Levels of Von Willebrand Factor Multimers and VWF-Cleaving Protease (ADAMTS-13) in Preterm and Neonate

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2007 by Sheba Medical Center.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT00701610
First received: June 18, 2008
Last updated: NA
Last verified: July 2007
History: No changes posted
  Purpose

Von Willebramd Factor (VWF) is an adhesive glycoprotein synthesized by megakaryocytes and endothelial cells.VWF has a central role in primary hemostasis and is a critical ligand for platelets adhesion and aggregation (1, 2).VWF 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 500-20,000 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-13(A Disintegrin And Metalloprotease with ThromboSpondin motif).If the proteolysis become defective the ULVWF will bind to platlets resulting in systemic thrombotic microangiophaties (TMA) such as thrombotic thrombocytopenic purpura(TTP)(5,6).

ADAMTS-13 belongs to the ADAMTS family of metalloproteases.The structure of ADAMTS-13 is conserved throughout vertebrates, indicating its important function (7).The metalloprotease function was first describe 11 years ago and has been cloned and characterized (8-13).The 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 (14,15).This cleavage produce VWF subunit fragments of 176 kDa and 140 kDa.

The activity of ADAMTS-13 depends on both Zn+2 and Ca+2 ions (16). Low levels or deficiency of ADAMTS-13 is seen in patient with TTP(17,18). 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 (19-21).Tsai 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-13(23).

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.


Condition
Von Willebramd Factor

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Levels of Von Willebrand Factor Multimers and VWF-Cleaving Protease (ADAMTS-13) in Preterm and Neonate

Further study details as provided by Sheba Medical Center:

Biospecimen Retention:   Samples Without DNA

blood will be taken from cord blood at birth from fullterm and preterm infantsinfants


Estimated Enrollment: 100
Study Start Date: August 2007
Estimated Study Completion Date: August 2009
Estimated Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
All infants born in our hospital between August 2007 and August 2009 will participate.

  Eligibility

Ages Eligible for Study:   24 Weeks to 42 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

All infants born n our hospital between August 2007 and August 2009 will enter

Criteria

Inclusion Criteria:

  • All infants born n our hospital between August 2007 and August 2009 will enter

Exclusion Criteria:

  • Thrombocytopenia, maternal aspirin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00701610

Contacts
Contact: tzipora strauss, M.D 972-5-2666-4446 t.tzipi@gmail.com

Locations
Israel
Sheba-Medical-Center Recruiting
Ramat-Gan, Israel, 52621
Contact: tzipora strauss, M.D    972-5-2666-4446    t.zipi@gmail.com   
Sponsors and Collaborators
Sheba Medical Center
  More Information

No publications provided

Responsible Party: Tzipora Strauss, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT00701610     History of Changes
Other Study ID Numbers: SHEBA-08-4132-TS-CTIL
Study First Received: June 18, 2008
Last Updated: June 18, 2008
Health Authority: Israel:Isael Health Ministry Pharmaceutical administration

Keywords provided by Sheba Medical Center:
Von Willebramd Factor (VWF)
All infants born in our hospital since August 2007 ill august 2009 will enter.
Therombocytopenia, maternal aspirin will be excluded

ClinicalTrials.gov processed this record on October 21, 2014