ADAMTS-13 is a plasma metalloprotease that cleaves von willebrand factor (vWF).At the present,it has been made great progresses on its structure, biological characteristics and function. ADAMTS-13 plays an important role in artery and venous thrombosis,besides controlling the cleaving of vWF, and the activity of the ADAMTS-13 can be effected by ion concentration and thrombin signal transduction pathway,but how the mechanism of ADAMTS-13 controlled is still not clear. This article reviews ADAMTS-13 changes,relevant mechanism and influencing factors of the enzyme regulation.
ADAM Proteins ; ADAMTS13 Protein ; Humans ; Thrombosis

ADAMTS13 Protein ; Humans ; Plasma Exchange ; Purpura, Thrombotic Thrombocytopenic

OBJECTIVETo detect the plasma activity of von Willebrand factor-cleaving protease (ADAMTS13) in the patients with prothrombotic status, and explore the effect and significance of ADAMTS13 in the prothrombotic status. The correlation of ADAMTS13 with von Willebrand factor (vWF), thrombospondin 1 (TSP1), C-reactive protein etc, and blood pressure was simultaneously analyzed．

METHODSThe activity of ADAMTS13 in patient groups (atherosclerosis, diabetes, acute promyelocytic leukemia, cancer and sepsis, a total of 260 cases) and in control group 50 cases were evaluated by residue collagen binding assay（R-CBA）, the protein levels of TSP1 and vWF were measured by ELISA kits； the correlation of ADAMTS13 activity with CRP, creatinine, and blood pressure was analyzed with statistical soft ware.

RESULTSThe activity of plasma ADAMTS13 in patient group was significantly lower than that in normal control group(P<0.05). And the protein levels of TSP1 and vWF in the patients with prothrombotic status were higher than those in the normal controls(P<0.05). Analysis of the correlation showed that the ADAMTS13 activity correlated negatively with the levels of TSP1 protein, blood sugar, blood pressure, D-dimer, creatinine,and CRP levels (P<0.05), however, the ADAMTS13 activity did not significantly correlate with the levels of serum lipids, blood type, platelet number and hemoglobin level(P>0.05).

CONCLUSIONThe plasma ADAMTS13 activity is decreased in the patients with prothrombotic status, suggesting that the decreased ADAMTS13 activity may participate in the occurrence of prothrombotic status, and the dectection of plasma ADAMTS13 activity may help the diagnosis of pro-thrombotic disease.

ADAMTS13 Protein ; Factor Analysis, Statistical ; Fibrin Fibrinogen Degradation Products ; Humans ; Sepsis ; Thrombosis ; von Willebrand Factor

OBJECTIVETo investigate the antigen levels and activity of von Willebrand factor cleaving protease ADAMTS13 in thrombotic thrombocytopenic purpura (TTP) patients and carriers.

METHODS28 samples from 13 TTP patients and 10 samples from the carriers were examined. The activity of ADAMTS13 was measured by residue collagen binding assay, and antigen by a newly developed sandwich ELISA.

RESULTSThe mean ADAMTS13 level in Chinese normal controls (CN) was (600.93 +/- 145.36) mU/ml (n = 26) comparable to the level (1000 mU/ml) in pooled normal Caucasian plasma, and the activity was (74.79 +/- 11.81)%. Both the antigen level and activity of ADAMTS13 in congenital TTP patients either before plasma exchange (pre-PE) or interval relapse were quite lower than those in normal control, but were increased after PE (post-PE). The antigen was (331.40 +/- 109.85) mU/ml (P < 0.01, n = 10), and activity was (66.79 +/- 12.82)% (P > 0.05). The ADAMTS13 levels pre-PE in idiopathic TTP was (98.7 +/- 82.08) mU/ml (n = 11, P < 0.01), and that post-PE was up to (449.4 +/- 232.33) mU/ml (P < 0.01, n = 10). The activity of ADAMTS13 in patients pre-PE and post-PE were (22.23 +/- 19.07)% (P < 0.01) and (60.92 +/- 22.33)% (P > 0.05) respectively. In a secondary TTP patient the ADAMTS13 antigen was much higher than that in CN, and the activity was 6.00%.

CONCLUSIONThe antigen and activity of ADAMTS13 in most TTP patients pre-PE are deficient, and these two indices in most TTP patients are paralleled. The reason for ADAMTS13 deficiency is congenital shortage or clearance by immune system, but it is unknown that why in some patients the ADAMTS13 antigen is extremely high but its activity is quite low.

ADAM Proteins ; blood ; immunology ; ADAMTS13 Protein ; Adult ; Female ; Humans ; Male ; Purpura, Thrombotic Thrombocytopenic ; blood ; immunology

OBJECTIVETo study the efficacy and safety of rituximab (RTX) in the treatment of idiopathic thrombotic thrombocytopenic purpura (ITTP).

METHODSAmong 17 ITTP patients, nine cases of the RTX group were administrated with RTX plus plasma exchange (PEX) and steroids. Eight cases of the control group received PEX plus steroids±other immune inhibitors. Patients received RTX 375 mg/m², 1 per week for 4 weeks. The laboratory parameters, including hemogram, LDH, ADAMTS13 activities and its inhibitors, and the ratio of B lymphocytes in peripheral blood were monitored. The number of PEX, total plasma volumes, remission time, relapse ratio and adverse effects in both groups were compared.

RESULTSThe median number of PEX/median total plasma volumes in the RTX and control group were 5(2-8)/9.6(4.0-15.4) L and 6(4-9)/11.2(7.5-14.6) L, respectively. Patients in the RTX and control group achieved hematologic remission at the median time of 15(5-20) days and 22(7-36) days, respectively. And the median time of immunological remission in the two groups was 2(2-8) and 2(2-4) weeks, respectively. ADAMTS13 activities increased significantly after 2 weeks in both two groups. There was no relapse in the RTX group, while 4 patients relapsed in the control group. The percentage of B lymphocytes in peripheral blood obviously deduced one week after first dose of RTX infusion compared with the level before treatment [(2.19±5.11)% vs (18.39±7.15)%, P<0.001], and began to gradually increase 9 months later. Severe adverse events were not observed in RTX group during the therapeutic procedure and follow-up, but one patient, who had sustained immunologic remission, died of severe pneumonia 7 months later.

CONCLUSIONIn the treatment of ITTP, RTX in conjunction with PEX and steroids appeared to be a safe and effective therapy, with fast and sustained remission in hematology and even in immunology, with lower relapse rate and less adverse effects. But patients needed to be paid attention to prevent and treat infectious events in time.

ADAM Proteins ; ADAMTS13 Protein ; B-Lymphocytes ; Humans ; Plasma Exchange ; Purpura, Thrombotic Thrombocytopenic ; Recurrence ; Rituximab ; Steroids

ADAMTS13, a plasma metalloprotease, specifically cleaves von Willebrand factor (vWF). Severe deficiency of plasma ADAMTS13 activity results in thrombotic thrombocytopenic purpura (TTP). In this review, the structure and function of ADAMTS13 protease and its relationship with TTP are summarized.
ADAM Proteins ; metabolism ; ADAMTS13 Protein ; Humans ; Purpura, Thrombotic Thrombocytopenic ; diagnosis ; pathology ; therapy

OBJECTIVE: To investigate the biological function of Cysteine rich (CysR) domain of a disintegrin and metalloprotease with thrombospondin type 1 repeats-13 (ADAMTS13) on cleavage of von Willebrand factor (vWF) and provide experimental evidence for exploring the pathogenesis of thrombotic thrombocytopenic purpura (TTP). METHODS: The six amino acids (EDGTLS) in ADAMTS13 CysR domain were point mutated one by one, and the mutant ADAMTS13 proteins were expressed and purified. The cleavage products of vWF polymer by wild-type or mutant ADAMTS13 under denaturing condition or shear stress were separated by 1% SeaKem HGT agarose gel and detected by Western blot. RESULTS: The mutant ADAMTS13 plasmids (M1: Glu515Ala; M2: Asp516Ala; M3: Gly517Ala; M4: Thr518Ala; M5: Leu519Ala; M6: Ser520Ala) were successfully constructed and the proteins of wild-type and mutant ADAMTS13 were purified. Wild-type ADAMTS13 almost completely cleaved the vWF polymer under denaturing condition, while the cleavage activity of M1 mutant was significantly reduced in the same condition (P<0.01). The cleavage activity of M1 mutant of ADAMTS13 was also significantly reduced compared with that of the wild-type under shear stress (P<0.01). The activity of M1 mutant to cleave the FRETS-vWF73 was dramatically reduced compared with that of wild-type ADAMTS13. However, the binding ability of M1 mutant to vWF was similar with that of wild-type ADAMTS13. CONCLUSION The CysR domain of ADAMTS13 plays an important role in the digestion of vWF under denaturing condition and shear stress. The Glu515 amino acid residue might be an important site for substrate recognition.
ADAM Proteins ; ADAMTS13 Protein/genetics* ; Humans ; Purpura, Thrombotic Thrombocytopenic/genetics* ; von Willebrand Factor/genetics*

Thrombotic thrombocytopenic purpura (TTP) is an acute, potentially life-threatening thrombotic microangiopathies (TMA). TTP has mainly been diagnosed by clinical findings, such as thrombocytopenia and microangiopathic haemolytic anemia. In addition, the reduced activity of von Willebrand factor-cleaving metalloproteinase ADAMTS13 below 10% has been accepted internationally as a diagnostic criterion for TTP. In clinic, the accurate diagnosis and early initiation of therapy can significantly improve the survival rate of patients. Therapy should be focused on increasing ADAMTS13 activity and eliminating or inhibiting ADAMTS13 antibody by the infusion or exchange of therapeutic plasma and corticosteroids. Both the administration of recombinant ADAMTS13 and reducing the release of human neutrophil peptides (HNPs) would be novel promising strategies for the prevention of platelet-vWFinteraction. This review briefly summarizes the recent advances in terms of pathogenesis, diagnosis and treatment of TTP.
ADAMTS13 Protein ; Anemia, Hemolytic ; Blood Platelets ; Humans ; Purpura, Thrombotic Thrombocytopenic ; von Willebrand Factor

A girl was admitted to the hospital on day 2 after birth due to jaundice of the skin and sclera for half a day. The main clinical manifestations were persistent severe jaundice and thrombocytopenia, and she was finally diagnosed with congenital thrombotic thrombocytopenic purpura (TTP). Her conditions were improved after phototherapy, exchange transfusion, and infusion of fresh frozen plasma, red blood cells, and platelets. Gene detection showed a homozygous mutation of c.3650T>C(p.I1217T) in the ADAMTS13 gene, while her parents had a heterozygous mutation at this locus. Congenital TTP is a rare autosomal recessive disease, and timely infusion of fresh frozen plasma can achieve a good clinical outcome. This is the first case of congenital TTP caused by homozygous mutation at this locus reported in China and overseas.
ADAMTS13 Protein ; Anemia ; China ; Female ; Humans ; Hyperbilirubinemia ; Infant, Newborn ; Purpura, Thrombotic Thrombocytopenic

Congenital thrombotic thrombocytopenic purpura, also known as Upshaw-Schulman syndrome, is a rare autosomal recessive genetic disorder. The main pathogenesis is homozygous or compound heterozygous variants of von Willebrand factor lyase (ADAMTS13) gene mapped to chromosome 9q34, which may result in severe lack of ADAMTS13 which cleaves von Willebrand factor (vWF) multimers in the plasma and increase the risk of microvascular thrombosis, leading to various complications. The advance of research on the pathogenesis of cTTP, recombinant human ADAMTS13 and gene therapy have made breakthroughs which may lead to cure of cTTP. This article has provided a review for the latest progress made in the diagnosis and treatment of cTTP.
ADAM Proteins/genetics* ; ADAMTS13 Protein/genetics* ; Homozygote ; Humans ; Purpura, Thrombotic Thrombocytopenic/therapy* ; von Willebrand Factor/genetics*