Inherited disorders of platelet function: selected updates

Abstract

To cite this article: Nurden AT, Nurden P. Inherited disorders of platelet function: selected updates. J Thromb Haemost 2015; 13 (Suppl. 1): S2-S9.Summary. The gene variants responsible for the primary genotype of many platelet disorders have now been identified. Next-generation sequencing technology (NGST), mainly exome sequencing, has highlighted genes responsible for defects in platelet secretion (NBEAL2, gray platelet syndrome), procoagulant activity (STIM1, Stormorken syndrome), and activation pathways (RASGRP2, Cal-DAG-GEFI deficiency and integrin dysfunction; PRKACG, cyclic adenosine monophosphate-dependent protein kinase deficiency). Often disorders of platelet function are associated with a modified platelet production with changes in platelet number and size and can accompany malfunction of other organs or tissues. Most families have private mutations, and gene variants may prevent protein synthesis, abrogate function, or result in aberrant activated proteins. Nevertheless, bleeding severity is difficult to predict by genotype alone suggesting other factors. A major new challenge of NGST is to identify these factors and help improve patient care. This review concentrates on recent developments and is illustrated from personal observations.

Should any genetic defect affecting α‐granules in platelets be classified as gray platelet syndrome?

“…Recent proteomic studies show just how diverse is this pool [2]. Inherited platelet bleeding disorders affecting a-granule biogenesis and platelet function, therefore, have a wide interest, both clinically and from a biological view [3]. The gray platelet syndrome (GPS) is the classic disorder of agranule biogenesis, being the object of many studies since the first report by Raccuglia in 1971 [4,5].…”

Coated platelets function in platelet-dependent fibrin formation via integrin α IIb β 3 and transglutaminase factor XIII

“…This functional redundancy of integrin α IIb b 3 and factor XIII might explain the poor correlation of the defect in α IIb b 3 with the bleeding tendency observed in Glanzmann thrombasthenia patients. 35 Although earlier studies found tissue type transglutaminase to be present in human platelets, 8,36 more recent studies showed it could not be detected on the platelet protein level. 37,38 Interestingly, in mouse platelets, tissue type transglutaminase (Tgm2) could be detected, albeit with a 25-fold lower expression in comparison to factor XIII (F13a).…”

The Glanzmann’s Thrombasthenia in Tunisia: A Cohort Study

“…Some studies revealed sex ratio of about 1 which is verified in our cohort with 14 women against 13 men (51% versus 49%) [2].…”

“…Prevalence of GT is unknown but it is estimated to be about 1.1 million and it is encountered in populations with a high rate of consanguinity [2]. A slight female predominance (58% vs. 42%) is reported, similar to other inherited platelet disorders (IPDs) [3].…”