Ignite Creation Date:
2024-05-05 @ 7:36 PM
Last Modification Date:
2024-10-26 @ 9:51 AM
Study NCT ID:
NCT00701610
Status:
UNKNOWN
Last Update Posted:
2008-06-19
First Post:
2008-06-18
Brief Title:
Levels of Von Willebrand Factor Multimers and VWF-Cleaving Protease ADAMTS-13 in Preterm and Neonate
Sponsor:
Sheba Medical Center
Organization:
Sheba Medical Center
Study Overview
Official Title:
Levels of Von Willebrand Factor Multimers and VWF-Cleaving Protease ADAMTS-13 in Preterm and Neonate
Status:
UNKNOWN
Status Verified Date:
2007-07
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Von Willebramd Factor VWF is an adhesive glycoprotein synthesized by megakaryocytes and endothelial cellsVWF has a central role in primary hemostasis and is a critical ligand for platelets adhesion and aggregation 1 2VWF is the carrier of circulating factor 8 as well VWF is stored in Wiebel-Palade bodies in endothelial cells and in platelets alfa granules in a form of Ultra-large UL multimers
The VWF multimers are composed from subunits which are linked by disulfide bonds that alternate between 2 C- terminal ends and 2 N- terminal ends in a head-to-head and tail-to-tail fashion 3 4 The biological activity of VWF has been shown to be related to the size of the multimers
VWF is released from endothelial cells toward the plasma as a multimers ranging from 500-20000 kD The UL multimers are hemostaticallly more effective than the smaller forms They spontaneously bind to platelets which lead to the formation of microthrombi in the circulation This mechanism is downregulated by the plasma protease ADAMTS-13A Disintegrin And Metalloprotease with ThromboSpondin motifIf the proteolysis become defective the ULVWF will bind to platlets resulting in systemic thrombotic microangiophaties TMA such as thrombotic thrombocytopenic purpuraTTP56
ADAMTS-13 belongs to the ADAMTS family of metalloproteasesThe structure of ADAMTS-13 is conserved throughout vertebrates indicating its important function 7The metalloprotease function was first describe 11 years ago and has been cloned and characterized 8-13The ADAMTS family of metaloploproteases is required in other systems such as genitourinary system ADAMTS1 collagen system ADAMTS2 and as a cleaving protease of VWF VWFCP - ADAMTS13 When VWF multimer is subjected to sufficient fluid shear stress ADAMTS-13 cleaves VWF at a unique 842Tyr- 843Met bond in domain A2 1415This cleavage produce VWF subunit fragments of 176 kDa and 140 kDa
The activity of ADAMTS-13 depends on both Zn2 and Ca2 ions 16 Low levels or deficiency of ADAMTS-13 is seen in patient with TTP1718 Mannuccio et al 19 showed that low levels of ADAMTS-13 are seen in other conditions such as healthy adults older than 65 years patients with cirrhosis uremia acute inflammation postoperative period In neonate and preterm infants the data is limited Few studies have shown that levels of ADAMTS-13 are low in neonate 19-21Tsai et al 22 observed that ADAMTS-13 activity is normal in cord blood compared to adults In preterm infants a pilot study showed that preterm have low levels of ADAMTS-1323
The aim of our study is to check ADAMTS-13 VWF multimers VWF antigen and VWF collagen binding activity in healthy and sick neonate and in preterm infants
The VWF multimers are composed from subunits which are linked by disulfide bonds that alternate between 2 C- terminal ends and 2 N- terminal ends in a head-to-head and tail-to-tail fashion 3 4 The biological activity of VWF has been shown to be related to the size of the multimers
VWF is released from endothelial cells toward the plasma as a multimers ranging from 500-20000 kD The UL multimers are hemostaticallly more effective than the smaller forms They spontaneously bind to platelets which lead to the formation of microthrombi in the circulation This mechanism is downregulated by the plasma protease ADAMTS-13A Disintegrin And Metalloprotease with ThromboSpondin motifIf the proteolysis become defective the ULVWF will bind to platlets resulting in systemic thrombotic microangiophaties TMA such as thrombotic thrombocytopenic purpuraTTP56
ADAMTS-13 belongs to the ADAMTS family of metalloproteasesThe structure of ADAMTS-13 is conserved throughout vertebrates indicating its important function 7The metalloprotease function was first describe 11 years ago and has been cloned and characterized 8-13The ADAMTS family of metaloploproteases is required in other systems such as genitourinary system ADAMTS1 collagen system ADAMTS2 and as a cleaving protease of VWF VWFCP - ADAMTS13 When VWF multimer is subjected to sufficient fluid shear stress ADAMTS-13 cleaves VWF at a unique 842Tyr- 843Met bond in domain A2 1415This cleavage produce VWF subunit fragments of 176 kDa and 140 kDa
The activity of ADAMTS-13 depends on both Zn2 and Ca2 ions 16 Low levels or deficiency of ADAMTS-13 is seen in patient with TTP1718 Mannuccio et al 19 showed that low levels of ADAMTS-13 are seen in other conditions such as healthy adults older than 65 years patients with cirrhosis uremia acute inflammation postoperative period In neonate and preterm infants the data is limited Few studies have shown that levels of ADAMTS-13 are low in neonate 19-21Tsai et al 22 observed that ADAMTS-13 activity is normal in cord blood compared to adults In preterm infants a pilot study showed that preterm have low levels of ADAMTS-1323
The aim of our study is to check ADAMTS-13 VWF multimers VWF antigen and VWF collagen binding activity in healthy and sick neonate and in preterm infants
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None