easy to understand

1. AUB PATOGENESIS
PALM COEIN
Dr dr Pinda Hutajulu SpOG K
Rumah Sakit dr Sudarso Pontianak

2. Back Ground
• Abnormal Uterine Bleeding is a common cases in
practice in reproduction age
• Significant social embrassement and effect on health
related quality of live
• New classification PALM COEIN by FIGO for
consistency nomenclature and management
• Patogenesis not unclear for every subject

3. Classification of AUB [PALM-
COEIN]
• Classification and Categorization
• Single entity examples
• Po A1 Lo Mo-Co Oo Eo Io No
• Multiple entity examples
• Po Ao L1 M1-Co Oo Eo Io No

5. Pathogenesis of AUB and
Polyp [PALM-COEIN]
• Endometrial and endocervical polypps.
• These epithelial proliferations comprise a variable vascular,
glandular, and fibromuscular and connective tissue component
• Arise because a limited portion of endometrium fails to be shed
at men- struation, and continues to proliferate each month.
• Some polyps undergo patchy surface necrosis, and others can
be seen to have prominent thin-walled surface vessels, which
may result in erratic light bleeding
• 0.5 to 4.7% of symptomatic polyps have atypical or malignant
features

6. Pathogenesis of AUB and
Adenomyosis [PALM-COEIN]
• Cells from the lining of the uterus migrate into muscle layer
• disruption of the endometrial–myometrial interface and
disorganization of the uterine junctional zone may play an
integral role in the pathogenesis of adenomyosis
• Disruption of the normal cycle-dependent contraction
waves of the junctional zone have been linked to
dysmenorrhea and heavy menstrual bleeding
•

7. Pathogenesis of AUB and
Leiomyomas PALM-COEIN
• Paradox is that many women have fibroids but also have entirely normal bleeding
patterns
• Directly impact the endometrium sufficient to distort the endometrial cavity, increase
endometrial surface and presence of fragile and engorged vasculature in perimyoma
environment.
• The increase in vascular flow observed along with these enlarged vessels can
overcome platelet action
• The complex cellular and molecular changes found in association with fibroids, with
impact on angiogenesis, alteration in vasoactive substrates and growth factors as well as
alteration in coagulation
• Expression of vascular endothelial growth factor (VEGF), basic fibroblast growth
factor (bFGF), heparin-binding epidermal growth factor, platelet-derived growth factor
(PDGF), parathyroid hormone-related protein (PTHrP) and prolactin is altered in women
with fibroids, all have potential angiogenic effects

8. There is alteration of plasminogen modulators and this may impact on
endometrial haemostasis and repair
Transforming growth factor beta (TGF-β) is produced in excess in the
endometrium in women with fibroids and is associated with reduced levels of
plasminogen activator inhibitor-1 (PAI-1), thrombomodulin and antithrombin III,
both in vivo and in endometrial stromal cells treated in vitro with TGF-β
Alterations in the blood plasma levels of circulating interleukin (IL)-13,
IL-17 and IL-10 have been reported. Whether these variations affect immune
function and inflammation implicated in endometrial breakdown and repair
Regard to the location of fibroids, it was previously thought that those
women with SM fibroids, particularly with those distorting the cavity, were more
likely to present with HMB

9. Pathogenesis of AUB and Malignancy
and hyperplasia PALM-COEIN
• Hyperplasia : increased volume of abnormal proliferative
type endometrium (gland to stroma ratio: 3:1), due to excess
estrogenic stimulation, increased VEGF expression with
disturbed angiogenesis,disturbed prostaglandin synthesis
and increased NO production
• Cancer endometrium: Polypoid, necrotic, myometrial
invasion cervical involvement
• Uterine sarcoma have been reported as rare (3–7/100,000
in the USA)but maybe a cause of AUB-M

10. Pathogenesis of AUB and
Coagulopathy (PALM-COEIN
• Coagulopathies are reported to affect 13% of the women
presenting with HMB, majority suffer from Von willibrand
deseases
• Disorders of hemostasis quantitative deficiency as in types 1 and
3 VMF, or a qualitative deficiency as in the type 2 variant of which
there are numerous subvariants
• Thrombocytopenia, the thrombocytopathies (such as Glanzmann
disease), and rarer deficiencies of factors II, V, VII, VIII, IX, X, XI,
and XII.33
• Heavy bleeding also occurs in some women on anticoagulant
drugs

11. Pathogenesis of AUB and Ovulatory
disfunction [PALM-COEIN]
• Causes of ovulatory/an-ovulatory disfunction
• Ovulatory DUB appears to occur when there is loss of local control
of the mechanisms which normally limit the volume of blood lost
during menstrual tissue shedding
• 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 bio-
synthesis of prostaglandins and other regulatory substances
necessary to control blood loss

12. Pathogenesis of AUB and
Endometrial [PALM-COEIN]
• Caused by local disturbance/s in endometrial
function - deficiencies or excesses of proteins or
other entities that have and adverse impact on
hemostatis.
• Perturbation of local glucocorticoid metabolism,
aberrant prostaglandin synthesis and excessive
plasminogen (resulting in premature clot lysis)

13. Pathogenesis of AUB and
Iatrogenic [PALM-COEIN]
• Gonadal steroids :
• Estrogens: lower doses of estrogen in OCPs are
insufficient to sustain endometrial integrity—
>bleeding
• Progestins: induced decidualization and
endometrial atrophy
• Intra Uterine Device: an increase in endometrial
vascular fragility might precipitate vessel breakdown
and, hence, breakthrough bleeding

14. Pathogenesis of AUB and Not
yet clasified [PALM-COEIN]
• 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 cause inflammation and abnormal
angiogenesis (fragile surface vessels) typically lead to unpredictable episodes of
light intermenstrual or postcoital bleeding
• Systemic diseases
• Renal failure: changes in the hypothalamic–gonadal axis in dialyzed women
• Thyroid disease: elevated TRH in hypothyroidism induces prolactin release,
causes 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)

15. Take Home Massage
• To make a firm diagnosis of AUB, one must point out
specific causes of abnormal genital tract bleeding —>
PALM-COEIN
• It advisable to consider the effect of any newdrugs on a
patient’s menstrual cycle understand the pathogenesis
of AUB
• Pathogenesis may contribute to better understanding of
the mechanisms of action that initiate, regulate and
lead to AUB.

16. TERIMA KASIH
TERIMA KASIH
TERIMA KASIH
TERIMA KASIH
TERIMA KASIH
TERIMA KASIH
TERIMA KASIH
TERIMA KASIH

18. kunci
• seorang bidan Atau dokter umum sudah cukup
bila mendiagnosa suatu AUB tau PUA namun
seorang dr spesialis obgyn sebaiknya dapat
mendiagnosa sampai pada penyebabnya yaitu
PALM-COEIN

19. Identifying AUB-M
• Endometrial Biopsy
• Post menopausal with bleeding or premenopausal with
heavy/irregular bleeding
• Post menopausal with EM cells on pap smear or
premenopausalwith atypical glandular cells on pap
smear
• Breast cancer patients on tamoxifen who complain of
abnormal bleeding
• Woman who are still menstruating after 52 years of age

20. Structured history for coagulopathy screen.
(Koudies et al,)
Criteria
1. Heavy bleeding since the menarche
2. One of the following:
• Postpartum haemorrhage
• Surgical-related bleeding
• Bleeding associated with dental work
3. Two or more of the following:
• Bruising 1–2 times/month
• Epistaxis 1–2 times per/month
• Frequent gum bleeding
• Family history of bleeding problem

21. • Initial haemostatis test
• CBC and platelets counts (decrease)
• PT (abnormal) and PTT(prolonged)
• Fibrinogen or TT

22. Unopposed oestrogen effects on the endometrium causing
marked proliferation and thickening resulting in HMB along with
an altered frequency of menstruation….observed at the extremes
of reproductive age
Drugs that affect dopamine levels, with their attendant effects
on the HPO axis