KEY POINTS:
- The FIGO systems 1 and 2 together help to define and diagnose abnormal uterine bleeding in the reproductive years
- In the setting of acute bleeding, management involves stabilization, diagnosis and treatment of underlying disorder
- If unstable, place large bore IVs and replace fluids and transfuse per lab parameters
- May require treatment of coagulopathy is bleeding is significant
- A massive transfusion protocol can be used to guide transfusion in acute bleeding and instability
- In chronic bleeding, coagulation pathways are often stable, and transfusion of PRBCs only may be required
BACKGROUND:
- Prevalence of abnormal bleeding in reproductive age women worldwide is estimated at 3% to 30% (Munro et al.Int J Gynaecol Obstet, 2018)
- Highest prevalence is noted during times of greatest instability in hormonal stimulation of uterine lining
- Adolescence
- During the 40 to 50’s (often coinciding with perimenopause)
- Adolescence: Work-up requires particular attention to: (ACOG CO 785)
- Anovulation (common in early menses)
- Bleeding disorders
- Von Willebrand disease, typically an autosomal dominant disorder of platelet function, commonly presents with menorrhagia and anemia in early menstruation
- There are several rare bleeding disorders that can present at menses initiation, including other platelet function disorders, coagulopathies, thrombocytopenia (idiopathic or immune) and fibrinolytic pathway defects
- Speculum exam and ultrasound are rarely indicated for adolescents
- Medical interventions are used primarily: Surgical intervention rarely required
- Cervical cancer can present as primary menorrhagia, even in the setting of previously normal cervical cancer screening results and should always be suspected and the cervix observed on exam if possible, in addition to an ultrasound and/or CT
- FIGO system 2: ‘PALM-COEIN’ | ‘PALM’ refers to structural issues and the ‘COEIN’ refers to issues not easily diagnosed via imaging or pathology
- Polyp
- Adenomyosis
- Leiomyoma
- Malignancy or hyperplasia
- Coagulopathy
- Ovulatory dysfunction
- Endometrial disorders
- Iatrogenic
- Not otherwise classified
Evaluation and Work-up
Step 1: Initial evaluation includes a thorough history including the following points
- Onset of bleeding
- Chronicity
- Menstrual history (regular cycles? flow during cycles?)
- Cervical cancer screening history
- Hormone exposure
- Risk factors for hyperplasia (e.g., diabetes, anovulation)
Step 2: Evaluate patient stability and impact of bleeding
- Rule out pregnancy as an etiology
- CBC: Hemoglobin / hematocrit, WBC, MCV and platelets
- Coagulation studies: May be indicated if bleeding is significant
- Iron studies: May be indicated in patients with chronic bleeding issues
Step 3: Diagnosis of etiology of bleeding
- Physical exam (speculum) to evaluate active bleeding and to rule out vaginal or cervical mass
Step 4: Differential
- Assess for ovulatory status / dysfunction based on clinical menstrual and ovulatory history
- Labs: beta-hCG, CBC, TIBC, TSH, Prolactin, CMP
- Screen for hematologic disorders (Kouides et al. Fertil Steril, 2005) | If positive, consider further evaluation including hematology consult
- Heavy menstrual bleeding since menarche
- One of the following
- Postpartum hemorrhage
- Surgical related bleeding
- Bleeding associated with dental work
- ≥2 of the following
- Bruising 1 to 2 times per month
- Epistaxis 1 to 2 times per month
- Frequent gum bleeding
- Family history of bleeding symptoms
Step 5: Imaging
- Ultrasound to assess for thickness of EEC, fibroid, polyp, Mullerian abnormalities
- Can also contribute to endometrial evaluation
- CT if cervical cancer suspected
Step 6: Endometrial sampling
- Sampling of the uterine lining for diagnosis of endometrial etiology
- This can be done via biopsy (generally in office procedure) or surgical D&C
- Sampling should be done in all women with risk factors for endometrial pathology
- High BMI
- Annovulation
- Diabetes
- Exogenous unopposed (or incompletely opposed) estrogen
- Age ≥45
Acute Management Options (ACOG CO 557)
- Estrogen therapy
- Estrogen instructs lining to grow, not shed | In patients without risk of blood clotting (take a clot risk history) acute treatment with estrogen can halt bleeding and allow for more definitive management
- Patient hospitalized: IV estrogen
- Premarin 25mg q6 hours up to 24 hours to halt bleeding | Follow with oral OCP taper (3 pills for 3 days, 2 pills for 2 days, then 1 pill a day) so that progestin can help to prevent overgrowth
- Patient not hospitalized: Oral OCPs | Many regimens are available
- Monophasic 30 to 35 mcg pill three times a day (3 pills at once can cause nausea) for 7 days
- After 7 days, taper to maintain effect using 2 pills a day for 3 days then one pill a day skipping the placebo week and finishing out 2 packs of pills
- Progesterone therapy
- Progesterone stabilizes the lining of the uterus and stops bleeding without stimulating growth | This is an appropriate start point if lining is thick on ultrasound | If someone has been bleeding for a while, the lining may be too thin to respond to progesterone and estrogen may be needed | Note: This therapy does not replace sampling in women at risk for hyperplasia or cancer
- Oral progesterone with MPA can be undertaken at 20mg three times a day for 7 days
- Intrauterine progesterone using an IUD can stop bleeding and prevent future growth effectively for many women
- Tranexamic Acid
- 1.3 g po three times a day for 5 days or
- 10mg/kg IV three times a day for 5 days
- Surgical therapy
- Dilation and curettage can halt bleeding in cases where there is significant lining present
- Interventional Radiology
- May be used for bilateral uterine artery occlusion with a temporary medium which does not impact future fertility
- Hysteroscopy
- Hysteroscopy can be used for removal of myomas or polyps if identified
- Endometrial ablation should only be entertained if patient has completed childbearing and has a secure birth control method identified
- It does not prevent conception, and there is a higher risk of abnormal placentation in pregnancies after endometrial ablation
- Hysterectomy in acute bleeding is a last resort intervention
PRIMARY SOURCES:
Schaffrath et al. Arch Gynecol Obstet, 2019
This retrospective cohort study looked at recurrence and reintervention rates after hysteroscopic intervention for intrauterine abnormalities
- 313 premenopausal women underwent hysteroscopy after ultrasound identified intrauterine pathology
- 262 had removal of identified pathology
- 51 had hysteroscopy but no pathology was identified at surgery
- Results
- Of the 262 with identified pathology, 136 (51%) had recurrence of symptoms and 101 (39%) had reintervention
- The following factors were predictive for reintervention: Heavy menstrual bleeding at baseline and multiparity
- Of the 51 women who had no identified pathology at initial hysteroscopy, 29 (60%) had recurrence of symptoms and 12 (24%) had reintervention
Brekelmans et al. Thromb Haemost, 2017
A study, using data derived from the AMPLIFY RCT, was designed to analyze the use of anticoagulants in cancer patients undergoing treatment of VTE
- Incidence of AUB was compared in 1122 women on apixaban (Eliquis) vs 1106 on enoxaparin/warfarin
- Results
- There was “clinically relevant non-major bleeding” in 2.5% of women on apixaban and 2.1% on enoxaparin/warfarin (OR 1.2; 95% CI, 0.7 to 2.0)
- A higher percentage of clinically relevant uterine bleeds were found in the apixaban group (OR 3.4; 95% CI, 1.8 to 6.7)
- Conclusion
- Overall, apixaban is not as likely to cause clinically relevant bleeding
- If it does occur, there is a higher chance of the bleeding being uterine in origin
PROFESSIONAL RECOMMENDATIONS:
ACOG Practice Bulletin 136
- The ACOG PB on AUB in the setting of ovulatory dysfunction notes the following
Among women aged 40–50 years, the incidence of endometrial cancer ranges from 13.6 cases to 24 cases per 100,000 women-years and increases to 87.3 cases per 100,000 in women aged 70–74 years
Among women younger than 45 years, there is a lower rate of advanced-stage disease, a higher degree of tumor differentiation, and a better prognosis compared with patients older than 45 years
Therefore, all women older than 45 years who present with suspected anovulatory uterine bleeding should be evaluated with endometrial biopsy (after pregnancy has been excluded)
REFERENCES:
ACOG Practice Bulletin 128: Diagnosis of Abnormal Uterine Bleeding in Reproductive-Aged Women