Total Red Blood Cell Transfusion Research Articles

Paediatric clinical decision support: Evaluation of a best practice alert for red blood cell transfusion.

Providing red blood cell (RBC) transfusion to paediatric patients with a haemoglobin (Hb) level of <7 g/dL is the current best practice, but it is often difficult to ensure appropriateness of RBC transfusion on a health system level. Electronic health record (EHR) clinical decision support systems have been shown to be effective in encouraging providers to transfuse at appropriate Hb thresholds. We present our experience with an interruptive best practice alert (BPA) at a paediatric healthcare system. An interruptive BPA requiring physician response was implemented in our EHR (Epic Systems Corp., Verona, WI, USA) in 2018 based on Hb thresholds for inpatients. The threshold was initially <8 g/dL and later changed to <7 g/dL in 2019. We assessed total activations, number of RBC transfusions and hospital metrics through 2022 compared to the 2 years prior to implementation. The BPA activated 6956 times over 4 years, slightly less than 5/day, and the success rate, with no RBC transfusions within 24 h of order attempt, was 14.5% (1012/6956). There was a downward trend in the number of total RBC transfusions and RBC transfusions per admission after implementation, non-significant (p = 0.41 and p = >0.99). The annual case mix index was similar over the years evaluated. The estimated cost savings based on acquisition costs for RBC units were 213,822 USD or about $51,891 per year. BPA implementation led to sustained change in RBC transfusion towards best practice, and there were long-term savings in RBC expenditure.

Contribution of Salvaged Blood Red Blood Cell Transfusion During Living Donor Liver Transplantation.

Transfusion of allogeneic blood products can have adverse effects and profoundly influence postoperative liver transplantation outcomes, including graft survival. To minimize allogeneic red blood cell (RBC) transfusion, salvaged blood can be used during liver transplantation. The aim of this study was to determine the contribution of salvaged blood to allogeneic RBC transfusion in living donor liver transplantation (LDLT) recipients. Data of 311 adult-to-adult LDLT recipients between January 2015 and April 2019 were analyzed. The primary outcome was a change in requirement for allogeneic RBCs due to the use of salvaged blood. Additionally, predictors of intraoperative allogeneic RBC transfusion were investigated. One hundred fifty-three (49.2%) recipients required allogeneic RBC transfusion. If recipients did not receive salvaged blood, 253 (81.4%) recipients would have needed allogeneic RBC transfusion. The total volume of salvaged blood transfused into recipients during surgery was 269,165mL, which corresponded to 993 units of allogeneic RBCs and accounted for 76.1% of total RBC transfusion volume. Multivariate analysis showed that male recipients, model for end-stage liver disease score, preoperative hemoglobin level, and volume of salvaged blood used during surgery were independent predictors of the need for intraoperative allogenic RBC transfusion. Intraoperative use of salvaged blood significantly reduced allogeneic RBC transfusion in LDLT recipients. It can help transplant teams manage transfusion of allogeneic RBCs during liver transplantation.

Impact of red blood cell transfusions on intestinal barrier function in preterm infants.

To determine the relationships of red blood cell (RBC) transfusion and enteral feeding to changes in intestinal permeability (IP) measured by the relative intestinal uptake of lactulose (La) and rhamnose (Rh) in preterm infants <33 wk gestation. Infants 240-326wk gestation received La/Rh solution enterally on study days 1, 8 and 15.Urinary La/Rh ratio was measured by HPLC. Hematocrit preceding transfusion, total RBC transfusion volume, volume/kg, and feeding status during each study interval (birth-d1; d1-d8, and d8-d15) were determined. Of the seventeen (40.5%) subjects who received≥1 transfusion during the study period, 12 (70.6%) infants were <28 wk gestation and 5 (29.4%) infants were≥28 wk gestation, p < 0.0001. Lower pre-transfusion hematocrit was observed in intervals preceding high IP (La/Rh > 0.05) than in intervals preceding low IP (La/Rh≤0.05) measurements (33 vs 35.8, p = 0.1051). RBC transfusions occurred more frequently in intervals preceding high IP than in intervals preceding low IP (26.8%; vs 8.3%, p = 0.0275) with 5-fold higher total RBC volume and volume/kg in intervals preceding any time point with high IP. RBC transfusion during an interval was associated with a three-fold increased risk of high IP (aOR 2.7; 95% C.I 0.564-12.814; p = 0.2143). Exclusive breast milk exposure and post-menstrual age reduced the risk for high IP following RBC transfusion. Both RBC transfusion number and volume was associated with subsequent high IP measurements in preterm infants <33 weeks gestation and potentially may contribute to impairment of the preterm intestinal barrier.

Impact of Real-Time Clinical Decision Support on Blood Utilization and Outcomes in Hospitalized Patients with Solid Tumor Cancer

Patients with cancer are frequently hospitalized, and anemia is a common complication of cancer care. Transfusion is often required and commonly occurs above guideline-supported thresholds. It was hypothesized that an educational intervention, combined with real-time clinical decision support (CDS), would reduce blood utilization among hospitalized solid tumor cancer patients without adversely affecting outcomes. A retrospective, historical control analysis was conducted comparing transfusion utilization among hospitalized solid tumor cancer patients before and after implementation of the educational intervention and CDS. The primary outcome was receipt of red blood cell (RBC) transfusion. Secondary outcomes included total RBC transfusions per 100 inpatient-days, readmission, outpatient transfusion within seven days of discharge, inpatient mortality, and odds of transfer to the ICU. The odds of receiving a transfusion were significantly reduced in the postintervention cohort (odds ratio [OR] = 0.52, p = 0.005). Among patients receiving transfusion, there was no significant difference between groups in the number of RBC transfusions per 100 inpatient-days (incidence rate ratio = 0.87, p = 0.26). There were also no significant differences in readmission, outpatient transfusion within seven days of discharge, or inpatient mortality, though patients in the postintervention cohort had lower odds of ICU transfer (OR = 0.29, p = 0.04). The combined use of an educational intervention and CDS in a hospitalized solid tumor cancer patient population was associated with lower blood utilization, similar patient outcomes, and unchanged short-term outpatient transfusion requirements. Hospitals should consider similar interventions to work toward appropriate resource allocation and mitigation of transfusion-associated risk in this patient population.

Platelet transfusions improve hemostasis and survival in a substudy of the prospective, randomized PROPPR trial

AbstractTransfusing platelets during massive hemorrhage is debated because of a lack of high-quality evidence concerning outcomes in trauma patients. The objective of this study was to examine the effect of platelet transfusions on mortality in severely injured trauma patients. This work analyzed PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial patients who received only the first cooler of blood products, which either did or did not contain platelets. Primary outcomes were all-cause mortality at 24 hours and 30 days and hemostasis. Secondary outcomes included cause of death, complications, and hospital-, intensive care unit (ICU)–, and ventilator-free days. Continuous variables were compared using Wilcoxon rank sum tests. Categorical variables were compared using Fisher's exact tests. There were 261 PROPPR patients who achieved hemostasis or died before receiving a second cooler of blood products (137 received platelets and 124 did not). Patients who received platelets also received more total plasma (median, 3 vs 2 U; P < .05) by PROPPR intervention design. There were no differences in total red blood cell transfusions between groups. After controlling for plasma volume, patients who received platelets had significantly decreased 24-hour (5.8% vs 16.9%; P < .05) and 30-day mortality (9.5% vs 20.2%; P < .05). More patients in the platelet group achieved hemostasis (94.9% vs 73.4%; P < .01), and fewer died as a result of exsanguination (1.5% vs 12.9%; P < .01). Patients who received platelets had a shorter time on mechanical ventilation (P < .05); however, no differences in hospital- or ICU-free days were observed. In conclusion, early platelet administration is associated with improved hemostasis and reduced mortality in severely injured, bleeding patients. This trial was registered at www.clinicaltrials.gov as # NCT01545232.

A Randomized Controlled Trial of Low-Dose Tranexamic Acid versus Placebo to Reduce Red Blood Cell Transfusion During Complex Multilevel Spine Fusion Surgery.

Multilevel spine fusion surgery for adult deformity correction is associated with significant blood loss and coagulopathy. Tranexamic acid reduces blood loss in high-risk surgery, but the efficacy of a low-dose regimen is unknown. Sixty-one patients undergoing multilevel complex spinal fusion with and without osteotomies were randomly assigned to receive low-dose tranexamic acid (10 mg/kg loading dose, then 1 mg·kg-1·hr-1 throughout surgery) or placebo. The primary outcome was the total volume of red blood cells transfused intraoperatively. Thirty-one patients received tranexamic acid, and 30 patients received placebo. Patient demographics, risk of major transfusion, preoperative hemoglobin, and surgical risk of the 2 groups were similar. There was a significant decrease in total volume of red blood cells transfused (placebo group median 1460 mL vs. tranexamic acid group 1140 mL; median difference 463 mL, 95% confidence interval 15 to 914 mL, P= 0.034), with a decrease in cell saver transfusion (placebo group median 490 mL vs. tranexamic acid group 256 mL; median difference 166 mL, 95% confidence interval 0 to 368 mL, P= 0.042). The decrease in packed red blood cell transfusion did not reach statistical significance (placebo group median 1050 mL vs. tranexamic acid group 600 mL; median difference 300 mL, 95% confidence interval 0 to 600 mL, P= 0.097). Our results support the use of low-dose tranexamic acid during complex multilevel spine fusion surgery to decrease total red blood cell transfusion.

Imaging of Body Iron Stores in Transfusion-Dependent Patients By Liver Dual- Energy CT

[Background] Chronic red blood cell transfusions, leading to iron overload, cause hepatic, cardiac, and endocrine dysfunction. It is very important to monitor body iron stores and to start optimal iron chelation therapy. Serum ferritin, which is widely used as a surrogate marker of body iron stores, elevate under inflammation or liver injury. Therefore, reliable techniques to evaluate body iron stores are needed. The liver iron concentration (LIC) is thought to be an indicator of total body iron stores and measurement of the T2* value by MRI has been a standard noninvasive technique to evaluate LIC. It should be worthwhile using CT, which is lower cost and widely applied in clinical setting. Dual-energy CT (DECT) is a technique to obtain additional information regarding tissue composition compared with what single-energy CT can provide. This technique is based on the fact that substances show different densities by two different energies. However, the role of DECT in monitoring LIC remains to be clarified. We examined whether a DECT could be a new technique for the measurement of LIC.[Patients and Methods] Eight transfusion-dependent patients underwent DECT. Patient 1 was a 54-year-old male with MDS (RCMD-RS). He received 66 U red blood cell transfusions in our hospital, and depended on transfusion in another hospital, but the total doses were not available. Patient 2 was a 37-year-old male with AML in 2nd relapse. His total red blood cell transfusions were 54 U. Patient 3 was a 66-year-old female with AML with MRC in 1st CR. She received 37 U red blood cell transfusions in our hospital, and depended on transfusion in another hospital, but total doses were not available. Patient 4 was a 47-year-old female who had received renal transplantation for chronic renal failure. She received 12 U red blood cell transfusions in our hospital, and had a long history of transfusion dependence in another hospital, but total doses were not available. Patient 5 was a 57-year-old male with MDS (RCMD). His total red blood cell transfusions were 148 U, and he received iron chelation therapy. Patient 6 was a 65-year-old male with AML with MRC. His total red blood cell transfusions were 82 U, and he received iron chelation therapy. Patient 7 was a 47-year-old male with AML in 3rd CR. He received 28 U red blood cell transfusions in our hospital, and depended on transfusion in another hospital, but total doses were not available. Patient 8 was a 52-year-old female with AA. Her total blood cell transfusions were 92 U.[Results] All patients were examined for serum ferritin and patients 1, 3, 4, 6, 7, and 8 also underwent liver MRI. Serum ferritin levels of patients 1, 3, 4, 6, 7, and 8 were 961, 2168, 7875, 795, 1921, and 5104 ng/ml, respectively. These patients showed hypointensity on MRI T2*-weighted images, and also showed liver iron deposition by DECT. Serum ferritin of patient 5 was 4042 ng/ml, and he showed liver iron deposition by DECT. Serum ferritin of patient 2 was 6113 ng/ml, and he did not show liver iron deposition by DECT.[Conclusion] Our results suggest that liver DECT could visualize liver iron deposition of transfusion-dependent patients and could be a new technique for the measurement of LIC instead of MRI. DisclosuresNo relevant conflicts of interest to declare.

Correlation between red blood cell transfusion volume and mortality in patients with massive blood transfusion: A large multicenter retrospective study.

This study aimed to explore the correlation between red blood cell (RBC) transfusion volume and patient mortality in massive blood transfusion. A multicenter retrospective study was carried out on 1,601 surgical inpatients who received massive blood transfusion in 20 large comprehensive hospitals in China. According to RBC transfusion volume and duration, the patients were divided into groups as follows: 0–4, 5–9, 10–14, 15–19, 20–24, 25–29, 30–39 and ≥40 units within 24 or 72 h. Mortality in patients with different RBC transfusion volumes was analyzed. It was found that patient mortality increased with the increase in the volume of RBC transfusion when the total RBC transfusion volume was ≥10 units within 24 or 72 h. Survival analysis revealed significant differences in mortality according to the RBC transfusion volume (χ2=72.857, P<0.001). Logistic regression analysis revealed that RBC transfusion volume is an independent risk factor [odds ratio (OR) = 0.52; confidence interval (CI): 0.43–0.64; P<0.01] for the mortality of patients undergoing a massive blood transfusion. When RBCs were transfused at a volume of 5–9 units within 24 and 72 h, the mortality rate was the lowest, at 3.7 and 2.3% respectively. It is concluded that during massive blood transfusion in surgical inpatients, there is a correlation between RBC transfusion volume within 24 or 72 h and the mortality of the patients. Patient mortality increases with the increase in the volume of RBC transfusion. RBC transfusion volume, the length of stay at hospital and intensive care unit stay constitute the independent risk factors for patient mortality.

Improved Hospital-Wide RBC Utilization Via Clinical Decision Support Is Associated With Stable Or Improving Patient Outcomes

BackgroundWe analyzed hospital-wide red blood cell (RBC) utilization and indicators for clinical patient outcomes at Stanford Hospital and Clinics (SHC) after implementation of real-time clinical decision support (CDS) for RBC transfusions consisting of a best practice alert (BPA) within the computerized provider order entry (CPOE). Study DesignA clinical effectiveness team from key clinical services developed a consensus with a suggested transfusion threshold of hemoglobin (Hgb) 7 g/dl, or 8 g/dl for patients with acute coronary syndromes. Implemented in 7/2010, orders for RBC units triggered an interruptive BPA above a Hgb threshold of 7 g/dl for patients otherwise not excluded from the guidelines (according to their problem list: acute coronary syndrome, status post cardiothoracic procedure, hemorrhage, or hemodynamic instability). The BPA contained the consensus guidelines, link to relevant literature, and an “acknowledgement” reason if provider chose to continue transfusion. Trends in hospital-wide RBC utilization and clinical patient outcomes were analyzed for all in-patients discharged from January 2008 through December 2012. ResultsThe Figure shows impact on RBC utilization, before and after the BPA was implemented. RBC transfusions decreased substantially in the interval immediately after July 2010, and have continued to decrease thereafter. For 2012 compared to 2009, total RBC transfusions decreased by 24% (p < 0.05). This decrease in utilization has occurred despite concurrent increases in patient discharge volumes, case mix complexity, volumes of elective surgeries, and organ transplantation cases (Table). Additionally, patient clinical outcomes including mortality, length of stay, and 30 day readmission rates have declined or remained stable. For a subgroup of stable inpatients, the percentage of those receiving RBC transfusions when hemoglobin exceeded 8 g/dl, decreased from 57-66% preceding the CDS to 35% after (p=0.02); for the most recent interval, only 27% of RBC transfusions occurred outside guidelines. Comparing 2009 to 2012, total RBC transfusions decreased by 7,186 units, or 24%. Compared to purchase costs in 2009, for 2012 the estimated net savings (at $225/unit) in purchase costs was $1,616,850. Total net savings for 2010-2012 was $4,308,300. [Display omitted] [Display omitted] ConclusionWe have substantially decreased RBC transfusions through real-time CDS, despite increasing volumes of health care delivery (patient discharges, elective surgeries, organ transplantation) and increasing complexity of case mix index. Moreover, hospital-wide patient quality indicators have been stable (mortality, 30 day readmission rates) or are improving (length of stay). CDS can be very effective for healthcare institutions to improve quality of care by simultaneously decreasing patient exposure to unnecessary RBC transfusion and by decreasing RBC supply costs along with the substantial transfusion-related costs. Disclosures:No relevant conflicts of interest to declare.

Transfusion-Related Iron Overload: A Covert Risk Of Supportive Cancer Care

BackgroundChronic transfusion support plays a key role in survival and quality of life for patients with hematological disorders. However, transfusion-related iron overload (TRIO) is a significant cause of morbidity and mortality in these patients.Adequate iron overload (IO) screening and use of iron chelators, if necessary, is now standard practice in chronically transfused individuals such as hemoglobinopathy patients. Screening practices for IO for patients receiving multiple red blood cell (RBC) transfusions for other reasons (e.g. cancer) are unknown. ObjectiveThis two part study aimed to detect pediatric (Jaffer et al., 2012) and adult populations at risk for TRIO and to evaluate and compare current screening practices. MethodsChildren (≤ 18 years) and adults (> 18 years) receiving at least 1 RBC transfusion from January 1, 2008 to December 31, 2011 at a tertiary care academic institution were identified using a transfusion registry database. Only those receiving chronic RBC transfusions were included in the study. Chronic transfusion was defined as ≥20 units of RBC or ≥ 20 RBC transfusions dosed at 15ml/kg within 12 consecutive months where transfusions were not given in the setting of an operating room, trauma or surgical procedures, not given 7 days prior/post-surgical procedures and not all given in one day. An adjudicator resolved study inclusion ambiguity. The analysis excluded hemoglobinopathy patients.Medical records were reviewed to collect patient demographics, diagnosis, and to evaluate IO screening practices and frequency of iron chelation therapy. ResultsA total of 343 patients met the eligibility criteria: 27 pediatric and 316 adult patients, with mean ages of 8.1 years (SD 5.7) and 62 years (SD 12.6), respectively. Table 1 summarizes demographics, number of transfusions, and IO screening and results. Ferritin levels were checked for 12 (44%) pediatric and 227 (72%) adult patients: 2 (17%) pediatric and 30 (13%) adult patients had values<500 μg indicating no further TRIO screening was required. In the pediatric population, 81% had a cancer diagnosis, and just under a third were tested for ferritin, whereas 64% of the adults had cancer, with nearly two-thirds tested for ferritin. A statistically significant difference was observed in the percentage of pediatric and adult cancer patients screened for IO. Of those cancer patients screened, ferritin level > 500 occurred in 71% of pediatric and 85% of adult patients, with an iron chelator reported in 1 adult. Total RBC transfusions ranged from 20 to 44 with a median of 26.5 for pediatrics and 20 to 176 with a median of 31 for adults. ConclusionDespite high rates of RBC transfusion, screening for TRIO was inconsistent. Although information regarding reasons for not screening for TRIO or not treating with chelation therapy was not collected, the possibilities include a lack of awareness of the risk of TRIO and lack of access to ferriscan and/or to oral iron chelator in Canada for conditions other than hemoglobinopathy and a select subset of MDS cases. Considering TRIO presents an additional, yet unidentified, co-morbidity of cancer therapy and that the therapy (e.g. anthracyclines) may potentiate the end organ effect of TRIO, it is vital to develop strategies to evaluate cancer patients at risk for TRIO and ensure they have access to appropriate iron chelation therapy. Research is needed to explore the comorbidities associated with failure to treat TRIO and to identify barriers to treatment so cancer patients can receive optimal care. Disclosures:Leber:Novartis Canada: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Heddle:Canadian Blood Services and Health Canada: Research Funding.

Successful immunosuppressive and iron chelation therapy for a severe aplastic anemia patient undergoing hemodialysis due to chronic renal failure

Immunosuppressive treatment using antithymocytic globulin (ATG) is the treatment of choice for severe aplastic anemia patients [1, 2]. Iron chelation therapy is also effective for patients with frequent blood transfusions [3–5]. However, the effects of these treatments on hemodialysis patients have not been reported. Here, we present a case of severe aplastic anemia on hemodialysis, treated with immunosuppressive and iron chelation therapy. A 49-year-old male presented in December 2007 with fever and pancytopenia. He required regular hemodialysis following history of chronic renal failure 25 years earlier, and had also been treated with recombinant epoetin beta. Laboratory studies revealed a white blood cell count of 1.2 9 10/ll, neutrophil cell count of 468/ll, platelet count of 0.9 9 10/ll, hemoglobin concentration of 5.4 g/dl, and reticulocytes at only 0.9 9 10/ll. Bone marrow biopsy revealed severe hypoplasia. He was diagnosed with severe aplastic anemia, and required frequent transfusions of PC and RBC to maintain a 2 9 10/ll platelet level and 8.0 g/dl hemoglobin concentration. He was given the antibiotic, meropenem, for febrile neutropenia, which rapidly controlled his fever. The same drug, epoetin beta, was continued for treatment. Cyclosporin A and granulocyte colony-stimulating factor (G-CSF) were given as the first therapy for severe aplastic anemia, but his bone marrow remained hypoplastic. Horse ATG was added at a dose of 15 mg/kg for 5 days. Methylprednisolone was used at a dose of 2 mg/kg/day for 5 days, and then tapered off. The only adverse event was a grade 2 allergic reaction. His hematopoietic system recovered slightly, and G-CSF was lowered, but transfusion frequency could not be reduced. An anabolic steroid was added, but yielded no improvement. Then, 8 months after the first ATG, a second rabbit ATG was given at a dose of 5 mg/kg for 5 days. Methylprednisolone was given concomitantly, and no significant adverse event was seen, except an acute allergic reaction. Total red-blood cell transfusion volume was over 80 Japanese units, so deferasirox was given. Bone marrow biopsy revealed a moderate number of positive granules on iron staining, which were not observed at the initial examination. The initial dose was 10 mg/kg/day, due to renal failure, but the serum ferritin level remained above 3000 ng/ml. The dose was increased to 20 mg/kg/day. Six months later, the serum ferritin level was below 1000 ng/ml. Transfusion frequency was reduced. One year later after the second ATG therapy, he became transfusionfree (Fig. 1). Bone marrow biopsy revealed the recovery of hematopoiesis, but on iron staining, a moderate number of positive granules were still observed. During this course of treatments, he continued dialysis three times per week in an open space, and bacterial infection was not a threat. J. Hiraga (&) R. Sakemura S. Mizuno Department of Hematology, Toyota Memorial Hospital, 1-1 Heiwa-cho, Toyota 471-8513, Japan e-mail: junji_hiraga@mail.toyota.co.jp

Estimation of cardiac left ventricular ejection fraction in transfusional cardiac iron overload by R2* magnetic resonance

Cardiac dysfunction due to transfusional iron overload is one of the most critical complications for patients with transfusion-dependent hematological disorders. Clinical parameters such as total red blood cell (RBC) transfusion units and serum ferritin level are usually considered as indicators for initiation of iron chelation therapy. We used MRI-T2*, MRI-R2* values, and left ventricular ejection fraction in 19 adult patients with blood transfusion-dependent hematological disorders without consecutive oral iron chelation therapy, and propose possible formulae of cardiac function using known parameters, such as total RBC transfusion units and serum ferritin levels. We found a positive correlation in all patients between both R2* values (reciprocal values of T2*) and serum ferritin levels (r = 0.81) and also total RBC transfusion volume (r = 0.90), but not when we analyzed subgroups of patients whose T2* values were over 30 ms (0.52). From the formulae of the R2*, we concluded that approximately 50 Japanese units or 2,900 pmol/L ferritin might be the cutoff value indicating possible future cardiac dysfunction.

Transfusion management of sickle cell patients during bone marrow transplantation with matched sibling donor

Sickle cell disease (SCD) patients have unique transfusion considerations during bone marrow transplantation (BMT), including prophylaxis against stroke and alloimmunization. Characterization of transfusion requirements is important for blood bank and clinician patient management. A retrospective analysis of red blood cell (RBC) and platelet (PLT) transfusion of SCD patients during myeloablative matched sibling donor (MSD) BMT at one institution from 1993 to 2007 was performed. Patient characteristics (RBC blood group antibodies, ABO-incompatible donor, BMT-related morbidity) and transfusion practices (RBC phenotype matching, transfusion threshold, and blood age) were assessed for effect on total RBC transfusion volumes. Twenty-seven patients received MSD BMT with 96% survival and 0% rejection. Six alloimmunized patients received RBCs with extended phenotype matching (C, c, E, e, K, Fy(a), Jk(b)), 14 nonalloimmunized received limited matching (C, c, E, e, K), and 7 did not have phenotype matching. Among 26 survivors, a median seven RBC transfusions (range, 3-15) and 13.5 PLT transfusions (range, 4-48) per patient were administered, equivalent to 64 mL/kg RBCs (range, 22-122 mL/kg) and 106 mL/kg PLTs (range, 26-343 mL/kg). BMT-related morbidity predicted increased RBC transfusions (p = 0.006). Venoocclusive disease was associated with greater RBC (p = 0.016) and PLT transfusion volumes (p = 0.016). Greater phenotype matching was associated with decreased RBC transfusions (p = 0.0247). SCD patients have high transfusion support during MSD BMT. Communication of BMT complications to the blood bank is essential for transfusion inventory management. Phenotype matching decreased RBC transfusions in this cohort and warrants further investigation in SCD transfusion therapy.

Red Blood Cell Transfusion Requirement at Diagnosis Adversely Affects Both Overall and Leukemia-Free Survival in Primary Myelofibrosis - Increased Serum Ferritin or Total Transfusion Burden Does Not

BACKGROUND: In myelodysplastic syndromes (MDS) without excess blasts, red blood cell (RBC) transfusion requirement has been associated with poorer overall (OS) and leukemia-free (LFS) survival, suggesting that transfusion dependency is a marker of more severe disease (JCO 2005; 23:7594). We recently reported similar results in refractory anemia with ring sideroblasts (RARS): RBC transfusion requirement was an IPSS-independent adverse prognostic factor, but neither serum ferritin nor transfusion burden had prognostic value (AJH 2008; 83:611). Here, we examine the prognostic relevance of serum ferritin, need for RBC transfusions at time of diagnosis, and total transfusion burden in primary myelofibrosis (PMF).METHODS: We reviewed medical records to ascertain the clinical and laboratory features of 185 consecutive patients diagnosed with PMF according to the 2001 World Health Organization (WHO) criteria. Patients were excluded if ferritin measurements at time of diagnosis were unavailable. OS and LFS curves were constructed by Kaplan-Meier method, taking the interval from the date of diagnosis to death, leukemic transformation, or last contact. Log-rank test was used to test the homogeneity of survival curves over different groups. Cox proportional hazards model was utilized to determine the impact of various clinical and laboratory variables on OS and LFS.RESULTS:Clinical characteristics at diagnosis: Median age was 58 years (range 15–81; 110 males). Median serum ferritin level at diagnosis was 164 ng/mL (range 1–3903) and was ≥1000 ng/mL in 22 patients (12%). 101 (55%), 65 (35%) and 19 (10%) patients were assigned low, intermediate- and high-risk disease category (Blood 1996; 88:1013). In addition, 32 (17%) patients required RBC transfusions, 33% had constitutional symptoms and 39% displayed ≥ 1% circulating blasts. Where evaluated, 40% of the patients had cytogenetic abnormalities and 56% JAK2V617F.Events during the disease course: At a median follow-up of 28 months (range 0.5–231), 79 (43%) deaths and 15 (8%) leukemic transformations were documented. During this period, 126 (68%) patients required some form of therapy other than transfusion, including splenectomy in 33 (18%); only 4 underwent allogeneic stem cell transplantation. Causes of death were documented in 33 instances and none were attributed to iron overload. Median peak serum ferritin level during the disease course was 231ng/mL (range 9–13,080); 144 (78%) patients had peak levels <1000 ng/mL, 28 (15%) between 1000 and 3000 ng/mL, and 13 (7%) above 3000 ng/mL. Number of total RBC transfusions ranged from none to 121. Iron chelation therapy was reported in 62 patients (34%).Prognostic factors for OS and LFS: Kaplan-Meier projected median survival was 72 months. By univariate analysis, increased serum ferritin level at diagnosis considered as either a continuous (p<0.0001) or categorical (≥ 1000 ng/mL) variable (p<0.0001), RBC transfusion requirement at diagnosis (p<0.0001) and higher number of total RBC units transfused during the course of the disease (p=0.004) were all associated with inferior survival.However, only RBC transfusion requirement at diagnosis sustained its prognostic significance when age and conventional prognostic risk scores were added to the multivariable model as covariates. Similarly, a peak serum ferritin level of > 3000 ng/mL documented during the disease course was not detrimental to survival. History of iron chelation therapy was associated with shortened survival (p=0.003). Multivariable analysis that included previously described risk factors for LFS also identified RBC transfusion requirement at diagnosis as an additional and independent risk factor.CONCLUSIONS: Serum ferritin level at time of diagnosis or during the disease course of PMF lacks independent prognostic value for either OS or LFS. The same is true for total transfusion burden. However, although hemoglobin <10 g/dL is a component of all currently utilized prognostic scoring systems for PMF, the presence of a more severe erythropoietic defect as indicated by RBC transfusion need at time of diagnosis has an additional adverse prognostic value for both OS and LFS.