Ignite Creation Date:
2024-05-06 @ 12:15 PM
Last Modification Date:
2024-10-26 @ 12:56 PM
Study NCT ID:
NCT03715673
Status:
UNKNOWN
Last Update Posted:
2020-01-13
First Post:
2018-10-19
Brief Title:
Von Willebrand Antigen and Activity as Novel Biomarkers of Hemostasis in Inflammatory Bowel Disease
Sponsor:
Assiut University
Organization:
Assiut University
Study Overview
Official Title:
Von Willebrand Antigen and Activity as Novel Biomarkers of Hemostasis in Inflammatory Bowel Disease
Status:
UNKNOWN
Status Verified Date:
2020-01
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:
The investigators are going to study von Willebrand antigen and activity levels in patients with inflammatory bowel disease The study will be on 46 patients who were diagnosed with inflammatory bowel disease mainly ulcerative colitis and Crohns disease divided into two arms group A will include 23 cases with active IBDcasesstatus and group B will include 23 cases with inactive IBD statuscontrol to compare the vWF antigen and activity expected to be higher in active disease group
The investigators will follow all of the patients for any arterial or venous thrombosis to evaluate IBD as a risk factor of thrombosis on the other hand they are looking to detect cases of acquired von Willebrand syndrome in some cases with bleeding that not explained by the inflammatory bowel disease status
The aim of the work
1 Assessment of VWF antigen in patients with inflammatory bowel disease and correlate it to disease activity
2 Evaluation of VWF antigen as a risk factor for thrombosis in inflammatory bowel disease patients
3 Detection of acquired von Willebrand disease in inflammatory bowel disease
The investigators will follow all of the patients for any arterial or venous thrombosis to evaluate IBD as a risk factor of thrombosis on the other hand they are looking to detect cases of acquired von Willebrand syndrome in some cases with bleeding that not explained by the inflammatory bowel disease status
The aim of the work
1 Assessment of VWF antigen in patients with inflammatory bowel disease and correlate it to disease activity
2 Evaluation of VWF antigen as a risk factor for thrombosis in inflammatory bowel disease patients
3 Detection of acquired von Willebrand disease in inflammatory bowel disease
Detailed Description:
VWF is a high-molecular-weight multimeric glycoprotein synthesized and released by vascular endothelial cells and megakaryocytes that play an important role in platelet-endothelial cell interaction and stabilizing the factor VIII FVIII coagulation protein
Von Willebrand factor VWF is an acute-phase protein and a marker of endothelial damage
VWF is crucial for platelet adhesion and aggregation High-molecular weight multimers HMWMs are involved in platelet aggregation under high shear stress but under normal conditions it presents solely in the subendothelium and released into the bloodstream following activation of endothelial cells
Coagulation and inflammation are simultaneously activated and respond in synergy as a preserved mechanism to repair the injured areas during tissue damage
This observation is particularly relevant in acute inflammatory diseases such as sepsis but it also seems to be very important in chronic inflammatory conditions such as inflammatory bowel disease
Inflammatory bowel disease IBD with its two main forms ulcerative colitis UC and Crohn disease CD is a chronic inflammatory condition characterized by local and systemic inflammation predominantly affecting the gastrointestinal tract and well known to be associated with a hypercoagulable state and subsequently with an increased risk for venous thromboembolism VTE
Thromboembolic complications such as Deep Venous Thrombosis DVT and Pulmonary Embolism PE represent amongst IBD complications an important and underestimated factor to be borne in mind which can significantly influence patients morbidity and mortality
In fact according to the latest population-cohort studies a 2 to 3-time fold increased risk of developing of thromboembolic complications was reported for IBD patients compared to general population
In particular as Grainge et al and Papa et al both demonstrate in their studies the incidence of thromboembolic events varies depending on the activity phase of the disease suggesting that there is a higher risk of thromboembolic complications especially during IBD flares with similar relative risk values for both Crohns Disease and Ulcerative Colitis
Although the causes of the increased risk of VTE in IBD are not yet completely understood endothelial dysfunction has been demonstrated in IBD and it is evident through increasing levels of endothelial injury markers The most frequently used biochemical markers of endothelial damage include von Willebrand factor vWF TM vascular cell adhesion molecule 1 VCAM-1 intercellular adhesion molecule 1 ICAM-1 and endothelin-1 ET-1
In 2017 Cibor et al published the first report of the effects of parameters associated with the structure and function of VWF on hemostasis in IBD On the one hand ADAMTS13 Ag was lower in IBD patients than in controls particularly in subjects with UC this resulted in an increased number of circulating multimers of VWF and thus an elevated thrombotic risk The prothrombotic effects are enhanced by markedly elevated VWF Ag
On the other hand the incidence of AVWS which leads to an increased risk for bleeding was higher in IBD patients These findings provide insight into the elevated risk for thromboembolic events and bleeding observed in UC and less frequently in CD The dysregulation of the balance between VWF function and ADAMTS13 reported herein might contribute to the complex hemostatic abnormalities observed in IBD
Currently the association between CD and AVWS is likely underestimated especially in cases of acute bleeding not related to disease activity
In 2017 Di Sabatino et al reported three cases of IBD patients who developed severe hemorrhagic manifestations due to the concomitant presence of an AVWS in addition to other three cases was described in the literature Such a condition can be life-threatening and its timely identiļ¬cation is mandatory to adopt the optimal therapeutic strategy
The association between AVWS and IBD might be more frequent than expected The autoimmune pathogenesis of IBD makes the association more likely The availability of specialized coagulation centers and correlation with clinical information should confirm the diagnosis
Methodology
Patients will be subjected to the following
Clinical assessment
1 The clinical assessment will include demographic data the presence of comorbidities cigarette-smoking habits previous history of thromboembolism and medications
2 Body mass index BMI will be calculated for all patients
3 In patients with CD and UC the following parameters will be evaluated disease duration disease location disease activity complications and past surgical procedures Complications are defined as abscesses fistulae and stenoses
4 Disease activity will be assessed according to ECCO-ESGAR Consensus Guidelines 2018
Laboratory assessment
The following will be done for all patients
1 WBC hematocrit platelet count
2 partial activated thromboplastin time
3 C-reactive protein CRP and fecal calprotectin
4 VWF Ag VWF RCo and VWF CB
Radiological tests
In cases with suspected arterial or venous thromboembolism the appropriate radiological study will be done ie venous doppler for deep venous thrombosis
Von Willebrand factor VWF is an acute-phase protein and a marker of endothelial damage
VWF is crucial for platelet adhesion and aggregation High-molecular weight multimers HMWMs are involved in platelet aggregation under high shear stress but under normal conditions it presents solely in the subendothelium and released into the bloodstream following activation of endothelial cells
Coagulation and inflammation are simultaneously activated and respond in synergy as a preserved mechanism to repair the injured areas during tissue damage
This observation is particularly relevant in acute inflammatory diseases such as sepsis but it also seems to be very important in chronic inflammatory conditions such as inflammatory bowel disease
Inflammatory bowel disease IBD with its two main forms ulcerative colitis UC and Crohn disease CD is a chronic inflammatory condition characterized by local and systemic inflammation predominantly affecting the gastrointestinal tract and well known to be associated with a hypercoagulable state and subsequently with an increased risk for venous thromboembolism VTE
Thromboembolic complications such as Deep Venous Thrombosis DVT and Pulmonary Embolism PE represent amongst IBD complications an important and underestimated factor to be borne in mind which can significantly influence patients morbidity and mortality
In fact according to the latest population-cohort studies a 2 to 3-time fold increased risk of developing of thromboembolic complications was reported for IBD patients compared to general population
In particular as Grainge et al and Papa et al both demonstrate in their studies the incidence of thromboembolic events varies depending on the activity phase of the disease suggesting that there is a higher risk of thromboembolic complications especially during IBD flares with similar relative risk values for both Crohns Disease and Ulcerative Colitis
Although the causes of the increased risk of VTE in IBD are not yet completely understood endothelial dysfunction has been demonstrated in IBD and it is evident through increasing levels of endothelial injury markers The most frequently used biochemical markers of endothelial damage include von Willebrand factor vWF TM vascular cell adhesion molecule 1 VCAM-1 intercellular adhesion molecule 1 ICAM-1 and endothelin-1 ET-1
In 2017 Cibor et al published the first report of the effects of parameters associated with the structure and function of VWF on hemostasis in IBD On the one hand ADAMTS13 Ag was lower in IBD patients than in controls particularly in subjects with UC this resulted in an increased number of circulating multimers of VWF and thus an elevated thrombotic risk The prothrombotic effects are enhanced by markedly elevated VWF Ag
On the other hand the incidence of AVWS which leads to an increased risk for bleeding was higher in IBD patients These findings provide insight into the elevated risk for thromboembolic events and bleeding observed in UC and less frequently in CD The dysregulation of the balance between VWF function and ADAMTS13 reported herein might contribute to the complex hemostatic abnormalities observed in IBD
Currently the association between CD and AVWS is likely underestimated especially in cases of acute bleeding not related to disease activity
In 2017 Di Sabatino et al reported three cases of IBD patients who developed severe hemorrhagic manifestations due to the concomitant presence of an AVWS in addition to other three cases was described in the literature Such a condition can be life-threatening and its timely identiļ¬cation is mandatory to adopt the optimal therapeutic strategy
The association between AVWS and IBD might be more frequent than expected The autoimmune pathogenesis of IBD makes the association more likely The availability of specialized coagulation centers and correlation with clinical information should confirm the diagnosis
Methodology
Patients will be subjected to the following
Clinical assessment
1 The clinical assessment will include demographic data the presence of comorbidities cigarette-smoking habits previous history of thromboembolism and medications
2 Body mass index BMI will be calculated for all patients
3 In patients with CD and UC the following parameters will be evaluated disease duration disease location disease activity complications and past surgical procedures Complications are defined as abscesses fistulae and stenoses
4 Disease activity will be assessed according to ECCO-ESGAR Consensus Guidelines 2018
Laboratory assessment
The following will be done for all patients
1 WBC hematocrit platelet count
2 partial activated thromboplastin time
3 C-reactive protein CRP and fecal calprotectin
4 VWF Ag VWF RCo and VWF CB
Radiological tests
In cases with suspected arterial or venous thromboembolism the appropriate radiological study will be done ie venous doppler for deep venous thrombosis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None