What is the most appropriate next step for a 14-year-old female with heavy menstrual bleeding, easy bruising, and prolonged bleeding from cuts, with normal complete blood count (CBC), coagulation studies, and fibrinogen levels?

From the Guidelines

The most appropriate next step for this 14-year-old female with heavy menstrual bleeding, easy bruising, and prolonged bleeding from cuts, despite normal CBC, coagulation studies, and fibrinogen levels, is to perform von Willebrand disease (vWD) testing, including von Willebrand factor antigen (vWF:Ag), von Willebrand factor activity (vWF:RCo), and factor VIII activity levels, as recommended by recent guidelines 1.

This approach is supported by the fact that vWD is the most common inherited bleeding disorder, affecting up to 1% of the population, and is frequently overlooked in adolescent females with menorrhagia. The normal coagulation studies (PT, PTT) and fibrinogen do not rule out vWD, as these tests specifically evaluate different aspects of the coagulation cascade. The combination of mucocutaneous bleeding symptoms (heavy periods, easy bruising, prolonged bleeding from cuts) with normal basic coagulation tests strongly suggests a platelet function disorder or vWD.

Key points to consider in the diagnosis and management of vWD include:

• Testing should ideally be done when the patient is not menstruating and not taking hormonal medications that could affect results.
• If vWD is confirmed, management may include desmopressin (DDAVP) for mild cases, typically given as intranasal spray at 150-300 mcg or intravenous infusion at 0.3 mcg/kg, or von Willebrand factor concentrates for more severe cases.
• Hormonal therapy such as combined oral contraceptives or a levonorgestrel IUD may also help control menstrual bleeding.
• Recent studies have highlighted the importance of considering vWD in the diagnosis and management of bleeding disorders of unknown cause (BDUC) 1.
• The use of tranexamic acid (TXA) and DDAVP has been reported in the management of heavy menstrual bleeding (HMB) in women with BDUC, with TXA being commonly added to combined oral contraceptives (COCP) when bleeding persists 1.

Overall, a comprehensive approach to the diagnosis and management of this patient's bleeding symptoms is necessary, taking into account the latest evidence and guidelines 1.

From the Research

Next Steps for Diagnosis and Management

Given the symptoms of heavy menstrual bleeding, easy bruising, and prolonged bleeding from cuts in a 14-year-old female with normal CBC, coagulation studies, and fibrinogen levels, the following steps are considered:

• Consider Inherited Bleeding Disorders: Inherited bleeding disorders, such as von Willebrand disease, should be considered in the differential diagnosis of menorrhagia, especially with a personal or family history of bleeding symptoms 2.
• Diagnostic Evaluation: A thorough history and physical examination are critical. Further investigation, including a von Willebrand disease workup (factor VIII, vWF antigen, and vWF functional assay), should be considered in patients with a personal history of other bleeding or a family history of bleeding 2.
• Importance of Accurate Diagnosis: Accurate diagnosis of the specific subtype of von Willebrand disease or other bleeding disorders is crucial because therapy will vary according to the subtype 3.
• Therapeutic Options: Desmopressin is the treatment of choice for type 1 von Willebrand disease and can be effective in raising endogenous factor VIII and von Willebrand factor levels 4, 5. For patients where desmopressin is not effective or contraindicated, plasma concentrates containing factor VIII and von Willebrand factor may be necessary 4, 5.
• Management of Menorrhagia: Treatment of menorrhagia in women with inherited bleeding disorders should be individualized. Hormonal therapies, antifibrinolytic drugs like tranexamic acid, and desmopressin can be considered as first-line treatments 2.

Considerations for Adolescents

• Testing for Inherited Bleeding Disorders: Girls from families with a history of von Willebrand disease or other inherited bleeding disorders should be tested pre-menarchally to determine if they have inherited the disease 2.
• Investigation Before Hormonal Therapy: In adolescents presenting with menorrhagia, an investigation for inherited bleeding disorders should be undertaken before instituting oral contraceptive therapy to avoid masking the diagnosis 2.