<p>Assessment and Monitoring of Patients with Immune-Mediated Thrombotic Thrombocytopenic Purpura (iTTP): Strategies to Improve Outcomes</p>

Abstract

Background: Acquired or immune-mediated TTP (iTTP) is a life-threatening thrombotic microangiopathy, characterized by the presence of microangiopathic hemolytic anemia and severe thrombocytopenia, and a variable degree of ischemic organ damage, related to a severe deficiency of ADAMTS13, which is a serine metalloprotease necessary for cleavage of large vWF multimers. There has been a dramatic decrease in mortality rates with the recognition of the pathophysiology of iTTP over the years. Although therapeutic plasma exchange (TPE) together with corticosteroids are the backbone of the upfront treatment of patients with iTTP with successful outcomes, patients may remain refractory and/or relapse following an initial response to this treatment. Methods: We performed a review regarding the pathogenesis, diagnosis, treatment strategies, monitoring, and prognosis of iTTP. Results: There are several new treatment strategies, which can be used among these patients, helping in improving outcomes of iTTP. Rituximab has been shown to be a safe and effective adjunct to TPE, especially in patients with refractory and/or relapse as well as it is increasingly used preemptively to prevent exacerbation or recurrence. Recently, caplacizumab, a nanobody targeting vWF, was approved as an addition to the current regimen of TPE and immunomodulation for patients of iTTP. Conclusion: Specific predictors of relapse in patients in remission can be relevant for an optimal patient management. Different models including ADAMTS13 biomarkers can provide a new screening strategy to identify patients who may predict outcomes and the risk of relapse, benefit from preemptive therapy prior to relapse.

Intracranial hemorrhage in immune thrombotic thrombocytopenic purpura treated with caplacizumab: COMMENT from Eşkazan et al

“…In other words, it creates a quick hematological response and imitates a remission; thus, patients may still be vulnerable to complications. 6 Although the patient most probably received PEX ± corticosteroids as an adjunct to caplacizumab in the fourth case, this information was not shared within the text. 3 And even if PEX was administered, we observe a rather quick cessation of PEX and discharge, which of course is the advantage of caplacizumab.…”

“…Prolonging caplacizumab or implementing second-line therapies can also be used in patients without ADAMTS-13 response, but preferably in the context of a trial, because ADAMTS-13 testing is not universally validated and available and its cut-off and standard methods are yet to be clarified. 6,7 The fourth case died due to bleeding because the drug was continued at the time of trauma, but if it had been discontinued beforehand, the patient could have died due to the thrombotic event like the third patient.…”

Do patients with immune-mediated thrombotic thrombocytopenic purpura receiving caplacizumab need antithrombotic therapy?

“…Acquired or immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy with an annual incidence of three cases per one million adults [1]. In the pathogenesis, autoimmune inhibition of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) -also known as von Willebrand factor -cleaving protease (vWFCP) takes role in accumulation of ultra large vWF (ULvWF) multimers, which bond to platelets and induce the formation of microthrombi, causing tissue ischemia, and organ dysfunction [1]. The main causes of morbidity and mortality in iTTP are the thromboembolic complications [2].…”

“…Caplacizumab is a bivalent humanized single-variable-domain immunoglobulin that targets the A1 domain of vWF [1]. It inhibits the interaction between vWF and platelet (GP)1b-IX-V receptor, thus, preventing platelet adhesion.…”

“…It inhibits the interaction between vWF and platelet (GP)1b-IX-V receptor, thus, preventing platelet adhesion. Caplacizumab has been introduced as an adjunct to plasma exchange (PEX) therapy and corticosteroids in iTTP [1,3]. In patients receiving caplacizumab, ischemic organ damage-related biomarkers tend to normalize more rapidly [4], and the composite endpoint of iTTPrelated death, iTTP recurrence, or major thromboembolic events (TEEs) are reduced significantly [4][5][6][7][8].…”