title: Clinical and laboratory phenotypes associated with the aspirin-like defect: a study in 17 unrelated families.
abstract: Aspirin-like defect (ALD) is a rare, mostly autosomal dominant inherited dysfunction of the intraplatelet arachidonic acid (AA) pathway leading to impaired thromboxane A2 signalling. We aimed to establish diagnostic criteria for ALD diagnosis and present clinical and laboratory phenotypes of 52 individuals from 17 unrelated families. Platelet in vitro function was determined on the basis of platelet aggregation response (PAR) to AA, adenosine diphosphate, collagen and ristocetin as well as PFA-100 closure times (CT). Using impaired PAR to AA (< or =10%) as the mandatory diagnostic criterion, ALD could be confirmed in 17 patients. Subsequently, family members were investigated and among 35 individuals an additional 13 ALD patients as well as 4 individuals with mild ALD (PAR to AA: 19-32%) were identified. At least one bleeding symptom was reported by 25 (74%) ALD patients and prolonged CT was detected in 24 (71%) of the cases, both significantly correlated with impaired PAR to AA (P = 0.001 and P = 0.002, respectively). An estimated 0.6% prevalence was determined for ALD in our paediatric patients with suspected coagulation disorders. Due to the mild bleeding symptoms, ALD is probably underdiagnosed. If ALD is suspected, PAR to AA is suitable for the identification of individuals at risk of increased haemorrhage.
authors.affiliation: Children's Hospital, Department of Paediatric Oncology and Haematology, University Hospital Carl Gustav Carus, Technical University, Dresden, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Rolf
authors.forename: Ralf
authors.initials: R
authors.lastname: Knoefler
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
authors.forename: Siegmund
authors.initials: S
authors.lastname: Gehrisch
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siegert
authors.forename: Eberhard
authors.initials: E
authors.lastname: Kuhlisch
authors.forename: Meinolf
authors.initials: M
authors.lastname: Suttorp
mesh_terms: D000293:Adolescent; D000328:Adult; D016718:Arachidonic Acid; D001760:Bleeding Time; D001791:Blood Platelet Disorders / Q000175:diagnosis* / Q000201:enzymology; D001792:Blood Platelets / Q000378:metabolism; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D005260:Female; D020141:Hemostatic Disorders / Q000175:diagnosis* / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010974:Platelet Aggregation / Q000187:drug effects*; D010979:Platelet Function Tests; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency*; D015398:Signal Transduction; D013577:Syndrome; D013928:Thromboxane A2 / Q000378:metabolism; D055815:Young Adult
chemical_list: D016718:Arachidonic Acid; D013928:Thromboxane A2; D011451:Prostaglandin-Endoperoxide Synthases