الفهرس 
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Abstract
Von Willebrand factor (VWF) is a multimeric glycoprotein found in the peripheral blood stream that is necessary for normal hemostasis.
It has Cellular Functions other than hemostasis such as osteoclastoenesis, leukocyte adhesion and extravasation , Angiogenesis , vascular smooth muscle cell proliferation , WPB formation , platelet cloaking and tumour cell apoptosis .
Von Willebrand disease (VWD) is a relatively common bleeding disorder caused by deficiency or dysfunction of Von Willebrand’s factor (VWF).
It is associated with a defect in primary hemostasis and also with a secondary defect in coagulation factor VIII.
Clinically, it manifests typically as mucocutaneous type of bleeding and menorrhagia in female.
Worldwide VWD prevalence is generally 1% of the normal population with type 1 VWD being the most common, whereas its prevalence is 1.1% in United States.
Von Willebrand disease is classified into partial quantitative deficiency (type 1) that accounts for 70% to 80% of all VWD, qualitative deficiency (type 2) that accounts for 20% VWD, and total deficiency (type 3) for approximately 5% to 10% resulting in secondary severe deficiency of FVIII. Type 2 VWD is divided further into 4 variants (2A, 2B, 2M, 2N) on the basis of the phenotype.
The major signs of VWD are:
1- Epistaxis
2- Easy Bruising
3- Heavy menstrual bleeding.
4- Longer than Normal Bleeding After Injury, Surgery, Childbirth, or Dental Work .
5- People with VWD might have longer-than-normal bleeding during or after dental work.
6- Angiodysplasia .
Complications of VWD includes Deep internal bleeding, Bleeding that occurs in deep muscle can cause the limbs to swell , Bleeding into the throat or neck. This can affect a person’s ability to breathe , Damage to joints so limitation of movement and Adverse reaction to VWD treatment .
Initial evaluation for VWD requires a combination of screening tests, as no single test can confirm the presence of fully functional VWF. Along with assessment of VWF protein presence, routine screening tests include assessment of VWF–platelet and VWF–FVIII interactions.
VWD SCREENING TESTS includes VWF antigen (VWF:Ag) , VWF ristocetin cofactor activity (VWF:RCo) , Factor VIII activity (FVIII:C) and VWF:RCo/VWF:Ag ,
VWD CONFIRMATORY TESTS includes VWF multimer distribution, VWF collagen binding (VWF:CB) , VWF–platelet binding (VWF:PB) , VWF-FVIII binding (VWF:FVIIIB) and VWF propeptide (VWFpp) .
Bleeding history is critically important for the diagnosis of VWD.
To that end, attempts have been made to quantify reported bleeding symptoms using bleeding assessment tools.
The International Society on Thrombosis and Haemostasis (ISTH) has developed and performed initial validation of a bleeding assessment tool for use in screening patients for VWD.
Normal ranges have been established for children, adult males, and adult females.
Minimal criteria defining a significant bleeding
For each specific bleeding symptom, the ISTH/SSC joint working group proposed
minimal criteria in order to classify a symptom as significant and thus receive a score of 1 or more
Current treatment of VWD includes desmopressin , plasma derived VWF concentrates ,Recombinent VWF concentrates and Antifibrinolytics .
Although treatment options for VWD remain largely unchanged , save for the new availability of recombinant VWF, there have been improvements in the ability to predict which patients will require treatment.
Adequate treatment is key to allowing patients to have the highest possible quality of life.
It is to be hoped that improvements in diagnosis and treatment will translate to improvements in quality of life for affected patients . However , more work is needed to identify those patients who will benefit most from treatment without overdiagnosis of VWD.
In the last several years, BATs have offered a standardized method of describing bleeding symptoms and evaluating disease severity.
Pediatric BATs are particularly useful for screening children for bleeding disorders because hemorrhagic symptoms, especially bruising and epistaxis, commonly overlap between healthy individuals and those with pathologies.
The best cutoff of bleeding score in diagnosis of type C VWF disease is≥22.5, area under curve 0.808, sensitivity 75%, specificity 89.3%, positive predictive value 50%, negative predictive value 96.2% and overall accuracy 87.5%
Von Willebrand antigen ranged from 0.99 to 69 IU/dl with median 12.2 IU/dl. Four patients had factor<3 (most probably type 3). Twenty -three patients (71.9%) had antigen<30 IU/dl, four patients had low VWF (from 30 to 50 IU/dl) and one patient had normal level (>50).
Von Willebrand activity ranged from 4 to 38.74 IU/dl with mean 17.26 IU/dl. Two patients had activity from 30 to 50 IU/dl and twenty-nine patients (93.5%) had antigen<30 IU/dl.
Concerning ratio, it ranged from 0.51 to 10.1 with median 1.3. with all patients had ratio >0.5
Based on that, larger percentage of patients (28 patients, 87.5%) had type 1 disease and four patients had type 3 [12.9%]
There is statistically significant negative correlation between bleeding score and both VWF activity and antigen
There is statistically significant positive correlation between bleeding score and ratio
There is statistically non-significant correlation between bleeding score and factor VIII
ISTH-BAT is an important bleeding assessment tool that has proven its utility for diagnostic purposes of inherited bleeding disorders such as VWD which is a common disorder .
Conclusion and recommendations
Von Willebrand disease (VWD) is a relatively common and serious bleeding disorder that has lots of complications .
A predictive bleeding score could reveal individuals who may benefit from repetitive testing and those for whom repetitive testing is unlikely to be of benefit.
Using BS leads to rapid suspicion and diagnosis of the disease so decreasing risk of complications .
Based on our results, we recommend using the ISTH/SSC BLEEDING assessment tool as a standardized questionnaire and a proposal for diagnosis of VWD .
The questionnaire should be collected by a physician or another adequately trained health-professional. Only symptoms and related treatments, if any, before and/or at diagnosis should be reported.