28/02/2024
Von Willebrand disease (vWD) :-
It is the most common hereditary blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of von Willebrand factor (vWF), a multimeric protein that is required for platelet adhesion. As well as humans, it is known to affect several breeds of dogs. Von Willebrand disease (VWD) is a genetic disorder caused by missing or defective von Willebrand factor (VWF), a clotting protein. VWF binds factor VIII, a key clotting protein, and platelets in blood vessel walls, which help form a platelet plug during the clotting process.
The symptoms of VWD may start at any age. They can range from very mild and barely noticeable to frequent and severe.
The main symptoms are:
large bruises or bruising easily
frequent or long-lasting nosebleeds
bleeding gums
heavy or long-lasting bleeding from cuts
in women, heavy periods and bleeding during or after labour
Common signs and symptoms of VWD
include frequent and prolonged nosebleeds,
easy bruising, and excessive bleeding after
surgery or dental work. In more severe cases, spontaneous bleeding in soft tissue and joints may occur.
Types :-
There are three main types of VWD based on qualitative or quantitative defects in VWF. A fourth type, acquired VWD, is not hereditary.
TYPE1 VWD is found in 60%-80% of patients. People with type 1 VWD have a quantitative deficiency of VWF. Levels of VWF in the blood range from 20%-50% of normal. The symptoms are usually mild.
TYPE 2 VWD is found in 15%-30% of patients. People with type 2 VWD have a qualitative deficiency in their VWF. Type 2 is broken down into four subtypes: type 2A, type 2B, type 2M and type 2N, depending on the presence and behavior of multimers, molecular chains of VWF. Symptoms are mild to moderate.
TYPE3 VWD is found in 5%-10% of patients. People with type 3 VWD have a quantitative deficiency of VWF. Symptoms are typically severe, and include spontaneous bleeding episodes, often into their joints and muscles.
ACQUIRED VWD. This type of VWD in adults results after a diagnosis of an autoimmune disease, such as lupus, or from heart disease or some types of cancer. It can also occur after taking certain medications.
Genetics
The vWF gene is located on the short arm p of chromosome 12 (12p13.2). It has 52 exons spanning 178kbp. Types 1 and 2 are inherited as autosomal dominant traits. Occasionally, type 2 also inherits recessively. Type 3 is inherited as autosomal recessive. However, some individuals heterozygous for type 3 may be diagnosed of vWD type 1, indicating an intermediate inheritance in that cases. vWD occurs in approximately 1% of the population and affects men and women equally.
Diagnosis:-
When vWD is suspected, blood plasma of a patient must be investigated for quantitative and qualitative deficiencies of vWF.
This is achieved by measuring the amount of vWF in a vWF antigen assay and the functionality of vWF with a glycoprotein (GP)Ib binding assay, a collagen binding assay, or a ristocetin cofactor activity (RiCof) or ristocetin-induced platelet agglutination (RIPA) assays. Factor VIII levels are also performed because factor VIII is bound to vWF which protects the factor VIII from rapid breakdown within the blood. Deficiency of vWF can then lead to a reduction in factor VIII levels, which explains the elevation in PTT. Normal levels do not exclude all forms of vWD, particularly type 2, which may only be revealed by investigating platelet interaction with subendothelium under flow, a highly specialized coagulation study not routinely performed in most medical laboratories.
A platelet aggregation assay will show an abnormal response to ristocetin with normal responses to the other agonists used. A platelet function assay may give an abnormal collagen/epinephrine closure time, and in most cases, a normal collagen/ADP time. Type 2N may be considered if factor VIII levels are disproportionately low, but confirmation requires a "factor VIII binding" assay.
Other tests performed in any patient with bleeding problems are a complete blood count-CBC (especially platelet counts), activated partial thromboplastin time-APTT, prothrombin time with International Normalized Ratio-PTINR, thrombin time-TT, and fibrinogen level. Testing for factor IX may also be performed if hemophilia B is suspected. Other coagulation factor assays may be performed depending on the results of a coagulation screen. Patients with von Willebrand disease typically display a normal prothrombin time and a variable prolongation of partial thromboplastin time.
Treatments:-
Treatment for VWD depends on the diagnosis and severity.
Desmopressin (DDAVP)-
The mainstay of treatment is DDAVP (desmopressin acetate), the synthetic version of a natural hormone vasopressin. It stimulates the release of VWF from cells, which also increases FVIII. DDAVP comes in two forms: injectable and nasal spray. Because DDAVP is an antidiuretic, causing the body to retain water, fluid restrictions are important so patients don’t develop hyponatremia, reduced sodium in the bloodstream. For patients with vWD type 1 and vWD type 2A, desmopressin is available as different preparations, recommended for use in cases of minor trauma, or in preparation for dental or minor surgical procedures. Desmopressin stimulates the release of vWF from the Weibel–Palade bodies of endothelial cells, thereby increasing the levels of vWF (as well as coagulant factor VIII) three- to five-fold. Desmopressin is also available as a preparation for intranasal administration (Stimate) and as a preparation for intravenous administration. Desmopressin is contraindicated in vWD type 2b because of the risk of aggravated thrombocytopenia and thrombotic complications. Desmopressin is probably not effective in vWD type 2M and is rarely effective in vWD type 2N. It is totally ineffective in vWD type 3
Cryoprecipitate :-
Cryoprecipitated Antihemophilic Factor, also called cryo, is a portion of plasma, the liquid part of our blood. Cryo is rich in clotting factors, which are proteins that can reduce blood loss by helping to slow or stop bleeding.
The blood clotting proteins found in cryo include:
Fibrinogen
Factor VIII
Factor XIII
Von Willebrand factor
Cryo is used to prevent or control bleeding in people whose own blood does not clot properly. This includes patients with serious but rare hereditary conditions such as Hemophilia A (who lack factor VIII) and von Willebrand disease.
Cryoprecipitate and fresh frozen plasma contain functional von Willebrand factor (vWF) but should be avoided if at all possible because of the potential transmission of viral disease. An additional drawback of fresh frozen plasma is the large infusion volume most often required.
Factor Replacement Therapy
Recombinant VWF (such as Vonvendi®) and medicines rich in VWF and factor VIII (for example, Humate P®, Wilate®, Alphanate®, or Koate DVI®) are used to treat people with more severe forms of VWD or people with milder forms of VWD who do not respond well to the nasal spray. These medicines are injected into a vein in the arm to replace the missing factor in the blood.
Antifibrinolytic Drugs
These drugs (for example, Amicar®, Lysteda®) are either injected or taken orally to help slow or prevent the breakdown of blood clots.
Birth Control Pills
Birth control pills can increase the levels of VWF and factor VIII in the blood and reduce menstrual blood loss. A doctor can prescribe these pills for women who have heavy menstrual bleeding.
