Inherited Macrothrombocytopenias

Abstract

Inherited macrothrombocytopenias are a clinically heterogeneous group of disorders, many of which cause moderate-to-severe bleeding tendencies in affected individuals, but which remain under-recognized and are frequently misdiagnosed as immune thrombocytopenia purpura. Diagnostic strategies to date have included a predominant phenotypic approach. The emergence of genetic testing and the implementation of next generation sequencing strategies in the investigation and diagnosis of these disorders have broadened our understanding of their pathogenesis, classification, and presentation. This review describes the increasingly expanding group of recognized inherited macrothrombocytopenias and highlights their pathophysiology and the role of phenotypic and genetic testing in their description and diagnosis.

Mean platelet diameter measurements to classify inherited thrombocytopenias

“…3,13,15,25,33 In some cases, despite rigorous investigation, a diagnosis is not achieved and disorders remain uncharacterised or are misdiagnosed as immune thrombocytopenia (ITP). 3,13,15,25,33 In some cases, despite rigorous investigation, a diagnosis is not achieved and disorders remain uncharacterised or are misdiagnosed as immune thrombocytopenia (ITP).…”

“…In summary, a step-wise, algorithmic approach using a number of phenotypic tests and more recently, genetic tests, is recommended to diagnose IT. 3,13,15,25,33 In some cases, despite rigorous investigation, a diagnosis is not achieved and disorders remain uncharacterised or are misdiagnosed as immune thrombocytopenia (ITP). These diagnostic challenges support a need for new, simple and reliable tests, developed in parallel to platforms such as next-generation sequencing, to improve our ability in recognising individuals with inherited, as opposed to acquired, thrombocytopenias.…”

“…Currently, diagnosis of IT is achieved through a combination of investigations ranging from morphological assessments (Figure 1), complex platelet function tests, ultrastructural analysis to genetic testing. 15,16 This may be a time-consuming and expensive process, and access to specialised tests may be limited to laboratories predominantly in developed nations. 17 In an attempt to streamline the diagnostic pathway and better classify IT, simple measures using platelet size have been evaluated.…”

Detection of mild inherited disorders of blood coagulation: current options and personal recommendations

“…The second-line tests are mainly used for diagnosing a specific inherited disorder or characterizing the defects otherwise identified by the abnormal first-line test, and typically involves measurement of 'clotting' factor activity (or concentration) with various techniques. The third-line tests are those used for the specific characterization of the inherited bleeding disorders, and may hence encompass molecular biology (to identify mutations or polymorphisms causing the deficiency), additional specialized tests for characterization of VWD type or other coagulation disorder or specific platelet function defects[36][37][38][56][57][58][59][60][61][62][63].…”

Hot Topics VI

“…Rabbolini et al then continued the further exploration into hemostasis, this time as related to primary hemostasis, and namely the group of inherited macrothrombocytopenias that remain underrecognized and which are frequently misdiagnosed as immune thrombocytopenia purpura. 30 Inherited macrothrombocytopenias represent a clinically heterogeneous group of disorders, many of which cause moderateto-severe bleeding tendencies in affected individuals. Diagnostic strategies to date have included a predominant phenotypic approach.…”