Aren't you worried about the possibility of type 2 von Willebrand disease (vWD), isn't Desmopressin (DDAVP) contraindicated?

Desmopressin (DDAVP) is Contraindicated in Type 2B von Willebrand Disease

Desmopressin (DDAVP) is contraindicated in patients with Type 2B von Willebrand disease as it can induce platelet aggregation and potentially worsen thrombocytopenia. 1

Understanding Type 2 von Willebrand Disease and DDAVP Contraindications

Von Willebrand disease (vWD) is the most common inherited bleeding disorder, affecting up to 1% of the population. When evaluating a patient with suspected vWD, it's critical to determine the specific subtype, as treatment approaches differ significantly based on the variant.

Type 2 vWD represents qualitative defects in von Willebrand factor (vWF) structure and function, and is further subdivided into:

• Type 2A: Loss of high and intermediate molecular weight multimers
• Type 2B: Enhanced binding to platelets with loss of high molecular weight multimers
• Type 2M: Decreased platelet-dependent function with normal multimer pattern
• Type 2N: Decreased FVIII binding capacity 2

Why DDAVP is Contraindicated in Type 2B vWD

The FDA label for desmopressin explicitly states: "Desmopressin acetate should not be used to treat patients with Type IIB von Willebrand's disease since platelet aggregation may be induced." 1

This contraindication exists because:

1. Type 2B vWD is characterized by gain-of-function mutations that cause enhanced binding of vWF to platelets
2. DDAVP administration releases additional abnormal vWF into circulation
3. This abnormal vWF spontaneously binds to platelets, causing platelet aggregation and potentially worsening thrombocytopenia 3

Diagnostic Considerations for Type 2 vWD

To determine if a patient has Type 2B vWD (where DDAVP is contraindicated), the following laboratory findings are characteristic:

• VWF:RCo <30 IU/dL
• VWF:Ag 30-200 IU/dL
• VWF:RCo/VWF:Ag ratio <0.5-0.7
• Loss of high molecular weight multimers
• Enhanced ristocetin-induced platelet aggregation (RIPA) at low doses of ristocetin 2

Treatment Alternatives for Type 2B vWD

For patients with Type 2B vWD requiring hemostatic support:

1. VWF-containing factor concentrates are the mainstay of treatment 4
2. Target VWF:RCo levels of ≥50 IU/dL for minor procedures and ≥80-100 IU/dL for major surgery 2
3. Consider adjunctive use of tranexamic acid (10-15 mg/kg IV every 8 hours) for 24-72 hours post-procedure 2

Management of Other vWD Subtypes

For other vWD subtypes:

• Type 1 vWD (mild to moderate): DDAVP is typically effective at 0.3 μg/kg IV diluted in 50ml saline, infused over 30 minutes 5, 2
• Type 2A and 2M: DDAVP may be effective in some patients; a trial test is recommended 3
• Type 2N: DDAVP may be effective but often requires factor concentrates for major procedures 3
• Type 3 vWD: DDAVP is ineffective; VWF-containing factor concentrates are required 4

Important Clinical Caveat

Even when DDAVP is not contraindicated, a test dose should be administered at the time of diagnosis to establish individual response patterns before using it for bleeding episodes or surgical procedures. This allows for personalized treatment planning and avoids unexpected treatment failures during critical situations 6.

When evaluating a patient with suspected vWD, always perform comprehensive laboratory testing including VWF:Ag, VWF:RCo, FVIII activity, and multimer analysis to accurately determine the subtype before considering DDAVP administration 2.