Treatment of severe, refractory and rapidly evolving thrombotic thrombocytopenic purpura

Abstract

A 36-year-old man presented to hospital with gross haematuria and evidence of severe, refractory thrombotic thrombocytopenic purpura. Initial treatment with high-volume plasma exchange therapy and early administration of rituximab failed to achieve a sustained clinical response. His clinical course was complicated by left hemianopsia and despite an urgent splenectomy he developed a large right-sided stroke with malignant cerebral oedema that required an emergent decompressive craniotomy. He also had numerous infectious complications as a consequence of an aggressive immunosuppressive strategy. While the patient did not respond to cyclophosphamide, cyclosporine, N-acetylcysteine, and one course of bortezomib, he eventually responded to a second course of bortezomib. One year later, the patient remains in remission and maintains excellent cognitive function. However, he has not completely recovered from his stroke and continues to participate in rehabilitation for his residual physical deficits.

2016 BMJ Publishing Group Ltd.

Figures

Figure 1

Clinical course, major events, and therapeutic interventions. (A) shows the timeline of platelet counts (×109/L, depicted by the solid purple line with the dashed purple line indicating the lower limit of normal) and serum lactate dehydrogenase levels (U/L, depicted by the solid blue line with the dashed blue line indicating the upper limit of normal). The laboratory results for ADAMTS13, inhibitory autoantibodies against ADAMTS13 (U/mL), and CD20+ B cells by flow cytometry are shown below the graph. (B) shows the timeline of complications from thrombotic thrombocytopenic purpura and aggressive immunosuppression. (C) shows the timeline of total daily volume (L) of plasma exchange therapy, indicated by the grey-shaded area. The frequency of plasma exchange therapy can be determined by the following: 8L or less, daily; 10L to 16L, twice daily; more than 16L, three times daily. The graph in (C) also shows all treatments the patient received for the thrombotic thrombocytopenic purpura and its neurological complications. Except for methylprednisolone, the graph includes the specific day for each therapy or intervention. LDH, lactate dehydrogenase; NAC, N-acetylcysteine; ND, not detectable; MCA, middle cerebral artery; PCA, posterior cerebral artery; VRE, vancomycin-resistant Enterococcus.