Investigating the thrombopoietic significance of preplatelet maturation in health and acquired thrombocytopenia

Kemble, Samuel (2021). Investigating the thrombopoietic significance of preplatelet maturation in health and acquired thrombocytopenia. University of Birmingham. Ph.D.

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Abstract

Circulating “preplatelets” (3-10μm in diameter) are platelet precursors that mature by transforming into barbell platelets and can undergo fission into two smaller platelets (2-3μm in diameter). In this study, we determine whether preplatelets are equivalent to immature platelets and whether they can transform into barbells and undergo fission into two mature platelets. By designing a new imaging cytometry methodology to accurately discriminate preplatelets and barbells in whole blood and in combination with microscopy, we have quantified and characterised these structures in humans and mice and demonstrated their analogy to immature platelets (displaying increased labelling with the immaturity markers thiazole orange and HLA I). Labelling with cytosolic dyes confirmed preplatelets exhibit the ability to transform into barbells and undergo fission. Accurate determination of immature platelets has the potential to non-invasively distinguish peripheral thrombocytopenia from dysfunctional platelet production. We demonstrate that preplatelet maturation events are significantly increased in response to enhanced peripheral destruction of platelets in human immune thrombocytopenia, acute thrombocytopenia in mice and absent following bone marrow ablation therefore, representing the rate of thrombopoiesis. Biotinylation in mice definitively proves that barbells are newly formed platelets. However, not all large platelets were immature, suggesting preplatelets are a subpopulation of large platelets.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):