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BACKGROUND Red blood cell (RBC) storage in blood banks is not exempt from cellular injury. Alterations not observed on RBCs freshly isolated from units can rapidly appear in circulation. The transfusion of old blood units, even if this is a controversial issue, could therefore have adverse effects on the recipient. We wanted to determine the respective effects of storage duration and recipient plasma on RBCs for transfusion into patients with severe sepsis. STUDY DESIGN AND METHODS Eleven stored RBC units were sampled at various time points, approximately Days 3 to 8 (referred to as fresh RBCs) and Days 38 to 42 (old RBCs) and tested in coincubation experiments with plasma obtained from 13 patients with severe sepsis and 17 healthy donors as controls. RBCs were tested after 24 or 48 hours at 37°C for the detection of senescence markers (phosphatidylserine exposure, calcium influx, and reactive oxygen species detection and decrease in size) with or without exposure to plasma. RESULTS We confirmed that a 42-day refrigerated storage of RBCs alone (without any incubation in plasma) had no significant effect on RBCs and no senescence marker detected. By contrast, ex vivo exposure to plasma samples altered both fresh and old RBCs, with a much larger effect for old RBCs, regardless of the plasma used (sepsis vs. control). CONCLUSION We show that the main factor affecting the senescence of RBCs for transfusion into patients with severe sepsis is the age of the stored units rather than the clinical status of the recipient.

Diagnosis of delayed hemolytic transfusion reactions (DHTR), one of the most dreaded complications of transfusion in patients with sickle cell disease (SCD), is challenging and not straightforward. Current diagnostic approaches are complex and not consensual; they are based on assessment of hemoglobin (Hb) drop and enhanced hemolysis, features also seen during classical vaso-occlusive events. In this observational study, we tested the hypothesis that the rate of decline in HbA after an index transfusion is a surrogate marker for the destruction of transfused RBC, which could be used diagnostically. We examined 421 transfusion episodes (in 128 patients of a French referral center for SCD) for which an Hb electrophoresis was obtained within 1 week following an index transfusion and repeated within 2 months (before a subsequent scheduled transfusion or during an acute complication). Chart review found DHTR to be present in 26 cases (6.2%), absent in 389 cases (92.4%), and possible in six cases (1.4%). As expected, DHTR was associated with accelerated hemolysis (increased serum bilirubin and lactic dehydrogenase concentrations) and a decline in total Hb as compared to the early post-transfusion value. However, the decline in HbA concentration appeared more effective in segregating between patients without DHTR and others. We propose a diagnostic nomogram for DHTR based on Hb A as a biologic marker of the survival of transfused RBCs. Am. J. Hematol. 91:1181-1184, 2016. © 2016 Wiley Periodicals, Inc.

Delayed hemolytic transfusion reaction (DHTR) is one of the most feared complications of sickle-cell disease (SCD). We retrospectively analyzed the clinical and biological features, treatments and outcomes of 99 DHTRs occurring in 69 referral center patients over 12 years. The first clinical signs appeared a median of 9.4 [IQR, 3-22] days after the triggering transfusion (TT). The most frequent DHTR-related clinical manifestation was dark urine/hemoglobinuria (94%). Most patients (89%) had a painful vaso-occlusive crisis and 50% developed a secondary acute chest syndrome (ACS). The median [IQR] hemoglobin-concentration nadir was 5.5 [4.5-6.3] g/dL and LDH peak was 1335 [798-2086] IU/L. Overall mortality was 6%. None of the patients had been receiving chronic transfusions. Among these DHTRs, 61% were developed in previously immunized patients, 28% in patients with prior DHTR. Among Abs detected after the TT in 62% of the episodes, half are classically considered potentially harmful. No association could be established between clinical severity and immunohematological profile and/or the type and specificity of Abs detected after the TT. Management consisted of supportive care alone (53%) or with adjunctive measures (47%), including recombinant erythropoietin and sometimes rituximab and/or immunosuppressants. Additional transfusions were either ineffective or worsened hemolysis. In some cases, severe intravascular hemolysis can be likely responsible for the vascular reaction and high rates of ACS, pulmonary hypertension and (multi)organ failure. In conclusion, clinicians and patients must recognize early DHTR signs to avoid additional transfusions. For patients with a history of RBC immunization or DHTR, transfusion indications should be restricted. Am. J. Hematol. 91:989-994, 2016. © 2016 Wiley Periodicals, Inc.

BACKGROUND The transfusion of red blood cell (RBC) concentrates is the main treatment for acute vaso-occlusive symptoms in sickle cell disease (SCD). Units of packed RBCs (pRBCs) must retain optimal characteristics for transfusion throughout the storage period. Transfused RBCs interact with the plasma and the endothelium that lines blood vessels and may be the target of immune-hematologic conflict if the patient produces antibodies against RBCs. Questions remain concerning the benefit-risk balance of RBC transfusions, in particular about the shelf-life of the units. STUDY DESIGN AND METHODS Plasma samples from 33 hemoglobin SS patients with SCD who had severe acute-phase symptoms or were in steady-state were put in contact with 10 fresh-stored and older stored samples from the same 10 RBC units. The factors affecting RBC survival (phosphatidylserine exposure, cytosolic calcium influx, cell size reduction) were analyzed. RESULTS We show that the effects of plasma samples from patients with SCD on pRBCs depend on the clinical condition of the patients and the duration of red cell storage. Signs of RBC senescence were correlated with the clinical status of the patient from whom the plasma sample was obtained. A decrease in RBC size and an increase in phosphatidylserine exposure were correlated with the duration of RBC storage. The behavior of cryopreserved pRBCs was similar to that of fresh refrigerated RBCs when challenged with patient plasma samples. CONCLUSION The key points of this study are that the clinical condition of patients with SCD can negatively affect the integrity of pRBCs for transfusion, and those effects increase with longer storage. Also, cryopreserved pRBCs behave similarly to fresh RBCs when challenged with plasma samples from patients with SCD in acute phase. Our data provide the first evidence that fresh RBCs stored for short periods may be of greater benefit to patients with SCD than RBCs that have been refrigerated for longer periods, particularly for those who have acute symptoms of SCD.

BACKGROUND Delayed hemolytic transfusion reaction (DHTR) is a life-threatening condition in sickle cell disease (SCD) patients that is frequently complicated by hyperhemolysis. Antibodies resulting from antigen disparity between donors of European ancestry and patients of African ancestry are common, but situations involving antibodies not classically of clinical significance are also encountered. Anti-HI is generally considered to be an innocuous naturally occurring antibody. STUDY DESIGN AND METHODS We describe two cases of hyperhemolysis with anti-HI and provide details of the reported cases. RESULTS Both SCD patients were polyimmunized and belonged to blood group B. They developed anti-HI that was reactive at 37°C, after the transfusion of group O red blood cell units matched for all known and produced antibodies classically considered to be clinically significant. Both patients developed DHTR with hyperhemolysis. In the first case, a pregnant woman, a second transfusion was unavoidable and the patient died from cardiac arrest. The state of the second patient improved without the need for further transfusion. CONCLUSION Three other cases of DHTR with anti-HI have been described in the literature in SCD patients. The two additional cases reported here definitively demonstrate that anti-HI is dangerous in SCD patients. As a result, ABO-identical matching (including A1 status) must be considered in SCD patients with anti-HI.