What is the treatment for von Willebrand (VW) disease with low factor VIII levels?

Treatment of von Willebrand Disease with Low Factor VIII Levels

The treatment of von Willebrand disease (VWD) with low factor VIII levels should begin with desmopressin (DDAVP) for type 1 and some type 2A VWD patients, followed by VWF/FVIII concentrates if desmopressin is inadequate, while patients with types 2B, 2M, 2N, and 3 VWD should be treated primarily with specific VWF/FVIII concentrates. 1

Treatment Algorithm Based on VWD Type

Type 1 VWD (Partial Quantitative VWF Deficiency)

• First-line treatment: Desmopressin (DDAVP) at 0.3 μg/kg actual body weight administered by intravenous infusion over 15-30 minutes 2
• DDAVP is effective in patients with FVIII levels ≥5% of normal 1, 3
• If used preoperatively, administer 30 minutes prior to procedure 2
• May repeat doses after 8-12 hours and once daily thereafter if needed, based on clinical condition and VWF/FVIII levels 2
• Tachyphylaxis may occur with repeated administration given more frequently than every 48 hours 2

Type 2 VWD (Qualitative VWF Defects)

• Type 2A: Initial trial of desmopressin; if inadequate response, switch to VWF/FVIII concentrates 1
• Type 2B, 2M, 2N: VWF/FVIII concentrates are first-line therapy 1, 4
• DDAVP is contraindicated in type 2B due to risk of thrombocytopenia 4
• Human-derived medium-purity FVIII concentrates complexed to VWF (e.g., Humate-P) are preferred for types 2B, 2M, 2N 1, 4

Type 3 VWD (Severe Quantitative VWF Deficiency)

• DDAVP is ineffective due to virtually complete absence of VWF 1, 3
• VWF/FVIII concentrates are the only effective treatment option 3, 5
• Dosing should be calculated to achieve a minimum of 30% of plasma factor concentration 1

Monitoring Treatment Response

• Prior to treatment, verify that FVIII coagulant activity levels are >5% 2
• Exclude presence of FVIII autoantibodies and abnormal molecular forms of FVIII antigen 2
• During treatment, assess:
  • Serum sodium (risk of hyponatremia with DDAVP) 2
  • Bleeding time 2
  • Factor VIII coagulant activity 2
  • Ristocetin cofactor activity 2
  • Von Willebrand antigen 2

Alternative Treatment Options

• If VWF/FVIII concentrates are unavailable, cryoprecipitate can be used 1
• Cryoprecipitate is indicated when:
  • There is no response to desmopressin 1
  • VWF/FVIII concentrates are unavailable 1
  • For patients with congenital fibrinogen deficiencies 1

Special Considerations

• For surgical procedures, VWF/FVIII levels should be maintained between 50-150 U/dL to prevent excessive bleeding 6
• Antifibrinolytic therapy (e.g., tranexamic acid) is an important adjunct to replacement therapy during surgeries involving mucosal surfaces 7
• For neuraxial anesthesia, VWF activity should be ≥50 IU/dL 1
• Patients with recurrent mucosal bleeding not controlled by VWF/FVIII concentrates may benefit from additional DDAVP or platelet concentrates 5

Clinical Pitfalls and Caveats

• DDAVP can cause systemic vasodilation leading to hypotension, tachycardia, and facial flushing 8
• Restrict free water intake during DDAVP treatment to prevent hyponatremia 2
• Repeated infusions of VWF/FVIII concentrates may lead to sustained high FVIII levels, potentially increasing risk of postoperative venous thromboembolism 6
• The necessity for repeat administration should be determined by laboratory response and clinical condition 2
• Prophylactic use of DDAVP in cardiac surgery has shown no benefit in multiple meta-analyses 8