Von Willebrand disease

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Von Willebrand disease is a bleeding disorder that slows the blood clotting process, causing prolonged bleeding after an injury. People with this condition often experience easy bruising, long-lasting nosebleeds, and excessive bleeding or oozing following an injury, surgery, or dental work. Mild forms of von Willebrand disease may become apparent only when abnormal bleeding occurs following surgery or a serious injury. People with this condition who have menstrual periods typically have heavy or prolonged bleeding during menstruation (menorrhagia), and some may also experience reproductive tract bleeding during pregnancy and childbirth. In severe cases of von Willebrand disease, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Symptoms of von Willebrand disease may change over time. Increased age, pregnancy, exercise, and stress may cause bleeding symptoms to become less frequent.

Von Willebrand disease is divided into three types. Type 1 has one subtype (1C), and type 2 is divided into four subtypes (2A, 2B, 2M, and 2N). Type 1 is the most common of the three types, accounting for 75 percent of affected individuals. Type 1 is typically mild, but some people are severely affected. Type 2 accounts for about 15 percent of cases. This type is usually of intermediate severity. Type 3 is the rarest form of the condition, accounting for about 5 percent of affected individuals, and is usually the most severe.

Another form of the disorder, acquired von Willebrand syndrome, is not caused by inherited gene variants (also called mutations). Acquired von Willebrand syndrome is typically seen in people with other disorders, such as diseases that affect bone marrow or immune cell function. This rare form of the condition is characterized by abnormal bleeding into the skin and other soft tissues, usually beginning in adulthood.

ORPHANET DEFINITION A rare, inherited bleeding disorder characterized by defective platelet adhesion and secondary coagulation defect that manifests as abnormal bleeding of variable severity occurring either spontaneously or in association with an invasive procedure. Three main subtypes are defined based on the type of von Willebrand factor defect: partial (type 1) or total (type 3) deficiency, and qualitative/functional anomalies (type 2).

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive; Autosomal dominant

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Point prevalence: 1-5 / 10 000; Worldwide; Value and class.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal platelet function · Very frequent (99-80%)

Any anomaly in the function of thrombocytes.

Abnormality of coagulation · Very frequent (99-80%)

An abnormality of the process of blood coagulation. That is, altered ability or inability of the blood to clot.

Abnormality of thrombocytes · Very frequent (99-80%)

An abnormality of platelets.

Reduced von Willebrand factor activity · Very frequent (99-80%)

Decreased activity of von Willebrand factor. Von Willebrand factor mediates the adhesion of platelets to the collagen exposed on endothelial cell surfaces.

Abnormal mitral valve morphology · Frequent (79-30%)

Any structural anomaly of the mitral valve.

Bruising susceptibility · Frequent (79-30%)

An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.

Epistaxis · Frequent (79-30%)

Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose.

Gastrointestinal angiodysplasia · Frequent (79-30%)

Dysplasia affecting the vasculature of the gastrointestinal tract.

Impaired ristocetin cofactor assay activity · Frequent (79-30%)

Abnormal response to ristocetin as manifested by reduced or lacking aggregation of platelets upon addition of ristocetin to platelet-poor plasma.

Menorrhagia · Frequent (79-30%)

Prolonged and excessive menses at regular intervals in excess of 80 mL or lasting longer than 7 days.

Reduced factor VIII activity · Frequent (79-30%)

Reduced activity of coagulation factor VIII. Factor VIII (fVIII) is a cofactor in the intrinsic clotting cascade that is activated to fVIIIa in the presence of minute quantities of thrombin. fVIIIa acts as a receptor, for factors IXa and X.

Deviation of finger · Occasional (29-5%)

Deviated fingers is a term that should be used if one or more fingers of the hand are deviated from their normal position, either to the radial or ulnar side. A deviation of a finger can be caused by an abnormal form of one or more of the phalanges of the affected finger, or by a deviation or displacement of one or more phalanges.

Gastrointestinal hemorrhage · Occasional (29-5%)

Hemorrhage affecting the gastrointestinal tract.

Joint hemorrhage · Occasional (29-5%)

Hemorrhage occurring within a joint.

Other findings in the same source

From: Orphanet

Additional reported features include Microcytic anemia (Occasional (29-5%)); Muscle hemorrhage (Occasional (29-5%)); Petechiae (Occasional (29-5%)); Prolonged partial thromboplastin time (Occasional (29-5%)); Thrombocytopenia (Occasional (29-5%)); Venous insufficiency (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

All ages

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive; Autosomal dominant

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Point prevalence: 1-5 / 10 000; Worldwide; Value and class.

Which doctor should you see?

The suggested department for discussing Von Willebrand disease is Haematology, with a haematologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which blood-cell, marrow, bleeding or clotting finding matters most?
• Does the diagnosis need confirmation or a more precise subtype?
• Which symptoms or laboratory changes should trigger earlier review?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Von Willebrand disease. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.