#280 Heavy Menstrual Bleeding, Anticoagulation & Coagulopathy in Menstruating Patients

June 21, 2021 | By Kate Grant

Hormonal Therapy, Venous thromboembolic disease, Anticoagulation, and Abnormal Uterine Bleeding with Dr. Bethany Samuelson Bannow

Explore the intersection of hematology and women’s health as we discuss heavy menstrual bleeding (HMB), gynecologic risks of therapeutic anticoagulation, and prescribing contraception in the setting of venous thromboembolic disease. 

Wondering how to expand your women’s health knowledge as an internist? Listen as our insightful guest Dr. Bethany Samuelson Bannow @bsamuelson_md (Oregon Health & Science University) helps us navigate the intersections between non-malignant hematology and menstrual health. This episode will empower you to tackle the stigma and overcome knowledge gaps with regard to abnormal menstrual bleeding, as well as learn treatment, and management pearls.  We also explore the intersection between therapeutic anticoagulation, heavy menstrual bleeding, and thromboembolic disease of different contraceptive options.  Finally, we face the themes of overcoming sexism, and even misogyny, in women’s health head-on throughout this episode. After all, half the population has a uterus.

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Credits

• Written and Produced by: Avital O’Glasser MD, FACP, FHM
• Infographic: Avital O’Glasser MD, FACP, FHM
• Cover Art : Kate Grant MBChB MRCGP DipGUMed
• Show Notes: Kate Grant MBChB MRCGP DipGUMed, Maddie Morgan, and Avital O’Glasser MD, FACP, FHM
• Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP; Avital O’Glasser MD, FACP, FHM
• Reviewer: Carolyn Chan, MD
• Editor: Matthew Watto MD, FACP (written materials); Clair Morgan of nodderly.com
• Guest: Bethany Samuelson Bannow, MD

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Sponsor: Green Chef GreenChef.com/curb100

CME Partner: VCU Health CE

The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit curbsiders.vcuhealth.org and search for this episode to claim credit.

Show Segments

• Intro, disclaimer, guest bio
• Guest one-liner
• Case 1 from Kashlak
• Definitions related to menstrual health
• Quantifying/defining heavy menstrual bleeding
• Overcoming stigma of asking about menstrual history/health
• Clinical evaluation/management of the patient with heavy menstrual bleeding
• Case 2 from Kashlak
• Risk of heavy menstrual bleeding (HMB) in the setting of therapeutic anticoagulation
• Hormonal and nonhormonal therapy options for HMB while anticoagulated
• Contraception options for someone who develops VTE
• Case 3 from Kashlak
• Counseling about VTE risk of different contraception options
• Take Home Points; Outro; Bonus clip

Women’s Hematology Pearls

1. Women’s health histories, including menstruation histories, are frequently stigmatized, leading to incomplete histories followed by underrecognized, underdiagnosed, and undertreated hematologic and/or gynecologic problems. 
2. Clinicians need to ASK, ASK, ASK and ASK about menstrual history in patients with uteruses. Several objective and subjective questions can be very high yield for raising concerns about menstrual abnormalities.
3. Approximately 20% of patients with heavy menstrual bleeding will have a bleeding diathesis, including non-specific platelet dysfunction, von Willebrand’s disease, or hemophilia carrier state
4. Anticoagulation studies were not designed to capture the significance of heavier menstrual bleeding.  
5. Rivaroxaban is confirmed to have a higher menstrual bleeding risk than vitamin K antagonists, which can also lead to interruption of therapy and risk of recurrent VTE.
6. Certain contraceptives, especially long acting reversible contraceptives (LARC), can be used to lessen heavy menstrual bleeding caused by therapeutic anticoagulation, as well as hemostatic agents.
7. Tranexamic acid DOES NOT CAUSE CLOTS and can be valuable for HMB (ex. 1300mg TID for 5 days). 
8. The development of a VTE while on contraception does NOT preclude continued therapy or substitution with another form of contraception.  OCPs have a lower thrombotic risk than pregnancy, especially with concurrent anticoagulation!
9. IUDs (Hormonal NOT copper) are your friend.

Women’s Hematology

Why does the intersection of hematology and women’s health matter?

Menstrual histories are frequently stigmatized, leading to incomplete health information.  This leads to hematologic and/or gynecologic problems being underrecognized, underdiagnosed, and undertreated–leading to adverse health effects and impaired quality of life.  

Sexism and Misogyny of Iron Deficiency  

12-18% of “fit and healthy” active women are iron deficient (Dugan 2021), and the widely accepted lab reference ranges for a normal hematocrit is lower for women, which delays recognition of anemia in women and leads to suboptimal care in menstrual and women’s health.  Iron deficiency can exist with or WITHOUT anemia. Patients can have symptomatic iron deficiency without anemia. 

There is a complex dynamic between stigmatized women’s health, sexism, and misogyny in medicine.  While clinicians may fault the challenges of discussing “sensitive” topics in medicine, data shows that we can discuss, and treat, “sensitive” men’s health problems such as erectile dysfunction (Samuelson Bannow 2021, Weyand 2020, Critchley 2020).  Consider these references with eye-opening titles for additional reading:

1. A Period Piece (written by Dr. Samuelson Bannow)
2. “They Don’t Really Take My Bleeds Seriously”: Barriers to Care for Women with Inherited Bleeding Disorders
3. The Misogyny of Iron Deficiency 
4. The Effect of Iron Deficiency and Anaemia on Women’s Health   
5. Sexism in the Management of Bleeding Disorders 
6. Menstruation: Science and Society

Assessing and Managing Heavy Menstrual Bleeding

Normal menstrual bleeding in healthy women is a median of 53mL blood loss per cycle and typically lasts 3-7 days, which occurs between the ages of 11-51.  Heavy bleeding is quantified as > 80mL blood loss per cycle.  You can measure this…BUT subjective questions and other clinical features can accurately predict heavy bleeding and negatively impacted quality of life (Menorrhagia I and Menorrhagia II studies).  Features to solicit: changing sanitary protection every 1-2 hours; needing pads and tampons together; changing protection overnight; passing clots size of 50pence piece/1” diameter; 7-10 days duration; low ferritin.  Any post-menopausal, post-coital, or intermenstrual bleeding meets criteria for abnormal uterine bleeding.

The definition of heavy menstrual bleeding (HMB) is also changing to reflect the negative impact on quality of life–i.e. Does it cause you to miss work or school; does it interfere with social activity?

Dr. Samuelson Bannow says these are her three highest yield questions in clinic:

1. “How heavy are your periods–moderate, heavy, or very heavy?”
2. “How often do you change your protection/menstrual products or double up?”
3. “Have you ever been diagnosed with iron deficiency or taken iron supplements?”

Overcoming stigma and discomfort in discussing menstrual health

“Talking about periods and tampons to me is like talking about my morning coffee” ~ Dr. Bethany Samuelson Bannow

Less than 10% of “well women visits” will have a full menstrual history documented (Weyand 2020).  Clinicians may not be trained how to ask, and we may feel uncomfortable asking.  Dr. Samuelson Bannow recommends getting comfortable with the questions and the terminology surrounding menstruation as well as menstrual products like pads and tampons–this is normal bodily function.  Acknowledge if you feel uncomfortable or awkward talking about it! She also recommends starting with open ended questions, such as: “tell me about your periods”.  Ask more closed ended questions to solicit the characteristics of heavy menstrual bleeding listed above. Family history of heavy menstrual bleeding can be very helpful–but be careful that HMB may be “normalized” with family cohorts.

Remember that transgender patients may also have a uterus, with or without suppressed menstruating.  Using the term “menstruating individual” or “menstruating patient” avoids gender-based discrimination. 

Pursuing thrombophilia evaluations for heavy menstrual bleeding

Dr. Samuelson Bannow estimates that approximately 20% of patients with HMB will have an underlying bleeding disorder.  Asking a bleeding ROS can inform the evaluation–ex. Mucocutaneous bleeding, GI bleeding, epistaxis, postpartum bleeding, or abnormal surgical bleeding.

Von Willebrand disease is common (1% of the population) and most commonly autosomal dominant, so family history should be positive for abnormal bleeding (Shankar 2004).  Ask about mucocutaneous bleeding from gums, the GI tract, rectum, epistaxis.  Also ask about postpartum bleeding lasting beyond 6 weeks.

Hemophilia is X-linked (CDC Hemophilia Inheritance Patterns).  Every daughter of a man with hemophilia is an obligate carrier, but there is also a 5% spontaneous mutation rate.  We have gained recognition that hemophilia carriers do have a higher bleeding risk than non-carriers (Plug 2006).  Male patients with hemophilia classically have joint bleeding; women carriers have heavier menses and can have severe or delayed postpartum bleeding (ex. 12 weeks postpartum).

Treatment/management of HMB

Dr. Samuelson Bannow starts with PT, PTT, and Von Willebrand’s panel (VW antigen, VW activity, and Factor VIII) in addition to a ferritin.  Consider repeating labs done prior to referral to hematology as delays in processing clotting factors can lead to false negative results; exercise/stress before phlebotomy can also affect results.

Treatment rule number 1: Treat the iron deficiency!

Treatment rule number 2: Treat the bleeding!  Tranexamic acid DOES NOT CAUSE CLOTS and can be valuable for HMB (ex. 1300mg TID for 5 days).  Contraception options can be used to manage HMB, especially intrauterine devices with levonorgestrel (do NOT use a copper IUD to control HMB!). Combination estrogen/progesterone oral contraceptive pills or Depot-Medroxyprogesterone every 90 days can also be prescribed by primary care clinicians.

In addition to bleeding predilection, there may be structural abnormalities or other primary gynecologic pathology contributing to heavy menstrual bleeding.  It’s never wrong to refer to gynecology!

Therapeutic Anticoagulation and Menstrual Bleeding

“The standard measures of bleeding outcomes used in clinical trials were not designed to capture the significance of monthly bleeding. Thus, studies of antithrombotic agents inevitably and grossly underestimate the significance of increased menstrual bleeding…we consistently fail to evaluate for this in a meaningful way, even in our highest-quality studies.” 

Samuelson Bannow 2021 

We have limited data to inform the risk of heavy menstrual bleeding for patients who need to take therapeutic anticoagulation (Godin 2017).  There is limited data regarding warfarin, and the more modern DOAC studies do not consider the effects of anticoagulants on menstruation.  Part of this is based on how “bleeding complications” are defined in studies (versus how HMB manifests)–ex. Did the patient require a PRBC transfusion or seek medical care. Clinicians also need to remember to ASK (ex. At anticoagulation clinic visits)!

Anecdotally, about a third of women in rivaroxaban will have HMB.  Rivaroxaban is associated with a higher risk of HMB and the need for more interventions to reduce menstruation than vitamin K antagonists (Byrk 2016, De Crem 2015, Martinelli 2016).  Rivaroxaban was also associated with more interruptions of therapy for 2-3 days AND a higher risk of recurrent VTE (likely due to the interruption of therapy) (Byrk 2016).   Apixaban may have less HMB than rivaroxaban, but adherence may be worse based on the BID dosing schedule (Myers 2016).

Have a conversation with your patient!  Discuss the risk of heavy menstrual bleeding when starting therapy, and engage in patient centered care regarding choice of a BID or once daily DOAC.  Check a ferritin level prior to starting a DOAC.

Management of HMB while on Anticoagulation

Provide anticipatory guidance about heavy bleeding, and management options when starting anticoagulation.  Empower women to report any abnormal bleeding while on anticoagulation–minimize the risk of a patient self-discontinuing therapy and increasing the risk of recurrent VTE.

You can have the patient complete one cycle on a DOAC to see if it causes HMB before deciding about adjunctive therapy–you can also have a patient-centered conversation about sustainability/tolerability of HMB if they will only be on anticoagulation for 3 months (ex. A provoked VTE).  Consider offering a Long acting reversible contraception/LARC (ex. Levonorgestrel IUD) to manage HMB, especially for longer term anticoagulation therapy.

Tranexamic acid DOES NOT CAUSE CLOTS (Wellington 2003).  Dr Samuelson-Bannow’s expert opinion is that tranexamic acid can be used to manage HMB while on DOAC therapy (off licence use).  However, it does prevent fibrinolysis, so don’t prescribe it in the first month post VTE. 

Contraception and VTE Risk/Management

Management of contraception for someone who develops VTE

Contraception (including combination OCPs (COCPs)) DOES NOT need to be stopped when a patient develops a VTE and is started on therapeutic anticoagulation.  The alternative of OCPs isn’t nothing–it’s pregnancy, which has a much higher risk of VTE than the therapy itself.

Dr Samuelson-Bannow’s opinion is that best evidence shows that OCPs can be continued (Martinelli 2016, Eischer 2014). However, you can also consider changing the form of contraception, such as switching to a LARC (levonorgestrel IUD or implant).  Do not switch to Depot-Medroxyprogestrone because this has a higher risk of VTE (van Hylckama Vlieg 2010, Tepper 2016).  Progestin only OCPs are also safe but require very strict daily dosing times (Le Moigne 2016, Tepper 2016). **Update – It came to our attention after our recording that a new progesterone only OCP (Drospirenone 4mg) was FDA approved in May 2020 and can be taken just like regular combined OCPs. (Letter JAMA 2020)

Contraceptive counseling and VTE risk 

Family history of VTE in first degree relatives may increase an individual’s risk for VTE. Offer a LARC (Gray 2018, Tepper 2017), or a progestogen only pill (POP) if they do not want a LARC. Avoid COCPs, patches, rings, and depot contraceptives as these increase clot risk (de Bastos 2014, Tepper 2017).

For those with no personal or family history risk of VTE, choose any type of contraception that works for the patient–ex. a combined oral contraceptive pill formulation with a low dose estrogen 20 mcg or 30 mcg, with second generation progestogen (levonorgestrel) or a third gen progestogen with desogestrel or gestodene. Any progestogen only method can also be chosen.  There is likely not a clinically meaningful higher risk of VTE for patches/rings over pills for a patient at low baseline risk of VTE.

Always counsel about symptoms of VTE and the importance of immediate medical help.

In concerned patients, do not start testing for hypercoagulable disorders, as these tests are low value, can give a false sense of security, and cause anxiety (expert opinion).

Menopause and VTE Risk 

Hormone therapy replacement (HRT) taken in oral form increases the VTE risk (Rossouw 2002, Cushman 2004, Curb 2006, Rovinski 2018).  Dr Samuelson Bannow’s opinion is to prescribe the lowest dose possible for the shortest time possible for menopausal symptoms and to apply a patient-centered approach to managing menopausal symptoms affecting quality of life.  

Estrogen-only treatment (without progesterone) is clinically appropriate for only a small number of patients (e.g. patients without a uterus, due to the risk of endometrial hyperplasia leading to risk of  malignancy) (ACOG 2013).  HRT via transdermal or intravaginal estrogen/progesterone does not seem to increase risk of VTE (Rovinski 2018). 

Take Home Points

1. Get comfortable talking about periods
2. Check ferritin in menstruating individuals
3. Try Tranexamic Acid for HMB
4. Remember, half the population has a uterus

Plug

Foundation for Women & Girls with Blood Disorders: “The Foundation for Women & Girls with Blood Disorders works to ensure all women and girls with blood disorders are correctly diagnosed and optimally managed at every life stage.”

Other Stuff

Glossary:

DOAC: Direct Oral Anticoagulant

LARC: Long Acting Reversible Contraception (includes IUDs and injections)

VTE: Venous Thromboembolism

COCP: Combined Oral Contraceptive Pill

POP: Progestogen Only Pill

HMB: Heavy Menstrual Bleeding

TXA: Tranexamic Acid

NSAIDs: Non-Steroidal Anti Inflammatory Drugs

PT: Prothrombin

PTT: Prothrombin Time

IMB: Intermenstrual Bleeding

PCB: Post Coital bleeding

PMB: Post Menopausal Bleeding

VWD: Von Willebrand’s Disease

Progesterone= naturally occurring hormone, Progestogen = synthetic hormone

Links*

1. Emperor of All Maladies (book) by Siddhartha Mukherjee, 
2. Foundation for Women & Girls with Blood Disorders

*The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on our Amazon.com links and buy something we earn a (very) small commission, yet you don’t pay any extra.

Goal

Listeners will explain the intersection between hematology and women’s health, gaining valuable information to improve patient outcomes and quality of life with both heavy bleeding and thrombotic disorders.

Learning objectives

After listening to this episode listeners will…  

1. Gain perspective on how to differentiate, and normalize, “normal” versus “abnormal” uterine and menstrual bleeding–and when to initiate further evaluation
2. Discuss the management of anticoagulant-associated uterine bleeding
3. Assess the VTE risk of common hormonal therapies 
4. Explore the management of estrogen-associated VTE

Disclosures

Dr. Samuelson Bannow reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

O’Glasser AY, Samuelson Bannow B, Williams PN, Watto MF. “#280 Heavy Menstrual Bleeding, Anticoagulation & Coagulopathy in Menstruating Patients Title”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list Final publishing date June 21, 2021.