Hema Lec 1

• Hemostasis is a complex physiologic process that leads to cessation of bleeding from a blood vessel.
• The functions of Hemostasis include keeping circulating blood in a fluid state, producing a clot to stop the bleeding, localizing the clot to the site of injury, and dissolving the clot as the wound heals.
• The stages of Hemostasis include Constriction of the blood vessel, Formation of a temporary "platelet plug", Activation of the coagulation cascade, and Formation of "fibrin plug" or the final clot.
• The elements of Hemostasis include Cellular elements such as cells of the vascular intima, extravascular tissue factor (TF)-bearing cells, and platelets, and Plasma components like coagulation and fibrinolytic proteins and their inhibitors.
• These processes are believed to pierce through or between sinusoid-lining endothelial cells, extend into the venous blood, and shed platelets.
• CYTOPLASM increases in volume and changes from basophilic, nongranular, and scant to completely granular and acidophilic.
• PLATELETS are formed at the ends of proplatelets and are released by microtubular action.
• PROPLATELETS are pseudopodial extensions of megakaryocytes that progressively branch and thin out.
• MEGAKARYOCYTES develop invaginated surface membranes (demarcation membranes) that provide a membrane reserve for proplatelet formation.
• THROMBOCYTOPOIESIS: A single megakaryocyte may shed 2000 to 4000 platelets.
• Primary Hemostasis is the initial response of the body to vascular injury, starting when platelets come in contact with exposed collagen, microfilaments, and the basement membrane of endothelial tissue.
• The main players in Primary Hemostasis are Vasoconstriction, platelet adhesion, Platelet secretions of granules, Platelet aggregate, and Formation of temporary platelet count.
• Secondary Hemostasis describes the activation of a series of coagulation proteins in the plasma, mostly serine proteases, to form a fibrin clot.
• The goal of Secondary Hemostasis is the generation of sufficient thrombin to convert fibrinogen to fibrin clot.
• The main players in Secondary Hemostasis are Intrinsic, Extrinsic, and Common Coagulation factors.
• Fibrinolysis is the final event of hemostasis, a gradual digestion and removal of the fibrin clot as healing occurs.
• The end goal of hemostasis is a stable fibrin, which is recovered through fibrinolysis.
• Platelet granules activate coagulation factor and recruit platelets in the area of the injury.
• Anucleated biconvex blood cells with an average diameter of 2.5 cm correspond to an MPV of 8-10fl.
• Hypersplenism is a condition where 80-90% of the platelets are in the spleen leading to thrombocytopenia.
• Megakaryopoiesis is the process where the cells of the megakaryocytic lineage include actively proliferating progenitor cells and postmitotic (nonproliferating) megakaryocytes undergoing maturational development.
• Megakaryocytes are the largest BM cells/ hematopoietic cells, account for less than 0.5% of all BM cells, and possess multiple chromosome copies (polyploid).
• Fibrin is generated by secondary hemostasis by clotting proteins Zymogens.
• Activated platelets appear spherical and produce pseudopods.
• Internal structure of platelets is complex, grabular, and scarcely visible in Light Microscope.
• Newly released platelets are larger, more metabolically active, and more effective hemostatically.
• Normal platelet count range is 150 to 400 x 10^9/L.
• Distribution of platelets is 1/3 in blood and 2/3 in spleen.
• Reticulated platelets, also known as stress platelets, appear in compensation for thrombocytopenia and are markedly larger than ordinary mature circulating platelets, with a mean platelet volume (MPV) of 12 to 14 fL.
• Maturation time for megakaryocytes in BM is 5 days.
• Average platelet counts are slightly higher in women than in men and slightly lower in both sexes when over 65 years old.
• Circulating, resting platelets appear biconvex/discoid.
• Asplenic individuals have 100% of the platelets in the blood.
• Life span of platelets in the circulation is 8-11 days.
• Wright-stained blood film: circular to irregular, lavender, granular.
• Platelets arise from unique bone marrow cells called megakaryocytes.
• Normal Wright-stained BMA smear is 30 to 50 um in diameter with a multilobulated nucleus and abundant granular cytoplasm.
• Megakaryocyte precursors MK-I or megakaryoblast are the earliest morphologically identifiable platelet precursor cells, beginning to develop most of its cytoplasmic ultrastructure, including procoagulant-laden a-granules, dense granules (dense bodies), and the demarcation system (DMS).
• Others regulating megakaryocyte production include Kit-ligand, IL-3, IL-6, and IL-11.
• Thrombopoietin (TPO) is the primary regulator of megakaryocyte and platelet development, influencing all stages of megakaryocyte production from early progenitor cells to the release of mature platelets from the bone marrow.