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G.E. Linder and S.T. Chou
Hydroxyurea is the primary treatment for prevention of recurrent ACS. Analysis of patients in the STOP trial showed a significantly decreased incidence of ACS in the chronic transfusion arm, and small studies suggest it may reduce frequency of ACS recurrence but not severity.32,33 Chronic transfusion therapy can be considered in patients with recurrent ACS when hydroxyurea is not well toler- ated or when hydroxyurea is insufficient to prevent severe, recurrent ACS.
Preoperative transfusion support
Operations, including cholecystectomy, splenectomy, and hip surgery, are common in patients with SCD and carry a significant risk of morbidity and mortality.34 The observational Cooperative Study of Sickle Cell Disease demonstrated that patients with SCD undergoing surgery had high rates of pain and ACS, as well as complications such as fever, bleeding, and death.34,35 The Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS) study randomized patients with hemoglobin SS and Sβ0 thalassemia SCD requiring low- or medium-risk opera- tions to transfusion or no transfusion preoperatively.36 The rate of postoperative ACS was markedly reduced among patients in the transfusion arm. The majority (85%) of study patients underwent medium-risk operations and, therefore, the relevance of these findings to low-risk sur- geries is uncertain. The effect of preoperative transfusion on postoperative pain crises was less clear. Multiple studies have found no significant reduction in postoperative pain in preoperatively transfused patients.2,36,37
The Preoperative Transfusion in Sickle Cell Disease Study Group conducted a multicenter study comparing perioperative complication rates among patients random- ized to a conservative preoperative transfusion regimen intended to increase hemoglobin concentration to 10 g/dL or an aggressive transfusion regimen to decrease HbS below 30%.38 There was no difference in rates of ACS, vaso-occlusive episodes, or other serious complications between the two study arms. As such, preoperative trans- fusion to achieve a hemoglobin of 9-11 g/dL, rather than a goal HbS level, is suggested. Recent guidelines recom- mend preoperative transfusion for patients undergoing surgery with general anesthesia that is expected to last longer than 1 hour.2 For patients with a high baseline hemoglobin that precludes simple transfusion, preopera- tive RCE should be performed. RCE should also be con- sidered for patients undergoing high risk cardiovascular or neurosurgical procedures.2
Transfusion support for transplantation and curative therapies
There are limited studies examining transfusion consid- erations in patients with SCD undergoing allogeneic or autologous hematopoietic stem cell transplantation. Blood transfusion prior to transplantation may reduce SCD-associated bone marrow changes and inflammation, possibly improving transplant outcomes. Reducing HbS levels to ≤30% prior to transplantation may also mini- mize SCD-related complications in the peri-transplant period. Recent studies and ongoing clinical trials utilize
Figure 1. Factors that contribute to alloimmunization in sickle cell disease. The prevalence of alloimmunization in sickle cell disease (SCD) is high compared to that in the general population. One of the key factors behind alloimmunization is recipient-donor mismatch of Rh and K antigens. The majority of Blacks lack C, E, and K antigens. The frequencies of C, E, and K are higher in blood donor populations, leading to increased risk of alloantigen exposure with red cell transfusion. Transfusing red cells matched for Rh and K decreases the rate of alloimmunization; however, RH genetic diversity contributes to a persistent risk of Rh antibody development. Most patients with SCD have one or more RH variants. Common RH alleles in patients with SCD are depicted in panel 2. Red boxes represent RHD exons, and blue boxes represent RHCE exons. The dashed line indicates gene deletion. Vertical lines reflect the positions of amino acid substitutions. Patients with RH variants can form antibodies against the Rh epitopes they lack. SCD is a chronic inflammatory state. Hemolysis leads to elevated levels of circulating hemoglobin and free heme, which activate macrophages and neutrophils, and leads to the secretion of pro-inflammatory cytokines. Patients with high levels of inflammation are at increased risk of alloimmunization. While the immunological pathways contributing to alloimmunization are complex, it is becoming increasingly clear that immune system dys- regulation influences antibody formation. IL-1: interleukin -; IL-6: interleukin-6; IFNγ: interferon gamma. Created with Biorender.com.
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haematologica | 2021; 106(7)