Learning the Ropes of Platelet Count Regulation: Inherited Thrombocytopenias

Abstract

Inherited thrombocytopenias (IT) are a group of hereditary disorders characterized by a reduced platelet count sometimes associated with abnormal platelet function, which can lead to bleeding but also to syndromic manifestations and predispositions to other disorders. Currently at least 41 disorders caused by mutations in 42 different genes have been described. The pathogenic mechanisms of many forms of IT have been identified as well as the gene variants implicated in megakaryocyte maturation or platelet formation and clearance, while for several of them the pathogenic mechanism is still unknown. A range of therapeutic approaches are now available to improve survival and quality of life of patients with IT; it is thus important to recognize an IT and establish a precise diagnosis. ITs may be difficult to diagnose and an initial accurate clinical evaluation is mandatory. A combination of clinical and traditional laboratory approaches together with advanced sequencing techniques provide the highest rate of diagnostic success. Despite advancement in the diagnosis of IT, around 50% of patients still do not receive a diagnosis, therefore further research in the field of ITs is warranted to further improve patient care.

Inherited Platelet Disorders: An Updated Overview

“…The two main groups of IPD are: Inherited thrombocytopenias, in which the most conspicuous defect is the low number of circulating normal-sized, large, or small platelets [ 4 , 5 , 6 ] ( Figure 1 , Table 1 ) Inherited platelet function disorders, characterized by dysfunctional, typically hypofunctional, platelets resulting from defects of the membrane receptors, granules, elements involved in signal transduction, or other defects of the biochemical platelet machinery [ 7 , 8 ] ( Figure 1 , Table 2 , Table 3 and Table 4 ) …”

“…Inherited thrombocytopenias, in which the most conspicuous defect is the low number of circulating normal-sized, large, or small platelets [ 4 , 5 , 6 ] ( Figure 1 , Table 1 )…”

Role of Thrombopoietin Receptor Agonists in Inherited Thrombocytopenia

“…The results showed that the use of preoperative prohemostatic treatments was associated with a lower bleeding frequency in patients with IPFD but not in ITs. DDAVP, alone or with antifibrinolytic agents, was the preventive treatment associated with lowest bleedings [ 32 , 33 ].…”

“…In this context, the need for prophylactic platelet transfusion before surgery should be carefully assessed in relation to the type of procedure and the patient’s features (PC and function, history of bleeding, overall evaluation of hemostasis) in order to avoid unnecessary transfusions. In fact, platelet transfusion, one of the most frequently used prophylactic treatments before surgery in ITs, has been revealed to be poorly effective, suggesting that either other treatments are required, or that the way platelet transfusions are employed (amount, type, timing) is inappropriate [ 32 , 33 ]. In this regard, dysfunctional platelets may impair the hemostatic function of healthy donor platelets, and the endogenous platelet count and the ratio of transfused versus endogenous platelets should be considered when treating selected IT patients with platelet transfusions [ 38 ].…”

“…Although, splenectomy has been effective in patients with WAS/X-linked thrombocytopenia (XLT), in terms of increasing PC and reducing the incidence of serious bleedings, as physicians have become more aware of the potential risks of subsequent severe infection, and recurrence of thrombocytopenia, the use of splenectomy is very rarely indicated in any form of IT [ 33 , 39 ].…”