Plasma von Willebrand factor antigen (vWF:AG) and thrombomodulin (TM) levels in adult thrombotic thrombocytopenic purpura/hemolytic uremic syndromes (TTP/HUS) and bone marrow transplant-associated thrombotic microangiopathy (BMT-TM)

Abstract Thrombotic thrombocytopenic purpura (TTP) after bone marrow transplantation (BMT) differs from classic TTP in its clinical course and therapy. A characteristic of classic TTP is the inhibition of a plasma protease that specifically cleaves von Willebrand factor (vWF), thus reducing its multimeric size. We investigated whether this protease was also inhibited in BMT-associated TTP. Plasma from patients with classic or BMT-associated TTP was incubated with recombinant vWF R834Q, a vWF mutant with enhanced sensitivity to the protease. The proteolysis of vWF multimers was analyzed and quantified on Western blot. Metalloprotease activity was strongly inhibited in the classic TTP patient group. However, metalloprotease activity was normal in the BMT-associated TTP patient group. The difference in activity between the two patient groups was highly significant (P = .0016). The results indicate that the etiologies of classic and BMT-associated TTP are indeed different and provide an explanation for the lack of success of plasma exchange in BMT-associated TTP.

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Clinical significance of measuring ADAMTS-13, its inhibitor and von Willebrand factor in obstetric and gynecological practice

Obstetrics Gynecology and Reproduction ◽

10.17749/2313-7347/ob.gyn.rep.2021.203 ◽

2021 ◽

Vol 15 (1) ◽

pp. 93-106

Author(s):

K. N. Grigoreva ◽

V. O. Bitsadze ◽

J. Kh. Khizroeva ◽

M. V. Tretyakova ◽

D. A. Ponomarev ◽

...

Keyword(s):

Thrombotic Thrombocytopenic Purpura ◽

Clinical Significance ◽

Von Willebrand Factor ◽

Thrombotic Microangiopathy ◽

Thrombocytopenic Purpura ◽

Pathological Conditions ◽

Von Willebrand ◽

Willebrand Factor

ADAMTS-13 is a crucial metalloproteinase involved in liberating fragments of von Willebrand factor (vWF) into the plasma as well as regulating its activity by cleaving "ultra-large" multimers into smaller and less active counterparts. Many pathological conditions, including those emerged during pregnancy are characterized by increased level of vWF and decreased ADAMTS-13 activity. In this regard, it is necessary to monitor the levels of vWF and ADAMTS-13 activity to prevent thrombotic thrombocytopenic purpura (Moschcowitz disease) as one of the most severe forms of thrombotic microangiopathy.

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von Willebrand Factor Proteolysis Is Deficient in Classic, but not in Bone Marrow Transplantation–Associated, Thrombotic Thrombocytopenic Purpura

Blood ◽

10.1182/blood.v93.11.3798.411k07_3798_3802 ◽

1999 ◽

Vol 93 (11) ◽

pp. 3798-3802 ◽

Cited By ~ 4

Author(s):

R. Martijn van der Plas ◽

Marion E. Schiphorst ◽

Eric G. Huizinga ◽

Ronald J. Hené ◽

Leo F. Verdonck ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Thrombotic Thrombocytopenic Purpura ◽

Patient Group ◽

Von Willebrand Factor ◽

Marrow Transplantation ◽

Thrombocytopenic Purpura ◽

Metalloprotease Activity ◽

Von Willebrand ◽

Willebrand Factor

Thrombotic thrombocytopenic purpura (TTP) after bone marrow transplantation (BMT) differs from classic TTP in its clinical course and therapy. A characteristic of classic TTP is the inhibition of a plasma protease that specifically cleaves von Willebrand factor (vWF), thus reducing its multimeric size. We investigated whether this protease was also inhibited in BMT-associated TTP. Plasma from patients with classic or BMT-associated TTP was incubated with recombinant vWF R834Q, a vWF mutant with enhanced sensitivity to the protease. The proteolysis of vWF multimers was analyzed and quantified on Western blot. Metalloprotease activity was strongly inhibited in the classic TTP patient group. However, metalloprotease activity was normal in the BMT-associated TTP patient group. The difference in activity between the two patient groups was highly significant (P = .0016). The results indicate that the etiologies of classic and BMT-associated TTP are indeed different and provide an explanation for the lack of success of plasma exchange in BMT-associated TTP.

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