Von Willebrand Antigen and Activity as Novel Biomarkers of Hemostasis in Inflammatory Bowel Disease
Von Willebrand Antigen and Activity as Novel Biomarkers of Hemostasis in Inflammatory Bowel Disease
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 Crohn's disease divided into two
 arms; group A will include 23 cases with active IBD(cases)status and group B will include 23
 cases with inactive IBD status(control) 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.
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 patient's 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 Crohn's 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 identiﬁcation 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 (i.e. venous doppler for deep venous thrombosis).
Inclusion Criteria:

 •Patients with inflammatory bowel disease either newly or previously diagnosed aged18 years
 and older.

 Exclusion Criteria:

 -  Pregnancy.

 -  Myocardial infarction.

 -  Stroke.

 -  Thromboembolism.

 -  Known hemorrhagic diathesis.

 -  Cancer.

 -  Renal insufficiency.

 -  Liver injury.

 -  Diabetes.

 -  patients who are on aspirin, heparin, oral anticoagulants, or oral contraceptives
 pills.