condition. Old and new therapy options in SCD including hydroxyurea, red blood cell exchange transfusion, ursodeoxycholic acid, voxelotor, l-glutamine and crizanlizumab have been reviewed to investigate the role of these options in treating SCH. The role of liver transplant, haematopoietic stem cell transplant and gene therapy in SCH patients have been reviewed.

Neonatal and Obstetrical Outcomes of Pregnancies Complicated by Alloimmunization.

Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in ∼4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors. We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes. A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion. Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia.

Management of COVID-19 in a Sickle Cell Anaemia Patient: A Case Report

BACKGROUND: COVID-19 has had a significant impact on global healthcare systems, causing severe cases with acute respiratory distress syndrome, multi-organ failure, and death. Survivors of the virus may also experience long-term health problems. Sickle cell disease (SCD), an inherited red blood cell disorder, is characterized by chronic hemolytic anemia, vascular occlusion, and organ deterioration. SCD primarily affects African Americans, and common symptoms include acute and chronic pain, as well as severe conditions like acute chest syndrome and stroke. METHODS: We present the case of a 19-year-old female with sickle cell anemia who presented with symptoms of illness, jaundice, and no fever after receiving intravenous paracetamol. They were stable overall, with a Glasgow Coma Scale (GCS) score of 15/15 and no abnormal chest sounds. The patient had red, soft stools for two days and reduced bowel movements. Bowel sounds were normal, and they had sufficient urine output but experienced lower limb edema without joint swelling. Blood pressure was 107/62 mm Hg, mean arterial pressure was 72 mm Hg, pulse rate was 104 beats per minute, respiratory rate was 21 breaths per minute, and random blood glucose level was 102.5 mg/dL. The patient tested positive for COVID-19 via Polymerase Chain Reaction (PCR) testing. Laboratory results revealed low hemoglobin (6.8 g/dL), red blood cell count (2.16 x 10^6/micL), and high white blood cell count (22.4 x 10^3/micL) with 75.4% neutrophils. Hematocrit was 18.5%, mean corpuscular volume (MCV) was 85.7 pictogram/cell, mean corpuscular hemoglobin (MCH) was 31.4, mean corpuscular hemoglobin concentration (MCHC) was 36.7 g/dL, and platelet count was 215/micL. Other laboratory findings included urea (8 mg/dL), total protein (6.8 g/L), total bilirubin (2.15 mg/dL), direct bilirubin (0.98 mg/dL), aspartate aminotransferase (AST) (107 IU/L), alanine aminotransferase (ALT) (30 IU/L), alkaline phosphatase (ALP) (178 IU/L), and C-reactive protein (CRP) (48 mg/L). The patient's management plan involved intravenous dextrose and sodium chloride infusion, ceftriaxone (Samixon®), warfarin as needed, paracetamol as needed, folic acid once daily, vitamin C and zinc supplementation, levofloxacin once daily, Enema (Enemax) as needed, Pantoprazole (pantodac) (40 mg), nebulized hypertonic saline solution three times daily, diclofenac sodium (vortex) (75 mg) twice daily, and rivaroxaban (15 mg) twice daily. The patient received two blood transfusions during their hospital stay, with the first occurring on the first day of admission. CONCLUSION: Sickle cell anemia patients are at a higher risk of severe COVID-19 infection and associated complications. Early detection and treatment of complications are crucial. Blood transfusion, particularly red blood cell exchange transfusion, may be beneficial in managing these patients, reducing respiratory distress and the need for intensive care. However, more research is needed to establish optimal management strategies. This case report provides valuable insights into the presentation and management of sickle cell anemia patients with COVID-19. Clinicians should consider the examination findings and laboratory investigations for diagnosis and management. Limitations of this report include the lack of baseline information and long-term follow-up data, emphasizing the need for further research to generalize the findings.

Acute Chest Syndrome at the Emory University Georgia Comprehensive Sickle Cell Center at Grady Health System

Background: Individuals who have sickle cell disease (SCD) are susceptible to several severe consequences, such as vasoocclusive crisis (VOC), which may further develop into acute chest syndrome (ACS), a specific type of acute lung injury. Although VOC can result in substantial morbidity, it is important to note that ACS is the primary cause of mortality among individuals with SCD. Despite the devastating consequences of ACS, no interventions exist that directly treat this complication. Consequently, when patients present with ACS, their treatment options are frequently limited to supportive care. The absence of ideal therapeutic interventions for individuals with SCD who are experiencing ACS is a significant factor in their increased rates of illness and death. A cohort of adult patients diagnosed with ACS was examined with the objective to evaluate indicators of disease severity and identify risk factors associated with recurrent ACS. Methods: The Emory University Georgia Comprehensive Sickle Cell Center, located at Grady Health System, offers a dedicated acute care unit (ACU) that operates around the clock. This unit is specifically designed to assess and manage SCD patients who present with sickle cell crises. A pilot retrospective study was undertaken to analyze 25 patients with ACS. The evaluation included the examination of admission laboratory results, demographic information, past medical history, co-morbidity, interventions for each ACS admission for each patient (refer to Table 1). Descriptive statistics were used to report frequencies or median and range (Table 2). Patient characteristics of patients with 1 ACS event versus those with recurrent ACS (>=2) were compared using fishers exact test or the Wilcoxon-rank-sum test. Statistical significance was set at 0.05. Analysis was completed using SAS 9.4 (Cary, NC). Results: A total of 47 ACS episodes were detected in a cohort of 25 individuals, resulting in a median of 1 ACS event per patient (range of 1 to 6). A total of 85% of the patients included in this study had homozygosity for SCD, whereas 36% of the patients were receiving hydroxyurea treatment. Chronic pain was reported in three-fourth of the cohort. Out of all the ACS events observed, only 40% necessitated red cell exchange transfusion. A correlation between a minimum hemoglobin (Hb) level of 3.3 g/dL and lactate dehydrogenase (LDH) levels over 4000 U/L was noted during ACS admission. These findings indicate the presence of intravascular hemolysis. Three individuals died to ACS. Next, we conducted a comparison between a group of 10 patients who experienced recurring ACS events, with a minimum of 2 to a maximum of 6 occurrences, and another group of 15 patients who only had a single ACS episode. The group of patients with recurrent ACS exhibits a median of 5.5 episodes of VOC that necessitate visits to the acute care unit within the year prior. In contrast, the group with a single ACS episode has a median of 1 event. There was a notable disparity in the frequency of transfusions received by patients with recurrent ACS compared to those who experienced only a single episode over the past year. Although no other variable demonstrated statistical significance, the recurrent ACS group exhibited lower levels of hemoglobin and higher levels of LDH in comparison to the group with a single ACS episode. Further examination of our patients with SCD could provide valuable insights into the potential factors that may predict ACS episodes. These factors include a patient's genetic background, the frequency of VOC, the use of hydroxyurea, evidence of hemolysis, and previous blood transfusions. Furthermore, the utilization of acute care unit by patients with SCD has had a positive effect in our cohort, on the reduction of red cell exchange transfusions and mortality rates from ACS, possibly from early identification and episodic transfusion, in comparison to similar cohorts with ACS.

Clocking the Processes and Challenges of Urgent Red Blood Cell Exchange for Acute Complications of Sickle Cell Disease

Background: Red blood cell exchange transfusion (RBCX) is the therapy of choice for some acute complications of sickle cell disease (SCD), including stroke, severe acute chest syndrome and multi-organ failure. Rapid initiation of RBCX is critical to reduce morbidity and mortality in those with acute complications of SCD. A typical RBCX procedure requires anywhere from 6-10 units of packed red blood cells (RBC) and measures are taken to provide higher-fidelity RBC matches (key RHCE and KEL antigens at a minimum, ±suitable KIDD, FY, Ss profiles for the sensitized). Our recent review of urgent apheresis transfers to our tertiary-care centre, including 26 for RBCX, demonstrated that the median time per transfer was approximately 4 hours. Not yet characterized is the additional time required to start RBCX once a patient arrives. The time required to investigate antibody repertoires, and to procure sufficient quantities of blood that can bypass these specificities, is of interest in a specialty center with substantial but not unlimited investigative expertise and inventory. Methods: This was a retrospective database and chart review of all patients referred to our apheresis service for urgent RBCX for severe complications of SCD between Jan 1, 2013 to Dec 31, 2020. Time stamps for admission, blood bank, and apheresis processes were extracted from the electronic medical record and blood bank database. Categorical variables were analyzed using nonparametric tests. Results: Thirty-eight patients were included (65.8% males, 35.2% females) (Table 1). HbSS was the most common SCD genotype represented (81.6%). Most patients (71.1%) were transferred from another hospital, with the remaining patients arriving through the emergency department (26.3%) and one (2.6%) as a direct admission from clinic. ACS +/- additional complications constituted the most common indication for RBCX (78.9%). Two patients died due to complications of multi-organ failure, the remaining patients were discharged from hospital. Six patients (15.8%) had a positive antibody screen. The majority had RBC phenotype (42.1%) or genotype +/- phenotype (36.8%) on file to facilitate extended matching, and sufficient appropriate units were available in the blood bank in 82% of cases. Four (10.5%) patients required top-up transfusions prior to RBCX due to significant anemia. The median number of units issued per procedure was 9 (IQR 2). The median times from index group and screen (G&S) collection to sample accession, and from accession to result were 23 minutes (IQR 26) and 46 minutes (IQR 31), respectively (Figure 1). The median time from G&S result to RBC units issued was 348.5 minutes (IQR 479). The median total time from patient admission (or determination of RBCX indication) to RBC units issued was 569 minutes (IQR 464). A positive antibody screen, patient origin (ED vs. transfer), and the availability of sufficient RBC units in house were associated with turnaround time from accession of the index G&S sample to the issuing of RBCs (p<0.01 for all). Patients having antibodies to high prevalence antigens (e.g. anti-U) or to multiple targets (demanding unique donor profiles) had some of the longest times to initiate treatment. These constraints necessitated orders and coordinated deliveries of units from across the geographic network of the national blood provider.Discussion: These data from the largest apheresis unit in the country characterize the time invested in blood preparation for an urgent RBCX for acute SCD complications. A positive antibody screen is predictive of increased time to procedure start, reflecting delays inherent to serologic investigations, product sourcing, and serologic crossmatch times. While the precise moment of a blood request was available for a minority of patients, the G&S time stamp was used as a surrogate, thus potentially overestimating turnaround times in the blood bank. Nevertheless, the serologic demands inherent to a case present a tension between speed (treating the disease) and safety (averting immune rejection reactions).

A Fatal Case of Hemophagocytic Lymphohistiocytosis Triggered By Babesiosis

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare condition characterized by hyperactivation of macrophages and T lymphocytes. While HLH is primarily inherited in a recessive manner among children, in adults, it is more commonly associated with underlying infections, autoimmune disorders, and malignancies. However, the association between HLH and Babesia infection remains exceptionally uncommon, with only a few reported cases in the medical literature. In this report, we present a unique case of HLH in the context of babesiosis, shedding light on the crucial clinical features and risk factors. By raising awareness of this rare differential diagnosis, we aim to contribute to early recognition and timely treatment, potentially reducing mortality from this treatable illness. Case Presentation: A 77-year-old male with history of deep vein thrombosis (DVT), Parkinson's disease, and lumbar radiculopathy on chronic prednisone, presented for progressive generalized weakness, leg pain, and confusion. Initial labs showed normocytic anemia, thrombocytopenia, low fibrinogen and elevated INR and liver enzymes (Table 1). Multiple ischemic signs were noted including acute on chronic DVT, as well as findings of marked splenomegaly with wedge infarcts and periportal lymphadenopathy on abdominal ultrasound and CT (Figure 1). The underlying etiology of these findings was unclear and broad differential work up was pursued. Given the anemia and thrombocytopenia on presentation, the patient received multiple blood products including platelets, red blood cells, fresh frozen plasma and cryoprecipitate, in addition to vitamin K. No schistocytes were seen peripherally, and DIC/TTP workup was negative. Multidisciplinary teams evaluated the risk versus benefit of anticoagulation with heparin drip considering evidence of multi-organ ischemic damage. It was briefly initiated, but later held due to persistent thrombocytopenia and abnormal liver function. Further work up only revealed hemolysis with a low haptoglobin and elevated LDH (Table 1). However, the follow up Coombs test was negative, ruling out immune mediated hemolysis. While symptomatic management continued, blood parasite screen obtained on admission indicated Babesia microti infection. Upon repeat testing, no evidence of babesia was identified on labs or blood smear. However, this finding was skewed by the multiple transfusions the patient received. Unfortunately, the clinical course rapidly declined, and the patient's family elected a transition to comfort care measures whereby the patient expired within two days of presentation. Remaining work up resulted posthumously, with CD25 levels elevated at 38,354.0 pg/mL. Coupled with the previously established splenomegaly, pancytopenia, hypertriglyceridemia, and elevated ferritin, these findings indicate a diagnosis of HLH, likely triggered by Babesia microti infection. Conclusion: HLH should be strongly suspected in patients from endemic regions, especially with additional risk factors such as age, genetics, and immunosuppression. Tools such as the HScore and the HLH-2004 criteria can aid in further patient risk stratification. Urgent treatment with steroids and addressing underlying babesiosis with atovaquone, azithromycin, and potentially red blood cell exchange transfusion, remains crucial for preventing decompensation and improving outcomes.

A retrospective study for association between post-transfusion hemoglobin S level and pre-transfusion hemoglobin S level at the next scheduled transfusion.

Patients with sickle cell disease (SCD) frequently undergo prophylactic red blood cell (RBC) exchange transfusion and simple transfusion (RCE/T) to prevent complications of disease, such as stroke. These treatment procedures are performed with a target hemoglobin S (HbS) of ≤30%, or a goal of maintaining an HbS level of <30% immediately prior to the next transfusion. However, there is a lack of evidence-based instructions for how to perform RCE/T in a way that will result in an HbS value <30% between treatments. To determine whether targets for post-treatment HbS (post-HbS) or post-treatment HCT (post-HCT) can help to maintain an HbS <30% or <40% between treatments. We performed a retrospective study of patients with SCD treated with RCE/T at Montefiore Medical Center from June 2014 to June 2016. The analysis included patients of all ages, and data including 3 documented parameters for each RCE/T event: post-HbS, post-HCT, and follow-up HbS (F/u-HbS), which is the pre-treatment HbS prior to the next RCE/T. Generalized linear mixed model was used for estimating the association between post-HbS or post-HCT levels and F/u-HbS <30%. Based on our results, targeting post-HbS ≤10% was associated with higher odds of having events of F/u-HbS <30% between monthly treatments. Targeting post-HbS ≤15% was associated with higher odds of events of F/u-HbS < 40%. As compared to post-HCT ≤30%, a post-HCT >30%-36% did not contribute to more F/u-HbS <30% or HbS <40% events. For patients with SCD undergoing regular RCE/T for stroke prevention, a post-HbS ≤10% can be used as a goal to help maintain an HbS <30% for 1 month, and a post-HbS ≤15% allowed patients to maintain HbS <40%.

5612994 A ONE-YEAR AUDIT OF PREGNANCY MANAGEMENT AND OUTCOMES IN WOMEN WITH SICKLE DISORDERS AT A SINGLE UK CENTRE

Background: Women with sickle cell disorders (SCD) have increased morbidity and mortality in pregnancy due to increased sickle and pregnancy-related complications and require multidisciplinary team management, including obstetrician and midwife with experience of high-risk antenatal care and haematologist with links to a Specialized Hemoglobinopathy Team1. About 15,000 individuals live with SCD in the UK, with 110-200 pregnancies per annum1. Aims: To determine whether King’s College Hospital followed recently published British Society of Haematology (BSH) guidelines for the management of pregnancy in SCD. Pilot a proposed BSH audit proforma and assess mode of delivery, neonatal birth weight and special care baby unit (SCBU) requirements for this cohort. Methods: Pregnancy management and outcomes were audited using a proforma based on recent BSH guidelines (Appendix 1). Review of electronic patient records (EPR) for all women attending joint obstetric hemoglobinopathy clinics with SCD who completed a pregnancy between 01/10/20 and 01/10/21, including miscarriage and termination of pregnancy (TOP). Results: 23 pregnancies resulted in 19 live births (one twin pregnancy), 3 miscarriages (10/40 + 1, 10/40 + 1, 14/40 + 6); and 2 TOPs (10/40, 10/40). Maternal haemoglobin genotype was 74% HbSS, 23% HbSC, and 4% HbS other. The average maternal age at delivery (excluding miscarriage and TOP) was 33.6 years (24.8-40.8 years). Average gestational age at delivery (excluding miscarriage and TOP) was 37.9 weeks (32/40 + 1 to 40/40 + 1). 13 pregnancies were delivered by Caesarean section (9 emergency) and 5 by vaginal delivery (4 forceps). 14 women who had a live birth underwent transfusion during pregnancy, 1 was transfused postnatally and 3 were not transfused. Maternal complications were recorded in 94% pregnancies (excluding miscarriage and TOP). 47% of women had sickle vaso-occlusive crises, 56% had an infection, 17% had acute kidney injury and 6% required Intensive Therapy Unit care. Neonatal complications were recorded in four neonates. Three had intrauterine growth restriction, and were delivered at 32 + 1, 33 + 6 and 38 + 1 gestation respectively, with one requiring care in SCBU. One neonate had jaundice requiring five days of phototherapy. The average neonatal birth weight was 2770g (960-3715g) with a birthweight centile ranging from 0-0.4 to 75-91. Discussion: Audit barriers included an initial lack of access to information due to separate EPR system (BadgerNet) for maternal notes, rectified by collaboration with the obstetric team and access to BadgerNet. Summary/Conclusion: This pilot audit enabled assessment of collecting required data for a proposed BSH audit proforma; monitoring compliance with newly published BSH guidelines for management of pregnancy in SCD1; and provided insight into pregnancy outcomes in women with SCD who delivered within a 12-month period at a single large centre. The higher-than-expected transfusion rate during pregnancy was likely due to ongoing recruitment to the TAPS2 trial, with eligible women offered randomisation to usual practice or pre-emptive red cell exchange transfusion 6-10 weekly from 6-20 weeks gestation. A high proportion of live births were delivered by Caesarean section, reflecting a high proportion of multiparous women with previous Caesarean sections in this cohort. Although complication rates were high, most complications were relatively minor and non-life threatening. Keywords: Pregnancy, Sickle cell disease Reference 1. Oteng‐Ntim E et al. Br J Haematol 2021;194(6):980-995.

Red cell exchange transfusions increase cerebral capillary transit times and may alter oxygen extraction in sickle cell disease.

Persons with sickle cell disease (SCD) suffer from chronic hemolytic anemia, reduced blood oxygen content, and lifelong risk of silent and overt stroke. Major conventional stroke risk factors are absent in most individuals with SCD, yet nearly 50% have evidence of brain infarcts by the age of 30 years, indicating alternative etiologies for ischemia. We investigated whether radiological evidence of accelerated blood water transit through capillaries, visible on arterial spin labeling (ASL) magnetic resonance imaging, reduces following transfusion-induced increases in hemoglobin and relates to oxygen extraction fraction (OEF). Neurological evaluation along with anatomical and hemodynamic imaging with cerebral blood flow (CBF)-weighted pseudocontinuous ASL and OEF imaging with T2 -relaxation-under-spin-tagging were applied in sequence before and after blood transfusion therapy (n = 32) and in a comparator cohort of nontransfused SCD participants on hydroxyurea therapy scanned at two time points to assess stability without interim intervention (n = 13). OEF was calculated separately using models derived from human hemoglobin-F, hemoglobin-A, and hemoglobin-S. Gray matter CBF and dural sinus signal, indicative of rapid blood transit, were evaluated at each time point and compared with OEF using paired statistical tests (significance: two-sided p < 0.05). No significant change in sinus signal was observed in nontransfused participants (p = 0.650), but a reduction was observed in transfused participants (p = 0.034), consistent with slower red cell transit following transfusion. The dural sinus signal intensity was inversely associated with OEF pretransfusion (p = 0.011), but not posttransfusion. Study findings suggest that transfusion-induced increases in total hemoglobin may lengthen blood transit times through cerebral capillaries and alter cerebral OEF in SCD.

Fat Embolization Syndrome Secondary to Steroid Treatment for Intractable Migraine

Sickle vaso-occlusive crises secondary to steroid therapy are well reported in the medical literature. Fat embolization syndrome (FES) is an uncommon yet serious complication that occurs due to bone marrow necrosis and is usually associated with increased mortality or damaging neurologic sequelae to the surviving patient. We report a case of FES secondary to steroid therapy administered for an unrelated condition. Our patient was initially admitted for intractable migraine. The initial work up for other intracranial emergencies was negative and she was administered steroids for intractable migraine. Within 24 hours of initiating steroid therapy, she developed pain in her neck and shoulders progressing to her chest and lower extremities. The initial signs of FES following steroid therapy in this patient included altered mental status and hypoxic respiratory failure. Cerebral imaging showed diffuse bilateral cerebral/cerebellar and brainstem micro-hemorrhages. Lung imaging showed bilateral diffuse lung infiltrates confirming acute chest syndrome. The patient was transferred to the intensive care unit for further management of her hypoxic respiratory failure secondary to acute chest syndrome (ACS). In addition to ACS, she had acute kidney and hepatocellular injury in keeping with multi-organ failure. Steroid therapy was discontinued and she was treated with red cell exchange transfusion for multi-organ failure. The patient had an almost complete resolution of multiple organ damage except for hypoesthesia of her lower jaw and lower lip- the "numb chin syndrome". This case report highlights the importance of recognizing potentially fatal multi-organ failure secondary to steroid therapy and for hematologists to consider concurrent red cell transfusions to attenuate the risk of such complications from steroid therapy.

Managing Kidney Disease in Patients with Sickle Cell Disease: A Quality Initiative at the Cleveland Clinic

Background Sickle cell disease (SCD) when complicated by sickle cell nephropathy and chronic kidney disease (CKD) is associated with high morbidity and mortality. Early intervention with appropriate specialist care and timely evaluation for transplant are essential to improve outcomes. There is considerable variability in the screening, diagnosis and management of renal complications in SCD. Current guidelines from the NHLBI (2014), ASH (2019) and expert opinion endorse (1) annual screening for proteinuria, (2) the initiation of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) in patients with significant proteinuria, (3) early involvement of nephrology for declining renal function, (4) testing for alternative etiologies of kidney disease, (5) referral for renal transplant in advanced CKD with regular red cell exchange in those being considered for transplant, and (6) combination therapy with hydroxyurea and erythropoiesis-stimulating agents (ESA) for patients with worsening anemia from CKD. We sought to audit our care of SCD patients along these metrics to devise effective interventions to improve outcomes in SCD patients with comorbid kidney disease. Methods We conducted a retrospective quality review of renal disease screening, referral, and management in adults with SCD who were seen in the outpatient setting at the Cleveland Clinic in the past 3 years. Results We reviewed 258 adults with SCD who were seen between July 2019 and July 2022. Of these, 16 patients had insufficient laboratory data and were excluded from further analysis. Our final cohort of 242 patients was comprised of 169 (70%) female patients and the median age was 42 (18-90) years. The majority [213 (88%)] had appropriate screening for proteinuria. Of 46 patients with significant proteinuria, 18 (39%) were on ACEi/ARB in part reflecting challenges with tolerance (hyperkalemia, cough, hypotension). CKD was present in 43 (18%) patients; 25 (58%) had CKD stage 3a, 5 (12%) stage 3b, 6 (14%) stage 4, and 7 (16%) were on dialysis. Nephrology was involved in 27 (63%) of those with CKD. Most [31 (72%)] were evaluated for other causes of CKD, however the extent of testing was inconsistent. Referral for renal transplant evaluation was made in 7 (16%) patients with CKD and approximately half [3 (43%)] of these patients were receiving regular red cell exchange transfusions. Only 2 (5%) patients received a kidney transplant. Of the subset of 13 patients with advanced CKD stages 4 or 5, 9 (69%) were receiving ESA and 3 (23%) were on combination hydroxyurea and ESA. In our larger cohort of 242, an additional 30 (12%) patients had isolated persistent microscopic hematuria and 44 (18%) patients demonstrated a trend of chronically rising creatinine within the laboratory normal range. Additional analysis is planned to evaluate screening and management in this at-risk cohort with more subtle presentation. Discussion The management of renal disease in SCD is complex and a paucity of data to support evidence-based guidelines presents a major challenge. We found that rates of screening for proteinuria and declining renal function in SCD patients were high, however the subsequent management was inconsistent. CKD in SCD is highly morbid, and patients with SCD continue to experience low rates of transplant evaluation and eligibility with devastating consequences. A root cause analysis, patient and provider education campaigns, and additional activities are planned to improve the management of kidney disease in patients with SCD.

BABESIA MICROTI INFECTION WITH LOW-GRADE PARASITEMIA CAUSING ARDS IN AN IMMUNOCOMPETENT PATIENT

BABESIA MICROTI INFECTION WITH LOW-GRADE PARASITEMIA CAUSING ARDS IN AN IMMUNOCOMPETENT PATIENT

Contribution of ADAMTS13‐independent VWF regulation in sickle cell disease

BackgroundVon Willebrand factor (VWF) is elevated in sickle cell disease (SCD) and contributes to vaso‐occlusion through its thrombogenic properties. VWF is regulated by ADAMTS13, a plasma protease that cleaves VWF into less bioactive multimers. Independent investigations have shown VWF to be elevated in SCD, whereas measurements of ADAMTS13 have been variable. ObjectivesWe assessed ADAMTS13 activity using multiple activity assays and measured levels of alternative VWF‐cleaving proteases in SCD. Methods/ PatientsPlasma samples were collected from adult patients with SCD (n = 20) at a single institution when presenting for routine red cell exchange transfusion therapy. ADAMTS13 activity was measured by FRETS‐VWF73, Technozym ADAMTS‐13 Activity ELISA kit and a full‐length VWF digestion reaction. Alternative VWF‐cleaving proteases were identified by ELISA. A cell culture model was used to study the impact of SCD stimuli on endothelial ADAMTS13 and alternative VWF‐cleaving proteases. ResultsADAMTS13 activity was found to be moderately deficient across the SCD cohort as assessed by activity assays using a VWF A2 domain peptide substrate. However, SCD plasma showed preserved ability to digest full‐length VWF, suggesting assay‐discrepant results. Neutrophil and endothelial‐derived proteases were found to be elevated in SCD plasma. Matrix metalloproteinase 9 specifically showed preferential cleavage of full‐length VWF. Upregulation of alternative VWF‐cleaving proteases occurred in endothelial cells exposed to SCD stimuli such as heme and hypoxia. ConclusionsThis is the first demonstration of accessory plasma enzymes contributing to the regulation of VWF in a specific disease state and may have implications for assessing the VWF/ADAMTS13 axis in other settings.

P-072: COST COMPARISON OF TRANSFUSION CHOICES IN OMAN FOR PATIENTS SUFFERING FROM SICKLE CELL DISEASE.

Purpose: The management of sickle cell disease (SCD) can be challenging, requiring different therapeutic approaches because SCD could induce multiple complications, precipitating multi-organ failure. Red blood cell (RBC) transfusion is well known as one of the disease-modifying therapies available for long-term management of this condition. It is supported by multiple randomised clinical trials for the prevention of disease complications such as stroke in adults and children with SCD. RBCs can be delivered via three methods: Simple transfusion(ST), manual exchange(ME) and automated red blood cell exchange(aRBCX). In a simple transfusion, patients receive additional units of blood. The purpose is to raise the haemoglobin (Hb) to a steady state and maintain the oxygen-carrying capacity of the blood. Manual exchange transfusion removes the patient’s sickle-shaped RBCs and replaces them with healthy ones — lowering the concentration of sickled cells without increasing blood viscosity. This is performed using repeated alternating isovolumetric phlebotomy and blood transfusion. Automated red blood cell exchange transfusion involves removing sickled RBCs from the patient and rapid replacement with healthy RBCs while maintaining isovolemia. An advantage of aRBCX is avoiding or minimising costly iron chelation therapy to treat iron overload. As Sickle Cell disease (SCD) management is a critical cost driver to health systems, this research intended to compare the cost-effectiveness of different transfusion modalities. We wanted to compare the following transfusion types: Automated red blood cell exchange (aRBCX), Top-up transfusion and Manual red blood cell exchange (mRBCX). More specifically, we wanted to perform this evaluation in Oman as 0.2% of the Omani population suffers from this disease, which is the most frequent genetic disorder with the highest incidence. Materials and methods: Variables that drive costs have been collected to populate a de Novo cost model. We collected data from the Royal Hospital and Sultan Qaboos University Hospital. The most significant cost drivers which we took into consideration were: disease incidence, cost blood transfusion, medical equipment, disposables, complications, chelation therapy, hospitalisation, lives lost. Results: Our results reflect a 5-year overview demonstrating the costs and benefits experienced by healthcare providers. When considering the cost of treatment, consequence, complications, lives lost, life years lost, aRBCX is dominant over the transfusion modalities. Yearly intervention cost per patient per year in Omani-Rial: [Top-up 1933.5;Manual 3101.5;aRBCX 5857.5].The yearly cost of treatment choice related cost per patient per year in Omani-Rial:[12128.88; 6233.41; 789.88].Cost of disease complications per patient per year in Omani-Rial:[12706;12864; 11346].Cost of lives lost per patient per year in Omani-Rial:[1315;1288;1102). The total yearly cost per patient per year in Omani-Rial is estimated:[28084;23487.5;19095] Conclusion: aRBCX is 47% more cost-effective when compared to Top-up transfusion. aRBCX is 23% more cost-effective when compared to mRBCX. aRBCX promotes reduction in overall resources, disease burden, bed retention and the need for chelation therapy when compared to top-up transfusion and manual exchange transfusion. Cost savings may lead to better adoption. We recommend researchers rerun these calculations on an individual hospital basis.The authors do not declare any conflict of interest

Comparative evaluation of efficacy and safety of automated versus manual red cell exchange in sickle cell disease: A systematic review and meta-analysis.

Exchange transfusion is a valuable treatment option in sickle cell disease (SCD) and is preferred over simple transfusion as it removes abnormal haemoglobin S (HbS) levels and reduces complications. This meta-analysis aims to evaluate the efficacy and safety profile of automated red cell exchange (aRBX) procedure over manual red cell exchange transfusion (MET) in SCD patients. A standard meta-analysis protocol was developed, and after performing a comprehensive literature search in PubMed/MEDLINE, Cochrane and International Clinical Trial Registry Platform (ICTRP), reviewers assessed eligibility and extracted data from nine relevant studies. A random effects model was used to estimate the pooled effect size calculated from the mean difference in HbS percentage, serum ferritin level and risk ratio for the adverse events. Quality assessment was done using the risk-of-bias assessment tool, and a summary of observations was prepared using standard Cochrane methodology with GradePro GDT. The random-model analysis revealed a mean difference of 4.10 (95% CI: -3.29-11.49;Z= 1.09;p= 0.28) for HbS percentage, mean difference of 435.29 (95% CI: -73.74-944.32;Z= 1.68;p= 0.09) for serum ferritin and pooled risk ratio of 1.35 (95% CI: 0.63-2.87; Z=0.77;p= 0.44) for adverse events. This meta-analysis did not reveal any significant benefit of aRBX in reducing HbS percentage and attenuating the serum ferritin level when compared with MET. There was also no significant increased risk of adverse events detected in association with aRBX.

Comparative study between chronic automated red blood cell exchange and manual exchange transfusion in patients with sickle cell disease: A single center experience from Saudi Arabia.

Red cell transfusion remains the gold standard in managing sickle cell disease (SCD) with severe complications. Offering red blood cell exchange (RBCX) either manual exchange transfusion (MET) or automated RBCX (aRBCX) can reduce the complications of chronic transfusion and maintain target Hb thresholds. This study audits the hospital experience of overseeing adult SCD patients treated with RBCX, both automated and manual, and compares the safety and efficacy. This retrospective observational study was conducted as an audit for chronic RBCX for adult patients with SCD in 2015-2019 at King Saud University Medical City, Riyadh, Saudi Arabia. A total of 344 RBCX for 20 adult SCD patients who were enrolled in regular RBCX, (11/20) patients had regular aRBCX with a total of (157) sessions, and (9/20) patients had MET with a total of (187) sessions. The median level of HbS% post-aRBCX was significantly lower than MET (24.5.9% vs. 47.3%, P < 0.010). Patients on aRBCX had fewer sessions (5 vs. 7.5, P < 0.067) with better disease control. Although the median yearly pRBC units per patient for aRBCX was more than the double needed for MET (28.64 vs. 13.39, P < 0.010), the median ferritin level was 42 μg/L in aRBCX versus 983.7 μg/L in MET, P < 0.012. Compared to MET, aRBCX was more effective in reducing HbS, with fewer hospital visits and better disease control. Although more pRBCs were transfused, the ferritin level was better controlled in the aRBCX group without increasing alloimmunization risk.

Combined preoperative plasma exchange and red blood cell exchange transfusion in a renal transplant patient with protein S deficiency and hemoglobin SC disease

BackgroundProtein S deficiency is associated with increased risk of venous thromboembolism, complicating the perioperative management of such patients. We present a patient with sickle cell disease (Hb SC genotype) and inherited protein S deficiency who underwent a living-donor renal transplant. To minimize thrombotic risk and sickle cell complications, both plasma exchange and red blood cell (RBC) exchange transfusion were performed pre-operatively. Methods and materialsPlasma exchange was utilized to increase protein S levels and to reduce the risk of post-operative venous thromboembolism, including allograft thrombosis, while RBC exchange was performed to reduce the risk of acute post-operative sickle cell disease complications. ResultsWith the use of combined pre-operative plasma exchange and RBC exchange transfusion, this patient with protein S deficiency and Hb SC underwent a successful renal transplant without acute sickle cell complications or thrombotic complications. ConclusionsThis case demonstrates the potential use of pre-operative plasma exchange in patients with protein S deficiency undergoing high thrombotic risk procedures.

Five-Year Outcomes of Chronic Red Blood Cell Exchange Transfusion Program for Patients with Sickle Cell Disease, the Experience of University of Nebraska Medical Center

▪Background:Red blood cell exchange (RBCX) is an effective therapy in treatment of acute and chronic complications of sickle cell disease (SCD). It involves exchanging patient's red blood cells (RBCs) with donor RBCs to significantly lower hemoglobin S concentration without subjecting the patient to the risk of iron overload. The University of Nebraska Medical Center (UNMC) established a chronic RBCX program in November 2015, which cared for patients with multiple hemoglobinopathies. In this study, we aim to evaluate some of the outcomes of patients with SCD who joined the program.Methods:This is a retrospective study based on review of medical records of patients with sickle cell disease. We reviewed the health records of patients with SCD who were enrolled in the chronic RBCX program between 11/2015-8/2020 at UNMC. We included patients with SCD, regardless of age, who underwent RBCX in the outpatient setting during the study period. Data were collected to assess if RBCX influenced the frequency of SCD crisis, emergency room visits, hospitalizations, and other sickle cell-related complications.Results:A total of 404 sessions of exchange transfusions were performed between November 2015 and August 2020 for 21 patients with SCD. The study included 9 adults (age ≥ 18 years) and 12 children with a median age of 12 years (2-31 years). During the study period, 3 adults left the program due to relocation out of state, patient's preference, or physician's decision. Table 1 summarizes the population demographic. The most common indication for enrollment in the RBCX program was recurrent sickle cell crisis (Figure 1). The mean number of emergency room visits before enrollment in the RBCX program was 22.5 visits (2-62 visits), which reduced after enrollment to 10.4 visits (0-65 visits), with a difference in mean of 12.1 visits (P=0.0021). The mean number of hospital admissions before enrollment in the RBCX program was 13.2 admissions(0-54 admissions), which also reduced to 6.7 admissions (0-50 admissions), with a significant difference in the means equal to 6. 6 admissions (P=0.0013) (Figure 2). Thirteen patients had a baseline ferritin > 500 ng/ml at enrollment; all of them had a decrease in their baseline ferritin during the study, with 4 of them achieving a new baseline < 500 ng/ml. Six patients had pre-existing antibodies at enrollment due to prior alloimmunization; however, no new alloantibodies were noticed after enrollment. The patients without preexisting antibodies were transfused with Rh and Kell matched blood. The patients with pre-existing antibodies were transfused with phenotypically matched blood. Three patients became pregnant during the study period, and their pregnancies were uncomplicated except for one patient with preeclampsia resulting in early delivery. There was no reportable death, acute chest syndrome, or stroke among the patients during the study period.ConclusionOutpatient chronic RBCX demonstrated safety and feasibility in both adults and children. It also showed promising outcomes in terms of reduction of sickle cell complications, number of emergency room visits and hospitalizations. These results can provide the basis for evaluating RBCX in a prospective study to better understand changes in quality of life and clinical outcomes of patients with SCD and limited therapeutic options. [Display omitted] DisclosuresGundabolu: Pfizer: Research Funding; Samus Therapeutics: Research Funding; BioMarin Pharmaceuticals: Consultancy; Bristol-Myers Squibb Company: Consultancy; Blueprint Medicines: Consultancy.

Non-crisis related pain occurs in adult patients with sickle cell disease despite chronic red blood cell exchange transfusion therapy

BackgroundChronic red blood cell transfusions reduce acute care utilization for sickle cell disease (SCD) pain. However, little is known about whether chronic transfusions treat or prevent the development of non-crisis pain. We investigated patient-report of pain in adults with SCD receiving chronic exchange transfusions (CET) compared to adults not on CET with similar disease characteristics. Study Method and DesignEleven participants receiving chronic exchange transfusion (CET) for at least one year were compared to 33 participants not receiving CET. Participants completed validated patient-reported outcomes regarding pain impact and quality of life at regularly scheduled visits or before CET. One year of health care utilization and opioid prescriptions were examined. ResultsAfter 1:1 propensity matching was performed for age, genotype, WBC and neutrophil counts, patients on CET had lower Pain Impact scores (-5.1, p = 0.03) and higher Neuropathic (7.4, p < 0.001) and Nociceptive Pain Quality (3.7, p < 0.001) scores, all indicating worse pain. However, CET was associated with a reduction in annual all cause admissions (-3.1, p < 0.001), length of stay (-2.1 days, p < 0.001) and ED visits (-2.7, p < 0.001). CET was not associated with differences in opioids dispensed. ConclusionsAfter adjusting for disease characteristics, CET was associated with worse pain impact and neuropathic and nociceptive pain quality, lower health care utilization and with similar levels of opioids dispensed. This data suggest that CET may reduce hospitalizations for acute pain but may not adequately treat nociceptive or neuropathic pain in SCD.

EARLY IDENTIFICATION FOR PREVENTING SEVERE BABESIA PARASITEMIA AND ARDS IN A POST-SPLENECTOMY PATIENT

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Babesiosis is an emerging health risk and a nationally notifiable disease in the United States.1 It can present as shock and multi-organ dysfunction in immunocompromised host. As babesiosis prophylaxis in patients with splenectomy is not common, it should be considered in post-splenectomy sepsis syndrome.1 This case describes a post-splenectomy patient with severe babesiosis presenting with refractory Acute Respiratory Distress Syndrome (ARDS). CASE PRESENTATION: 59-year-old man presented to emergency department with 2 weeks of worsening generalized weakness, fever, and headaches, not getting better on oral antibiotics prescribed outpatient. His Computed Tomography (CT) head, lumbar puncture was normal. He developed severe respiratory distress and was emergently intubated. Chest imaging revealed bilateral pulmonary infiltrates. Arterial blood gas analysis confirmed severe ARDS with a PaO2/FiO2 (P/F) ratio <100. The patient was managed with lung protective ventilation and prone positioning. Peripheral smear revealed intraerythrocytic ring inclusions consistent with Babesia microti trophozoites (Figure1). Testing for other bacterial infections, viral pathogens, and tick-borne illnesses were negative. Labs were significant for hemoglobin (Hb) 10.8 g/dl, platelet count 170 K/uL, haptoglobin <10 mg/dl, lactate dehydrogenase 373 U/L, aspartate aminotransferase 68 U/L and alanine aminotransferase 71 U/L. He was treated with atovaquone and azithromycin. Doxycycline was initiated for possible co-infection with other tick-borne illnesses. The patient also had red cell exchange transfusion given his critical condition and history of splenectomy. He was evaluated for Veno-venous extracorporeal membrane oxygenation (ECMO), but cannulation was deferred due to initial improvement with prone positioning. Though there was initial improvement, his hemodynamic status continued to decline requiring initiation of vasopressor support and was transitioned to comfort care after prolonged intubation with goals of care discussions with family. DISCUSSION: Early recognition and diagnosis of babesia, especially in patients with asplenia, is imperative as babesiosis can progress to refractory ARDS, shock and multi-organ dysfunction. Clinicians should have a high index of suspicion for a patient living in an endemic area who presents with unexplained nonspecific symptoms and laboratory findings including thrombocytopenia, hemolytic anemia, and/or elevation of liver enzymes. If clinical suspicion is high, sever real-time PCR assays are useful to detect low-grade parasitemia and are more sensitive than blood smears.2 Prone positioning has been shown to improve outcomes with ARDS if used early and for longer sessions and may help patients avoid need for ECMO.3 CONCLUSIONS: Our case reveals the importance of early recognition of babesiosis in immunocompromised patients living in endemic areas for preventing refractory ARDS. REFERENCE #1: Rosner F, Zarrabi MH, Benach JL, Habicht GS. Babesiosis in splenectomized adults: review of 22 reported cases. The American journal of medicine. 1984 Apr 1;76(4):696-701. REFERENCE #2: Sanchez E, Vannier E, Wormser GP, Hu LT. Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: a review. Jama. 2016 Apr 26;315(16):1767-77. REFERENCE #3: Guérin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, Clavel M. Prone positioning in severe acute respiratory distress syndrome. New England Journal of Medicine. 2013 Jun 6;368(23):2159-68. DISCLOSURES: No relevant relationships by Kinjal Banerjee, source=Web Response No relevant relationships by Taesung Kwon, source=Web Response No relevant relationships by Thomas Lettich, source=Web Response No relevant relationships by Sanjeev Shrestha, source=Web Response No relevant relationships by Cynthia Tsai, source=Web Response