Evaluation of Menses in Congenital Bleeding Disorders

• Conditions: Congenital Coagulation Factors Deficiency; Haemophilia Carriers; Von Willebrand Disease

• Registration Number: NCT01261936
• Lead Sponsor: University of L'Aquila

Brief Summary

Menorrhagia is the term used to define excessive menstrual blood losses, as often based on a subjective judgment of women. Many arbitrary values, expressed in milliliters of blood, have been proposed to define this symptom: 60 on each cycle has also been confirmed in our preliminary study on 87 healthy women. The quantitative determination of menstrual blood losses is nevertheless rarely performed, only in research settings. Although menorrhagia is a quite frequent symptom in healthy women apparently haemostatically competent in the fertile age (20-30%), its incidence becomes very high in women affected by congenital coagulation factors deficiency and (50-62.9%) inherited platelet defects, e.g. Glanzmann's Thromboasthenia (GT); also in von Willebrand Disease the bleeding symptom "menorrhagia" has an high prevalence (60-75%)(8); for GT an incidence of 90% has been reported.

This explains the need for a study focused on the evaluation of menorrhagia in CBDs, addressed to answer to the following, still unsolved questions:

1. Definition of the entity of menstrual blood losses in women affected by CBDs

2. Elaboration of specific treatment schedules for each type of CBD

3. Impact of different specific treatment schedules on kinetic and entity of menstrual losses (how does treatment modify losses?).

Detailed Description

The following is a multicentric, observational, cross-over study intended to apply an easy and simple system for the quantitative determination of menstrual losses in women affected by Congenital Bleeding Disorders (CBDs).

The evaluation of menstrual losses represents a scarcely studied field in this specific subset of patients (1), but it is very interesting because of the high incidence of menorrhagia,changeable according to each type of CBDs, but between 60 and 100% in women in the fertile age.

The system adopted for the determination of menstrual losses, called QUEM (QUantitative Evaluation of Menses),is based on the collection of tampons and pads in standard bags which are readily vacuum sealed with a simple device for the whole of woman's period. QUEM has already been validated in preliminary in vitro and ex vivo studies (both in 87 healthy women and in women with CBDs), by comparing it with the gold standard, the Alkaline Haematin Method. A correlation coefficient close to 1 was obtained.

In the current study QUEM will be applied to women in the fertile age (between 18 e 45 years),with an ascertained diagnosis of CBD (FVII, FX, FII deficiencies, Glanzmann and von Willebrand disease, symptomatic Hemophilia A and B carriers), followed up for heavy periods at their reference hemophilia centre and needing a specific treatment will be enrolled in this multicentric study. Also women with apparently normal menses but a severe bleeding disorder will be enrolled. Women with ascertained menorrhagia will be treated with specific replacement therapies, already commonly adopted in clinical practice based on the type of CBD and scheduled to reduce heavy periods.

The study will evaluate 4 consecutive menstrual cycles, the first and the second period without treatment (when possible) and the following two by the administration of the specific treatment.

The bleeding anamnesis (bleeding score) will be performed by applying an international reference method, already validated in von Willebrand Disease type 1 (vWD1) \[2\] and adopted in an Italian multicentric study on 814 patients affected by different types of VWD \[3\]. The determination of this score has been considered useful also for other CBDs. This study has already been approved by the IRC of "San Salvatore Hospital"- L'Aquila-Italy. The study is already enrolling, in Italy, women. All the needed materials and equipments will be provided; patients will be carefully informed about the objectives of the study and they will follow a short course illustrating the use and the characteristics of the method proposed (QUEM).

Study Timeline

• Study Start: 2010-02
• Status Verified: 2010-12
• Study First Submitted: 2010-12-16
• Study First Submitted QC: 2010-12-16
• Last Update Submitted: 2010-12-16
• Study First Posted: 2010-12-17
• Last Update Posted: 2010-12-17
• Study Completion: 2011-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

1. Age between 18 and 45 years;

2. Ascertained diagnosis of one of the following inherited bleeding disorders:

   1. Von Willebrand Disease type 1, 2, 3 severe and moderate (VWF:RCo < 30 %),as diagnosed following Italian guidelines [4]
   2. Glanzmann Thromboasthenia
   3. Congenital Coagulation Factor VII, II or X deficiency
   4. A and B Haemophilia Carriers (Factor VIII and IX <25%);

3. Bleeding Severity score > 2

4. Signing the consent form.

Exclusion Criteria

1. Under continuous anti-hemorrhagic prophylaxis 2. Affected by an active cancer or anti-phospholipid antibodies syndrome 3. History of liver, kidney or endocrine disorders 4. Submucous uterine fibroids, uterine polyps or malignancy 5. Use of oral contraceptives or intrauterine devices in the past three months 6. Treatment with non-steroidal anti-inflammatory drugs

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Quantitative determination of menstrual blood losses	1 year	Quantitative determination of menstrual blood losses in women in the fertile age( between 18 and 45 years) affected by an inherited haemorrhagic disorder diagnosed on the basis of the current International Standard Criteria.This study is preliminary to the evaluation of the efficacy of each

Secondary Outcome Measures

Name	Time	Method
treatment schedule evaluation	monthly	Elaboration of specific treatment schedules for each type of CBD, as evaluated by QUEM
kinetic definition of menses	monthly	Kinetic definition of menses (hours and days of flow) with and without specific treatment
Influence of treatment on menstrual blood losses	monthly	To define the influence of substitutive therapies on menstrual losses

Trial Locations

Locations (3)

IRCCS "Casa Sollievo della Sofferenza"-Thrombosis and Haemostasis Center; 🇮🇹 San Giovanni Rotondo, FG, Italy

Thrombosis and Hemostasis Center-University of L'Aquila; 🇮🇹 L'Aquila, Italy

Hematology Department-University of Palermo; 🇮🇹 Palermo, Italy