rare bleeding disorders in the netherlands

Conditions: Rare Bleeding Disorders

Summary: rationale: rare bleeding disorders (deficiency of fibrinogen, factor ii, v, v\&viii, vii, x, xi, xiii, α2-antiplasmin or plasminogen activator inhibitor 1) are not well defined with respect to their clinical phenotype, laboratory phenotype en genotype. at present, little is known about their clinical presentation, bleeding scores, bleeding episodes, health-related quality of life, laboratory parameters, genetics and current treatment. there are large differences in bleeding tendency and weak correlations with the level of factor deficiencies. therefore, it is essential to perform thorough research in patients with rare bleeding disorders and perform laboratory and genetic tests, to seek explanations for the variety in clinical phenotype. objective: the purpose of the rbin study is to describe the epidemiology, bleeding tendency, laboratory parameters, quality of life and genetics of all known patients in the netherlands with rare bleeding disorders. in addition, the study aims to examine the relationship between clinical phenotype, laboratory phenotype and genotype. study design: explorative cross-sectional multicenter observational study study population: all patients registered in dutch haemophilia treatment centers with known disorders of the coagulation factors fibrinogen, factor ii, v, v \& viii, vii, x, xi, xiii, α2-antiplasmin and plasminogen activator inhibitor type 1, aged 1 years and older. main study parameters/endpoints: description of the clinical phenotype, laboratory phenotype, genotype and quality of life. nature and extent of the burden and risks associated with participation, benefit and group relatedness: participating patients will be invited for one visit to their treatment center in order to draw blood, take a saliva sample and perform questionnaires. this will take approximately 40 to 120 minutes. since the population of patients with rare bleeding disorders is very small it is important to include all patients, also minors (children \<18 years), in the study (around one third of known patients are minors). therefore, this study may be regarded as group-related. the risk associated with participation is negligible.

primary objectives: * describe the epidemiology, clinical presentation, bleeding score, bleeding episodes, quality of life, laboratory parameters, genetics and treatment of homozygous and known heterozygous individuals (of all ages) with rare bleeding disorders (disorders of fibrinogen, fii, fv, fv \& viii, fvii, fx, fxi, fxiii, alpha-2-antiplasmin and pai-1 deficiency) in the netherlands; * examine the relationship between the clinical and laboratory presentation (clinical and laboratory phenotype), and between phenotypes and genetics (genotype); * examine the relationship between quality of life, phenotype and genotype; * validate the established factor activity levels for patients to remain without symptoms. secondary objectives: * compare the clinical presentation, bleeding score, quality of life and laboratory parameters of individuals with a rare bleeding disorder (disorders of fibrinogen, fii, fv, fv \& viii, fvii, fx, fxi, fxiii, alpha-2-antiplasmin and pai-1 deficiency) to those of individuals with haemophilia a or b in cooperation with the hin-6 investigators * establish a firm base for a future dutch registry for homozygous and known heterozygous individuals with rare bleeding disorders * to develop a standard set of patient-reported, clinical and administrative data to be collected on a regular basis * liaise with the pro-rbdd study, a similar study in italy, to work towards a pan-european study linking phenotype to genotype in individuals with rare bleeding disorders * to assess if the nha can distinguish mild clinical phenotypes in patients with similar factor activity levels * to evaluate the usefulness of saliva coagulation biomarker tests in the management of patients with a rare bleeding disorder * to examine whether age-dependent laboratory changes in factor concentrations and fibrinolysis occur in individuals with rare bleeding disorders and if so, whether they influence clinical phenotype * to evaluate if patients with rare bleeding disorders are protected from arterial thrombosis

Eligibility criteria:
inclusion criteria: * established homozygous or known heterozygous rare bleeding disorder due to deficiency or dysfunction of fibrin, fii, fv, fv \& fviii, fvii, fx, fxi, fxiii, alpha-2-antiplasmin and pai-1 ; * age 1 year and older; * for patients ≥ 16 years old; written informed consent. * for patients 12-16 years old; written informed consent from both the patient and their parents/legal guardian(s). * for patients \<12 years old; written informed consent from their parents/legal guardian(s). exclusion criteria: * no informed consent given; * residency outside of the netherlands

Keywords: fibrinogen factor ii factor v factor v & viii factor vii factor x factor xi factor xiii α2-antiplasmin plasminogen activator inhibitor 1 epidemiology genetics phenotype