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Other gynaecological bleedings in women affected by bleeding disorders
 
Haemorrhagic ovarian cysts
Haemorrhagic ovarian cysts may result from bleeding into the residual follicle (the corpus luteum) at the time of ovulation. This may result in bleeding into the follicle, intraperitoneal bleeding, bleeding into the broad ligament of the uterus or bleeding into the retroperitoneum. Haemorrhagic ovarian cysts are frequent particularly among VWD affected women (6%) [20], whereas in haemophilia carriers (10%) or women affected by other bleeding disorders (particularly in FXIII deficiency: 20-50%) the higher prevalence of ovarian cysts may also be associated with no bleeding. In women with bleeding disorders without documented haemorrhagic ovarian cysts, a high prevalence of mid-cycle pain or "Mittelschmerz", associated with bleeding at the time of ovulation, was reported (2/3 of the times) [21].
 
Endometriosis
Endometriosis is a painful inflammatory condition characterized by the presence of endometrial tissue at ectopic sites. The rate of endometriosis is increased in women with heavier menses presumably due to the increased rate of retrograde menstruation, a probable aetiology of endometriosis [22]. Whether identification of bleeding disorders and appropriate intervention to reduce the menstrual loss would have an impact on the rate of endometriosis is currently unknown
 
Endometrial hyperplasia and polyps
Endometrial hyperplasia is an abnormal proliferation of the glands and stroma of the endometrium caused by continuous exposure to oestrogen. The most common presenting symptom of this condition is abnormal uterine bleeding [23]. Polyps are masses resulting from a proliferation of the glandular tissue that lines the cervix or the uterus. Polyps also present with bleeding [24].
 
Fibroids
There is no evidence that women with bleeding disorders are more likely to develop fibroids (leiomyoma), even if a higher prevalence (32% vs 17% of controls) [25] ] was reported in women with VWD. Fibroids are known to contribute to the development of heavy menstrual bleeding. In most of the studies of the prevalence of bleeding disorders among women with menorrhagia, the presence of fibroids was an exclusion [1-26], or their presence was not reported [27-31]. The presence of fibroids, or other uterine pathology, however, does not preclude a bleeding disorder. Fibroids may unmask a previously subclinical bleeding tendency and, in a Women with a diagnosed bleeding disorder, may cause problematic bleeding.
 
Miscarriages
Miscarriage is common in the general population, with 12-13.5% of recognized pregnancies resulting in spontaneous miscarriage [32-33].
An increased risk of miscarriage and placental abruption resulting in fetal loss or premature delivery among women with deficiency of FXIII [35-38] or fibrinogen [4] has been reported. It is generally believed that women with bleeding disorders are protected by the hypercoagulable state of pregnancy but whether women with other bleeding disorders have an increased risk of miscarriage is unclear.
In women with VWD and in haemophilia carriers the reported prevalence of miscarriage was respectively of 22-25% and 31% [24-39-40].
 
Bleeding during pregnancy

Pregnancy is accompanied by increased concentrations of fibrinogen, FVII, FVIII, FX and von Willebrand factor (VWF). Factor VIII and VWF levels rise even in haemophilia carriers or women with VWD. Factor II, FV and FIX are relatively unchanged. Free protein S, the active, unbound form, is decreased during pregnancy secondary to increased levels of its binding protein, the complement component C4b. Plasminogen activator inhibitor type 1 (PAI-1) levels are increased. All of these changes contribute to the hypercoagulable state of pregnancy, and, in women with bleeding disorders, contribute to improved haemostasis. Despite improved haemostasis, bleeding during pregnancy is a common symptom reported in women with bleeding disorders [41-44].

 
Postpartum haemorrhage
Postpartum haemorrhage is an anticipated problem among women with bleeding disorders. At the end of a normal pregnancy, an estimated 10-15% of a woman's blood volume, or at least 750 mL/min, flows through the uterus [45]. Normally after delivery of the infant and placenta, the uterine musculature or myometrium contracts around the uterine vasculature and the vasculature constricts in order to prevent exsanguination. Retained placental fragments and lacerations of the reproductive tract may also cause heavy bleeding, but the single most important cause of postpartum haemorrhage is uterine atony [46]. Despite the critical role of uterine contractility in con trolling postpartum blood loss, women with bleeding disorders are at an increased risk of postpartum haemorrhage. There are multiple case reports and several case series documenting the incidence of postpartum haemorrhage in women with bleeding disorders [4] but there are limited data that compare women with bleeding disorders and controls.
Delayed or secondary postpartum haemorrhage is rare in the general population (0.7% more than 24 h after delivery [47-48]). However, a higher prevalence of delayed postpartum haemorrhage was reported among women affected by VWD, FXI deficiency and haemophilia carriers [42-49-50], making delayed postpartum haemorrhage more than 10-25 times more common among women with bleeding disorders.
 
 
 

 
 
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