Immature Platelet Dynamics in Immune-Mediated Thrombocytopenic States

Abstract

A major challenge encountered by clinicians is differentiating presentations characterized by significant thrombocytopenia due to overlapping clinical symptoms and signs in the setting of ambiguous laboratory results. Immature platelets represent the youngest platelets that can be measured in peripheral blood by current hematology analyzers. These young platelets are larger, with higher RNA content recently released from the bone marrow. Thrombocytopenic presentations caused directly or indirectly by immune responses can lead to compensatory bone marrow responses seeking to normalize the platelet count; thus obtaining absolute immature platelet counts may be informative while triaging patients. Over the last decade, their use has expanded beyond being an early biomarker of bone marrow reconstitution post-hematopoietic stem cell transplantation to being used to establish bone marrow responses to infection and thrombocytopenias due to immune etiologies. Its accessibility as part of more detailed platelet indices obtained with routine laboratories makes it a promising option to understand the bone marrow's real-time response to disease states characterized by thrombocytopenia. This review will look at the immature platelet count as a biomarker, while presenting current attempts trying to understand how it could be used in thrombocytopenias occurring secondary to a given immune etiology.

Routine and Advanced Laboratory Tests for Hemostasis Disorders in COVID-19 Patients: A Prospective Cohort Study

“…IP fractions or counts have been established to measure bone marrow platelet production, as reticulocyte count for red cells [ 22 ]. They are the youngest circulating platelets, derived from megakaryocytes, and thus present a larger size, an important RNA content, and a higher activity [ 23 ]. Thus, they are suspected to be implicated in thrombosis during some pathological settings.…”

Case Report: Hypergranular Platelets in Vaccine-Induced Thrombotic Thrombocytopenia After ChAdOx1 nCov-19 Vaccination

“…Our work highlights a previously unreported observation of platelet hypergranularity in the early stages of VITT with increased capacity for secretion and, possibly, platelet-hyperactivity contributing to vaccine-induced thrombosis. The hypergranular platelets may have been immature platelets, known to be prothrombotic and hyper-reactive with high dense-granules content ( 16 ) and are increased in other immune thrombocytopenic conditions such as immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura ( 17 ), contributing to thrombotic events. The increased presence of immature platelets is most likely caused by platelet overproduction, secondary to platelet consumption or hypoproduction ( 17 ).…”

“…The hypergranular platelets may have been immature platelets, known to be prothrombotic and hyper-reactive with high dense-granules content ( 16 ) and are increased in other immune thrombocytopenic conditions such as immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura ( 17 ), contributing to thrombotic events. The increased presence of immature platelets is most likely caused by platelet overproduction, secondary to platelet consumption or hypoproduction ( 17 ). The reduction in hypergranular/immature platelet populations over time in our patient was most likely caused by the resolution of platelet count to normal range, contributing to the decrease in platelet granule counts and dense-granule secretion (ATP release) we observed between VITT platelets from days 2 and 72, feasibly reducing our patient's thrombotic risk.…”

Immature Platelet Fraction in Patients with Chronic Liver Disease, A Marker for Evaluating Cirrhotic Changes.

“…These factors include the development of complications such as variceal bleed, ascites, hepatorenal syndrome, and spontaneous bacterial peritonitis etc. 10 The severity of liver disease can be assessed by platelet numbers. Cirrhotic thrombocytopenia is mainly associated with inadequate production of thrombopoietin and decrease the production of platelets, but the underlying mechanism is not yet fully cleared.…”