Decreasing alloimmunization-specific mortality in sickle cell disease in the United States: Cost-effectiveness of a shared transfusion resource.

Red blood cell alloimmunization and consequent delayed hemolytic transfusion reaction (DHTR) incidence and mortality in patients with sickle cell disease (SCD) are high. A shared transfusion resource has decreased both in other countries, while in the United States cost concerns persist. We conducted a Markov cohort simulation of a birth cohort of alloimmunized patients with SCD to estimate lifetime DHTR incidence, DHTR-specific mortality, quality-adjusted life expectancy (QALE), and costs with the implementation of a shared transfusion resource to identify antibody history versus without (i.e., status quo). We conducted our analysis using a lifetime analytic time horizon and from a United States health system perspective. Implementation of shared transfusion resource projects to decrease cumulative DHTR-specific mortality by 26% for alloimmunized patients with SCD in the United States, relative to the status quo. For an average patient population of 32 000, this intervention would generate a discounted increment of 4000 QALYs at an incremental discounted cost of $0.3 billion, resulting in an incremental cost-effectiveness ratio of $75 600/QALY [95% credible interval $70 200-81 400/QALY]. The results are most sensitive to the baseline lifetime medical expenditure of patients with SCD. Alloantibody data exchange is cost-effective in 100% of 10 000 Monte Carlo simulations. The resource would theoretically need a minimum patient population of 1819 patients or cost no more than $5.29 million annually to be cost-effective. By reducing DHTR-specific mortality, a shared transfusion resource in the United States projects to be a life-saving and cost-effective intervention for patients with SCD in the United States.

CD8+ T cells mediate antibody-independent platelet clearance in mice.

Platelet transfusion provides an important therapeutic intervention in the treatment and prevention of bleeding. However, some patients rapidly clear transfused platelets, preventing the desired therapeutic outcome. Although platelet clearance can occur through a variety of mechanisms, immune-mediated platelet removal often plays a significant role. Numerous studies demonstrate that anti-platelet alloantibodies can induce significant platelet clearance following transfusion. In fact, for nearly 50 years, anti-platelet alloantibodies were considered to be the sole mediator of immune-mediated platelet clearance in platelet-refractory individuals. Although nonimmune mechanisms of platelet clearance can often explain platelet removal in the absence of anti-platelet alloantibodies, many patients experience platelet clearance following transfusion in the absence of a clear mechanism. These results suggest that other processes of antibody-independent platelet clearance may occur. Our studies demonstrate that CD8(+)T cells possess the unique ability to induce platelet clearance in the complete absence of anti-platelet alloantibodies. These results suggest a previously unrecognized form of immune-mediated platelet clearance with significant implications in the appropriate management of platelet-refractory individuals.