Clinical and laboratory phenotypes associated with the aspirin‐like defect: a study in 17 unrelated families

Abstract

SummaryAspirin-like defect (ALD) is a rare, mostly autosomal dominant inherited dysfunction of the intraplatelet arachidonic acid (AA) pathway leading to impaired thromboxane A 2 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 Ò closure times (CT). Using impaired PAR to AA (£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 = 0AE001 and P = 0AE002, respectively). An estimated 0AE6% 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.

Elevated platelet count, C-reactive protein and thromboxane analog-induced platelet aggregation in patients with Gulf War veterans’ illnesses

“…Those whose platelets failed to aggregate (<10% of maximum aggregation) in response to arachidonic acid (AAÀ) were considered to have taken aspirin or other agents that inhibit platelet cyclooxygenase 1 (COX1), or to have an aspirin-like aggregation defect [16] regardless of their history. A primary analysis of data derived from all GWVIþ and GWVIÀ patients was performed.…”

Sodobni pristop za diagnosticiranje prirojenih motenj delovanja trombocitov

“…Aspirin--like defects) (16), motnje skladiščenja substanc (angl. "storage-pool" disease) v gostih trombocitnih zrncih (sindrom Hermansky-Pudlak (17,18), sindrom Che di ak-Higashi (17,(19)(20)(21), in Grisellijev sindrom (17)), motnje skladiščenja substanc v zrncih alfa (sindrom ARC (angl.…”

Clinical and laboratory phenotype associated with the aspirin‐like defect

“…We read with great interest the recent paper regarding the clinical and laboratory characterization of aspirin‐like defects (ALDs) (Rolf et al , 2009). We agree with the authors that ALDs are presently a group of heterogeneous and poorly defined disorders, that also includes storage pool disorders [Online Mendelian Inheritance in Man (OMIM) no.…”

“…This is particularly relevant due to ALD bleeding potential, which could be life‐threatening in conditions of trauma, surgery, intake of drugs affecting hemostasis. However, we would like to raise some concerns on the laboratory assays, diagnostic and classification criteria used and proposed by Rolf et al (2009).…”

“…The point‐of‐care PFA‐100 also needs intra‐laboratory standardization (as specified by Rolf et al , 2009) and depends on extra‐platelet factors (erythrocytes, hematocrit, von Willebrand factor). Moreover, PFA‐100 is not recommended for monitoring aspirin, because of its indirect and poor sensitivity to the AA pathway: this assay is sensitive to adhesive proteins instead and is triggered by collagen or ADP, thus not primarily reflecting the AA pathway (Hayward et al , 2006).…”