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Transfusion of red blood cells (RBCs) is frequently required for care of individuals with sickle cell disease (SCD). Alloimmunization rates are high and may be reduced by matching for RBC antigens that can cause alloimmunization.During the PROACTIVE Feasibility Study, patients with SCD age 2 years or older admitted for pain without acute chest syndrome were enrolled for possible randomization to preventive blood transfusion or standard care. Transfusion and antibody histories were obtained at each site, and antibody screening was done, to assess transfusion burden and alloimmunization prevalence. Participating sites were surveyed regarding antigen matching practice.A total of 237 patients (169 SS, 42 SC, 15 Sβ(0) -thalassemia, 11 Sβ(+) -thalassemia), 118 males and 119 females, were enrolled. Mean age was 19.3 years (range, 2.0-68.0); there were 122 children and 115 adults. A total of 75.8% had received at least a single transfusion of RBCs before the study. Thirty-four patients (14.4%) had a history of at least one alloantibody and 17 of these had more than one. When surveyed, 19 sites (83% of responders) reported antigen matching to at least include C, E, and K for transfusion of all patients with SCD.Though antigen typing before transfusion of people with SCD and providing antigen-negative units is now widely employed by sickle cell centers, the alloimmunization rate remains quite high in contemporary sickle cell populations and may be due in large part to transfusions received at institutions not providing extended matching.

Acute chest syndrome (ACS) is the leading cause of death in sickle cell disease. Severe ACS often develops in the course of a vaso-occlusive crisis (VOC), but currently there are no predictors for its development. Secretory phospholipase A2(sPLA2), a potent inflammatory mediator, is elevated in ACS, and previous work suggests that sPLA2 predicts impending ACS. We prospectively evaluated sPLA2concentration during 21 admissions for VOC; 6 of these patients went on to develop ACS. Elevation of sPLA2 was detected all 6 patients 24 to 48 hours before ACS was clinically diagnosed. Adding the requirement for fever raised the specificity of sPLA2 to 87% while retaining 100% sensitivity. These data indicate that sPLA2 can be useful in alerting the clinician to patients with impending ACS. In addition, sPLA2 may be useful for instituting early therapies to prevent or reduce the clinical morbidity of ACS.

Acute chest syndrome (ACS) is the leading cause of death in sickle cell disease. Severe ACS often develops in the course of a vaso-occlusive crisis (VOC), but currently there are no predictors for its development. Secretory phospholipase A2(sPLA2), a potent inflammatory mediator, is elevated in ACS, and previous work suggests that sPLA2 predicts impending ACS. We prospectively evaluated sPLA2concentration during 21 admissions for VOC; 6 of these patients went on to develop ACS. Elevation of sPLA2 was detected all 6 patients 24 to 48 hours before ACS was clinically diagnosed. Adding the requirement for fever raised the specificity of sPLA2 to 87% while retaining 100% sensitivity. These data indicate that sPLA2 can be useful in alerting the clinician to patients with impending ACS. In addition, sPLA2 may be useful for instituting early therapies to prevent or reduce the clinical morbidity of ACS.

Phosphatidylserine (PS), exclusively present in the inner monolayer of the normal red blood cell (RBC) membrane, is exposed in subpopulations of sickle cells. PS-exposing RBCs were found predominantly among the densest and the very light sickle cells. Within the light RBC fraction, PS exposure was found on reticulocytes, transferrin receptor–expressing reticulocytes, and mature RBCs. The last subset contained low-density valinomycin-resistant RBCs, previously shown to have high Na+ and low K+content. This subpopulation contained the highest percentage of PS-exposing cells. The PS-exposing sickle cells did not show the sustained high cytosolic Ca++ levels that have been shown to activate scramblase activity. Data from this study indicate that PS exposure can occur at different stages in the life of the sickle RBC and that it correlates with the loss of aminophospholipid translocase activity, the only common denominator of the PS-exposing cells. The additional requirement of scramblase activation may occur during transient increases in cytosolic Ca++.

Cerebral infarction occurs in one quarter of all children with sickle cell anemia (SCA). There is an increased risk of stroke in siblings with SCA, suggesting genetic factors may influence risk of stroke. The authors investigated whether HLA type was associated with risk of stroke in children with SCA. Fifty-three patients with SCA underwent complete HLA typing at both HLA class I (HLA-A, B) and HLA class II (HLA-DR, DQ, DP) loci. Of the 53 patients, 22 had magnetic resonance imagining (MRI)–documented evidence of cerebral infarction, and the remaining 31 patients had negative MRI scans. Comparison of the results of HLA typing between the SCA patients with a positive and those with a negative MRI documented that the 2 groups differed with respect to the class I HLA-B (P = .012), and the class II HLA-DRB1 (P = .0008) and DQB1 (P = .029). Susceptibility associations at the HLA-DRB1 locus included both DR3 alleles, where DRB1*0301 and *0302 were both associated with an increased risk of stroke. Protective associations were found in the DR2 group, where DRB1*1501 was protective for stroke. DQB1*0201, which is in linkage disequilibrium with DRB1*0301, was also associated with stroke. Similarly, DQB1*0602, in linkage disequilibrium with DRB1*1501, was protective. Specific HLA alleles may influence the risk of stroke in children with SCA. HLA typing may prove useful in identifying SCA patients at higher risk for stroke.