Post-Transfusion Hemophagocytosis Without Hemophagocytic Lymphohistiocytosis

Abstract

Hemophagocytosis refers to ingestion of hematopoietic elements or mature blood cells by another cell, typically by cells conventionally associated with phagocytic capacity. Although the finding of hemophagocytosis as a prominent feature in a patient's bone marrow might prompt consideration of a hemophagocytic syndrome (HPS) such as hemophagocytic lymphohistiocytosis (HLH) in a clinician's or pathologist's differential diagnosis, this morphologic feature can be nonspecific in the absence of other clinical and laboratory features of pathologic immune activation, which is the sine qua non of HPS/HLH. We describe three patients whose clinical presentations included transfusion-dependent anemia and whose bone marrow aspirates showed unexpectedly brisk hemophagocytosis of mature red blood cells. Despite striking morphologic hemophagocytosis, no patient met criteria for diagnosis of an HPS. Transfusion-associated hemophagocytosis and hyperferritinemia must be carefully distinguished from HLH through clinical and laboratory assessment. Biomarkers of pathologic immune activation are important diagnostic aids.

Bone marrow haemophagocytosis indicates severe infection with severe acute respiratory syndrome coronavirus 2

“…A wellknown trigger to induce haemophagocytosis is blood transfusion. 20,21 In addition, the development of haemophagocytosis has been described in patients who suffer from malignant neoplasia, autoinflammatory diseases such as lupus erythematosus, or non-SARS-CoV-2 infectious diseases. 12 Bone marrow aspiration as an invasive diagnostic procedure is mostly performed on patients with haematological diseases, who are also at higher risk of suffering from haemophagocytosis.…”

“…Their control group consisted of 20 random bone marrow aspirates, of which 40% also showed at least one cell with haemophagocytosis, but alternative risk factors for haemophagocytosis were not reported. A well‐known trigger to induce haemophagocytosis is blood transfusion 20,21 . In addition, the development of haemophagocytosis has been described in patients who suffer from malignant neoplasia, autoinflammatory diseases such as lupus erythematosus, or non‐SARS‐CoV‐2 infectious diseases 12 .…”

Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes

“…The HScore was developed specifically for secondary, and especially malignancy associated, HLH in adults, but unfortunately does not include any cytokine-related criteria [28]. Initially named for the hemophagocytosis seen on tissue biopsy; hemophagocytosis in bone marrow aspirate is a common but non-specific feature in adults [29,30]. Clinical and laboratory features include fevers (often described as "hectic" in that they may exceed 40 • C), organomegaly, cytopenias, coagulopathy, and profound hyperferritinemia often >10,000 μg/L; which often rapidly worsen despite initial empiric anti-microbial therapy resulting in eventual multisystem organ failure [24,31].…”

Hemophagocytic Lymphohistiocytosis Secondary to Immune Checkpoint Inhibitor Therapy

“…Soluble CD25/soluble interleukin-2 receptor (sIL-2R) alpha is a more specific biomarker, although it needs to be specifically studied in the ICI-HLH setting [ 23 ]. Further, hemophagocytosis in bone marrow can be seen in sepsis, after blood transfusions [ 24 ], etc. Overall, it is important to recognize the clinical and laboratory features of HLH and perform a comprehensive evaluation to find the underlying etiology [ 25 ].…”