Managing alloimmunization, delayed hemolytic transfusion reactions, and hyper-hemolysis in sickle cell disease

Date
2020
DOI
Authors
Guo, Anqi
Version
OA Version
Citation
Abstract
Sickle cell disease (SCD) is an inherited blood disorder in which polymerization of a mutated form of hemoglobin results in a sickled shape of red blood cells, leading to anemia due to premature destruction of RBCs. Other morbidities include end-organ damage, pain attacks known as “sickle cell crisis,” bacterial infections, and stroke. Transfusion therapy remains a necessary treatment of sickle cell disease. Transfusions given to lower the levels of sickle RBCs and viscosity have shown to decrease the risk of stroke by 90% during clinical trials. However, chronically transfused patients can become alloimmunized and develop delayed hemolytic transfusion reactions (DHTR), a life-threatening condition. The presentation of DHTR can vary, and its severity is unpredictable. In the most severe cases, patients destroy their own RBCs along with the transfused RBCs, a condition known as hyper-hemolysis. Additional transfusions can aggravate these symptoms and lead to death. Clinicians’ awareness of DHTR events is poor because its clinical presentations mimic those of vaso-occlusive crisis. Furthermore, immunohematology at times detect no newly formed antibodies. Mortality due to DHTR have been reported to be as high as 11.5%. Currently, 5.4 million people suffer from sickle cell disease. An overwhelming 80% of SCD occurs in Sub-Saharan Africa, while also occurring frequently in people of African origin living in other parts of the world. Annually, over 100,000 patients are affected by SCD, utilizing over one billion dollars per year in healthcare costs. Lastly, current projections estimate that by 2050 the number of newborns with sickle cell disease will exceed 400,000. While there are no drugs that specifically target DHTR, immunosuppressants such as intravenous immunoglobulins, steroids, eculizumab, and tocilizumab have shown to improve outcomes in DHTR. However, these treatments may prove to be insufficient. Moreover, numerous adverse health effects are associated with using immunosuppressants, including exacerbation of vaso-occlusive pain and hemolytic anemia already present in SCD patients. Currently, alloimmunization can be prevented by extended-matching of blood antigen, increasing blood donations from Africa Americans and other minority groups, and the use of rituximab. While hematopoietic stem cell transplantation remains a viable alternative to transfusing therapy, it remains highly under-utilized. This literature review aims to evaluate the current prevention and treatment methods used to manage DHTR to expose gaps in knowledge and identify ways to improve clinical outcomes in SCD patients. Results suggest: (1) While it is not cost-effective to implement extended matching in all SCD patients, there is potential in strategies to increase blood donation in minority groups. Genotyping of blood antigens may also be considered. (2) Treatment options are sorely lacking for DHTR. Case studies document positive outcomes using immunosuppressants, but there are few clinical trials and evidence-based studies to confirm their efficacy in larger cohorts. (3) Effective treatment of DHTR relies on prospective studies that further elucidate the pathophysiology of alloimmunization and DHTR. (4) The lack of effective treatments for DHTR can be attributed to structural violence. Advocacy and awareness are instrumental in improving care for DHTR and SCD.
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