Coagulation Testing and Anticoagulants Quiz

Hematology 2 Lecture Notes Summary

• Megakaryopoiesis: A process differentiating into megakaryocytes, leading to platelet production. Megakaryocytes are the largest cells in bone marrow, polyploid (multiple chromosome copies).
• Platelet Production: Megakaryocytes mature and produce 1000-2000 to 4000 platelets via proplatelet processes which pierce through endothelial cells.
• Megakaryocyte Progenitor Cells: Develop from a common myeloid progenitor and are influenced by transcription factors GATA-1 and MYB.
• Growth Factors and Cytokines: Several growth factors/cytokines, including thrombopoietin (TPO), megakaryocyte colony stimulating factor (Meg-CSF), and interleukins (IL-3, IL-11), are involved in megakaryopoiesis.
• Platelets: Small (2-4 µm), typically discoid cells with granules. Normal count: 150-400 x 10^9/L. Platelets are produced in the bone marrow and stored in the body (esp. the spleen), with 2/3 available and 1/3 sequestered.
• Platelet Ultrastructure: Organelles like alpha granules (storage), dense granules (storage), mitochondria and peroxisomes are fundamental components. Membrane systems SCCS and DTS also play an important role. Surrounding the zone is the peripheral zone, physical/chemical barrier between intra/extracellular environments.
• Hemostasis (Primary and Secondary): Primary hemostasis involves immediate vasoconstriction, activated platelet adhesion/aggregation to form the initial platelet plug, while secondary involves the activation of coagulation proteins (factors) to generate a stable fibrin clot.
• Coagulation factors are glycoproteins, majority from the liver. Other sites of production are monocytes, endothelial cells, and megakaryocytes. Factors are numbered with Roman numerals.
• Anticoagulants: The body has numerous anticoagulants that work in tandem to prevent excessive clotting. These proteins include but are not limited to; Prostacyclin, nitric oxide, tissue factor pathway inhibitor, thrombomodulin, heparin sulfate, and 13-HODE. These molecules regulate processes that include platelet aggregation, and vasoconstriction.
• Coagulation Mechanism & Inhibitors: Serine proteases including thrombin, and coagulation factors (II, VII, IX, X, XI, XII) participate in the coagulation cascade, while protein C, protein S, and antithrombin play key roles as inhibitors.
• Fibrinolysis (Tertiary Hemostasis): Involves the breakdown of clots. Enzymes such as tissue plasminogen activator (TPA) and urokinase plasminogen activator (UPA) activate plasminogen, while plasminogen inhibitor (PAI-1) inhibits this process.
• Hemostasis Testing: Various tests like bleeding time, clotting time, activated partial thromboplastin time (APTT), and prothrombin time (PT) assess the components and process of hemostasis.
• Qualitative Platelet Disorders: Disorders can be inherited (e.g., von Willebrand disease, Glanzmann thrombasthenia) or acquired (e.g., uremia, medications). A variety of testing methods exist to determine underlying causes.
• Quantitative Platelet Disorders : Quantitative disorders like thrombocytopenia or thrombocytosis are often related to dysfunction, or overproduction of platelets. There are a number of causative factors related to decreased or increased platelet production.
• Specimen Collection and Handling: Proper blood-to-anticoagulant ratios, storage temperature, and collection procedures are critical for valid hemostasis tests.
• Anticoagulants for hemostasis testing: Different anticoagulants (e.g., citrate, EDTA) have special applications for different types of analysis. Citrate is used for multiple tests, and EDTA is involved in platelet or complete blood counts.