Glucocorticoid-induced thrombotic microangiopathy in paroxysmal nocturnal hemoglobinuria: A case report and review of literature

Abstract

BACKGROUND

Thrombotic microangiopathy (TMA) is a group of disorders that converge on excessive platelet aggregation in the microvasculature, leading to consumptive thrombocytopenia, microangiopathic hemolysis and ischemic end-organ dysfunction. In predisposed patients, TMA can be triggered by many environmental factors. Glucocorticoids (GCs) can compromise the vascular endothelium. However, GC-associated TMA has rarely been reported, which may be due to the lack of awareness of clinicians. Given the high frequency of thrombocytopenia during GC treatment, particular attention should be given to this potentially fatal complication.

CASE SUMMARY

An elderly Chinese man had a 12-year history of aplastic anemia (AA) and a 3-year history of paroxysmal nocturnal hemoglobinuria (PNH). Three months earlier, methylprednisolone treatment was initiated at 8 mg/d and increased to 20 mg/d to alleviate complement-mediated hemolysis. Following GC treatment, his platelet counts and hemoglobin levels rapidly decreased. After admission to our hospital, the dose of methylprednisolone was increased to 60 mg/d in an attempt to enhance the suppressive effect. However, increasing the GC dose did not alleviate hemolysis, and his cytopenia worsened. Morphological evaluation of the marrow smears revealed increased cellularity with an increased percentage of erythroid progenitors without evident dysplasia. Cluster of differentiation (CD)55 and CD59 expression was significantly decreased on erythrocytes and granulocytes. In the following days, platelet transfusion was required due to severe thrombocytopenia. Observation of platelet transfusion refractoriness indicated that the exacerbated cytopenia may have been caused by the development of TMA due to GC treatment because the transfused platelet concentrates had no defects in glycosylphosphatidylinositol-anchored proteins. We examined blood smears and found a small number of schistocytes, dacryocytes, acanthocytes and target cells. Discontinuation of GC treatment resulted in rapidly increased platelet counts and steady increases in hemoglobin levels. The patient’s platelet counts and hemoglobin levels returned to the levels prior to GC treatment 4 weeks after GC discontinuation.

CONCLUSION

GCs can drive TMA episodes. When thrombocytopenia occurs during GC treatment, TMA should be considered, and GCs should be discontinued.

Keywords: Aplastic anemia; Paroxysmal nocturnal hemoglobinuria; Glucocorticoid; Methylprednisolone; Thrombotic microangiopathy; Platelet transfusion refractoriness; Case report

Core Tip: Glucocorticoid-associated thrombotic microangiopathy has rarely been reported. Here, we report a patient with paroxysmal nocturnal hemoglobinuria whose hematological parameters worsened during methylprednisolone treatment, and increasing methylprednisolone doses further exacerbated the cytopenia. Observation of platelet transfusion refractoriness suggested the possibility of thrombotic microangiopathy development. Significant hematological improvement was achieved after discontinuation of methylprednisolone treatment, confirming that methylprednisolone treatment acted as the triggering factor to promote platelet aggregation within the microcirculation. Given the wide use of glucocorticoids in clinical practice and the high incidence of thrombocytopenia during glucocorticoid treatment, particular attention should be given to this potentially fatal complication.