Platelet Formation and Production
Platelets are created in the bone marrow through fragmentation of megakaryocyte cytoplasm. 1
Megakaryocyte Development and Platelet Production
- Platelets are anucleated blood cells that originate from bone marrow precursor cells known as megakaryocytes 1, 2
- Megakaryocytes are giant polyploid cells that reside within the bone marrow and are derived from hematopoietic stem cells 3
- The process of platelet formation involves a complex series of remodeling events powered by the cytoskeleton 2, 4
- Each megakaryocyte can produce approximately 3,000 platelets through extension of cytoplasmic projections called proplatelets 5, 3
- These proplatelets extend through the endothelial barrier of sinusoid vessels in the bone marrow 5
Regulation of Platelet Production
- Thrombopoietin is the primary regulator of platelet production and is produced mainly in the liver, as well as in the bone marrow and kidney 1
- Thrombopoietin binds to high-affinity receptors on platelets and megakaryocytes 1
- In the presence of high platelet mass, thrombopoietin levels decrease, reducing platelet production 1
- Conversely, when platelet mass is low, thrombopoietin levels rise, stimulating thrombopoiesis 1
- Under physiologic circumstances, platelets are produced daily at a baseline rate, but production can increase up to 10-fold during times of increased need 1
Platelet Characteristics and Lifespan
- Platelets have a maximum circulating lifespan of 10 days 1
- The size of a resting, discoid platelet is approximately 2-4 μm 1
- Platelets are the smallest type of cells found in human body fluids 1
- Platelets provide a circulating source of chemokines, cytokines, and growth factors, which are preformed and packaged in storage granules 1
Clinical Implications
- Abnormalities in platelet production can result in thrombocytopenia (platelet count <150,000/μL), which increases the risk of bleeding 4
- Conversely, thrombocythemia (platelet count >600,000/μL) can increase the risk of thrombotic events 4
- Understanding platelet production is crucial for developing treatments for platelet disorders and improving platelet transfusion technologies 6
- Transcription factor mutations can disrupt megakaryopoiesis or thrombopoiesis, resulting in thrombocytopenia 3
Important Considerations
- While megakaryocytes and proplatelets are produced in the bone marrow, the final remodeling and release of platelets may primarily occur in the downstream microcirculation 5
- Platelets become easily activated during cold temperatures and during blood collection and handling, which can result in the release of extracellular vesicles 1
- Metabolic changes due to inflammation, aging, or diseases such as cancer can affect platelet biogenesis 3
Understanding the complex process of platelet production is essential for developing new approaches to treat platelet disorders and improve platelet transfusion technologies for clinical use.