A role for tissue plasminogen activator in thrombotic thrombocytopenic purpura

Abstract Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by generalized microvascular occlusion. TTP has been related to severe deficiency of ADAMTS13, an enzyme that cleaves von Willebrand factor multimers into less adhesive molecules. However, ADAMTS13 deficie...

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Bibliographic Details
Published in:Medical hypotheses 2014-12, Vol.83 (6), p.747-750
Main Authors: Hoirisch-Clapauch, Silvia, Nardi, Antonio Egidio
Format: Article
Language:English
Subjects:
ADAM Proteins - deficiency
ADAMTS13 Protein
Autoimmunity
Blood Platelets - metabolism
Body Mass Index
Cushing Syndrome - metabolism
Fibrinolysin - metabolism
Humans
Hyperinsulinism - metabolism
Internal Medicine
Purpura, Thrombotic Thrombocytopenic - blood
Remission Induction
Tissue Plasminogen Activator - metabolism
von Willebrand Factor - metabolism
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Summary:Abstract Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by generalized microvascular occlusion. TTP has been related to severe deficiency of ADAMTS13, an enzyme that cleaves von Willebrand factor multimers into less adhesive molecules. However, ADAMTS13 deficiency correlates poorly with severity of thrombocytopenia or microangiopathic hemolysis, with the frequency of neurologic complications or the response to plasma exchange. Also, some patients with severe hereditary ADAMTS13 deficiency consistently relapse every few weeks, whereas others remain asymptomatic into their forties. Taken together, these findings suggest that an additional element is missing in the pathophysiology of TTP. We postulate that both low ADAMTS13 activity and low tissue-plasminogen activator activity are required to trigger TTP attacks. Tissue-plasminogen activator end product, plasmin, extensively degrades von Willebrand factor, breaking-down the bonds between platelets and the blood vessel wall, so that low tissue-plasminogen activator activity prevents a mechanism similar to that of ADAMTS13. The hypothesis that low tissue-plasminogen activator activity plays an important role in TTP pathogenesis is further substantiated by TTP comorbidity. Problems prevalent in patients with TTP attacks or with long-term TTP remission, including increased body mass index, major depression, cognitive abnormalities, hypertension, and premature death, are somehow associated with low tissue-plasminogen activator activity.
ISSN:0306-9877
1532-2777
DOI:10.1016/j.mehy.2014.09.032