Von Willebrand disease - Clinicals, Diagnosis, and Management

Hematology

Clinicals - History

Fact Explanation
Bleeding from trivial wounds Von Willebrand Factor(vWF) serves two functions: it binds to factor VIII in the circulation and prevents its early metabolism and helps platelets adhere to exposed subendothelial collagen at the site of vascular injury. Deficiency or dysfunctions of vWF leads to impaired platelet response and clot formation leading to abnormal, excessive bleeding. Bleeding from trivial wounds
Von Willebrand Factor(vWF) serves two functions: it binds to factor VIII in the circulation and prevents its early metabolism and helps platelets adhere to exposed subendothelial collagen at the site of vascular injury. Deficiency or dysfunctions of vWF leads to impaired platelet response and clot formation leading to abnormal, excessive bleeding.
Easy bruising Skin bruising commonly found in von Willebrand disease. Easy bruising
Skin bruising commonly found in von Willebrand disease.
Epistaxis Deficiency or dysfunction of vWF will lead to impairment in platelet adhesion in response to vascular injury which will give rise to spontaneous nose bleeds which is common in von Willebrand Disease.. Epistaxis
Deficiency or dysfunction of vWF will lead to impairment in platelet adhesion in response to vascular injury which will give rise to spontaneous nose bleeds which is common in von Willebrand Disease..
Oral cavity bleeding Common site of bleeding in von Willebrand Disease. Oral cavity bleeding
Common site of bleeding in von Willebrand Disease.
Menorrhagia Found in menstruating females with von Willebrand Disease. Mainly due to disruption of the normal platelet response. Menorrhagia
Found in menstruating females with von Willebrand Disease. Mainly due to disruption of the normal platelet response.
History of abnormal, excessive bleeding during dental extraction, minor surgery or trauma and post partum hemorrhage. Deep bleeds are due to defective intrinsic coagulation owing to low plasma levels of factor VIII in the absence of von Willebrand factor and mucosal bleeds are due to defective platelet response. History of abnormal, excessive bleeding during dental extraction, minor surgery or trauma and post partum hemorrhage.
Deep bleeds are due to defective intrinsic coagulation owing to low plasma levels of factor VIII in the absence of von Willebrand factor and mucosal bleeds are due to defective platelet response.
Family history of bleeding disorder Most commonly found (80%) von Willebrand Disease type 1 has an autosomal dominant type transmission across generations. Family history of bleeding disorder
Most commonly found (80%) von Willebrand Disease type 1 has an autosomal dominant type transmission across generations.
History of lymphoproliferative disorders, monoclonal gammopathies, autoimmune diseases like SLE Acquired von Willebrand disease can be found in these conditiions due to formation of antibodies against vWF and removal of vWF from circulation by aberrant binding to tumor cells. History of lymphoproliferative disorders, monoclonal gammopathies, autoimmune diseases like SLE
Acquired von Willebrand disease can be found in these conditiions due to formation of antibodies against vWF and removal of vWF from circulation by aberrant binding to tumor cells.
History of cardiac defects such as ventricular septal defect, aortic stenosis There is shear-induced conformational changes in the vWF leading to increased proteolysis of VWF which results low plasma levels. History of cardiac defects such as ventricular septal defect, aortic stenosis
There is shear-induced conformational changes in the vWF leading to increased proteolysis of VWF which results low plasma levels.
History of hypothyroidism There is a reduction in synthesis of vWF leading to low plasma levels. History of hypothyroidism
There is a reduction in synthesis of vWF leading to low plasma levels.

Clinicals - Examination

Fact Explanation
Conjunctival pallor Due to anemia. Conjunctival pallor
Due to anemia.
Petechiae and ecchymosis As a result of bleeding under the skin due to minor blood vessel injury. Petechiae and ecchymosis
As a result of bleeding under the skin due to minor blood vessel injury.
Palpable swellings over muscles and joint swellings Due to muscle hematoma and hemearthrosis which are found in more severe cases. Palpable swellings over muscles and joint swellings
Due to muscle hematoma and hemearthrosis which are found in more severe cases.

Investigations - Diagnosis

Fact Explanation
Ristocetin co-factor activity - vWF:RCoF Von Willebrand Factor (vWF) interacts with the antibiotic ristocetin and platelet glycoprotein Ib and mediates platelet adhesion. In von Willebrand disease this test result will be low. Ristocetin co-factor activity - vWF:RCoF
Von Willebrand Factor (vWF) interacts with the antibiotic ristocetin and platelet glycoprotein Ib and mediates platelet adhesion. In von Willebrand disease this test result will be low.
Collagen binding activity - vWF:CBA vWF binds to type I or type III collagen and facilitate platelet adhesion to the subendothelial matrix at the site of vascular injury. In von Willebrand disease this test result will be low. Collagen binding activity - vWF:CBA
vWF binds to type I or type III collagen and facilitate platelet adhesion to the subendothelial matrix at the site of vascular injury. In von Willebrand disease this test result will be low.
von willebrand factor antigen levels (vWF:Ag) Definetive diagnosis can be made if the antigen levels are less than 30 IU/dL. Antigen levels can fluctuate daily, therefore recommends testing patients on two separate occasions. Conditions such as strenuous exercises which can falsely elevate antigen levels should be avoided before the test. von willebrand factor antigen levels (vWF:Ag)
Definetive diagnosis can be made if the antigen levels are less than 30 IU/dL. Antigen levels can fluctuate daily, therefore recommends testing patients on two separate occasions. Conditions such as strenuous exercises which can falsely elevate antigen levels should be avoided before the test.
Factor VIII assay vWF prevents the early metabolism of factor VIII and therefore in von Willebrand disease low factor VIII levels can be found. However, a normal factor VIII level does not rule out VWD. Factor VIII assay
vWF prevents the early metabolism of factor VIII and therefore in von Willebrand disease low factor VIII levels can be found. However, a normal factor VIII level does not rule out VWD.
Bleeding time Can be increased or normal in some patients. Bleeding time
Can be increased or normal in some patients.
Platelet count To rule out thrombocytopenia. Platelet count
To rule out thrombocytopenia.
Prothrombin time To exclude other bleeding disorders due to clotting factor defects. Prothrombin time
To exclude other bleeding disorders due to clotting factor defects.
PTT (partial thromboplastin time) This test will be abnormal only if there is significant reduction in factor VIII level secondary to vWF deficiency, so test will be prolonged in von Willebrand disease type 3 and will be normal in mild disease such as type 1 and some subtypes of type 2. PTT (partial thromboplastin time)
This test will be abnormal only if there is significant reduction in factor VIII level secondary to vWF deficiency, so test will be prolonged in von Willebrand disease type 3 and will be normal in mild disease such as type 1 and some subtypes of type 2.
Platelet Function Analyzer-100 A system for analysing platelet function using platelet agonists (ADP and Epinephrin). Closure times correlate inversely with plasma VWF activity levels, so CT-collagen ADP and EPI results will be high in von willebrand disease.
Note: The use of bleeding time to assess platelet function is discouraged; the Platelet Function Analyzer-100 is preferred.
Platelet Function Analyzer-100
A system for analysing platelet function using platelet agonists (ADP and Epinephrin). Closure times correlate inversely with plasma VWF activity levels, so CT-collagen ADP and EPI results will be high in von willebrand disease.
Note: The use of bleeding time to assess platelet function is discouraged; the Platelet Function Analyzer-100 is preferred.

Investigations - Management

Fact Explanation
Serum electrolytes - Na+ Desmopressin is generally administered for short periods in von Willebrand disease type 1 and some of type 2. However, if a longer duration or shorter intervals are required, the patient should be monitored for fluid and electrolyte problems because desmopressin may lead to symptomatic hyponatremia. Serum electrolytes - Na+
Desmopressin is generally administered for short periods in von Willebrand disease type 1 and some of type 2. However, if a longer duration or shorter intervals are required, the patient should be monitored for fluid and electrolyte problems because desmopressin may lead to symptomatic hyponatremia.
Hemoglobin level To detect the degree of anemia. Hemoglobin level
To detect the degree of anemia.

Management - Supportive

Fact Explanation
Patient and family education Extremely important since it is a hereditary disease and patient will require family support. Must educate to avoid aspirin, other NSAIDs and other platelet inhibiting drugs Patient and family education
Extremely important since it is a hereditary disease and patient will require family support. Must educate to avoid aspirin, other NSAIDs and other platelet inhibiting drugs
Immunization - Hepatitis A, B Treatment include transfusion of blood products, so as a preventive measure to overcome the risk of transmission of blood borne infections patients should vaccinated against them. Immunization - Hepatitis A, B
Treatment include transfusion of blood products, so as a preventive measure to overcome the risk of transmission of blood borne infections patients should vaccinated against them.
Restriction of fluids to maintenance levels Should be considered in patients receiving Desmopressin (especially for young children and in surgical settings) to avoid the occurrence of hyponatremia and seizures. Restriction of fluids to maintenance levels
Should be considered in patients receiving Desmopressin (especially for young children and in surgical settings) to avoid the occurrence of hyponatremia and seizures.

Management - Specific

Fact Explanation
Desmopressin (DDAVP) Used to stop spontaneous bleeding and to prevent bleeding at the time of surgical procedures.
Patients with low vWF antigen levels (type 1) may benefit from desmopressin (DDAVP), which increases endothelial release of vWF antigen.
Desmopressin (DDAVP)
Used to stop spontaneous bleeding and to prevent bleeding at the time of surgical procedures.
Patients with low vWF antigen levels (type 1) may benefit from desmopressin (DDAVP), which increases endothelial release of vWF antigen.
Factor replacement therapy - Alphanate (a high-purity concentrate containing factor VIII) and Humate-P Can use if treatment with desmopressin is unsuccessful. Treatment duration varies by procedure.
Note: Cryoprecipitate is no longer recommended for VWF or factor VIII replacement.
Factor replacement therapy - Alphanate (a high-purity concentrate containing factor VIII) and Humate-P
Can use if treatment with desmopressin is unsuccessful. Treatment duration varies by procedure.
Note: Cryoprecipitate is no longer recommended for VWF or factor VIII replacement.
Oral antifibrinolytic agents (epsilon-aminocaproic acid (Amicar) and tranexamic acid) Antifibrinolytic agents prevent the clot lysis
They are very useful for mucous membrane bleeding.
Oral antifibrinolytic agents (epsilon-aminocaproic acid (Amicar) and tranexamic acid)
Antifibrinolytic agents prevent the clot lysis
They are very useful for mucous membrane bleeding.
Topical agents, such as bovine or human thrombin and fibrin sealants Use for accessible minor bleeding. Topical agents, such as bovine or human thrombin and fibrin sealants
Use for accessible minor bleeding.
Combined oral contraceptives and the levonorgestrel-releasing intrauterine device (Mirena) Use as the treatment for menorrhagia due to Von Willebrand Disease. They prevent bleeding by acting on endometrium where there is no relation with regards to vWF levels. Note: patient should be informed about the contraceptive benefit and should not be used in females who are trying to become pregnant. Combined oral contraceptives and the levonorgestrel-releasing intrauterine device (Mirena)
Use as the treatment for menorrhagia due to Von Willebrand Disease. They prevent bleeding by acting on endometrium where there is no relation with regards to vWF levels. Note: patient should be informed about the contraceptive benefit and should not be used in females who are trying to become pregnant.
Platelet concentrates Used to prevent heavy bleeding. Platelet concentrates
Used to prevent heavy bleeding.
Referrel to a genetic counselor and to a pediatric hematologist Before or during pregnancy, women with VWD should be referred to a genetic counselor to discuss the inheritance of the disease and also to a pediatric hematologist for evaluation of the infant after delivery. Referrel to a genetic counselor and to a pediatric hematologist
Before or during pregnancy, women with VWD should be referred to a genetic counselor to discuss the inheritance of the disease and also to a pediatric hematologist for evaluation of the infant after delivery.

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