Hematology: Platelet Function and Hemostasis

Coagulation and Hemostasis - Introduction

• Hemostasis is the process of maintaining blood as a fluid within blood vessels under normal conditions and preventing excessive blood loss upon injury.
• Hemostasis maintains a balance between procoagulant (clotting) and anticoagulant (anti-clotting) factors.
• Blood flows through a closed circulatory system.
• The hemostatic system activates when needed.
• Blood coagulation is a mechanism that transforms plasma (fluid) into a gel by converting the soluble protein fibrinogen into the insoluble form, fibrin.

Three Major Compartments

• Hemostasis requires the interaction of three major compartments: vascular integrity, platelets, and plasma (coagulation and fibrinolytic systems).
• Vascular integrity is important for maintaining blood fluidity.
• Platelets are inactive (in resting state).
• Plasma compartments include coagulation and fibrinolytic systems for normal clotting (and breakdown of clots).

Four Overlapping Processes/Stages

• Hemostasis includes four overlapping processes: vasoconstriction, primary hemostasis, secondary hemostasis, and fibrinolysis.
• Vasoconstriction is an immediate response to injury, narrowing the blood vessel to minimize blood loss.
• Primary hemostasis involves platelet activation and aggregation to form a temporary (primary hemostatic) plug to stop bleeding.
• Secondary hemostasis is the coagulation cascade, where coagulation factors interact to form a stable fibrin-platelet plug.
• Fibrinolysis is the breakdown of the clot (fibrin) to restore blood fluidity after the wound is healed.

Blood Vessels Structure Summary

• Blood vessels consist of three layers: tunica adventitia (outer layer), tunica media (middle layer), and tunica intima (inner layer).
• The adventitia provides structural support and shape.
• The media consists of elastic and muscular tissue to regulate blood vessel diameter.
• The intima contains endothelial cells, providing a pathway for blood movement.

Blood Vessel Characteristics

• Normal healthy blood vessels have an antithrombotic endothelial lining.
• The endothelial cell surface is negatively charged, repelling circulating proteins and platelets.
• Blood vessels produce and secrete substances that inhibit platelet activation (PGI2, NO, ADPase) and coagulation (heparin sulfate, thrombomodulin, TFPI).
• Blood vessels also have fibrinolytic properties (t-PA) to break down clots.

Platelets: Summary

• Platelets are small cell fragments, not true cells.
• They are produced by megakaryocytes in the bone marrow.
• Platelets circulate in the blood for 7-10 days.
• Platelets are removed by the spleen and liver.

Platelet Production Regulation

• Interleukin-3 (IL-3), IL-6, IL-11, and stem cell factor (SCF) influence megakaryocyte development.
• Thrombopoietin (TPO) is the major regulator of platelet production, acting on various stages.
• TPO is produced primarily in the liver, with some production in the spleen and kidneys.

Platelet Function - Summary

• Platelets play a critical role in hemostasis, involving adhesion, activation, granule secretion, and aggregation.
• Adhesion to exposed collagen initiates platelet activation.
• Platelets then change shape and release granules, creating a plug (and promoting healing).

Platelet Activation Summary

• Platelet activation is a cascade of events initiated by exposure to collagen.
• Changes include metabolic changes in biochemistry, morphological changes to shape & surface receptors, and granule release.

Platelets - Secretion Summary

• Platelets release various substances (like ADP, serotonin, TXA2, PF4) after activation.
• These substances promote platelet aggregation and further activation.
• Secretions may also aid in wound healing, like PDGF and other growth factors.

Platelets Aggregation Summary

• Platelets aggregate, sticking to each other, with fibrinogen as the bridge.
• This aggregation forms a stable plug to prevent further blood loss.
• Calcium is required for platelet aggregation.

Platelet Biochemistry Summary

• Platelet activation involves signaling cascades that depend on calcium and other factors.
• The arachidonic acid pathway is important, producing various regulatory substances.
• Specific enzymes are involved in the regulation of these pathways for a physiological response.

Meta Megakaryocyte

• The megakaryocyte nucleus remains after platelets are released.
• The nucleus is phagocytosed by macrophages.
• The nucleus is broken down in the process.

Demarcation Membrane System (DMS) Summary

• The DMS is an internal membrane system that forms in megakaryocytes, subdividing the entire cytoplasm.
• Platelets are released by fragmentation.
• Groups of platelets surround DMS creating Proplatelets.
• Proplatelets then break up into individual platelets and travel to the bloodstream.

Platelets Structure Summary

• Platelets have a characteristic shape, are anucleate, and have a specific internal structure essential for their function.
• Four zones are important: peripheral zone, structural zone, organelle zone, and membrane systems.
• The glycocalyx is the outer coat, containing glycolipids, glycoproteins, and mucopolysaccharides. It helps regulate platelet-platelet interactions, and how platelets interact with vessels.

Test your knowledge on the processes involved in hemostasis, particularly focusing on platelet function and formation of a platelet plug. This quiz covers critical concepts such as primary hemostasis, fibrinolysis, and the role of megakaryocytes. Perfect for students of hematology or those interested in blood health.