Journal Reading

Abnormal Uterine Bleeding

(Non Structural Abnormalities)

Samdaniel Sutanto
11.2016.350

Pembimbing :
dr. Johanes Benarto, Sp.OG

Kepaniteraan Klinik Obstetri dan Ginekologi

Fakultas Kedokteran Universitas Kristen Krida Wacana
Rumah Sakit Umum Daerah Cengkareng
Periode 18 Juni 2018 – 25 Agustus 2018
Introduction
• Definition of Abnormal Uterine Bleeding (AUB)
• A bleeding from the uterine corpus that is abnormal in regularity, volume,
frequency, or duration and occurs in the absence of pregnancy

Acute AUB Chronic AUB Intermenstrual Bleeding

An episode of heavy
bleeding that (in opinion
Abnormal uterine Occurs between defined
of clinician) is of sufficient
bleeding present for most cyclic and predictable
quantity to require
of the previous six months menses
immediate intervention to
prevent further blood loss
Table - Suggested “normal” limits for menstrual
parameters in the mid-reproductive years

Adapted from Munro MG et al. Am

J Obstet Gynecol 2012 Oct:259-65
Assessment
• Signs and symptoms of hypovolemia
and potential hemodynamic instability

+
Stabilization :
• 1 or 2 large IV lines
• Prepare blood / clotting factor
replacements

Evaluate the most likely etiology

of AUB
Etiologies
• Multifactorial
• Acute = chronic
• To determine:
• Patient history
• Physical
examination
• Laboratory tests
• Imaging tests

Adapted from American College of Obstetricians and Gynecologists.

Management of acute abnormal uterine bleeding in nonpregnant
reproductive-aged women. Obstet Gynecol 2013;121:891–6.
Etiologies
• History:
• Current bleeding episode
• Related symptoms
• Past menstruation
• 13% von Willebrand disease
• 20% coagulation disorders
(coagulation factor
deficiencies, hemophilia,
platelet function disorders)
• Gynecologic and medical
history
• Systemic diseases (leukemia,
liver failure)
• Medications (anticoagulants,
chemotherapeutic agents)
Adapted from American College of Obstetricians and Gynecologists.
Management of acute abnormal uterine bleeding in nonpregnant
reproductive-aged women. Obstet Gynecol 2013;121:891–6.
Etiologies

• Physical Examination
• Signs of acute blood loss
• Hypovolemia
• Anemia
• Find the etiologies → pelvic exam
• Trauma of the genital tract
• Determine the amount and intensity of bleeding
• Identify any uterine enlargement and irregularity
Etiologies
• Laboratory Tests:
• Indication for further tests:
• Positive screening results
• Initial lab abnormalities
• Other tests:
• Thyroid disorders
• Liver disorders
• Sepsis
• Leukemia
• Endometrial tissue sampling
• Pelvic USG
Adapted from American College of Obstetricians and Gynecologists. Management
of acute abnormal uterine bleeding in nonpregnant reproductive-aged women.
Obstet Gynecol 2013;121:891–6.
Structural Causes of AUB

P Polyp
A Adenomyosis
L Leiomyoma
M Malignancy and hyperplasia
Non Structural Causes of AUB

C Coagulopathy
O Ovulatory dysfunction
E Endometrial
I Iatrogenic
N Not yet classified
AUB-C – Coagulopathy
• Approximately 13% of women with heavy menstrual bleeding (HMB)
have hemostasis disorders, most often von Willebrand disease.
• An autosomal inherited disorder of hemostasis quantitative
deficiency as in type 1 and 3 von Willebrand factor (vWF), or
qualitative deficiency as in type 2 vWF.
• Thrombocytopenia, platelet dysfunction (such as Glanzman disease),
and coagulation factor deficiencies
• HMB also occurs in some women on anticoagulants
AUB-O – Ovulatory Dysfunction
• Causes of ovulatory / anovulatory dysfunction
• Ovulatory DUB appears to occur when there is loss of local control of
the mechanisms which normally limit the volume of blood loss during
menstrual tissue bleeding
• Anovulatory DUB creates an endocrinologic endometrial milieu of
unopposed estrogen, facilitate the development of endometrial
hyperplasia and endometrial adenocarcinoma, with their thin-walled,
tortuous, fragile and superficial endometrial vessels
• Absence of cyclical production of progesterone and the related
biosynthesis of prostaglandins and other regulatory substances
necessary to control blood loss
AUB-E – Endometrial

• Cause by local disturbance/s in endometrial function – deficiencies of

vasoconstrictor (endothelin-1 and prostaglandin F2α) or excessive
production of plasminogen activator, prostaglandin E2 and
prostacyclin (I2)
AUB-I – Iatrogenic
• Gonadal steroid
• Estrogen: lower dose of estrogen in oral contraceptives (OCs) are insufficient
to sustain endometrial integrity → bleeding
• Progestin: induce decidualization and endometrial atrophy
• Intrauterine device : an increase in endometrial vascular fragility
might precipitate vessel breakdown and, hence, breakthrough
bleeding
AUB-N – Not Yet Classified
• Arteriovenous malformation: coils of distended and superficial, thin-
walled, fragile vessels in the myometrium and endometrium
• Chronic endometritis: low-grade infection of the ectocervix or endocervical
infection with Chlamydia or gonorrhea → inflammation and abnormal
angiogenesis (fragile surface vessels) typically lead to unpredictable
episodes of light intermenstrual or postcoital bleeding
• Systemic disease:
• Renal failure: changes in the hypothalamic-gonadal axis in dialyzed women
• Thyroid disease: elevated TRH in hypothyroidism induces prolactin release, cause
menstrual dysfunction
• Cirrhosis hepatis: quantitative and qualitative platelet abnormalities → prolongation
of the bleeding time (parenchymal cells produce most of the factors and inhibitors of
clotting and fibrinolysis)
Adapted from Whitaker L et al. Best
Pract Res Clin Obstet Gynaecol 2016
Jul;34:54-65.
von Willebrand Disease in Women
• History taking • Physical examination
• Heavy menstrual bleeding since • Petechiae, ecchymosis, or other
menarche evidence of recent bleeding
• One of the following conditions: • Management
• Postpartum hemorrhage
• Acute
• Surgery-related bleeding
• Bleeding associated with dental work • Long-term: ACOG Committee
Opinion 580
• Two / more following conditions:
• Epistaxis, one / two times per month
• Frequent gum bleeding
• Family history of bleeding symptoms
Adapted from American College of Obstetricians and Gynecologists. Von
Willebrand disease in women. Committee Opinion No. 580. Obstet Gynecol
2013;122:1368–73
von Willebrand Disease in Women

Adapted from American College of

Obstetricians and Gynecologists.
Von Willebrand disease in women.
Committee Opinion No. 580.
Obstet Gynecol 2013;122:1368–
73
Guidelines for Investigations

Investigations of AUB
General assessment Determine ovulatory Screening for systemic
• Not related to pregnancy status disorders of hemostasis
• Not emanating from cervix • Predictable cyclic menses • Structured history: 90%
or another location every 22-35 days sensitivity
• Evaluation for anemia – Hb • von Willebrand factor
and/or hematocrit (vWF), hematologist

1 2 3

Adapted from Munro MG et al. Int J Gynaecol Obstet.

2011 Apr;113(1):3-13.
Guidelines for Investigations

Investigations of AUB
Evaluation of the Evaluation of structure of Myometrial assessment
endometrium endometrial cavity • US and +/- hysteroscopy
• Endometrial sampling if risk • To identify polyps, submucous • MRI : leiomyoma - adenomyosis
factors are persistent myoma
• TVUS – endometrial thickness • TVUS is not 100% sensitive –
small lesions undetectable
• If suboptimal – proceed to SIS
or hysteroscopy
4 5 6

Adapted from Munro MG et al. Int J Gynaecol Obstet.

2011 Apr;113(1):3-13.
Treatment
• Two main objectives: • Chronic:
• Control of heavy bleeding • Levonorgestrel intrauterine system
• Reduce menstrual blood loss in • OCs
subsequent cycle • Progestin therapy
• Acute: • Tranexamic acid
• Medical management: • NSAIDs
• IV conjugated equine estrogen,
combined OCs and oral progestin
• No bleeding disorders
• Patients w/ bleeding disorders:
• Desmopressin
• Recombinant factors
Treatment
IV Conjugated Equine Estrogen
• Stop bleeding in 72% • Suggested dose
participants within 8 hours • 25 mg IV
compared with 38% participants • Dose schedule
treated with placebo • Every 4-6 hours for 24 hours
• Contraindications
• Breast cancer
• Venous or arterial
thromboembolic disease
• Liver dysfunction or disease
Treatment
Combined OCs and Progestin
• 88% OCs vs 76% • Combined oral contraceptives
medroxyprogesterone acetate • Suggested dose: 35 mcg
• Dose schedule: 3 times/day for 7
• Bleeding stop in 3 days days
• Consider contraindications • Contraindications:
• Cigarette smoking, hypertension,
DVT, pulmonary embolism,
thromboembolic disorders, CVD,
ischemic heart disease
• Migraine with aura
• Breast cancer
• Liver disease
• Diabetes w/ vascular involvement
• Valvular heart disease
Treatment
Combined OCs and Progestin
• 88% OCs vs 76% • Oral progestin
medroxyprogesterone acetate • Suggested dose: 20 mg PO
• Bleeding stop in 3 days • Dose schedule: 3 times/day for 7
days
• Consider contraindications • Contraindications:
• DVT or pulmonary embolism, arterial
thromboembolic disease
• Breast cancer
• Impaired liver function or liver
disease
Treatment
Antifibrinolytics
• Tranexamic acid
• Prevent fibrin degradation
• Reduce bleeding by 30-55%
• Suggested dose:
• 1,3 g PO or 10mg/kg IV (max 600
mg/dose)
• Dose schedule: 3 times/day for 5
days
• Contraindications:
• Acquired impaired color vision
• Thromboembolic disease
Treatment
Patients w/ bleeding disorders:
• Desmopressin
• Intranasal / IV / SC
• von Willebrand disease
• Risk fluid retention, hyponatremia
• Contraindications: massive
hemorrhage, IV fluid resuscitation
• Recombinant factors VIII, vWF
• Control severe hemorrhage
• Factor-specific replacements
• Other factor deficiency
• NSAIDs contraindications
• Effect on platelet aggregation
• Effect on liver function
Treatment
Patients w/ bleeding disorders:
• Desmopressin
• Intranasal / IV / SC
• von Willebrand disease
• Risk fluid retention, hyponatremia
• Contraindications: massive
hemorrhage, IV fluid resuscitation
• Recombinant factors VIII, vWF
• Control severe hemorrhage
• Factor-specific replacements
• Other factor deficiency
• NSAIDs contraindications
• Effect on platelet aggregation
• Effect on liver function
Treatment

Chronic AUB
• Levonorgestrel intrauterine
system
• OCs
• Progestin therapy
• Tranexamic acid
• NSAIDs
Surgical Management
• Consideration:
• Clinical
• Bleeding
• Drugs contraindication
• Response
• Underlying medical condition
• Future fertility (modality)
• Dilation and Curettage (D&C)
• Endometrial ablation
• Remove or destroy endometrial lining of
the uterus in women w/ HMB
• Uterine artery embolization
• Hysterectomy
Surgical Management
• Uterine artery embolization
• Interventional radiologist uses
catheter to deliver small particles
that block the blood supply to the
uterine corpus
Conclusion
• The etiologies of acute AUB should be classified based on PALM-
COEIN system
• Medical management should be the initial treatment for most
patients and decisions is based on patient’s medical history and
contraindications to therapy
• The need of surgical management is based on the clinical stability,
severity of bleeding, contraindications to medical management, and
underlying medical conditions
• Once the acute bleeding is treated, transitioning the patient to long-
term maintenance therapy is recommended
References
1. American College of Obstetricians and Gynecologists. Management of acute
abnormal uterine bleeding in nonpregnant reproductive-aged women. Obstet
Gynecol 2013;121:891–6.
2. Munro MG et al. FIGO classification system (PALM-COEIN) for causes of
abnormal uterine bleeding in nongravid women of reproductive age. Int J
Gynaecol Obstet. 2011 Apr;113(1):3-13.
3. Munro MG et al. The FIGO systems for nomenclature and classification of
causes of abnormal uterine bleeding in the reproductive years: who needs
them?. Am J Obstet Gynecol 2012 Oct:259-65
4. American College of Obstetricians and Gynecologists. von Willebrand disease in
women. Committee Opinion No. 580. Obstet Gynecol 2013;122:1368–73
5. Whitaker L et al. Abnormal uterine bleeding. Best Pract Res Clin Obstet
Gynaecol 2016 Jul;34:54-65.