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Vignette finalist: Blood Transfusions in Sickle Cell Disease

The Lown Institute Vignette Competition challenges medical students and trainees to shine a light on everyday overuse and underuse – common practices that either give patients unnecessary tests and procedures, or that fail to give patients necessary care. Sharing stories of the downstream consequences of overuse can be a powerful counterbalance to the ‘more is better’ culture and can help clinicians recognize and avoid overuse. 

This year, we received vignette submissions from students and trainees all over the country (and internationally!) on topics from avoiding polypharmacy to inappropriate stenting to navigating clinical guidelines. 

We’re publishing the top vignettes on our website. Learn more about the competition and read all the vignettes here.


Blood Transfusions in Sickle Cell Disease

Neil Keshvani, MD
Srikanth Nagalla, MD
Arjun Gupta, MD

University of Texas Southwestern Medical Center

Story from the Front Lines:

A woman in her 50s with homozygous sickle cell disease (SCD) with multiple prior episodes of vaso-occlusive pain crises (VOC) and transfusion-related iron overload treated with deferasirox in the past presented to the emergency department with three days of diffuse body pain worse in the legs and lower back. She did not report chest pain, cough, shortness of breath, vision changes, fevers, chills, or weakness. These symptoms were similar to previous instances of pain crises. Her medications included folic acid and hydroxyurea.

On examination, she was afebrile with blood pressure 143/95 mm Hg, pulse 78/minute, respiratory rate 18/minute, and oxygen saturation 97% on room air. Conjunctival pallor was noted. She was tender to palpation along the paraspinal muscles and over the lower extremities. Initial laboratory evaluation revealed hemoglobin 6.8 g/dL (baseline 7-7.4 g/dL over the last 3 months, reference range 11.2–15.7 g/dL), absolute reticulocyte count 249 x 109/L (reference range, 42–123 x109/L), ferritin 943 ng/mL (reference range, 13–150 ng/mL), and creatinine 0.6 mg/dL (reference range, 0.5-0.9 mg/dL). A chest X-ray revealed no infiltrates, and she was admitted and treated for an uncomplicated VOC with hypotonic intravenous fluids, hydromorphone patient-controlled analgesia, and incentive spirometry. One unit of packed red blood cells was transfused given the hemoglobin level <7 gm/dL, and pre-transfusion screening revealed Anti-E, cold agluttinin, anti-JkA, and anti-BgA antibodies. A post transfusion hemogram revealed a hemoglobin level of 8.2 g/dL. She was discharged 2 days later with improved pain control and close hematology follow-up.

Teachable Moment:

An estimated 100,000 Americans have SCD, a broad entity that includes hemoglobin containing two mutant globin genes, at least one of which is the sickle mutation.1 Those with the homozygous mutation (HbSS) are most severely affected. Blood transfusions are a critical component of management and can be potentially life-saving in patients with SCD, but only in certain clinical settings. Not all anemic patients with SCD require transfusion. SCD affected individuals have diminished red blood cell lifespan due to chronic hemolysis. Many remain asymptomatic, even with baseline hemoglobin values between 6-8 g/dL.1,2 Unlike the general population, a hemoglobin level <7 g/dL without symptoms is not an indication for blood transfusions in patients with SCD.

Acute complications of SCD such as acute symptomatic anemia, acute chest syndrome, acute stroke, and ischemic organ damage are all indications for blood transfusions – either simple or exchange. However, this evidence does not extend to uncomplicated VOCs, which are the most common cause of hospital admission in SCD.2 Early research showed an inverse relationship between hemoglobin and pain crises – pain crises occurred more often in patients who were less anemic.1 The pain rate varied directly with hematocrit, and it is postulated that the decreased viscosity of anemia may improve the vaso-occlusion causing pain. Despite the lack of clinical efficacy, 27% of patients with SCD admitted for a VOC in the 2006 Nationwide Inpatient Sample underwent a blood transfusion.3 Recognizing inappropriate transfusions as a major problem, the American Society of Hematology Choosing Wisely campaign recommends against routinely transfusing patients with SCD with chronic anemia or uncomplicated pain crisis without an appropriate clinical indication.

In addition to their usual risks, blood transfusions can cause 2 crucial toxicities in patient with SCD. First, repetitive simple transfusions can cause iron overload, which was found to be present in one-third of 141 adult SCD patients at post-mortem.4 This can progress to organ dysfunction including heart failure. Second, transfusion recipients are sensitized to donor red blood cell antigens (usually Rh and Kell system antigens), a process known as allo-immunization. This can occur despite traditional blood typing and cross matching techniques. The incidence of allo-immunization in patients with SCD ranges from 18%-47%, compared to only 5% in multiply-transfused non-SCD affected individuals. 2,3 Allo-immunization can result in delayed hemolytic transfusion reactions (DHTR), a potentially fatal process associated with hyperhemolysis and marked anemia. In a five-year retrospective review of patients with SCD at an academic UK center, 7.7% of patients with SCDs undergoing a transfusion suffered a DHTR, and other studies have shown the rate to be as high as 20%.5 This patient with SCD had already suffered complications from blood transfusions (iron overload and allo-immunization) and received an unnecessary transfusion for uncomplicated VOC, putting her at risk for additional complications.

In summary, transfusions can be life-saving in certain acute complications of SCD, but routine use in patients with uncomplicated VOC or chronic asymptomatic anemia should be discouraged. Patients with SCD are more susceptible to harms from blood transfusion, including allo-immunization and iron overload. Individuals with SCD should not routinely be transfused to attain a certain hemoglobin level; rather, a careful assessment of symptoms, clinical status, and laboratory parameters should be performed before transfusing patients with SCD.

References:

  1. National Heart Lung and Blood Institute. Division of Blood Diseases and Resources. The management of sickle cell disease. 4th ed. Bethesda, MD: The Institute; 2002.
  2. Josephson CD, Su LL, Hillyer KL, Hillyer CD. Transfusion in the patient with sickle cell disease: a critical review of the literature and transfusion guidelines. Transfus Med Rev. 2007;21(2):118-133.
  3. Telen MJ, Afenyi-Annan A, Garrett ME, Combs MR, Orringer EP, Ashley-Koch AE. Alloimmunization in sickle cell disease: changing antibody specificities and association with chronic pain and decreased survival. Transfusion. 2015;55(6 Pt 2):1378-1387.
  4. Porter J, Garbowski M. Consequences and management of iron overload in sickle cell disease. Hematology American Society of Hematology Education Program. 2013;2013:447-456.
  5. Vidler JB, Gardner K, Amenyah K, Mijovic A, Thein SL. Delayed haemolytic transfusion reaction in adults with sickle cell disease: a 5-year experience. Br J Haematol. 2015;169(5):746-753.