What is the recommended treatment for a patient with a von Willebrand's antigen activity ratio of 0.70, indicating mild type 2 von Willebrand disease (VWD)?

Treatment for von Willebrand Disease Type 2 with VWF:RCo/VWF:Ag Ratio of 0.70

For a patient with a von Willebrand factor antigen activity ratio of 0.70, indicating mild type 2 von Willebrand disease, desmopressin (DDAVP) should be tried first with a test dose before any procedures, followed by von Willebrand factor concentrates if desmopressin response is inadequate. 1

Diagnosis Confirmation

The VWF:RCo/VWF:Ag ratio of 0.70 indicates a borderline value between type 1 and type 2 von Willebrand disease (VWD). According to the NHLBI/NIH guidelines, a ratio of <0.5-0.7 is recommended to distinguish Type 2 VWD variants from Type 1 1. With a ratio of exactly 0.70, this patient is at the upper threshold for type 2 VWD classification.

Type 2 VWD represents a qualitative defect in VWF function, with several subtypes:

• Type 2A: Decreased VWF-dependent platelet adhesion with selective deficiency of high-molecular-weight VWF multimers
• Type 2B: Increased VWF affinity for platelet GP Ib
• Type 2M: Decreased VWF-dependent platelet adhesion without selective deficiency of high-molecular-weight VWF multimers
• Type 2N: Markedly decreased VWF binding affinity for FVIII

Treatment Algorithm

First-Line Treatment:

1. Desmopressin (DDAVP) Trial
   • Dosage: 0.3 mcg/kg (maximum 20 mcg) administered intravenously over 15-30 minutes 2
   • Perform a trial test to determine response before using for procedures or bleeding episodes
   • Monitor VWF levels, factor VIII activity, and bleeding time after administration

Second-Line Treatment (if DDAVP is ineffective):

1. VWF/FVIII Concentrate
   • Indicated for patients who don't respond adequately to desmopressin
   • Particularly important for major surgery or significant bleeding episodes 3
   • Concentrates with normal or near-normal high molecular weight multimers (HMWM) are preferred (VWF:RCo/VWF:Ag ratio >0.7) 4

Adjunctive Therapy:

1. Tranexamic Acid
   • Can be used alone for minor bleeding or as adjunct to other therapies
   • Particularly useful for mucosal bleeding (epistaxis, menorrhagia)

Important Considerations

Desmopressin Cautions:

• Not recommended for Type 2B VWD due to risk of thrombocytopenia 5
• Monitor for hyponatremia, especially with repeated doses
• Restrict free water intake during treatment 2
• Tachyphylaxis may occur if given more frequently than every 48 hours 2

Monitoring Parameters:

• Before treatment: VWF:RCo, VWF:Ag, factor VIII levels, bleeding time
• During treatment: serum sodium, bleeding time, factor VIII activity, ristocetin cofactor activity, and VWF antigen 2

Special Situations:

• Surgery: Administer desmopressin 30 minutes prior to procedure if patient is responsive 2
• Spontaneous bleeding: Doses may be repeated after 8-12 hours and once daily thereafter if needed 2

Practical Recommendations

• Avoid medications that impair platelet function (NSAIDs, aspirin) as they increase bleeding risk 6
• For women with heavy menstrual bleeding, consider hormonal therapies (combined oral contraceptives) 6
• Evaluate for iron deficiency, especially in patients with chronic bleeding 6
• The response to desmopressin varies among type 2 VWD subtypes, with type 2M showing better response than other type 2 variants 3

Common Pitfalls to Avoid

1. Assuming all type 2 VWD patients respond similarly to desmopressin - Response varies by subtype
2. Failing to perform a desmopressin trial test - Essential to determine individual response
3. Not monitoring for hyponatremia with repeated desmopressin doses
4. Using VWF concentrates lacking high molecular weight multimers for mucosal bleeding - These are less effective 4
5. Using concentrates with very high FVIII/VWF ratio - May increase thrombosis risk 4

The management approach should be guided by the patient's bleeding history, specific type 2 VWD subtype, and response to desmopressin, with VWF concentrates reserved for those who don't respond adequately to desmopressin or who require sustained hemostatic correction.