Hematology Week 2 Study Notes

Hematology - Week 2 Study Notes

• Platelets are non-nucleated blood cells, circulating at a concentration of 150 to 400 x 10⁹/L.
• Platelet counts are slightly higher in women than in men, and lower in both sexes who are older than 65.
• Platelets arise from megakaryocytes in the bone marrow.
• Megakaryocytes are the largest cells in the bone marrow, with 30 to 50 µm diameter, a multilobulated nucleus, and abundant granular cytoplasm.
• A normal Wright-stained bone marrow aspirate smear shows 2-4 megakaryocytes per 10x magnification low power field.
• Megakaryocyte development involves endomitosis, a type of cell division where DNA replicates but the cell doesn't divide.
• Megakaryocytes mature through several stages, including megakaryoblast, promegakaryocyte, and megakaryocyte, characterized by increasing nuclear lobularity and cytoplasmic maturation.
• Megakaryocyte progenitors arise from common myeloid progenitors under the influence of GATA-1.
• Thrombopoietin (TPO) is a hormone critical for megakaryocytopoiesis and thrombopoiesis.
• Platelets circulate for 8-9 days.
• A single megakaryocyte can shed 2,000-4,000 platelets.
• Platelet activation involves adhesion, aggregation, and secretion.
• Platelet adhesion: Platelets bind to components of the vascular matrix (e.g., collagen, von Willebrand factor).
• Platelet aggregation: Platelets adhere to each other forming aggregates.
• Platelet activation leads to the release of granular contents containing various factors like thromboxane A2 (TXA2), adenosine diphosphate (ADP), and other vasoactive substances that mediate the clotting cascade.
• Platelet activation triggers a shape change from discoid to more spherical with pseudopods, increasing interaction with other surfaces.
• Platelets have various receptors including integrins (GPIIb/IIIa, GPIb/IX/V, GPVI) for adhesion and activation.
• Platelet activation can be triggered by various factors (e.g., thrombin, ADP, collagen).
• Platelets release factors involved in inflammation, oxidative stress, angiogenesis and thrombosis.
• Platelets have diverse surface proteins (including GPIb/IX/V and GPVI) specialized to bind various components of the vessel wall and blood to mediate adhesion and aggregation.
• Platelet granules contain various substances involved in platelet activation and blood coagulation.
• Platelet structure reflects specific functions, with a specialized cytoskeleton and a surface membrane with various receptors maintaining its shape.

Platelet Structure and Function

• Platelet cytoplasm contains membrane-bound granules like alpha granules (α-granules), dense granules, and lysosomes.
• Alpha granules contain clotting factors, growth factors, and other proteins.
• Dense granules contain ADP, ATP, serotonin, and calcium.
• Lysosomes contain enzymes.
• Platelet cytoskeleton consists of microtubules and microfilaments crucial for maintaining shape.
• The platelet membrane has a phospholipid bilayer structure with integral and peripheral proteins.
• Receptors on the platelet membrane are vital for interaction with the vasculature.
• Platelet activation involves changes in shape and release of granule contents.
• Platelets play a role in primary hemostasis.

Platelet Activation Pathways

• There are numerous pathways activated through the binding of various agonists with their specific receptors.
• Activation initiated from the outside-in pathway is the binding of collagen, von Willebrand factor or specific receptors.
• The inside-out pathway is through membrane receptors like thrombin and ADP, mediating platelet activation.
• Activated platelets facilitate aggregation.
• Cyclooxygenases convert arachidonic acid to thromboxane A2 or prostacyclin, crucial for hemostasis.
• Platelets through a series of reactions that amplify initial stimuli with positive feedback loops, resulting in coordinated actions that are essential for wound healing.