Successful treatment with plasma exchange in life-threatening hyperhemolytic syndrome unrelated to sickle cell disease.

INTRODUCTION: Hyperhemolytic syndrome (HHS) is a severe form of delayed transfusion reaction primarily described in sickle cell anemia patients which is characterized by a hemoglobin decrease to pre-transfusion levels or lower, often with reticulocytopenia and no evidence of auto- or allo-antibodies. CASE PRESENTATION: We present two cases of severe HHS in patients without sickle cell anemia refractory to treatment with steroids, immunoglobulins, and rituximab. In one case, temporary relief was achieved with eculizumab. In both cases, plasma exchange resulted in a profound and immediate response allowing for splenectomy and resolution of hemolysis. DISCUSSION/CONCLUSION: We discuss the pathophysiology of HHS, its presentation and treatment and expand on the possible role of plasma exchange in this setting.

Storage-induced damage to red blood cell mechanical properties can be only partially reversed by rejuvenation.

BACKGROUND: The storage of red blood cells (RBC) is associated with impairment of their properties that can induce a circulatory risk to recipients. In a preceding study (2009), we reported that post-storage rejuvenation (RJ) of stored RBC (St-RBC) efficiently reduced the storage-induced RBC/endothelial cell interaction, while only partially reversing the level of intracellular Ca(2+), reactive oxygen species, and surface phosphatidylserine. In the present study, we examined the RJ effectiveness in repairing St-RBC mechanical properties. METHODS: RBC, stored in CPDA-1 without pre-storage leukoreduction, were subjected to post-storage RJ, and the deformability, osmotic fragility (OF), and mechanical fragility (MF) of the rejuvenated St-RBC (St-RBCRj) were compared to those of untreated St-RBC and of freshly-collected RBC (F-RBC). RESULTS: 5-week storage considerably increased OF and MF, and reduced the deformability of St-RBC. All alterations were only partially (40-70%) reversed by RJ, depending on the extent of the damage: the greater the damage, the lesser the relative effect of RJ. CONCLUSION: The findings of the present and preceding studies suggest that different St-RBC properties are differentially reversed by RJ, implying that some of the changes occur during storage and are irreversible.

Circulatory risk in the transfusion of red blood cells with impaired flow properties induced by storage.

Red blood cell (RBC) flow properties (FPs), specifically their deformability, aggregability, and adherence to endothelial cells, play major roles in blood circulation. Their impairment, as occurs under various blood banking conditions, may contribute to circulatory impairment in recipients. Recent studies and meta-analyses show that the transfusion of stored RBCs (stRBCs) may be less beneficial than that of freshly collected units, which may thus adversely affect recipients, especially their circulatory function, thereby pointing to a potential role in the alteration of FPs of stRBCs. In this review, we present an up-to-date summary of the studies on the FP of stRBCs, clearly showing that they may be impaired at an early stage of storage, which may contribute considerably to transfusion-associated circulatory impairment in recipients. The alteration of the FPs of stRBC is attenuated by prestorage leukoreduction and/or poststorage "rejuvenation." However, because these procedures, especially rejuvenation, are costly and are associated with an increased risk of bacterial contamination, there is an urgent need to establish better methods of improving the hemodynamic function of stRBCs before their transfusion. It is therefore proposed that the FPs of stRBC may be important measures of the outcome of RBC transfusions. Monitoring such functions would thereby introduce necessary criteria and new tools for the quality control of stRBC units, making an important contribution to transfusion therapy.

Rejuvenation treatment of stored red blood cells reverses storage-induced adhesion to vascular endothelial cells.

BACKGROUND: Blood banking procedures are associated with elevated adherence of red blood cells (RBCs) to blood vessel wall endothelial cells (ECs), which can introduce a circulatory risk to recipients. This study was undertaken to examine the possibility of repairing this damage by a poststorage "rejuvenation" procedure before transfusion. STUDY DESIGN AND METHODS: Stored RBCs were treated with rejuvenation solution (Rejuvesol, enCyte Systems, Inc.), and their adhesion to cultured human microvascular ECs was determined as a function of shear stress using a cell flow properties analyzer. The adherence of rejuvenation-treated stored RBCs (stRBCs) was compared to that of untreated stRBCs and of freshly donated RBCs. RESULTS: Strong elevation of stRBC/EC adhesion was induced by cold storage and it correlated with translocation of phosphatidylserine (PS) to the RBC surface, a known mediator of RBC/EC adhesion. The role of RBC surface PS in stRBC/EC interaction was confirmed by the suppression of adhesion after the blocking of the stRBC surface PS with annexin V. Concomitantly, RBC storage elevated intracellular levels of reactive oxygen species (ROS) and Ca(2+), the latter known to facilitate PS externalization. Poststorage rejuvenation treatment of stRBCs reversed all the above changes (ROS, Ca(2+), PS), along with complete suppression of the enhanced RBC/EC adhesion, restoring it to that of normal, freshly collected RBCs. CONCLUSION: Poststorage RBC rejuvenation treatment is effective in reversing the storage-induced RBC/EC interaction. This provides further documentation for the potential clinical benefit of poststorage rejuvenation.

Blood banking-induced alteration of red blood cell flow properties.

BACKGROUND: Blood banking procedures are associated with damage to red blood cell (RBC) membranes, which can impair their flow properties, namely, their deformability, aggregability, and adherence to endothelial cells (ECs) and thus possibly introducing a circulatory risk to recipients. This study was undertaken to comprehensively explore the effect of cold storage and gamma irradiation on RBC flow properties. STUDY DESIGN AND METHODS: RBC flow properties were monitored as a function of shear stress with a computerized cell flow properties analyzer. Because we had previously studied storage effect on RBC aggregability (Transfusion 1999;39:277-81), here we determined the storage effect on RBC adherence and deformability, by measuring them before (control) and during storage. Gamma irradiation effect on RBC aggregability, adherence, and deformability was determined before (control) and after irradiation. RESULTS: Cold storage significantly elevated the number of adherent RBCs and the strength of their interaction with ECs, and was marked by decreased RBC deformability as early as 2 weeks into the storage period. The elevation of RBC-EC interaction was well correlated with translocation of phosphatidylserine to the RBC surface. Gamma irradiation induced an immediate and marked increase in the number of rigid cells, but did not affect RBC adherence and aggregability. CONCLUSION: RBC flow properties appear to be especially sensitive to cold storage and gamma irradiation because they are impaired long before the expiration date. Because impaired RBC flow properties facilitate circulatory disorders, the potential circulatory risk of transfusion RBC with blood banking-impaired rheology should be considered.

Chimerism in the immunohematology laboratory in the molecular biology era.

Dual or multiple cell populations, induced by chimeras, have been the subject of many studies. This long-standing fascination with chimeras has revealed a good deal of knowledge about human inheritance. Although historically most chimeras were caused by natural events, certain current medical intervention therapies are increasing the number of situations that can lead to a mixed cell population, that is, the chimeric condition, in humans. Medical therapies such as transfusion, stem cell transplantation, kidney transplantation, and artificial insemination induce temporary and sometimes permanent chimeras. Such natural or therapeutically induced presentations of chimerism can present challenging issues to the clinical immunohematology laboratory with regard to interpretation of results and subsequent patient management. The purpose of this review was to highlight some of these chimeric states and hypothesize how testing DNA from various tissues can cause apparent discrepancies between phenotype and genotype results.

The rare Lu:-6 phenotype in Israel and the clinical significance of anti-Lu6.

BACKGROUND: Lu6 is a high-incidence antigen of the Lutheran blood group. Examples of anti-Lu6 are rare and are of uncertain clinical significance. CASE REPORT: Three patients were encountered in whom anti-Lu6 was detected on pretransfusion screening. The patients were all Iranian Jews and were not known to be related. In vitro studies to ascertain the potential clinical significance of the antibody using the monocyte monolayer assay (MMA) were negative in two patients. The third patient received a two-unit transfusion of incompatible Lu6 RBCs with no signs of hemolysis. However, after the transfusion, the MMA and a chemiluminescence test were positive, whereas a chromium survival study was normal. Thus, the antibody may have changed in its clinical significance. CONCLUSION: Although anti-Lu6 does not appear to be a clinically significant RBC antibody in all circumstances, transfusion of Lu6 RBCs in patients with anti-Lu6 should be performed cautiously.