Transfusion strategies in thalassemia and sickle cell disease SITE-SIMTI-SIdEM Good Practice

Abstract

This document is the tool through which the knowledge developed by biomedical research is transferred to daily clinical practice. It does not offer standards of care to which one can refer in acritical and decontextualized manner: these standards must be able to be expressed, for each individual case, on the basis of available clinical information, preferences of the patients and other contextual situations, accurately examined in light of the expertise of healthcare professionals. It is therefore up to the expertise and judgement of the professionals, who carefully listen to particular requests and consider the values expressed by patients, to establish which procedures or treatments are more appropriate to manage individual clinical cases.The Good Practice (GP) is organized in two large sections: a main section which, for each topic of interest, reports a short specific introduction and continues with recommendations for clinical practice in order to allow the reader to access the interpretation of the evidence and the recommendations made by the Authors. No. 4 Enclosures where the following is reported: Enclosure 1 - transfusion yield; Enclosure 2 - perioperative management and prevention of postoperative complications; Enclosure 3 - donation of blood, hematopoietic stem cells (HSCs), organs and tissues; Enclosure 4 - table of matching levels.

Figure 1

Association between hemoglobin levels, morbidity and mortality in β-thalassemia

Figure 2

DHTR risk calculation Patients undergoing a chronic transfusion protocol are considered low-risk DHTR. For patients receiving episodic transfusions, 3 scores, resulting from statistical analysis, are considered DHTR risk factors. (1) History of red blood cell immunization. A score of 6 is assigned if the patient has a history of at least 1 clinically significant antibody (other than anti-Rh o anti-K) classically known to be involved in transfusion reactions such as anti-Jk^b, Fy^a, S, Hb^S. A score of 5 is assigned if the patient has a history of only anti-Rh/-K antibodies and/or considered non clinically (clin) significant (for example, autoantibodies or non-specific antibodies [Ab]). Therefore, a patient who has an anti-Rh plus an anti-Jkb is assigned a score of 6 (and not 6 + 5). (2) Cumulative transfusions of 12 units or less. (3) A previous DHTR. By adding the scores, a DHTR risk score is calculated and the transfusion is adjusted accordingly. Patients with a score <8 are considered low risk. Episodically transfused patients who are at low risk for DHTR are transfused with Rh (D, C, E, c, e) and K matched red blood cells, which is extended to Fy, Jk and Ss only of the patient has developed antibodies to any of these antigens. *AUS, antibody with unknown specificity; **Patients with a score between 8 and 14 have an intermediate risk. For such patients the extent of matching should be based on the history of DHTR and on the number of previous transfusions; those with no history of DHTR who have been transfused only a few times are considered to be at lower risk similar to low-risk patients, but should be monitored closely anyway. However, patients with intermediate DHTR risk who have a history of DHTR and few transfusions in the past (≤12), are generally considered high risk and receive extended matched red blood cells (Fy, Jk, Ss). Patients with a score >14 are considered high risk for DHTR. Episodically transfused patients with a high risk for DHTR (based on the predictive score) always receive extended matched red blood cells (Fy, Jk, Ss). Prophylactic use of rituximab should be considered for patients with a history of alloantibodies and serious DHTR, recently eculizumab has also been used prophylactically when transfusion therapy is necessary.

Figure 3

Recommended guidelines for the diagnosis of DHTR in adult sickle cell disease patients Our evaluation criteria for diagnosing DHTR in recently transfused adult SCD patients are based on clinical and laboratory features (pain, anemia, urine colour, elevated LDH) and immunohematological tests, that may or may not reveal the presence of new antibodies. If DHTR is suspected, it is recommended to use the immediate post-transfusion total Hb in g/dL and HbA% following the nomogram shown, to determine the probability that a patient has DHTR. The formula can be calculated directly by using the link provided in the figure.

Figure 4

Recommended treatment for patients presenting with post-transfusion hemolysis In such cases transfusions must be stopped unless (as indicated by the asterisk) the patient has deep anemia (total <3 g/dL with shock or hyperlactatemia), in which case rituximab is indicated for patents with +DAT or +test di screening or + elution associated with a low dose of methylprednisolone to prevent the steroid from aggravating or triggering a VOC. Symptomatic patients who develop DHTR should be treated immediately with intravenous immunoglobulins (IVIg), adding erythropoietin (EPO) if DHTR is also associated with reticulocytopenia. Administer anticoagulant prophylactic therapy to reduce the risk of thrombosis associated with EPO administration. Supportive therapy is always indicated. If the patient presents severity criteria (acute chest syndrome or acute pulmonary hypertension, stroke or organ failure), additional treatment with eculizumab may be effective in this case, if not vaccinated against meningitis use antibiotic prophylaxis until vaccination is possible.