Heavy Menses in Adolescents: When to Think about Von Willebrand Disease

CLINICAL ACTIONS:

Irregular menses is not unusual in adolescents, especially while the hypothalamic–pituitary–adrenal axis is becoming established. However, heavy menstrual bleeding, especially in tandem with anovulation can lead to significant morbidity and may reflect an underlying bleeding disorder which requires further work-up. Heavy menstrual bleeding is defined as

Excessive menstrual blood loss that interferes with a woman’s physical, social, emotional, or material quality of life. It can occur alone or in combination with other symptoms 

History

  • The nature of the bleeding
    • Length: Number of days: ≥7
    • Quality: ‘Gushing’ or ‘Flooding’ sensation
    • Quantity: Soaking a tampon or pad in ≤2 hours  
    • Impact on daily living and quality of life: Missing school and social events
  • Associated symptoms
    • Associated severe pelvic pain or pressure that may indicate associated gyn abnormality, especially endometriosis
  • Symptoms suggesting of underlying bleeding disorder
    • Personal history of anemia
    • Family history of bleeding disorder
    • Excessive bleeding during or after procedures
      • Tooth extraction
      • Other surgeries
      • Pregnancy
    • Epistaxis and easy bruising are associated with underlying bleeding disorders   
  • Note: The National Hemophilia Foundation provides an online version of the Philipp et al. screening tool (see ‘Learn More – Primary Sources’ below) that recommends further laboratory testing for an underlying bleeding disorder if ≥1 of the following criteria are met
    • Duration of menses ≥7 and ‘flooding/ gushing’ sensation or soaking ≤2 hours  
    • Anemia treatment
    • Family history of bleeding disorder
    • History of excessive bleeding associated with procedures

Physical Exam

  • Same principles apply as to any work-up for excessive bleeding including assessment of the following
    • Hemodynamic stability: Vital signs | orthostatic pressures  
    • Evidence of anemia: Pallor | Bruising | Petechiae
    • Abdominal and pelvic exam
      • Rule out trauma as a source
      • ACOG states that “speculum examination typically is not required” in this population
    • Endocrine status: ≥Tanner stage 3 breast development (Beyond breast budding | Further enlargement of breast tissue and areola, with no separation of their contours)
  • Compared to adults, structural causes such as fibroids are less frequent in this population
    • Routine ultrasound should not be obtained
  • However, if patient not responding to treatment, ultrasound should be based on “clinical judgement”
    • ACOG states that “transabdominal ultrasound may be more appropriate than transvaginal”

Labs

Basic Labs

  • Urine hCG | GC and chlamydia (if sexually active)
  • Anemia
    • CBC| Ferritin
    • If concern regarding hemodynamic stability or severe anemia: T&C
  • Coagulation
    • PT | PTT | INR | Fibrinogen | VWF activity & antigen | Factor VIII activity
  • Endocrine: TSH
    • PCOS (if clinically suspicious): Testosterone (free/total) DHEAS, Prolactin

Specialized Labs

  • Some of the specialized labs for Von Willebrand Disease (VWD) are detailed below in ‘Key Points’
  • Will require involvement of hematology and experienced laboratory

SYNOPSIS:

Menorrhagia is the most common finding in women of reproductive age. For adolescents, heavy bleeding can be very disruptive to quality of life, including participation in academics and extra-curricular activities. Heavy bleeding often starts at the onset of menses, but may not become overt until cycles become ovulatory. If an ObGyn or women’s healthcare provider is suspicious of an underlying bleeding disorder, specialty labs are required and coordinated care with an hematologist is recommended.   

KEY POINTS:

Von Willebrand Disease (VWD) – A Disorder of Platelet Function  

VWD Types

  • Type 1 (approximately 30% of VWD): Usually autosomal dominant but may also be autosomal recessive
    • Partial quantitative deficiency of normal vWF
    • Hemostasis factor assays: ↓VWF antigen | ↓VWF activity | VWF activity equals VWF antigen | Factor VIII approximately 1.5x VWF antigen levels
  • Type 2 (approximately 60% of VWD): 2A usually autosomal dominant but may also be autosomal recessive | 2B and 2M are autosomal dominant | 2N is autosomal recessive
    • Qualitative deficiency of VWF
    • Divided in to 4 subgroups (2A, 2B, 2M, 2N) based on VWF function that is altered  
    • Hemostasis factor assays for 2A, 2B and 2M: ↓VWF antigen | ↓VWF activity | VWF activity < VWF antigen | Normal or ↓Factor VIII
    • Hemostasis factor assays for 2N: Normal or ↓VWF antigen | Normal or ↓VWF activity | VWF activity equals VWF antigen |↓Factor VIII
  • Type 3 (approximately 60% of VWD): Autosomal recessive
    • Absent VWF with severe manifestations
    • Hemostasis factor assays: No VWF antigen | No VWF activity | ↓↓↓Factor VIII

Additional VWD considerations

  • Further testing
    • Hematologic: There are further specialized tests to refine the diagnosis and determine the correct type such as ‘multimers’ and other platelet (ristocetin-induced) aggregation studies (see ‘Learn More – Primary Sources’)
    • Molecular genetic testing: The VWF gene has been identified and diagnostic testing is available
  • Role of VWF
    • Mediates platelet adhesion and aggregation at the sites of vascular injury
    • Carries factor VIII (FVIII): Prolongs factor VIII half-life | Helps concentrate factor VIII at the site of the damaged endothelium
  • Presentation of VWF
    • Dependent on type: Type 1 usually mild but can be severe if VWF levels are <15 IU/dL | 2A, 2B and 2M will present with mild to moderate bleeding | Type 2N and type 3 will present with severe bleeding
    • PT usually normal

Other Bleeding Disorders to Consider

  • Other disorders (autosomal recessive) associated with platelet dysfunction include
    • Glanzmann thromasthenia: Abnormal platelet membrane glycoproteins that serve as receptors for fibrinogen  
    • Bernard-Soulier syndrome: Deficiency in platelet membrane glycoprotein complex that is a receptor for VWF
  • Coagulopathies: Deficiency in major clotting factors
  • Thrombocytopenia: Idiopathic or immune
  • Fibrinolytic pathway defects

Learn More – Primary Sources:

ACOG Committee Opinion 785: Screening and Management of Bleeding Disorders in Adolescents With Heavy Menstrual Bleeding

National Hemophilia Foundation: Philipp Screening Tool

NICE Guideline 88: Heavy menstrual bleeding: assessment and management

WHO Tanner Chart

GeneReviews: von Willebrand Disease