Caplacizumab: First Case of Thrombotic Thrombocytopenic Purpura Refractory Treated in Spain outside Clinical Trial

Rizo Lm,Maestro As,Gomez Jmo,Gonzalez Ll,Garcia Ng,Mateo Ms,De Oteyza Jp

doi:10.16966/2470-1009.153

Abstract

Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy, caused by a deficiency of ADAMTS-13 (a desintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). It is considered a medical emergency and its standard treatment is based on plasma exchange associated with high doses of corticosteroids. Those patients refractory to standard treatment have a high risk of morbidity-mortality. Through this clinical case, a patient refractory to all the treatments is presented. She was treated whit caplacizumab that is humanized bivalent antibody acting against the domain A1 of the von Willebrand factor and prevents interaction with the glycoprotein Ib-IX-V (GPIb-IX-X). After one year from the end of treatment, the patient remains stable and asymptomatic. Caplacizumab is a good choice in those patients who do not respond to any of the standard treatments and that can lead to a decrease in mortality in patients with refractory thrombotic thrombocytopenic purpura.

Highlights

Thrombotic Thrombocytopenic Purpura (TTP) is a thrombotic microangiopathy, caused by a severe deficiency of ADAMTS-13 which leads to platelet consumption in von Willebrand factor-platelet aggregates and microvascular thrombosis [1].Under normal conditions the von Willebrand Factor (VWF) acts as a central protein of primary hemostasis
The endothelium secretes the ultra-long multimeric von Willebrand factor (VWF-UL) in response to damage, and later they are fragmented by protein ADAMTS-13 [2]
Congenital TTP is caused by a constitutional deficiency of ADAMTS-13, while idiopathic TTP is due to the auto antibodyinhibited function of ADAMTS-13 [3]

Summary

Introduction

Thrombotic Thrombocytopenic Purpura (TTP) is a thrombotic microangiopathy, caused by a severe deficiency of ADAMTS-13 (a desintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) which leads to platelet consumption in von Willebrand factor-platelet aggregates and microvascular thrombosis [1]. The patient began treatment with corticosteroids 1 mg/kg/ day and daily plasma exchange by extending the initial study with hormones, tumor markers, rheumatic tests, serology, immunology, urine analysis and ADAMTS-13 determinations. The value of the latter was less than 1%. The patient experienced a clear improvement 48-72 hours after the beginning of the administration, which was observed in the progressive increase in the number of platelets, as can be seen in figure 1 Due to this clear improvement, the pattern of corticosteroids was decreasing in successive days maintaining daily plasma replacement and the weekly rituximab.

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Discussion

Conclusions