Hyperhemolysis Syndrome in SCD Patient: Reminder of a Rare but Life-Threatening Complication of Blood Transfusion
Authors: Sweidan Aroob , Vuyyala Sowjanya , Xie Peter , Alhyari Mohammad , Dabak Vrushali S. , Otrock Zaher K. 
Published: November 2021

Abstract
Background: Sickle cell disease (SCD) patients are at risk of developing multiple complications from transfusions, including alloimmunization to red blood cell (RBC) antigens, delayed hemolytic transfusion reactions, and hyperhemolysis syndrome (HS). HS is a serious complication of transfusion characterized by the destruction of both transfused and autologous RBCs with resulting severe anemia and post transfusion hemoglobin lower than pretransfusion levels. We report the case of a middle age female patient with known SCD who developed severe HS following a blood transfusion. We aim to remind physicians of the importance of conservative blood transfusions in SCD patients in order to avoid serious transfusion-related complications.
Case report: A 57-year-old African American patient, with known history of SCD who was doing well with a baseline hemoglobin (Hgb) of 6-7 g/dl. Transfusion history included 4 units of Packed Red Blood Cell (PRBC) during the 5 years prior to this presentation, all of which for mild, non-resolving vaso-occlusive pain crisis. Her most recent transfusion was 7 days prior to her presentation, she received 1 unit of PRBC for a Hgb level of 6.3 g/dl, associated with mild musculoskeletal pain and fatigue. She presented to the Emergency Department 4 days later with worsening fatigue, decreased oral intake and dark urine. On presentation, she was normotensive, afebrile and mildly tachycardic. She had increasing oxygen requirements to maintain O2 saturation above 94%. Her blood work showed a Hgb of 2.8 g/dl (12-15 g/dL), hematocrit 8.3 % (36-46 %), RBC count 0.87 M/uL (4.15-5.55 M/uL), Mean Corpuscular Volume 95.5 fl (80-100 fl), elevated White Cell Count at 28.4 K/uL (3.8-10.6 K/uL), and platelet count 125 K/uL (150-450 K/uL). Hemolysis labs showed low haptoglobin of &lt; 30 mg/dl (30-200 mg/dl), elevated Lactate Dehydrogenase at 3420 IU/L (&lt; 250 IU/L), total bilirubin 2.7 mg/dl (&lt; 1.2 mg/dl), direct bilirubin 0.6 mg/dl (0-0.3 mg/dl), and reticulocyte count 3.5% (0.5-1.5 %; reticulocytopenia relative to degree of anemia). A disseminated intravascular coagulation (DIC) panel showed fibrinogen of 263 mg/dL (200-450 mg/dL), D-dimer greater than 20 ug/mL (&lt; 0.50 ug/ml), prothrombin time of 19.8 seconds (s) (11.5-14.5 s), and partial thromboplastin time of 32 s (22-36 s). High sensitivity troponin was elevated at 650 ng/L (&lt; 19 ng/L). Antibody screen and direct antiglobulin test (DAT) were negative. Peripheral blood smear showed severe anemia with marked anisopoikilocytosis including numerous blister cells, occasional sickle cells and numerous nucleated red blood cells. The recent history of blood transfusion and the current laboratory workup were consistent with HS.
Patient was admitted to the intensive care unit (ICU) for management; she initially received 1g intravenous iron dextran and intravenous immunoglobulin (IVIG) 0.4 g/kg for 5 days. She was also started on erythropoietin, folic acid, and vitamin B12. Her reticulocyte count improved to 19%. Given no improvement in Hgb levels, systemic steroids were started after ruling out infectious etiologies. She initially received methylprednisolone 125mg daily for 2 days, followed by oral prednisone 60mg daily for 7 days. Patient had increased oxygen requirements during admission, had an elevated lactate to 4 mmol/L, and had a drop in Hgb to 2.1 g/dL. She was still managed conservatively with oxygen supplementation and intravenous crystalloid fluids. The decision was to avoid transfusions unless they were life-saving. Patient remained in the ICU unit for 5 days, then was transferred to the hematology floor where she remained hospitalized for 7 days. Oxygen requirements and patient's symptoms steadily improved, hemolysis labs trended down, and reticulocyte count improved. Hgb levels improved gradually to highest of 5.7 g/dl prior to discharge. Patient was then discharged to follow up with her hematologist in the outpatient setting.
Conclusion: This case aims to highlight the importance of early recognition of HS to avoid wrong management with RBC transfusion. Our patient had severe anemia and was managed with transfusion-free approach with good outcome. This case is also meant to remind physicians of the importance of conservative blood transfusions in SCD patients in order to avoid serious and life-threatening transfusion-related complications.

Disclosures
No relevant conflicts of interest to declare.