Advances in the Pathogenesis, Diagnosis, and Treatment of Thrombotic Thrombocytopenic Purpura

Abstract

Abstract. Thrombotic thrombocytopenic purpura (TTP) and the hemolytic uremic syndrome (HUS) are both characterized by thrombocytopenia, microangiopathic hemolysis, and organ dysfunction. Other disorders occasionally present with similar manifestations. Recent studies have demonstrated that deficiency in the von Willebrand factor cleaving protease AD-AMTS13, due to genetic mutations or autoimmune inhibitors, causes TTP. Molecular cloning of ADAMTS13 elucidates the structure of the protease, raising the prospect for advances in diagnosis and treatment of the disease. Assay of ADAMTS13 activity distinguishes TTP from HUS and other types of thrombotic microangiopathy (TMA); therefore, the term TTP/HUS should be avoided because it obscures the known or potential differences among the various types of TMA.

Renal thrombotic microangiopathies/thrombotic thrombocytopenic purpura in a patient with primary Sjögren’s syndrome complicated with IgM monoclonal gammopathy of undetermined significance

“…Recent studies indicate that the severe deficiency of a VWF cleaving metalloproteinase, ADAMTS13, is the main cause of platelet thrombosis in TMA / TTP [8,9]. In our case, low ADAMTS13 activity and the presence of schistocytosis may suggest ADAMTS 13-related TMA / TTP rather than APS in the present case.…”

Thrombotic thrombocytopenic purpura following salvage chemotherapy with paclitaxel, ifosfamide and cisplatin in a patient with a refractory germ cell tumor: A case report and review of the literature

“…In drug-induced TTP cases, ADAMST13 deficiency may not be observed (17). In TTP patients who have a normal enzyme level, chemotherapeutic agents cause endothelial toxicity leading to activation of a calpain or other proteases, the decrease of the tissue plasminogen activator level and an increase in the inhibitor of plasminogen activator level (18). Clinicians should establish a diagnosis of TTP and start managing the disease without waiting for the ADAMST13 activity level.…”

“…2 ; IV; days 1-5), were consequently administered every three weeks. Post-treatment positron emission tomography/ CT demonstrated a non-homogeneous soft-tissue mass in the left paraaortic area from the level of the left renal hilus to the aortic bifurcation, with moderate enhancement with 18 F-fluorodeoxyglucose (maximum standardized uptake vale, 2.43). The patient underwent a retroperitoneal lymph node dissection with retroperitoneal mass and lymph node excision, and the pathology report was again compatible with a seminoma.…”

ADAMTS13 is expressed in hepatic stellate cells

“…1,2 The VWF-cleaving protease is essential for preventing platelet aggregation in the circulation, and deficiency of the protease is associated with thrombotic thrombocytopenic purpura (TTP), a disease characterized by the development of VWF-platelet-rich thrombi in the arterioles and capillaries. 3 Recent studies identified this protease as ADAMTS13, a member of the reprolysin-type zinc metalloprotease family. [4][5][6] The human ADAMTS13 gene, spanning 37 kb on human chromosome 9q34, comprises 29 exons that encode a polypeptide of 1427-amino-acid residues and possibly several splicing isoforms.…”