What is the recommended peri‑operative management, including laboratory assessment, desmopressin (DDAVP) use, factor VIII/VWF concentrate, and antifibrinolytic therapy, for a patient with von Willebrand disease type 1 undergoing an invasive procedure?

Perioperative Management of Von Willebrand Disease Type 1

For patients with von Willebrand disease type 1 undergoing surgery, desmopressin (DDAVP) 0.3 μg/kg IV is the first-line treatment, administered 30 minutes before the procedure, with tranexamic acid as an important adjunct for mucosal procedures; VWF/FVIII concentrates are reserved for patients who fail DDAVP trial or have inadequate response. 1

Pre-Operative Laboratory Assessment

Before any surgical intervention, obtain the following baseline tests 1:

• Complete blood count with platelet count to identify thrombocytopenia 1
• Prothrombin time (PT) and activated partial thromboplastin time (PTT) to assess coagulation pathways 1
• VWF antigen (VWF:Ag) 1
• VWF ristocetin cofactor activity (VWF:RCo) 1
• Factor VIII coagulant activity (FVIII) 1

Critical consideration: Calculate the VWF:RCo to VWF:Ag ratio. If this ratio is <0.5-0.7, perform VWF multimer analysis to exclude Type 2B VWD before administering DDAVP, as DDAVP is contraindicated in Type 2B due to risk of severe thrombocytopenia 1.

Pre-Analytical Variables That Affect Testing

Be aware that VWF levels can be falsely elevated by 1:

• Acute or chronic inflammatory illness
• Pregnancy or estrogen/oral contraceptive use
• Patient stress, anxiety, or recent exercise
• Blood group (non-O individuals have higher baseline levels)
• Ethnicity (African-Americans have higher baseline VWF than Caucasians)

Laboratory handling: Blood samples must be transported at room temperature and plasma separated promptly at room temperature to prevent cryoprecipitation 1.

DDAVP Trial Before Surgery

Perform a test dose of DDAVP at the time of diagnosis to establish individual patterns of biological response and predict clinical efficacy during actual bleeding or surgery 2. This is essential because response varies significantly among Type 1 VWD patients 3, 4.

DDAVP Administration Protocol

For Type 1 VWD patients with FVIII and VWF levels ≥10 U/dL 5:

• Dose: 0.3 μg/kg IV diluted in 50 mL saline 1
• Infusion time: Over 30 minutes 1
• Timing: Administer 30 minutes prior to scheduled procedure 1
• Duration of effect: Transiently corrects deficiency for 8-12 hours 5

Important caveat: DDAVP is not effective in Type 3 VWD or severe forms of Type 1 and 2 VWD 2. It should not be used in Type 2B VWD due to risk of transient thrombocytopenia 2.

VWF/FVIII Concentrate Replacement

When DDAVP is inadequate or contraindicated 1, 4:

• Use human-derived medium-purity FVIII concentrates complexed to VWF 1
• Target levels: Maintain FVIII between 50-150 U/dL to balance efficacy with thrombotic risk 6
• For neuraxial anesthesia: VWF activity should be ≥50 IU/dL 1

Dosing strategy: Calculate dosage to achieve minimum 30% of plasma factor concentration, with adjustments based on procedure type and bleeding risk 1. Sustained high FVIII levels may increase risk of postoperative venous thromboembolism, so careful monitoring and appropriate timing of repeated infusions is critical 6.

Alternative if Concentrates Unavailable

Cryoprecipitate can be used when VWF/FVIII concentrates are unavailable or when there is no response to desmopressin 1. However, virally-inactivated concentrates are preferred when available 3.

Antifibrinolytic Therapy

Tranexamic acid (TXA) is an essential adjunct, particularly for procedures involving mucosal surfaces 4, 7:

• Minor procedures: TXA used in 72% of cases 7
• Major surgery: TXA used in 59% of cases, often combined with DDAVP (32% of respondents) 7
• Deliveries: TXA used in 58% of cases 7

TXA is inexpensive, widely available, and effective across a range of bleeding scenarios 7. Management algorithms using TXA ± DDAVP have shown hemostatic efficacy >90% in small series, though evidence quality is low 7.

Perioperative Medication Management

Hold DDAVP 3-7 days pre- and post-surgery depending on procedure type and bleeding risk 1. Use caution with concurrent antiplatelet agents or anticoagulants due to increased bleeding risk 1.

Algorithm for Treatment Selection

Step 1: Confirm Type 1 VWD diagnosis with laboratory testing and exclude Type 2B 1

Step 2: Perform DDAVP trial dose if not previously done 2

Step 3: For minor procedures:

• First-line: DDAVP + TXA 7, 1
• If inadequate: Add VWF/FVIII concentrates 1

Step 4: For major surgery:

• First-line: DDAVP + TXA (if DDAVP responder) 7
• Alternative: VWF/FVIII concentrates + TXA (if DDAVP non-responder or contraindicated) 1, 6
• Monitor FVIII levels to maintain 50-150 U/dL 6

Step 5: If bleeding occurs despite prophylaxis:

• Add DDAVP if not given previously 7
• Consider platelets and/or fresh frozen plasma 7
• Escalate to VWF/FVIII concentrates or recombinant factor VIIa if first-line fails 7

Common Pitfalls to Avoid

• Do not use DDAVP in Type 2B VWD without first excluding this subtype through multimer analysis 1, 2
• Do not allow FVIII levels to remain sustained above 150 U/dL due to thrombotic risk 6
• Do not rely solely on baseline VWF levels without considering inflammatory states, hormonal influences, or blood group that may mask deficiency 1
• Do not assume DDAVP efficacy without a prior test dose as response varies significantly 2