Von Willebrand Disease-Classification and Treatment

Introduction

• Von Willebrand disease is the most common inherited bleeding disorder. It’s estimated prevalence varies from 1 in 100 to 1 in 10,000. In most of the cases it is autosomal dominant type of inheritance.

Physiological Functions Of Von Willebrand Factor

• von Willebrand Factor has a dual role in hemostasis. A major Adhesion molecule- attaches the platelets to the sub endothelium via the platelet factor Gp1b. (needs multimeric form of von Willebrand Factor). A binding protein for Factor VIII, increases the t_1/2 of Factor VIII. Patients usually have platelet disorder like presentation with mucosal bleeding except in severe forms which behave like hemophilia. Most patients present with: Mucosal bleed, Menorrhagia and Surgical bleeds

Classification Of Von Willebrand Disease  And Types

• Type 1 is the most common type of von Willebrand disease with (60- 80%incidence) is due to genetically low von Willebrand Factor levels.
• Type 1C: has short (t1/2) half-life of von Willebrand Factor, and thereby increased clearance of von Willebrand Factor.
• Type 2A: Decreased multimerization of von Willebrand Factor, hence less platelet binding.
• Type 2B: increased binding of von Willebrand Factor to platelets and cleared from circulation along with platelets.  Type 2b Is associated with Thrombocytopenia. 
• Type 2M : A defect in the ability of von Willebrand Factor to bind to platelet GP1b.
• Type 2N: A defect in the ability of von Willebrand Factor to bind to factor VIII.
• Type 3: Most severe form- Complete absence of von Willebrand Factor and factor VIII. 
• Most common type – Type 1 von Willebrand Disease (60-80%).
• 2^nd most common type- Type 2A.

• Type 3 is most severe form von Willebrand Disease.
• TYPE 2B is associated with gain of function mutation.
• Type 3, Type 2N: behave as mild hemophilia.
• Autosomal hemophilia is seen in: Type 2N von Willebrand disease.

Also Read: Aneuploidies Including Turner And Klinefelter Syndrome

What is platelet type Pseudo Von Willebrand disease?

• The answer is Pseudo (platelet-type)-Von Willebrand disease is a rare autosomal dominant bleeding disorder caused by an abnormal function of the glycoprotein lb protein; the receptor for von Willebrand factor. 
• There is a mutation  in platelet GP 1b factor  occurring thereby more binding to von Willebrand Factor inappropriately and leading to the clearance of both. This is similar to type 2B von Willebrand disease and both the diseases require platelet transfusion.

Investigations

If the von Willebrand Factor Antigen Assay shows levels <30IU/dl, then it is diagnostic of von Willebrand disease. If the von Willebrand Factor Antigen Assay shows levels >50IU/dl, then it is normal. If the von Willebrand Factor Antigen Assay shows levels in between 30-50 IU/dl, then it is low. Genetic diagnosis is not typically performed partly because of the larger size of von Willebrand factor gene and the large number of benign sequence variations.

Treatment

• Type1 von Willebrand disease except for type1c: The drug of choice is desmopressin, given via intranasal or intravenous route with the dose of 0.3 micrograms/kg.
• Type 2 and type 3 von Willebrand disease: von Willebrand factor concentrates are given.
• Type1C and Non responsive Type1 von Willebrand disease also need von Willebrand Factor concentrates with a dose - 40-60 Ristocetin cofactor activity units/kg. Antifibrinolytics are given in all types of von Willebrand Disease for mucosal bleeds. Oral EACA(epsilon aminocaproic acid)- 50-100mg/kg every 6 hourly. Oral tranexamic acid 1300mg TDS for 5days.

Also Read: Genomic Imprinting, Uniparental Disomy And Related Disorders

Preparations Of Von Willebrand Factor

• Humate -P : contains von Willebrand Factor and Factor8
• Wilate: contains von Willebrand Factor and Factor8
• Vonwendi: recombinant form with no Factor VIII.

Supportive Treatment

• Hormonal therapy is given for treating menorrhagia. For treating epistaxis local treatment dressing is done. For treating iron deficiency anemia oral iron is given in the dose of 3-4mg/kg/day. If there is no anemia, but only low iron stores then oral iron in the dose of 1-3mg/kg/day is given.
• Desmopressin is relatively contraindicated in type 2B von Willebrand disease as it may accelerate von Willebrand factor platelet binding and clearance.
• Anti fibrinolytic agents are contraindicated in the setting of upper urinary tract bleeding due to the risk of ureteral obstruction. 

Conditions Associated With Low Von Willebrand Factor Levels

• Blood group O
• Hypothyroidism
• Valproate 

Conditions Associated With Elevated Von Willebrand Factor Levels

• Stress
• Exercise
• Pregnancy

Acquired Von Willebrand Disease This Is Seen In Lymphoproliferative Disorders Like

• Monoclonal gammopathy of unknown significance (MGUS)
• Multiple myeloma
• Waldenstroms Macroglobulinemia
• Heyde’s Syndrome:  Heyde’s syndrome is a multisystem disorder characterized by the aortic stenosis (AS), gastrointestinal bleeding due to Angiodysplasia, and it responds to  Aortic valve replacement.

Also Read: Marfan Syndrome : Signs, Diagnosis, Management and Prognosis

Hope you found this blog helpful for your NEET SS Pediatrics Hematology preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.