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The Genome
CMECNE

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

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Learning Objectives and CME/Disclosure Information

This activity is intended for healthcare providers delivering care to women and their families.

After completing this activity, the participant should be better able to:

1. Describe the key findings on history that suggest an underlying bleeding disorder in the setting of heavy menstrual bleeding
2. Explain the importance of the VWF protein in platelet function

Estimated time to complete activity: 0.5 hours

Faculty:

Susan J. Gross, MD, FRCSC, FACOG, FACMG
President and CEO, The ObG Project

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires instructors, planners, managers and other individuals who are in a position to control the content of this activity to disclose any real or apparent conflict of interest (COI) they may have as related to the content of this activity. All identified COI are thoroughly vetted and resolved according to PIM policy. PIM is committed to providing its learners with high quality CME activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest.

Faculty: Susan J. Gross, MD, receives consulting fees from Cradle Genomics, and has financial interest in The ObG Project, Inc.

Planners and Managers: The PIM planners and managers, Trace Hutchison, PharmD, Samantha Mattiucci, PharmD, CHCP, Judi Smelker-Mitchek, MBA, MSN, RN, and Jan Schultz, MSN, RN, CHCP have nothing to disclose.

Method of Participation and Request for Credit

Fees for participating and receiving CME credit for this activity are as posted on The ObG Project website. During the period from 1/15/2020 through 1/15/2021, participants must read the learning objectives and faculty disclosures and study the educational activity.

If you wish to receive acknowledgment for completing this activity, please complete the post-test and evaluation. Upon registering and successfully completing the post-test with a score of 100% and the activity evaluation, your certificate will be made available immediately.

For Pharmacists: Upon successfully completing the post-test with a score of 100% and the activity evaluation form, transcript information will be sent to the NABP CPE Monitor Service within 4 weeks.

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education

Postgraduate Institute for Medicine designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Continuing Nursing Education

The maximum number of hours awarded for this Continuing Nursing Education activity is 0.5 contact hours.

Read Disclaimer & Fine Print

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 ACOG opinion includes the 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

NICE Guideline 88: Heavy menstrual bleeding: assessment and management

WHO Tanner Chart

GeneReviews: von Willebrand Disease

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Related ObG Topics:

Are We Meeting the ACOG Screening Guidelines for Von Willebrand Disease in Adolescents with Menorrhagia?
Is Heavy Menstrual Bleeding a Sign of a Bleeding Disorder in Adolescents?

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This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.

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presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

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