Introduction

Von Willebrand Disease is an inherited bleeding disorder that affects the blood’s ability to clot normally. The blood uses proteins or different factors to plug blood vessels when there is an injury. People with von Willebrand Disease are missing the von Willebrand Factor, named for Erik von Willebrand who first described it. When this factor is absent medication is needed to facilitate proper blood clotting.

The disease occurs in about 1% to 2% of the population. The likelihood of men and women inheriting von Willebrand disease is the about the same, and all ethnic groups are affected. People who have family members with bleeding disorders have a higher chance of having similar issues.

Symptoms of von Willebrand Disease include frequent nosebleeds, heightened sensitivity to bruising, and bleeding after dental work. Internal bleeding can be life threatening but it is rare among those diagnosed with the disease. Women might have heavy menstrual bleeding. When a person is tested for von Willebrand Disease, levels of the von Willebrand clotting factor are measured. Those levels may vary so multiple testing is often done.

Type I

This is the mildest and most prevalent form of von Willebrand Disease accounting for 60-80% of all people affected. The von Willebrand Factor is low in Type I people and very often clotting Factor VIII is low as well. People usually live a normal lifestyle and usually only have bleeding trouble after surgeries and some dental procedures.

Type I vWD is inherited by a child from his or her parents. Only one parent needs to have the disease because the Type I trait is dominant. This means that the missing clotting factor will mask any of the normal von Willebrand Factor that the other parent has.

Type II

Type II vWD has multiple forms: A, B, M and N. About 20-30% of people who have vWD, are affected. In Type 2A, low levels of von Willebrand Factor do not allow platelets to clot normally. In the Type 2B form of vWD, the von Willebrand Factor is defective in such a way that platelets clot too much. Treatment of Type 2B is different than most other von Willbrand Disease treatments.

Type II vWD is a dominant trait which means a child will inherit the condition because one of the parents has vWD.

Platelet-type

Platelet-type vWD is a very rare form of the clotting disease. Platelet-type vWB mimics Type 2B vWB in that the number of platelets clotting is higher than normal; however the condition is caused by a platelet defect not missing clotting factor.

Platelet-type vWD is a dominant trait meaning that a child will inherit the condition because one of the parents has vWD.

Hemostasis: How does bleeding stop?

Damage to small blood vessels and capillaries frequently occurs. When these vessels are damaged, there are three basic mechanisms that promote hemostasis or the stoppage of bleeding.

Following damage, there is an immediate reflex that promotes vasoconstriction, thus diminishing blood loss. Exposed collagen from the damaged site will promote the platelets to adhere.

When platelets adhere to the damaged vessel, they undergo degranulation and release cytoplasmic granules, which contain serotonin, a vasoconstrictor, and ADP and Thromboxane A₂.

The ADP attracts more platelets to the area, and the Thromboxane A₂ promotes platelet aggregation, degranulation, and vasoconstriction. Thus ADP and Thromboxane A₂ promote more platelet adhesion and therefore more ADP and thromboxane. The positive feedback promotes the formation of a platelet plug.

The final hemostatic mechanism is coagulation.

Damaged tissue releases factor III, which with the aid of Ca²⁺ will activate factor VII, thus initiating the extrinsic mechanism. Factor XII from active platelets will activate factor XI, thus initiating the intrinsic mechanism.

Both active factor VII and active factor XI will promote cascade reactions, eventually activating factor X.

Active factor X, along with factor III, factor V, Ca²⁺, and platelet thromboplastic factor (PF3), will activate prothrombin activator.

Prothrombin activator converts prothrombin to thrombin.
Thrombin converts fibrinogen to fibrin.

Fibrin initially forms a loose mesh, but then factor XIII causes the formation of covalent cross links, which convert fibrin to a dense aggregation of fibers. Platelets and red blood cells become caught in this mesh of fiber, thus the formation of a blood clot.



Reproduced with permission. © 2009 The McGraw-Hill Companies, Inc.