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Menorrhagia and bleeding disorders in adolescent females

Schattauer 2012
Menorrhagia and bleeding
disorders in adolescent females
S. Halimeh
Medical Thrombosis and Haemophilia treatment Center Duisburg, Germany
manifestation of bleeding
disorders, endometriosis, miscarriage, von störung, Endometriose, Fehlgeburt, von- disorders
In women, von Willebrand disease (VWD) is Das von-Willebrand-Syndrom (VWS) ist die the most common inherited bleeding disorder. häufigste angeborene Blutgerinnungsstö- Since VWD and other inherited bleeding dis- rung. Pathologisch verstärkte bzw. verlänger- orders are autosomal disorders, they affect te Monatsblutungen (so genannte Menorrha- ing disorders are autosomal disorders and women and men. Menorrhagia, or heavy gie) gehören zu den häufigsten Symptome bei menstrual bleeding (HMB), is the most com- Frauen mit Gerinnungsstörungen. Objektiv gesehen sind diese starken Monatsblutungen philia; in this study women were affected. order experience. Objectively, it is defined as so definiert, das der Menstruationszyklus bleeding that lasts for more than seven days mehr als sieben Tage andauert oder aber der or results in the loss of more than 80 ml of Blutverlust mehr als 80 ml pro Zyklus beträgt. The index case
blood per menstrual cycle. The prevalence of Die Prävalenz der Menorrhagie bei Frauen mit A girl at the age of eight years described menorrhagia in a woman with a bleeding dis- einer Blutgerinnungsstörung reicht von 32 bis multiple bleeding symptoms (easy bruising, order ranges from 32 to 100% in patients with 100% bei Patientinnen mit VWS, 5 bis 98% bei epistaxis) and ultimately exsanguinated to VWD, from 5 to 98% in patients with a pla- death during her fourth menstrual cycle at telet dysfunction and from 35 to 70% in tionsstörung und 35 bis 70% bei Frauen mit women with a rare factor deficiency. A de- tailed history and a careful physical exam are Menorrhagia, or heavy menstrual bleeding the first steps towards a diagnosis in adoles- körperliche Untersuchung sind die ersten cents, adding a PBAC > 100 increased the sen- Schritte zur Abklärung einer Menorrhagie, bei sitivity of the screening tool further to 95%. Vorliegen eines PBAC-Scores > 100 erhöht Laboratory testing should be made at the time sich die Empfindlichkeit des Screening-Tools of menstrual bleeding in an effort to capture weiter auf 95%. Labortests sollten zum Zeit- HMB is defined as bleeding that lasts for the lowest level of VWF : Ag and FVIII : C. punkt des 2.–3. Tages der Monatsblutung more than seven days or results in the loss Treatment options for menorrhagia in VWD: durchgeführt werden, in dem Bemühen, den of more than 80 ml of blood per menstrual (1) antifibrinolytic therapy with tranexamic untersten Normwert der von-Willebrand-as- acid, (2) the non-transfusional agent desmo- soziierten Laborwerte erfassen zu können. pressin (DDAVP), (3) purified blood products Behandlungs optionen für Menorrhagie bei The average menstrual blood loss is 25–80 that contain factor VIII and VWF concentrated einem VWS: (1) antifibrinolytische Therapie ml without significant clots. This definition from plasma and (4) hormonal preparations. examsäure, (2) Desmopressin is taken from population studies, which toren, die Faktor VIII und VWF enthalten und women experience losses of over 80 ml per menstrual blood loss can be difficult in Correspondence to:
Menorrhagie und Blutungsstörungen bei
clinical practice. One study found that vari- adoleszenten Frauen
ables that predicted a blood loss higher Medical Thrombosis and Haemophilia treatment Center Hämostaseologie 2012; 32: ■■
Königstraße 13, 47051 Duisburg, Germany doi:10.5482/ha-1181
than 80 ml per menses were clots greater than one inch, low ferritin levels, or chang- quantifying menstrual blood loss includes Downloaded from on 2012-01-06 | IP: Note: Uncorrected proof, prepublished online For personal or educational use only. No other uses without permission. All rights reserved.
S. Halimeh: Menorrhagia, bleeding disorders
the use of a pictorial bleeding assessment ity and specificity for scores higher than menorrhagia is defined as a complaint of calendar (PBAC) (ǠFig. 1). 100. The total menstrual score of more than The PBAC score has been validated in 100 was associated with a blood loss of occurring over several consecutive cycles in more than 80 ml (5). Subjectively, women during their reproductive years. Prevalence of VWD
The prevalence of menorrhagia in a woman with a bleeding disorder ranges from ● 5 to 98% in patients with platelet dysfunction (7–8) and 35 to 70% in women with a rare coagu-lation factor deficiency (9–12). The prevalence of the laboratory diagnosis of VWD in the general population is estimated to be approximately 1% (13). VWD in adolescents with menorrhagia included more than 540 patients (ǠTab. 1) with a prevalence between 3% and 36%, depending on the clinical setting (12, 14–22). Haemorrhagic ovarian cysts
Haemorrhagic ovarian cysts are less com-mon, but perhaps a more specific manifes-tation of a bleeding disorder. Women who have VWD or another bleeding disorder can have ovulation-associated bleeding that results in haemorrhagic ovarian cyst formation and bleeding into the peri-toneum, broad ligament, or retro peri- ● A lightly stained towel will score 1 point, toneum. While these cysts were not necess- ● a moderately stained towel 5 points. ● A towel which is saturated with blood will score 20 points. creased incidence of haemorrhagic ovarian ● A lightly stained tampon will score 1 point, cysts may have contributed to the higher ● a moderately stained tampon 5 points. prevalence of cysts reported in women with ● A tampon that is fully saturated will score 10 point. – 1p scores 1 point, – a 50p sized clot scores 5 points and Endometriosis
Once you have finished your period total up your scores. A score of 100 or greater may indicate that you have heavy periods and you should seek ad-vice from your doctor. However if your score is less than 100 and you have with bleeding disorders. Although there is concerns about your period you should always consult your GP.
disagreement as to the etiology of endome-triosis, the prevailing theory is that it results Fig. 1 Pictorial blood assessment chart and scoring system for assessment of menstrual blood loss
from retrograde menstruation (26). Retro- (reproduced with kind permission by John Wiley and Sons from: Higham JM, O'Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol 1990; 97: 734–739) strual blood out of the uterine cavity (27). Downloaded from on 2012-01-06 | IP: Note: Uncorrected proof, prepublished online For personal or educational use only. No other uses without permission. All rights reserved.
S. Halimeh: Menorrhagia, bleeding disorders
Women with endometriosis have been Tab. 1 Prevalence studies in bleeding disorders associated with menorrhagia in adolescents
shown to suffer from heavier menstrual
bleeding (28). Because their menses are study (ref.)
heavier, women with bleeding disorders Chi et al. 2010 (22) Miscarriages
There are several case reports and series documenting the increased risk of mis - carriage resulting in fetal loss or premature factor XIII (29) or fibrinogen (30). Reports of miscarriage in women with bleeding Claessens et al. 1981 (15) Tab. 2 Miscarriages in women with bleeding disorders
Screening for bleeding
study (ref.)
sample size, population
type of study prevalence of problem
Patient's history
A detailed history and a through physical exam are the first steps towards a diagnosis in adolescents with bleeding disorders. (33) Bleeding history red flags warranting Kirtava et al. 2003 86 women with VWD and case control 15% of pregnancies In a recent study by Phillip, a screening questionnaire of eight questions (questions based on the historical red flags ) resulted in 82% sensitivity for detecting any bleeding disorders (VWD, platelet function defect, or clotting factor deficiency). Adding a PBAC > 100 increased the sensitivity of the Laboratory testing
An ideal screening panel to rule out any (clottable fibrinogen) defects of fibrinogen an effort to capture the lowest level of bleeding disorder in an adolescent pres- enting with menorrhagia is not yet clearly ● ristocetin cofactor activity (VWF : RCo), defined. Laboratory testing should include a ● VWF antigen level (VWF : Ag). Treatment of adolescents
complete blood count to assess the haemo - There is a high degree of variability in VWF cytopenia. Prothrombin time (PT) and assays over time as well as with routine Treatment of VWD is often complex be-activated partial thromboplastin time stressors such as blood drawn. Therefore, it cause a combination of therapies is often (aPTT) should be part of an initial screen is recommended to test more than once for required (39). Furthermore, VWD sub-although not sensitive for bleeding dis- a definitive diagnosis. It is also suggested types subtypes respond differently to treat- orders. Other tests to investigate qualitative that at least one of these testing should take ment (40). Therefore, a haematologist (thrombin clotting time) and quantitative place at the time of menstrual bleeding in should manage adolescents with Downloaded from on 2012-01-06 | IP: Note: Uncorrected proof, prepublished online For personal or educational use only. No other uses without permission. All rights reserved.
4 S. Halimeh: Menorrhagia, bleeding disorders
uterine bleeding, but it is less potent and Screening
has more side effects than tranexamic acid. mild tachycardia, headache, and flushing. Tranexamic acid had been used for Tranexamic acid alone or in combination Bleeding history red flags
many years in Europe and elsewhere, but of DDAVP provides a good option for had not been approved for use in the treatment of HMB in adolescent girls, 1. Prolonged bleeding from trivial wounds United States until recently (November especially very young girls and those who do not accept hormonal treatments. These cations. A recent case control study on agents can also be used in combination 2. Heavy, prolonged, or recurrent bleeding thromboembolic disease and tranexamic with hormonal therapies during the period acid found an odds ratio 3.2 for the use of or breakthrough bleeding. 3. Bruising with minimal with minimal or isms), but this value did not reach statistical Factor VIII and VWF concentrates
The most side effect is gastrointestinal In adolescents with severe bleeding dis- symptoms (nausea and diarrhea). These orders, regular prophylaxis with specific are the main reason for discontinuing clotting factors may be necessary to control 5. Heavy prolonged, or recurrent bleeding treatment or reducing the dose resulting in HMB not responding to other medical reduced efficacy. Tranexamic acid has treatments. Purified blood products that successfully been used for the control of contain factor VIII and VWF concentrated menorrhagia in women with a variety of from plasma (50) can be administered dur- irregular bleeding or recurrent ovulation Desmopressin
greater than an inch in diameter and/or changing a pad or tampon more than The non-transfusional agent desmopressin Hormonal preparations
pressin) is a synthetic analogue of the anti- 9. Blood relative with a bleeding disorders diuretic hormone vasopressin (45–47). It Combined contraceptive hormones, con- increases plasma concentration of VWF taining both estrogen and a progesterone, and factor VIII in the circulation and reduce menstrual loss by inducing regular increases platelet adhesiveness. menorrhagia caused by bleeding disorders tion and treatment of bleeding episodes in istered as combined with expertise in treating VWD. There are some patients with mild bleeding dis- four main agents used to stop and/or pre- vent excessive bleeding for VWD-related philia A. For home treatment in women ● vaginal rings. menorrhagia (41): with bleeding disorders and HMB, DDAVP as intranasal spray has been shown to be ef- fective with a significant reduction in cents. COCs are useful for cycle regulation Antifibrinolytic therapy
PBAC scores and improvement in quality and improved menstrual pain and premen-of life (48). In the same study, however, strual tension. They are also highly reliable Antifibrinolytic therapy is performed with tranexamic acid was shown to be more ef- and safe contraceptives for these girls with no adverse effects on their future fertility or nasal spray and oral tranexamic acid has attainment of their peak bone mass (51). been shown to be more effective in reduc- ing menstrual blood loss (49) compared to mal uterine bleeding (AUB) in girls and Tranexamic acid, an antifibrinolytic agent, DDAVP alone. In addition, this regime also women with bleeding disorders, with an has been shown to significantly (40–50%) helps reduce the necessary dose and added advantage of preventing ovulation reduce menstrual blood loss in women duration of DDAVP use, thus reducing the bleeding. with HMB (42). However, it does not potential risk of hypernatraemia. Hyper- reduce the duration of menses of regulate natraemia and potentially water intoxi- the menstrual cycle. Aminocaproic acid has cation is a small risk of DDAVP use, due to girls in general and those with bleeding dis- also been successfully used to decrease its antidiuretic effect. Downloaded from on 2012-01-06 | IP: Note: Uncorrected proof, prepublished online For personal or educational use only. No other uses without permission. All rights reserved.
S. Halimeh: Menorrhagia, bleeding disorders
inherited risk of thrombosis. Minor side ef- References
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