Primary Hemostasis Flashcards Flashcards

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TPO

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Thrombopoietin (TPO) is a liver-derived hormone that binds the MPL receptor on megakaryocytes and platelets. It stimulates megakaryocyte proliferation and differentiation, driving platelet production through endomitosis and proplatelet shedding. TPO helps maintain the platelet count in circulation.

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Megakaryocyte

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Megakaryocytes are large bone marrow cells that give rise to platelets via proplatelet shedding. They undergo endomitosis to become polyploid, increasing cytoplasmic volume for platelet production. Each megakaryocyte can yield 2,000–4,000 platelets.

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Endomitosis

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Endomitosis is a unique mitotic process where DNA replicates without cytokinesis, producing polyploid megakaryocytes. It is regulated by RUNX1 and NF-E2, which promote polyploidy ($8N$, $16N$, and rarely $128N$). This polyploidy provides more cytoplasm for platelet production.

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MK-I Megakaryoblast

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MK-I is the earliest megakaryocyte precursor (diameter $14–18\,\mu m$). About 20% of precursors belong to this stage, and α-granules and dense granules begin forming during early maturation.

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MK-II Promegakaryocyte

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MK-II is the next stage (diameter $15–40\,\mu m$) with an indented nucleus and about 25% of precursors. It shows progression toward full ploidy with continued granule development.

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MK-III Megakaryocyte

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MK-III is mature (diameter $30–50\,\mu m$) with a multilobed nucleus and α + dense granules. This stage marks full maturation and the start of thrombocytopoiesis.

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Proplatelet shedding

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Proplatelet shedding is the process by which a mature MK extends proplatelets through the BM sinusoid and releases platelets. Output is $2{,}000$–$4{,}000$ platelets per MK, with daily production ~ $10^{11}$ platelets and a turnover of $8–9$ days.

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GPIb/IX/V

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GPIb/IX/V is the platelet receptor complex that binds von Willebrand factor and mediates primary adhesion to exposed subendothelial collagen. Defects can cause Bernard-Soulier syndrome.

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GPIIb/IIIa

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GPIIb/IIIa is the fibrinogen receptor on activated platelets, mediating platelet-platelet aggregation by binding fibrinogen and von Willebrand factor; it stabilizes the forming plug.

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GPVI

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GPVI is a platelet collagen receptor that triggers TXA2 and ADP release, promoting inside-out activation of integrins and adhesion to exposed collagen.

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GPIa/IIa

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GPIa/IIa (α2β1) is a collagen receptor that supports platelet adhesion to exposed collagen; its activity increases with inside-out signaling to strengthen adhesion.

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P2Y12

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P2Y12 is an ADP receptor coupled to Gi; it lowers intracellular cAMP and promotes irreversible platelet aggregation. It is a major target of antiplatelet therapies.

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P2Y1

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P2Y1 is an ADP receptor coupled to Gq; it increases intracellular Ca$^{2+}$ and supports initial reversible aggregation and shape change.

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PAR1

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PAR1 is a protease-activated thrombin receptor; its activation triggers G-protein signaling leading to platelet activation and aggregation.

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PAR4

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PAR4 is another thrombin receptor; together with PAR1 it mediates robust thrombin-induced platelet activation.

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PGI2

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Prostacyclin (PGI$_2$) is produced by endothelial cells and inhibits platelet activation by increasing intracellular cAMP; it also causes vasodilation.

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TXA2

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Thromboxane A2 ($TXA$_2$) is a platelet-derived prostanoid that promotes aggregation by activating TP receptors; it has a short half-life (~30 s) and is rapidly converted to TXB2.

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TFPI

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Tissue Factor Pathway Inhibitor (TFPI) inhibits the extrinsic coagulation pathway by blocking the tissue factor–VIIa complex.

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Thrombomodulin

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Endothelial thrombomodulin binds thrombin to activate protein C, shifting the balance toward anticoagulation and reducing clot formation.

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vWF

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von Willebrand Factor mediates platelet adhesion to exposed collagen by binding to GPIb/IX/V and also stabilizes factor VIII in plasma.