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Titolo:
Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease
Autore:
Furlan, M; Lammle, B;
Indirizzi:
Univ Hosp Bern, Cent Hematol Lab, Inselspital, CH-3010 Bern, Switzerland Univ Hosp Bern Bern Switzerland CH-3010 pital, CH-3010 Bern, Switzerland
Titolo Testata:
BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
fascicolo: 2, volume: 14, anno: 2001,
pagine: 437 - 454
SICI:
1521-6926(200106)14:2<437:AAPOTT>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEMOLYTIC-UREMIC SYNDROME; MICROVASCULAR ENDOTHELIAL-CELLS; VONWILLEBRAND-FACTOR MULTIMERS; INDUCED PLATELET-AGGREGATION; FACTOR-H DEFICIENCY; PLASMA-EXCHANGE; ANTI-CD36 ANTIBODIES; CALPAIN ACTIVITY; IN-VIVO; APOPTOSIS;
Keywords:
thrombotic thrombocytopenic purpura; TTP; haemolytic uraemic syndrome; HUS; von Willebrand factor; VWF; protease; deficiency; constitutional; acquired; pathogenesis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
93
Recensione:
Indirizzi per estratti:
Indirizzo: Furlan, M Univ Hosp Bern, Cent Hematol Lab, Inselspital, CH-3010 Bern, Switzerland Univ Hosp Bern Bern Switzerland CH-3010 3010 Bern, Switzerland
Citazione:
M. Furlan e B. Lammle, "Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease", BEST P R C, 14(2), 2001, pp. 437-454

Abstract

Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) are today often regarded as variants of one syndrome denoted as TTP/HUS, characterized by thrombocytopenia caused by intravascular platelet clumping, microangiopathic haemolytic anaemia, fever, renal abnormalities and neurological disturbances. Unusually large von Willebrand factor multimers have been observed in plasma from patients with chronic relapsing forms of TTP. Their appearance in patients with classic TTP is caused by deficiency of a specific von Willebrand factor-cleaving protease. A constitutional deficiency of this protease has consistently been found in familial cases of TTP, whereas in acquired TTP the protease deficiency is caused by the presence of an inhibiting autoantibody. A normal activity of von Willebrand factor-cleaving protease has been established in patients with HUS. In this chapter, we report 23 cases with severe constitutional protease deficiency: about one half of these patients had their first acute episode as children, whereas the other half had their first TTP event at an adult age, several of them during their first pregnancy. Two of these 23 individuals with congenital protease deficiency, both older than 35 years, have never had an acute TTP event. These results indicate that a deficiency of von Willebrand factor-cleaving protease alone is not sufficient to cause acute TTP. Patients with long-lasting dormant protease deficiency have been found to experience multiple relapses of TTP after having had their first acute episode. In one protease-deficient, plasma-dependent patient with chronic relapsing TTP, we estimated that 5% of normal protease activity is sufficient to remove the most adhesive von Willebrand factor multimers and prevent the formation of platelet microthrombi. The deficiency of von Willebrand factor-cleaving protease is a very strong risk factor for TTP, but the development of an acute bout requires a trigger, possibly causing the activation or apoptosis of endothelial cells in the microcirculation. It is unclear whether antiendothelial cell antibodies, cytokines or other agents are involved in triggering thrombotic microangiopathy. The release of platelet calpain (and/or other proteases), leading to a degradation of von Willebrand factor and to plateletaggregation, has been reported in patients during their acute TTP episode. It is unknown whether calpain directly triggers an acute event or whether it merely reflects its release during the aggregation of platelets by the unusually large von Willebrand factor multimers. With regard to the heterogeneous aetiologyof thrombotic microangiopathies, requiring distinct therapeutic measures, a new classification of thrombotic microangiopathy should replace the current, frequently inappropriate clinical discrimination between TTP and haemolytic uraemic syndrome.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 07:33:25