An 85‐year‐old man without co‐morbidities presented with anorexia, asthenia and pruritus shortly after a first dose of Pfizer‐BioNTech COVID‐19 vaccine. His full blood count showed a normal haemoglobin concentration, severe thombocytopenia (platelet count 34 × 109/l), neutrophilia (neutrophil count 9.2 × 109/l), mild eosinophilia (eosinophil count 0.6 × 109/l) and lymphopenia (lymphocyte count 0.5 × 109/l). These anomalies had not been found on a blood count carried out a few days before administration of the vaccine. Clinical examination showed neither organomegaly nor signs of bleeding. A bone marrow aspirate showed low cellularity with absence of megakaryocytes in all examined films; myeloid and erythroid cells were present at all stages of maturation with a myeloid/erythroid ratio of 5:1. Eosinophils constituted 20% of nucleated cells. Haemophagocytosis was observed with scattered histiocytes engulfing nucleated cells and erythrocytes (top images, all images ×100 objective). The most conspicuous finding was the presence of atypical large lymphocytes with uniformly dense or clumped chromatin, moderate to abundant agranular hyperbasophilic cytoplasm and numerous vacuoles (top and bottom left). These lymphocytes sometimes evoked plasma cells (top right). The same morphological appearance was found in the infrequent peripheral lymphocytes (bottom right). There was also vacuolation of neutrophils and eosinophils in both the bone marrow and the blood. Haemophagocytic lymphohistiocytosis (HLH) secondary to the vaccine was suspected but diagnostic criteria were not met. Biochemistry showed C‐reactive protein 13.8 mg/l (normal range <8 mg/l), triglyceride 2.7 mmol/l (HLH‐2004 diagnostic criteria >3 mmol/l), ferritin 378 µg/l (HLH‐2004 diagnostic criteria >500 µg/l) and fibrinogen 4.3 g/l (HLH‐2004 diagnostic criteria <1.5 g/l).
The spectrum of clinicopathological features of COVID‐19 includes macrophage activation syndrome, which is characterized by the activation of cytotoxic T cells with haemophagocytosis and the massive release of inflammatory cytokines defining the ‘cytokine storm syndrome’. Macrophage activation appears to play an important pathogenetic role in SARS‐CoV‐2 infection. This syndrome has different clinicopathological features from HLH.
Most deaths from COVID‐19 occur in the elderly. Vaccines are undoubtedly the most important measure to reduce mortality in this group. In this patient, quantitative and qualitative cytological abnormalities in blood and bone marrow secondary to SARS‐CoV‐2 vaccine shared some features with those seen in COVID‐19.
