Challenging Case of Hemolytic Anemia and Splenic Sequestration in Sickle Cell Disease
Authors: Catueno Samanta , Vargas Carlos , Bista Bibek , Bai Yu , Austin Mary , Frost Maria , Raj Reeja , Srivaths Lakshmi 
Published: June 2024

Presentation Date: 6/8/2024

Presentation Start Time: 6:00:00 PM

Background

Warm autoimmune hemolytic anemia (wAIHA) is rare in Sickle cell disease (SCD). Splenic sequestration is an SCD crisis, with Red Blood Cells (RBC) trapped in splenic reticulo-endothelial system causing a decrease in hemoglobin, with management involving RBC transfusion. Delayed hemolytic transfusion reaction (DHTR) and Hyperhemolysis syndrome (HS in SCD are caused by RBC alloimmunization, wherein RBC transfusion is avoided or attempted very carefully for severe anemia.

Management of SCD patients presenting simultaneously with wAIHA, splenic sequestration, and possible DHTR/HS poses a major clinical challenge.

Results

A 5-year-old female with SCD (Hb SS) on hydroxyurea (HU), presented with decline in Hemoglobin (Hb) to 8.8 g/dl, increase in spleen size, Vaso Occlusive Crisis (VOC)/orbital bone marrow infarction. She received one unit of crossmatch compatible RBC, that was inadvertently not matched for Rh/Kell antigens. Due to persistently low Hb (∼5-6 gm/dL), poor compliance with HU and office visits, and severe VOC, decision was made to start her on chronic transfusion regimen.

A month after the transfusion, anti-D, anti-C and anti-E Antibodies and a non-specific IgG were newly identified in the patient’s plasma with a negative DAT. Fully phenotypically matched RBC units were repeatedly crossmatch incompatible. She received one unit of PRBC, with an unspecific IgG antibody detected on DAT elution, premedicated with methyl prednisone, and Intravenous Immunoglobulin (IVIG) after PRBC in early January 2024. Her posttransfusion Hb was 10 g/dl, HbS 47 and HbA 37%. Labs done 1 week after the transfusion reported Hb 4.2 g/dl, HbS 57% and HbA 17%, when patient was admitted with severe anemia and splenomegaly 6 cm below left costal margin. Labs showed Hb nadir of 3.1 g/dl, reticulocyte 24%, LDH 963 u/L, Bilirubin 4.6 mg/dl and Haptoglobin &lt; 8, non-specific IgG in DAT eluate. With diagnosis of warm AIHA, splenic sequestration, and possible DHTR/HS, patient was admitted to PICU and was started on Methylprednisolone 1 mg/kg Q6, IVIG 1 gm/kg daily x 5 days, and Rituximab 375 mg/m2 weekly x 4, with consideration of plasmapheresis if patient did not respond to this medical treatment. Slow PRBC (+1 incompatible unit) transfusion in small aliquots (total of 10 ml/kg) was given after receiving first dose of Rituximab, with no adverse reactions. After Hb and hemolysis labs improved, slow steroid wean was initiated. The patient had a relapse of wAIHA and splenic sequestration 1 week after discharge, requiring PRBC transfusion and laparoscopic splenectomy. The patient is currently on a slow prednisone wean and has received 2 doses of Rituximab, with Hb stable at ∼9 g/dl, and reticulocyte count at ∼ 16%. Evaluation for Bone marrow transplantation as definitive treatment for SCD has been initiated.

To our knowledge, there have been no case reports describing the combination of wAIHA, splenic sequestration and possible DHTR/HS. The development of alloantibodies has been well described in SCD in up to 40% of cases, and a retrospective review showed development of autoantibodies in 8% of a cohort of pediatric patients with SCD and history of transfusion. Splenic sequestration is a well-recognized, serious SCD complication.

Our case presents a distinctive scenario involving multiple complications of SCD: wAIHA, splenic sequestration and possible DHTR/HS, contributing to recurrent life-threatening anemia, with significant management challenges. However, with prompt multi-disciplinary care involving carefully matched PRBC transfusions, medications for AIHA, and laparoscopic splenectomy, the patient’s critical condition improved.

Conclusions

This case highlights the various major complications associated with SCD management and the collaborative, multi-disciplinary management that was crucial for this patient’s recovery. Clinicians should maintain a high level of suspicion for autoantibody development, particularly in patients with existing erythrocyte alloantibodies. While prevention of DHTR is done by avoiding exposure to immunogenic RBC antigens by finding completely matched donors, it is challenging when emergent transfusion is required. In our patient, IVIG infusion, steroids, Rituximab, and least incompatible PRBC transfusion helped to treat her ongoing immune-mediated hemolysis, splenic sequestration, subsequently requiring laparoscopic splenectomy for recurrent splenic sequestration/hemolysis.