The milestones provide a national standard for evaluation that will be used for the assessment of all residents in Accreditation Council for Graduate Medical Education-accredited pathology training programs.

Red blood cell transfusion continues to play a vital role in sickle cell disease (SCD) management. Although the risks of transmissible infectious agents continue to decline, sickle cell patients often receive chronic transfusions frequently leading to alloimmunization. Delayed hemolytic transfusion reaction (DHTR) is a possible, life-threatening, adverse effect of a blood transfusion due to recipient RBC autoantibodies or alloantibodies. Some etiologies of DHTR remain unexplained since there are cases of DHTR in which there is an absence of detectable autoantibodies or alloantibodies. Phosphatidylserine (PS) is a phospholipid at the extracellular face of the RBC membrane and is associated with the macrophage clearance of sickled erythrocytes. In several ways this abnormality could contribute to the pathophysiology of sickle cell anemia. Studies have shown that exposure of PS on RBC membrane may promote blood coagulation and could also contribute to observed increases in adhesion of sickle erythrocytes to endothelial cells, and both processes may contribute to microvascular occlusion during sickle cell crisis. The exposure of PS on sickle cell erythrocytes could also be partly responsible for the decreased RBC survival characteristic of the disorder. Potential consequences of such pathologic PS exposure include an exacerbation of the anemia due to enhanced reticuloendothelial clearance and activation of coagulation cascade. 1 Phosphatidylserine exposure is a signal for eryptosis, a suicidal RBC death involving membrane shedding and leading to the physiologic clearance of apoptotic cells by macrophages, via specific PS receptors. 2,3 According to Chadebech and colleagues, PS-RBCs from donor RBC concentrates may account for these mechanisms of destruction in the SCD environment. As PS increases RBC adhesion, it facilitates engulfment and macrophage clearance by the reticuloendothelial system. According to Setty and colleagues, PS can be exposed on human RBC by the action of ionophore on control RBCs. We decided to perform an Abstract Delayed hemolytic transfusion reactions (DHTRs) may occur when there is an antigen mismatch between transfused RBCs and recipient RBC antibodies where sensitized RBCs are cleared by macrophages or complement activation leading to immunoglobulin G (IgG) mediated hemolysis. Some DHTR etiologies remain unknown since there are cases of DHTR when an RBC autoantibody or alloantibody is absent. Mechanisms have been proposed to explain these types of cases of DHTR, including bystander or reactive hemolysis by hyperactive macrophages. Studies in patients with sickle cell disease (SCD) have shown abnormalities in the structure and function of the RBC membranes including exposure of phosphatidylserine (PS) leading to macrophage clearance of sickled erythrocytes. We report on a case demonstrating that DHTR may occur as a result of PS exposure on antigen-matched RBC, resulting in macrophage clearance and hemolysis without detection of autoantibodies or alloantibodies. An in vitro measurement showed ...

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