Von Willebrand disease
Von Willebrand disease is the most common inherited bleeding disorder, caused by deficient or dysfunctional von Willebrand factor, producing mucocutaneous bleeding from impaired platelet adhesion plus a mild secondary factor VIII deficiency. Diagnosis rests on the vWF antigen, ristocetin cofactor activity, and factor VIII activity panel, and management centers on desmopressin for type 1, vWF concentrate for severe or desmopressin-unresponsive disease, and antifibrinolytics for mucosal bleeding.
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What this article covers
- Overview
Definition: von Willebrand disease (vWD) is a deficiency or dysfunction of von Willebrand factor (vWF), the glycoprotein that mediates platelet adhesion to injured subendothelium and carries and…
- Epidemiology
Population prevalence: up to 1% of the population carries a vWD-associated genotype, though symptomatic disease is far less common because of variable penetrance, especially in type 1; diagnosed more…
- Risk factors
Family history of mucocutaneous bleeding: types 1, 2A, 2B, and 2M are autosomal dominant with variable penetrance, so a first-degree relative with similar bleeding is the strongest clue.
- Pathophysiology
Normal vWF biology: vWF is synthesized and stored in vascular endothelial cells (Weibel-Palade bodies) and platelet alpha granules; after secretion, ultra-large multimers are cleaved to smaller…
- Clinical features
Mucocutaneous bleeding pattern: epistaxis, gum and gingival bleeding, easy bruising, prolonged bleeding after minor cuts, and mucosal gastrointestinal bleeding are the hallmark, reflecting the primary-hemostasis defect.
- Differential diagnosis
Hemophilia A or B: X-linked recessive; hemarthrosis and deep muscle bleeding rather than mucosal bleeding, isolated factor VIII or IX deficiency with normal vWF studies (hemophilia A; hemophilia A and B).
- Diagnosis
Confirm with the vWD laboratory panel, not a single test, then subtype by the ristocetin cofactor to antigen ratio: the diagnosis is established by a reduced or dysfunctional vWF on the panel of vWF…
- Management
Confirm subtype first, then for type 1 (and desmopressin-responsive type 2A/2M) give desmopressin (DDAVP) as first-line therapy, releasing stored vWF and factor VIII from endothelial cells; check…
- Complications
Hemorrhage from trauma, surgery, or childbirth: the principal complication, ranging from prolonged procedural bleeding to postpartum hemorrhage, particularly when the diagnosis is unrecognized before a procedure.
- Prognosis
Generally favorable with recognition and planning: most patients, particularly type 1, have normal life expectancy and manage bleeding effectively once diagnosed.
- Prevention
Pre-procedural desmopressin trial: in known type 1/2A/2M vWD, document a desmopressin trial (factor levels at baseline, 60 minutes, and 4 hours) before any elective surgery or dental extraction, and…
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Related articles
- Hemophilia A
Hemophilia A is an X-linked recessive deficiency of factor VIII that produces deep bleeding into joints, muscles, and after surgery in male patients, diagnosed by an isolated prolonged aPTT that corrects on a mixing study and confirmed by a reduced factor VIII activity assay. Management is factor VIII replacement or emicizumab for moderate to severe disease, desmopressin for mild disease, and antifibrinolytics for mucosal bleeding, with inhibitor development the most serious treatment complication.
- Coagulation disorders: an overview
The approach to a bleeding patient starts by using the bleeding pattern, the platelet count, and the PT/aPTT to localize the defect to primary hemostasis (platelets or von Willebrand factor), secondary hemostasis (coagulation factors), or a combined process such as DIC or liver disease. A mixing study then separates a factor deficiency, which corrects, from an inhibitor, which does not, and directs the specific factor or von Willebrand assay that confirms the diagnosis.
- Platelet disorders
Platelet disorders span a quantitative axis (thrombocytopenia from decreased production, increased destruction, or sequestration) and a qualitative axis (normal-count platelets that fail to adhere or aggregate), plus reactive or clonal thrombocytosis, and all present with mucocutaneous bleeding rather than deep hematomas. Diagnosis starts with a platelet count and smear to exclude pseudothrombocytopenia, adds platelet function testing when the count is normal but bleeding is mucocutaneous, and management is cause-directed.
- Thrombotic thrombocytopenic purpura (TTP)
Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy caused by severe ADAMTS13 deficiency that lets ultralarge von Willebrand factor multimers drive platelet microthrombi; the key dyad of microangiopathic hemolytic anemia plus thrombocytopenia without another cause mandates the PLASMIC score, an ADAMTS13 activity and inhibitor level, and emergent plasma exchange started before results return.
- Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
Hereditary hemorrhagic telangiectasia is an autosomal dominant vascular dysplasia, most often from ENG or ACVRL1 mutations, causing mucocutaneous telangiectasias and visceral arteriovenous malformations diagnosed by the Curacao criteria. Management combines iron repletion and epistaxis control with lifelong screening and embolization of pulmonary arteriovenous malformations to prevent paradoxical stroke and brain abscess.