(vWD) is the most common
Hereditary Coagulation abnormality described in humans. It arises from a qualitative or quantitative deficiency of
Von Willebrand Factor (vWF), a multimeric protein that is required for
Platelet adhesion. It is known to affect
Human s and, in
Veterinary Medicine ,
Dog s.
The various types of vWD present with varying degrees of
Bleeding Tendency . Severe
Internal or
Joint Bleeding is rare (only in type 3 vWD);
Bruising ,
Nosebleed s,
Heavy Menstrual Periods (in women) and blood loss during
Childbirth (rare) may occur.
When suspected, . A platelet aggregation assay will show an abnormal response to ristocetin with normal responses to the other agonists used. A
Platelet Function Assay (PFA) will give an abnormal collagen/
Adrenaline closure time but a normal collagen/
ADP time. Type 2N can only be diagnosed by performing a "factor VIII binding" assay. Detection of vWD is complicated by vWF being an acute phase reactant with levels rising in
Infection ,
Pregnancy and
Stress .
Other tests performed in any patient with bleeding problems are a
Full Blood Count (especially
Platelet counts),
APTT (activated partial thromboplastin time),
Prothrombin Time ,
Thrombin time 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.
There are three hereditary types of vWD described - type 1, type 2 and type 3. There are inherited and acquired forms of vWD. Most cases are hereditary, but ''acquired'' forms of vWD have been described. The
International Society On Thrombosis And Haemostasis 's (ISTH) classification depends on the definition of quallitative and quantitative defects.
Type 1 vWD (60-80% of all vWD cases) is a quantitative defect (heterozygous for the defective gene) but may not have clearly impaired
Clotting , most patients usually end up leading a nearly normal life. Trouble may arise in the form of bleeding following surgery (including dental procedures), noticeable easy bruising, or
Menorrhagia (heavy
Periods ). Decreased levels of vWF are detected (10-45% of normal, i.e. 10-45 IU).
Type 2 vWD (20-30%) is a qualitative defect and the bleeding tendency can be mild. There are normal levels of vWF, but the multimers are structurally abnormal, or subgroups of large or small multimers are absent. Four subtypes exist: 2A, 2B, 2M and 2N.
This is an abnormality of the synthesis or protelysis of the vWF multimers resulting in the presence of small multimer units in circulation. Factor VIII binding is normal.
This is a "gain of function" defect leading to spotaneous binding to platelets and subsequent rapid clearance of the platelets and the large vWF multimers. A mild
Thrombocytopaenia may occur. The large vWF multimers are absent in the circulation and the Factor VIII binding is normal.
This is caused by decreased or absent binding to GPIb on the platelets. Factor VIII binding is normal.
This is a deficiency of the binding of vWF to factor VIII. This type gives a normal vWF antigen level and normal functional test results but has a low factor VIII. This has probably lead to some 2N patients being misdiagnosed in the past as having hemophilia A.
Type 3 is the most severe form of vWD (homozygous for the defective gene) and may have severe
Mucosal Bleeding , no detectable
VWF Antigen , and may have sufficiently low
Factor VIII that they have occasional
Hemarthoses (joint bleeding), as in cases of mild
Hemophilia .
Acquired vWD can occur in patients with autoantibodies. here the function of vWF is not inhibited but the vWF-antibody complex is rapidly cleared from the circulation.
A form of vWD occurs in patients with
Aortic Valve Stenosis , leading to
Gastrointestinal Bleeding (
Heyde's Syndrome ). This form of acquired vWD may be more prevalent than is presently thought.
Acquired vWF has also been described in the following disorders
Wilms Tumour ,
Hypothyroidism and
Mesenchymal Dysplasias .
''See also
Von Willebrand Factor for the normal function of that coagulation factor''
vWF is mainly active in conditions of high blood flow and
Shear Stress . Deficiency of vWF therefore shows primarily in organs with extensive small vessels, such as the
Skin , the
Gastrointestinal Tract and the
Uterus . In
Angiodysplasia , a form of
Telangiectasia of the
Colon , shear stress is much higher than in average
Capillaries , and the risk of bleeding is increased concomitantly.
The individual's ABO blood group can influence presentation and pathology of vWD. Those individuals with blood group O have a lower mean level than individuals with other blood groups.
The vWF gene is located on
Chromosome twelve (12p13.2). It has 52 exons spanning 178kbp. Types 1 and 2 are inherited as
Autosomal Dominant traits and type 3 is inherited as
Autosomal Recessive . Occasionally type 2 also inherits recessively.
In humans, the incidence of vWD is roughly about 1 in 100 individuals. Because most forms are rather mild, they are detected more often in women, whose bleeding tendency shows during
Menstruation . The actual abnormality (which does not necessarily lead to disease) occurs in 0.9-3% of the population.
Patients with vWD normally require no regular treatment. However, they are always at increased risk for bleeding. Prophylactic treatment is sometimes given for patients with vWD who are scheduled for surgery. They can be treated with human derived medium purity
Factor VIII concentrates. Mild cases of vWD can be trialled on
Desmopressin (1-desamino-8-D-arginine vasopressin, DDAVP), which works by raising the patient's own plasma levels of vWF by inducing release of vWF stored in the
Weibel-Palade Bodies in the endothelial cells.
vWD is
Named after
Erik Adolf Von Willebrand , a
Finnish Pediatrician (
1870 -
1949 ). He first described the disease in
1926 .
- ''Harrison's textbook of Internal Medicine'', Chapter 177.
- Sadler, J. E. "Biochemistry and Genetics of von Willebrand factor." Annu Rev Biochem 1998; 67:395-424. ( fulltext )
- Mannucci PM. ''Treatment of von Willebrands disease.'' N Engl J Med 2004;351:683-94. PMID 15306670
- Laffan m. Brown S. etal. The diagnosis of von Willebrand disease: a guideline from the UK Haemophilia Centre Doctors Organisation. Haemophilia; 2004, 10, 199-217
