Case
A 19-year-old female with a history of sickle cell anemia and hemoglobin SS, presents with a 2-day history of worsening lower back pain and dyspnea. Physical exam reveals oxygen saturation of 87% on room air, a temperature of 39.2° C, respiratory rate of 24 breaths per minute, and right-sided rales. Her hemoglobin is 5.3 g/dL (baseline hemoglobin of 7.8 g/dL). Chest radiograph reveals a right upper lobe pneumonia, and she is diagnosed with acute chest syndrome.
What are indications and complications of acute transfusion in sickle cell anemia?
Background
Chronic hemolytic anemia is a trademark of sickle cell anemia (SCA) or hemoglobin (Hb) SS as is acute anemia during illness or vaso-occlusive crises. Blood transfusions were the first therapy used in sickle cell disease, long before the pathophysiology was understood. Transfusion of red blood cells (RBC) increases the percentage of circulating normal Hb A, thereby decreasing the percentage of abnormal, sickled cells. This increases the oxygen-carrying capacity of the patient’s RBCs, improves organ perfusion, prevents organ damage, and can be life saving. SCA patients are the largest users of the United States rare donor blood bank registry.1
Unfortunately, transfusion comes with many risks including infection, transfusion reactions, alloimmunization, iron overload, hyperviscosity, and volume overload.
As SCA is a low-prevalence disease in a minority population, very few studies have been performed. Currently, the guidance available regarding blood transfusion is primarily based on expert opinion.
What to transfuse
Spencer Grant/Science Source
No studies definitively recommend the type of RBC transfusion SCA patients should receive.2 Academic medical centers and sickle cell centers use non-sickle cell, leukoreduced (white blood cells removed), and phenotypically matched RBC for transfusion.Intensive phenotypic matching including ABO, Rh, and minor antigens, and sometimes S may reduce alloimmunization and hemolytic transfusion reactions.1
Leukoreduced and intensive phenotypically matched RBC are not possible in many medical centers. Previous studies have noted decreased incidence of febrile nonhemolytic anemia transfusion reactions, cytomegalovirus transmission, and human leukocyte antigen alloimmunization in leukoreduced blood transfusions, however, these studies did not include SCA patients.2
Complications from transfusion
Complications from blood transfusions include febrile nonhemolytic transfusion reaction, acute hemolytic transfusion reaction (ABO incompatibility), transfusion-associated lung injury (TRALI), transfusion-associated circulatory overload (TACO), infections, and anaphylaxis. The National Heart, Lung, and Blood Institute guidelines specifically highlight the complications of delayed hemolytic transfusion reaction, iron overload, and hyperviscosity in SCA.Approximately 30% of SCA patients have alloantibodies.2 SCA patients may also develop autoimmunization, an immune response to their own RBC, particularly if the patient has multiple autoantibodies.
Infection is a risk for all individuals receiving transfusion. Screening for hepatitis B, hepatitis C, HIV, human T-cell lymphotropic virus, syphilis, West Nile virus, Trympanosoma, and bacteria are routinely performed but not 100% conclusive. Other diseases not routinely screened for include Creutzfeldt-Jakob disease, Babesia, human herpesvirus-8, dengue fever, malaria, and newer concerns such as Zika virus. 2,3
Febrile nonhemolytic transfusion reactions present as an increase in body temperature of more than 1° C during or shortly after receiving a blood transfusion in the absence of other pyrexic stimulus. Febrile nonhemolytic transfusion reaction occurs more frequently in patients with a previous history of transfusions. The use of leukoreduced RBCs reduces the occurrence to less than 1%.2
TRALI presents with the acute onset of hypoxemia and noncardiogenic pulmonary edema within 6 hours of a blood transfusion in the absence of other etiologies. The mechanism of TRALI is caused by an inflammatory response causing injury to the alveolar capillary membrane and the development of pulmonary edema.1
TACO presents with cardiogenic pulmonary edema not from another etiology. This is usually seen after transfusion of excessive volumes of blood or after excessively rapid rates of transfusion.1
Delayed hemolytic transfusion reaction (DHTR) may be a life-threatening immune response to donor cell antigens. The reaction is identified by a drop in the patient’s hemoglobin below the pretransfusion level, reticulocytopenia, a positive direct Coombs test, and occasionally jaundice on physical exam.2 Patients may have an unexpectedly high hemoglobin S% after transfusion from the hemolysis of donor cells. The pathognomonic feature is development of a new alloantibody. DHTR occurs more often in individuals who have received recurrent transfusions and has been reported in 4%-11% of transfused SCA patients.3 Donor and native cells hemolyze intra- and extravascularly 5-20 days after receiving a transfusion.2 DHTR is likely underestimated in SCA as it may be confused for a vaso-occlusive crisis.
Iron overload from recurrent transfusions is a slow, chronic process resulting in end organ damage of the heart, liver, and pancreas. It is associated with more frequent hospitalizations and higher mortality in SCA.3 The average person has 4-5 g of iron with no process to remove the excess. One unit of packed red blood cells adds 250-300 mg of iron.2 Ferritin somewhat correlates to iron overload but is not a reliable method because it is an acute-phase reactant. Liver biopsy is the current diagnostic gold standard, however, noninvasive MRI is gaining diagnostic credibility.
Hb SS blood has up to 10 times higher viscosity than does non–sickle cell blood at the same hemoglobin level. RBC transfusion increases the already hyperviscous state of SCA resulting in slow blood flow through vessels. The slow flow through small vessels from hyperviscosity may result in additional sickling and trigger or worsen a vaso-occlusive crisis. Avascular necrosis is theorized to be a result of hyperviscosity as it occurs more commonly in sickle cell patients with higher hemoglobin. It is important not to transfuse to baseline or above a hemoglobin of 10 g/dL to avoid worsening hyperviscosity.2