Von Willebramd Factor Clinical Trial
Official title:
Levels of Von Willebrand Factor Multimers and VWF-Cleaving Protease (ADAMTS-13) in Preterm and Neonate
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.
| Status | Recruiting |
| Enrollment | 100 |
| Est. completion date | August 2009 |
| Est. primary completion date | August 2008 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 24 Weeks to 42 Weeks |
| Eligibility |
Inclusion Criteria: - All infants born n our hospital between August 2007 and August 2009 will enter Exclusion Criteria: - Thrombocytopenia, maternal aspirin |
Observational Model: Cohort, Time Perspective: Prospective
| Country | Name | City | State |
|---|---|---|---|
| Israel | Sheba-Medical-Center | Ramat-Gan |
| Lead Sponsor | Collaborator |
|---|---|
| Sheba Medical Center |
Israel,