What are the treatment options for heavy menstrual bleeding and rectal bleeding in patients with Von Willebrand disease?

Treatment of Heavy Menstrual Bleeding and Rectal Bleeding in Von Willebrand Disease

For patients with Von Willebrand disease experiencing heavy menstrual bleeding and rectal bleeding, initiate tranexamic acid (TXA) as first-line therapy, with desmopressin (DDAVP) added for type 1 VWD or as second-line for refractory bleeding, while reserving VWF/FVIII concentrates for severe bleeding, type 2B/2M/2N/3 VWD, or when other treatments fail. 1, 2, 3

Initial Treatment Approach for Heavy Menstrual Bleeding

First-Line Therapy

• Tranexamic acid (TXA) is the preferred initial treatment for heavy menstrual bleeding in VWD patients, as it directly addresses mucosal bleeding without the limitations of hormonal or replacement therapies 1
• TXA can be used alone or in combination with hormonal contraceptives (combined oral contraceptive pill or intrauterine device) for enhanced bleeding control 1

Second-Line Therapy Based on VWD Type

• For Type 1 VWD with factor VIII levels >5%: Add desmopressin 0.3 μg/kg IV diluted in 50 mL saline infused over 30 minutes if TXA alone is inadequate 2, 3
• Desmopressin raises endogenous factor VIII and VWF three- to fivefold, correcting both coagulation and platelet adhesion defects in most type 1 patients 4, 5
• For Type 2A VWD: Trial desmopressin first; if inadequate response, switch to VWF/FVIII concentrates 2

Third-Line and Type-Specific Therapy

• For Type 2B, 2M, 2N, and Type 3 VWD: VWF/FVIII concentrates are first-line therapy as desmopressin is ineffective or contraindicated 2, 3
• Desmopressin is absolutely contraindicated in type 2B VWD due to risk of thrombocytopenia 2
• Human-derived medium-purity FVIII concentrates complexed to VWF are preferred for types 2B, 2M, and 2N 2
• For type 3 VWD, desmopressin is completely ineffective due to virtually complete absence of VWF, making VWF/FVIII concentrates the only effective option 2, 3

Treatment of Rectal Bleeding in VWD

Acute Bleeding Management

• Initiate TXA immediately for mucosal bleeding, as it is highly effective for gastrointestinal bleeding in VWD patients 1, 6
• Add desmopressin for type 1 VWD patients with factor VIII levels >5% if bleeding continues despite TXA 2, 3
• Desmopressin will stop bleeding in hemophilia A and VWD patients with episodes of spontaneous or trauma-induced mucosal bleeding 3

Refractory or Severe Bleeding

• If bleeding continues after initial treatment with TXA and desmopressin, switch to bypassing agents such as recombinant factor VIIa (rFVIIa at 90-120 μg/kg every 2-3 hours) or activated prothrombin complex concentrates (aPCC at 50-100 IU/kg every 8-12 hours) 7
• Bypassing agents are effective in 90% of bleeding episodes when used as first-line therapy for severe bleeding 7
• For patients with factor VIII levels ≤5% or significant bleeding, immediately administer bypassing agents rather than attempting desmopressin 7

Type-Specific Considerations for Rectal Bleeding

• Type 2B, 2M, 2N, and Type 3 patients: Use VWF/FVIII concentrates as primary therapy, not desmopressin 2, 3
• Dosing of VWF/FVIII concentrates should achieve a minimum of 30% of plasma factor concentration 2
• If VWF/FVIII concentrates are unavailable, cryoprecipitate can be used as an alternative 2

Critical Monitoring and Safety Considerations

Pre-Treatment Assessment

• Test for von Willebrand activity before starting desmopressin in patients with bleeding history 2
• Determine the specific VWD type, as type 2B patients should not receive desmopressin due to increased risk of thrombocytopenia 2, 7
• Use caution with concurrent antiplatelet agents or anticoagulants due to increased bleeding risk 2

Monitoring for Treatment Failure

• Signs of treatment failure include: no change in blood loss over time, hemoglobin decrease despite red blood cell replacement, and increasing dimensions of internal bleeding on imaging 7
• Monitor for desmopressin-related adverse effects, particularly water retention and hyponatremia with risk of seizures, especially in elderly patients 7

Adjunctive Therapy

• Tranexamic acid should be used as adjunctive treatment except when combined with aPCC 7
• Antifibrinolytic treatment is an important adjunct during bleeding involving mucosal surfaces 8, 6

Common Pitfalls to Avoid

• Do not use desmopressin in type 2B VWD as it can worsen thrombocytopenia 2, 3
• Do not rely on desmopressin for type 3 VWD as these patients have virtually complete absence of VWF and will not respond 2, 3, 5
• Do not use desmopressin in patients with factor VIII levels ≤5% as it is ineffective and delays appropriate treatment 3
• Patients with severe homozygous VWD with factor VIII coagulant activity and VWF antigen levels <1% are least likely to respond to any treatment except concentrates 3
• Avoid combining TXA with aPCC due to thrombotic risk 7