COVID-19 as a Potential Trigger for Immune Thrombotic Thrombocytopenic Purpura and Reason for an Unusual Treatment: A Case Report

Abstract

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder characterized by severely reduced activity of the von Willebrand factor (VWF)-cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) due to autoantibodies. This leads to the development of pathogenic multimers of VWF, causing a thrombotic microangiopathy with decreased number of platelets, hemolysis, and life-threatening tissue ischemia of mostly brain, heart, and kidneys. Standard treatment of iTTP involves daily plasma exchange to remove ultra large multimers of VWF, inhibitors, substituting ADAMTS13, and the accompaniment of an immunosuppressive treatment with steroids. Recently, caplacizumab was approved for iTTP. Caplacizumab is a nanobody binding the A1 domain of VWF, blocking its interaction with glycoprotein Ib–IX–V platelet receptor and therefore preventing platelet aggregation. VWF activities may serve as therapeutic drug monitoring of caplacizumab, whereas ADAMTS13 activities may be used for biomarkers to guide caplacizumab treatment modalities and overall treatment duration. Additional immunosuppressive treatment by inhibiting autoantibody formation (e.g., the use of Rituximab, a chimeric monoclonal antibody directed against the B-cell antigen CD20) is a further treatment option. Infections are well-known causes for an acute episode for patients with iTTP. The novel SARS-CoV-2 virus is mainly associated with acute respiratory distress as well as diffuse endothelial inflammation and increased coagulopathy. However, little is known about an infection with SARS-CoV-2 virus triggering iTTP relapses. We herein report the case of an acute iTTP episode accompanying a SARS-CoV-2 infection.

Coronavirus Disease 2019-Associated Thrombotic Microangiopathy: Literature Review

“…The search revealed 46 cases of TMA in association to COVID-19 in adult patients, which are collected in Table 1 and Table 2 . Certain cases [ 25 , 26 , 27 , 28 ] were excluded due to missing data or to the fact that the presented case also received a vaccine against COVID-19 prior to the occurrence of TMA.…”

Impact of Concomitant Thrombotic Thrombocytopenic Purpura on COVID-19 Mortality and Morbidity: A Nationwide Inpatient Sample Analysis

“…20 An intriguing observation is that COVID-19 patients frequently exhibit diminished ADAMTS13 levels likely due to endothelial dysfunction. 21 This reduction has significant implications, as a clear inverse correlation exists between ADAMTS13 levels and COVID-19 patient mortality, whether TTP is present or not. 22…”

Hereditary thrombotic thrombocytopenic purpura and COVID‐19: Impacts of vaccination and infection inrare disease

“…A number of autoimmune phenomena and diseases have been described in the context of COVID‐19 15 and after SARS‐CoV‐2 vaccinations. 24 COVID‐19 has been reported as a trigger for first episodes of iTTP as well as relapses 12 , 13 , 14 , 15 and SARS‐CoV2 vaccination was suggested also as a trigger of iTTP. 16 Nevertheless, two epidemiologic studies clearly suggest that SARS‐CoV‐2 vaccination is unlikely to trigger new‐onset iTTP.…”

“…So far, there are no reports of COVID-19 in hTTP patients. Immune-mediated TTP (iTTP) is more prevalent than hTTP 10,11 and a number of case reports and case series have described first acute iTTP episodes as well as relapses associated with COVID-19 [12][13][14][15] and with SARS-CoV-2 vaccination. 16 Nevertheless, two comprehensive epidemiologic studies suggest that SARS-CoV-2 vaccination does not increase the risk of first episodes of iTTP, but may induce an acute iTTP bout or a relapse in asymptomatic subjects with a (severely) deficient ADAMTS13 activity.…”