title: High prevalence of bleeders of unknown cause among patients with inherited mucocutaneous bleeding. A prospective study of 280 patients and 299 controls.
abstract: OBJECTIVE
  Mucocutaneous bleeding (MCB) is the main expression of inherited disorders of primary hemostasis. However, the relative prevalence of these disorders, their clinical differential diagnosis, and the proportion of patients with MCB of unknown cause (BUC) after an initial comprehensive laboratory testing are unknown.
  
  
  METHODS
  We studied prospectively 280 consecutive patients with MCB and 299 matched controls, using strict inclusion and exclusion criteria. A single physician recorded the clinical data in a bleeding score and estimated the severity of bleeding in clinical categories. Laboratory criteria for the diagnosis of von Willebrand's disease (VWD) and platelet function defects were established from reference values derived from controls.
  
  
  RESULTS
  Fifty patients (17.9%) had VWD (type 1VWD=45, type 2=5). Platelet function defects and mild clotting factor deficiencies were found in 65 (23.2%) and 11 (3.9%) patients, respectively. Thirteen (11.5%) patients had combined defects. The remaining 167(59.6%) patients had BUC, with prolonged bleeding time in 18.6% as their only abnormality. All these disorders, including BUC, were clinically undistinguishable. Moreover, no relationship was found between the severity of bleeding and VWF/platelet function variables.
  
  
  CONCLUSIONS
  The diagnostic efficacy of a first laboratory testing in patients with hereditary MCB is 40.4%. Most patients have a disease(s) of high prevalence but unknown pathogenesis. Concurrent bleeding disorders in the same patient are frequent. Our results support the proposal that low plasma VWF levels, but also platelet function defects, should be considered risk factors rather than unequivocal causes of hemorrhages.
authors.affiliation: Department of Clinical Laboratory, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Teresa
authors.initials: T
authors.lastname: Quiroga
authors.forename: Manuela
authors.initials: M
authors.lastname: Goycoolea
authors.forename: Olga
authors.initials: O
authors.lastname: Panes
authors.forename: Eduardo
authors.initials: E
authors.lastname: Aranda
authors.forename: Carlos
authors.initials: C
authors.lastname: Martínez
authors.forename: Sabine
authors.initials: S
authors.lastname: Belmont
authors.forename: Blanca
authors.initials: B
authors.lastname: Muñoz
authors.forename: Pamela
authors.initials: P
authors.lastname: Zúñiga
authors.forename: Jaime
authors.initials: J
authors.lastname: Pereira
authors.forename: Diego
authors.initials: D
authors.lastname: Mezzano
mesh_terms: D000293:Adolescent; D000328:Adult; D001760:Bleeding Time; D001791:Blood Platelet Disorders / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D019090:Case Management; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D020147:Coagulation Protein Disorders / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006470:Hemorrhage / Q000097:blood / Q000209:etiology*; D006474:Hemorrhagic Disorders / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008487:Medical History Taking; D008875:Middle Aged; D009092:Mucous Membrane; D010641:Phenotype; D010979:Platelet Function Tests / Q000295:instrumentation / Q000379:methods; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D012701:Serotonin / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction; D012871:Skin Diseases / Q000209:etiology*; D013030:Spain / Q000453:epidemiology; D011795:Surveys and Questionnaires; D014842:von Willebrand Diseases / Q000097:blood / Q000145:classification / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology
chemical_list: D006454:Hemoglobins; D012701:Serotonin; D004837:Epinephrine