Which anemia is associated with the 52 syndrome?

Hemophagocytic Syndrome (52-Day Syndrome)

The anemia associated with "52 syndrome" is hemophagocytic syndrome (HPS), a rare but life-threatening condition characterized by bone marrow and organ infiltration by activated macrophages that phagocytose red blood cells, typically presenting around 52 days post-transplantation. 1

Clinical Presentation and Timing

• HPS develops at a median of 52 days after transplantation in kidney transplant recipients, which is the origin of the "52 syndrome" terminology 1
• Fever is universally present (100% of cases), making it a cardinal feature that should trigger immediate suspicion 1
• Hepatosplenomegaly occurs in approximately 53% of patients (9 of 17 cases in the retrospective analysis) 1
• The syndrome carries a poor prognosis with approximately 47% mortality (8 of 17 patients died) despite treatment 1

Pathophysiology of Anemia in HPS

• The anemia results from bone marrow and organ infiltration by activated nonmalignant macrophages that actively phagocytose erythrocytes 1
• This represents a normocytic anemia with normal or low reticulocytes, as the bone marrow's compensatory response is impaired by the infiltrative process 1
• The macrophage activation leads to increased phagocytic activity, directly removing red blood cells from circulation 1

Triggering Factors and Risk Profile

Immunosuppression-related triggers:

• Antilymphocyte globulin use within 3 months preceding presentation occurred in 65% of cases (11 of 17 patients) 1
• Calcineurin inhibitors (cyclosporine, tacrolimus) and OKT3 are associated with microangiopathy and hemolysis 1

Infectious triggers (53% of cases):

• Viral infections: CMV, Epstein-Barr virus, human herpes virus 6 and 8 1
• Other infections: tuberculosis, toxoplasmosis, Pneumocystis carinii pneumonia 1

Malignancy-related:

• Posttransplantation lymphoproliferative disease was present in 12% of cases (2 of 17 patients) 1

Diagnostic Approach

Essential laboratory findings:

• Complete blood count showing normocytic anemia with normal or low reticulocyte count 1
• Bone marrow examination is diagnostic, revealing hemophagocytosis by activated macrophages 1
• Ferritin levels are typically markedly elevated due to the inflammatory state and iron sequestration 1
• Hepatosplenomegaly on imaging supports the diagnosis 1

Key differentiating features from other anemias:

• Unlike iron deficiency anemia, ferritin is elevated rather than decreased 1
• Unlike hemolytic anemia, reticulocyte count is not elevated 1
• The presence of fever, hepatosplenomegaly, and recent immunosuppression distinguishes it from anemia of chronic disease 1

Management Principles

Immediate interventions:

• Anti-infectious therapy targeting identified pathogens (viral, bacterial, or parasitic) 1
• Tapering of immunosuppression to allow immune recovery while balancing transplant rejection risk 1
• Supportive care with transfusions as needed for symptomatic anemia 1

Critical pitfall to avoid:

• Do not delay treatment while awaiting bone marrow biopsy results if clinical suspicion is high, as the 47% mortality rate demands urgent intervention 1
• The combination of fever, cytopenias, hepatosplenomegaly, and recent antilymphocyte therapy in a transplant recipient at approximately 52 days post-transplant should trigger immediate empiric treatment 1