How is von Willebrand disease diagnosed and treated?

Von Willebrand Disease: Diagnosis and Treatment

Diagnosis

Order VWF antigen, VWF ristocetin cofactor activity, factor VIII activity, complete blood count with platelet count, PT, and aPTT simultaneously when VWD is suspected. 1

Clinical Assessment

• Look for mucocutaneous bleeding patterns: nosebleeds, easy bruising, gingival bleeding, prolonged bleeding from minor wounds, menorrhagia, postpartum hemorrhage, and bleeding after surgery or dental extractions 2, 3
• Distinguish hereditary from acquired disease by asking about personal and family bleeding history—absence of both strongly suggests acquired von Willebrand syndrome (AVWS) rather than congenital VWD 4
• Screen for underlying conditions in suspected AVWS: lymphoproliferative disorders, monoclonal gammopathies, autoimmune diseases, and cardiovascular conditions 4
• Document physical findings including ecchymoses, hematomas, petechiae, telangiectasia, and joint or skin laxity 4

Laboratory Interpretation

• PT and aPTT are frequently normal in VWD and cannot exclude the diagnosis—they must be interpreted only as part of a comprehensive panel 1
• VWF ristocetin cofactor activity is the single most useful screening test because it mimics VWF-platelet receptor interactions 1
• Calculate the VWF activity-to-antigen ratio: values <0.5–0.7 indicate a qualitative defect (type 2 VWD) and mandate VWF multimer analysis to differentiate type 2 variants from type 1 disease 4, 1
• Low VWF antigen, low VWF activity, and reduced factor VIII levels establish the diagnosis 4

Classification

• Type 1 VWD (partial quantitative deficiency) accounts for ~75% of symptomatic cases and presents with mild bleeding 2, 5
• Type 2 VWD (qualitative deficiency) includes four subtypes: 2A (absent high-molecular-weight multimers), 2B (increased platelet affinity), 2M (normal multimers but reduced platelet binding), and 2N (poor factor VIII binding) 2, 5
• Type 3 VWD (virtually complete quantitative deficiency) is rare (1 in 1,000) and causes severe, life-threatening bleeding 2, 6
• Multimer analysis distinguishes type 2A from 2M, ristocetin-induced platelet agglutination identifies type 2B, and factor VIII binding assays detect type 2N 5, 7

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Treatment

Desmopressin 0.3 μg/kg IV (maximum 28 μg) is first-line therapy for most type 1 VWD patients and should be given 30 minutes before procedures or during acute bleeding. 4, 1

Desmopressin (DDAVP) Therapy

• Desmopressin stimulates endothelial release of stored VWF, raising plasma VWF and factor VIII levels 3–6-fold within 30–90 minutes 4, 1
• Repeat dosing at 12–24 hour intervals is possible, but tachyphylaxis develops after 3–5 doses due to depletion of endothelial VWF stores 4, 1
• Desmopressin is effective in most type 1 and some type 2 VWD patients but is contraindicated in type 2B (can cause thrombocytopenia) and ineffective in type 3 8

VWF/Factor VIII Concentrates

• Use plasma-derived or recombinant VWF concentrates in type 3 VWD, severe type 1, type 2B, type 2N, and in patients who fail desmopressin 4, 8
• These concentrates are virucidally treated, effective, and safe but do not always correct bleeding time 8

Perioperative and Procedural Management

• Maintain VWF activity ≥50 IU/dL throughout surgery and the postoperative period using desmopressin, VWF/FVIII concentrates, or cryoprecipitate 4, 1
• Monitor VWF levels intraoperatively and postoperatively to guide additional dosing 1
• Add tranexamic acid as adjunctive antifibrinolytic therapy when appropriate 4, 1
• For neuraxial anesthesia, ensure VWF activity ≥50 IU/dL before needle placement 4

Management of Specific Bleeding Manifestations

Epistaxis

• Apply firm, sustained nasal compression first 1
• Give desmopressin 0.3 μg/kg IV 30 minutes before nasal packing 1
• Use only resorbable packing materials—non-resorbable packs increase bleeding risk in VWD 4, 1
• Apply topical vasoconstrictors and consider nasal cautery for focal bleeding sources 1
• Perform nasal endoscopy for refractory epistaxis to locate posterior sources 1

Menorrhagia

• Hormonal therapies are effective adjunctive measures for heavy menstrual bleeding 3
• Combine with desmopressin or VWF concentrates as needed based on severity 3

Acquired Von Willebrand Syndrome (AVWS)

• AVWS in ECMO patients develops within hours, persists throughout support, and resolves rapidly after weaning 4
• Use a multidisciplinary approach: minimize anticoagulation, replace blood products, and consider desmopressin or VWF concentrates to restore high-molecular-weight multimers 4
• Treat the underlying disorder (lymphoproliferative, autoimmune, or cardiovascular disease) as definitive therapy may resolve the acquired VWF deficiency 4

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Critical Pitfalls to Avoid

• Never rely on PT/aPTT alone to rule out VWD—normal coagulation studies are common and misleading 1
• Never use non-resorbable nasal packing in VWD patients—it predisposes to uncontrolled epistaxis 4, 1
• Do not overlook underlying conditions in adults with new-onset mucocutaneous bleeding and no personal or family bleeding history—this pattern suggests AVWS 4
• Do not give desmopressin to type 2B patients—it can precipitate thrombocytopenia 8