Role of red blood cell transfusion in management of SCD

• Red blood cell transfusions in people with SCD may be in the form of simple transfusions or exchange transfusions, either manual or automated (82). Simple transfusions consist of a transfusion of red blood cells only. Manual exchange involves manual phlebotomy followed by a transfusion. Automated exchange involves removal and replacement of red blood cells using an apheresis system (83). Red blood cell transfusion in a person with SCD aims to increase tissue oxygenation; to decrease viscosity by diluting the relative amount of sickle haemoglobin-containing red blood cells; and to suppress endogenous erythropoiesis (82).
• Red blood cell transfusions are used for chronic prophylaxis against vaso-occlusive events in select patients. Chronic transfusion therapy has also been shown to be beneficial in the prevention of stroke (84), recurrent acute chest syndrome (85), sickle-cell crises not responsive to hydroxycarbamide (86), and pulmonary hypertension (87). Role of red blood cell transfusion in management of SCD during pregnancy
• During pregnancy, when, historically, hydroxycarbamide has been contraindicated, prophylactic blood transfusion has been used to correct anaemia and to reduce the frequency of SCD complications triggered by haemoglobin level, or by the relative proportion of adult or sickle haemoglobin. Guidance from the WHO African region is that a preventive transfusion programme be instituted in addition to specific obstetrical measures (23). Available evidence on prophylactic red blood cell transfusion in pregnant women with SCD
• The systematic review conducted to inform this guideline found that, compared to usual care (indicated therapeutic transfusion), prophylactic transfusion may reduce the risk of sickle-cell crisis (RR 0.28, 95% CI 0.12 to 0.67; one trial, 72 women; low certainty) (45, 88, 89). The effect of prophylactic transfusion on the risk of splenic sequestration, acute chest syndrome and caesarean section is uncertain (one trial; 72 women; very low certainty). No other priority maternal outcomes were reported.
• The same systematic review found that the effect of prophylactic transfusion compared to usual care (indicated therapeutic transfusion) on the risk of perinatal death, stillbirth/fetal death, neonatal death, preterm birth (<37 weeks), intrauterine growth restriction, and Apgar score <7 at 5 minutes is uncertain (one trial, 76 fetuses; very low certainty) (45). No other priority newborn outcomes were reported.
• An earlier systematic review of nonrandomized studies found that prophylactic transfusions may positively affect several adverse maternal and neonatal outcomes, including maternal mortality, vaso-occlusive pain episodes, pulmonary complications, pulmonary embolism, pyelonephritis, perinatal mortality and preterm birth, in women with SCD (90). It noted, however, that the evidence stems from a relatively small number of studies with methodological limitations and that a prospective, multicentre, randomized trial is needed to determine whether the potential benefits balance the risks of prophylactic transfusions.
• A randomized controlled feasibility trial (n=34) of serial prophylactic exchange transfusion versus standard care in pregnant women with SCD in seven hospitals in the United Kingdom of Great Britain and Northern Ireland (91) was published after the commissioned systematic review search date. Although several priority outcomes were reported, no conclusive indications of effect were found. The authors also call for a multicentre international trial. Approach to transfusion in pregnant women with SCD
• Decision making about red blood cell transfusion needs to be made on an individual basis, with consideration given to the balance of benefits of transfusion against the risks of transfusion reactions, hyperhaemolysis, blood-borne infections, iron overload and alloimmunization, costs and availability.
• Not all women are able to receive blood transfusions due to multiple red cell alloantibodies or previous severe delayed haemolytic transfusion reactions.
• While iron-chelation therapy is generally used to prevent iron overload in people on chronic simple transfusion, currently used chelators are not recommended in pregnancy. Availability and safety of red blood cell transfusion
• In many parts of the world, chronic transfusion therapy is either not available, not feasible, or is available but without the possibility of iron-chelation therapy to prevent the inevitable and potentially fatal consequences of iron overload (82). In these settings, the advice in non-pregnant adults has been to consider replacing transfusion therapy with, or transitioning from initial transfusion therapy to, hydroxycarbamide at maximal tolerable doses (82).
• A consistent supply of blood relies on regular donations and effective health-care infrastructure (92). Donation rates differ around the world and some HICs see up to seven times more donations than LICs, where the lack of timely, safe transfusions leads to otherwise avoidable deaths (92). In 2010, WHO passed a resolution on blood products that urges Member States to take all the necessary steps to establish, implement and support nationally coordinated, efficiently managed and sustainable blood and plasma programmes according to the availability of resources, with the aim of achieving self-sufficiency, unless special circumstances preclude it (93).
• Blood products used during pregnancy need to be screened for cytomegalovirus in addition to routine blood-borne pathogens, as recommended in the WHO safe blood transfusion guidelines (94)