Management of Von Willebrand Disease

Remarks:

• This recommendation does not apply to patients for whom desmopressin is not a reasonable treatment option (eg, those with type 3 VWD). Desmopressin is contraindicated in type 3 VWD because of a lack of efficacy and in type 2B VWD because of increased platelet binding with subsequent thrombocytopenia.

• Many patients with type 2 VWD do not respond to desmopressin and require other modes of treatment. However, a desmopressin trial may be helpful to confirm diagnosis, and desmopressin may still be useful in some instances of mild bleeding for type 2 VWD patients.

• Patients undergoing major surgery, including in sites where even a small amount of bleeding may result in critical organ damage (eg, central nervous system surgery), should not receive desmopressin as sole therapy.

• It is optimal to confirm desmopressin responsiveness before using desmopressin for therapeutic interventions, but because this may not always be practical, adult patients with type 1 VWD whose baseline VWF levels are ≥0.30 IU/mL can be presumed to be desmopressin responsive. Although they can receive desmopressin without requiring a trial, it is reasonable to obtain VWF levels to confirm response after administration. Patients with type 1 VWD and VWF levels of <0.30 IU/mL may not respond to desmopressin, hence the recommendation for a trial.

• This recommendation does not address the choice between treating with tranexamic acid and VWF concentrate.

Good practice statements.

• The administration of desmopressin to patients with type 2B VWD is generally contraindicated, because this may cause thrombocytopenia as a result of increased platelet binding.
• Furthermore, desmopressin is generally contraindicated in patients with active cardiovascular disease (eg, coronary heart disease, cerebrovascular disease, and peripheral vascular disease), patients with seizure disorders, patients age <2 years, and patients with type 1C VWD in the setting of surgery. Desmopressin has been used safely in many women during pregnancy, including those with bleeding disorders and diabetes insipidus. It should be avoided in women with preeclampsia and those with cardiovascular disease. IV fluid infusion and oxytocic medications are often used during labor and delivery, both of which increase the risk of desmopressin-induced hyponatremia.
• Patients receiving desmopressin are at risk for hyponatremia from free water retention; therefore, they should receive normal saline if IV fluid replacement is required, and oral free water fluid intake should be restricted to prevent hyponatremia.
• Patient counseling about desmopressin should include strategies to mitigate risks associated with hyponatremia (eg, free water restriction and education about signs and symptoms of hyponatremia that should lead to prompt medical evaluation) and cardiovascular disease.

Remark:

• It is important to reassess the bleeding risk throughout the course of treatment.

Good practice statements.

• Patients considered for treatment require individualized analyses of the risks and benefits of the specific therapy plan in conjunction with a multidisciplinary team that includes cardiovascular medicine specialists, hematologists, and the patient.
• Patient education about the risks and benefits of using antiplatelet agents or anticoagulant therapy should be provided to inform shared decision making.
• Patients with a severe bleeding phenotype (eg, severe type 1, type 2, or type 3 VWD) may require prophylaxis with VWF concentrate to prevent bleeding while on antiplatelet or anticoagulant therapy; similar precautions may apply to patients with type 1 VWD and concurrent additional bleeding problems.
• Desmopressin therapy is generally contraindicated in individuals with cardiovascular disease (eg, coronary heart disease, cerebrovascular disease, and peripheral vascular disease) and/or increased risk of thrombosis.

Remarks:

• When it is possible to keep both trough levels at ≥0.50 IU/mL for at least 3 days or as long as clinically indicated after the surgery (instead of choosing only 1), this should be the preferred option.

• The specific target levels should be individualized based on the patient, type of procedure, and bleeding history as well as availability of VWF and FVIII testing.

• The duration of the intervention can vary for specific types of surgeries.

Remarks:

• Individualized therapy plans should consider the variation in bleeding risk for the specific procedure in question. Individualized therapy plans are especially important for patients who may be overtreated when VWF activity is increased to ≥0.50 IU/mL by any therapy and addition of tranexamic acid (eg, those undergoing cutaneous procedures, such as superficial skin biopsy).

• Patients with type 3 VWD will require VWF concentrate to achieve any significant increase in VWF activity levels. Use of desmopressin is contraindicated in this population because of a lack of efficacy.

• Many patients with type 2 VWD (including patients with type 2B VWD) will also require treatment with VWF concentrate rather than desmopressin.

• For patients at higher risk of thrombosis, it may be desirable to avoid the combination of extended increased VWF and FVIII levels (>1.50 IU/mL) and extended use of tranexamic acid.

• Dental proceduralists may consider use of local hemostatic measures (eg, gelatin sponges or fibrin glue, tranexamic acid rinse) as part of an individualized procedural plan.

Remarks:

• This recommendation does not imply that the interventions considered can be prescribed only as monotherapy. In some cases, multiple options can be combined, especially if control of heavy menstrual bleeding is less than optimal with the initial therapy.

• Desmopressin is not effective in type 3 and many type 2 VWD patients and is contraindicated in type 2B VWD.

• Women may require additional treatment directed at bleeding symptoms for the first several menstrual cycles after placement of a levonorgestrel-releasing intrauterine system.

Good practice statements.

• When feasible, the panel encourages the development of multidisciplinary clinics in which gynecologists and hematologists see patients jointly to facilitate the management of heavy menstrual bleeding for patients with bleeding disorders.
• Decisions regarding the use of a levonorgestrel-releasing intrauterine system should be made in the setting of shared decision making with multidisciplinary input (eg, gynecology professionals, hematology professionals, and patients).
• For some patients, there may be other benefits with use of hormonal therapy, such as treatment of menstrual pain and management of endometriosis- and polycystic ovary syndrome–related symptoms.
• Both iron deficiency and anemia resulting from iron deficiency are associated with adverse outcomes, including diminished health-related quality of life. Patients with heavy menstrual bleeding should be regularly assessed and treated for iron deficiency and/or anemia.
• Women with known bleeding disorders and heavy menstrual bleeding should undergo a standard gynecologic assessment that is recommended for women with heavy menstrual bleeding in the general population to rule out common pelvic pathologies, such as fibroids and polyps, especially those not responding to first-line treatment.
• Special consideration is required in terms of adverse effects of therapy for those who are at high risk of endometrial hyperplasia/malignancies, such as women age >35 years and those with polycystic ovaries, high body mass index, and comorbidities, such as diabetes and hypertension.

Good practice statements.

• Tranexamic acid may be given systemically via the oral or IV route. The oral dose is 25mg/kg (typically 1000-1300 mg) 3 times per day for 10 to 14 days or longer if blood loss remains heavy.
• Patients who intend to breastfeed should be provided education about the safety of tranexamic acid during breastfeeding in conjunction with its benefits in reducing bleeding.