Platelet Differentiation and Hemostasis
1. Platelet Differentiation
Thrombopoiesis Process:
Originates from myeloid stem cells in the bone marrow which differentiate into megakaryocytes.
Endomitosis: A process where DNA replicates without cytoplasmic division, creating large polyploid cells.
Fragmentation: Megakaryocyte cytoplasm breaks off into small, anucleated fragments called platelets (thrombocytes).
Regulation: Primarily controlled by Thromboxoeitin (TPO) produced in the liver and kidneys, alongside IL-6.
Platelet Characteristics:
No nucleus; average lifespan of approximately 10 days.
2. Components of Blood, Platelets, and Clotting Factors
Blood Composition:
Composed of plasma (liquid matrix) and formed elements (erythrocytes, leukocytes, and platelets).
Platelet Components:
Contain Alpha and Delta/Dense granules storage sites for mediators like calcium, ADP, and von Willebrand factor (vWF).
Clotting Factors:
Most are inactive enzyme precursors (zymogens) synthesized in the liver.
Designated by Roman numerals (e.g., Factor I is fibrinogen, Factor II is prothrombin).
3. Platelets' Role in Hemostasis and Clotting Pathways
Mechanisms of Hemostasis:
Vascular Spasm: Prompt vasoconstriction to reduce blood loss.
Primary Hemostasis (Platelet Plug):
Adhesion: Endothelial damage exposes collagen and vWF. Platelets bind to vWF via the GPIb receptor.
Activation: Platelets change shape and release ADP and Thromboxane A₂ (TxA_{2}).
Aggregation: Platelets link via fibrinogen bridges using the GPIIb/IIIa receptor.
Secondary Hemostasis (Coagulation Cascade):
Activation of clotting factors leads to the formation of a stable fibrin clot.
Clotting Pathways:
Extrinsic Pathway: Triggered by Tissue Factor (Factor III) following tissue trauma. Monitored by Prothrombin Time (PT).
Intrinsic Pathway: Triggered by collagen exposure or internal vessel damage. Involves Factors XII, XI, IX, and VIII. Monitored by Partial Thromboplastin Time (PTT).
Common Pathway: Convergence at Factor X. Factor Xa converts prothrombin (II) to thrombin (IIa), which then converts fibrinogen (I) to fibrin (Ia).
Regulation:
Antithrombin III (AT-III): Inactivates thrombin and other factors.
Proteins C and S: Degrade Factors Va and VIIIa to prevent excessive clotting.
4. Fibrinolysis and Its Significance
Process:
Conversion of inactive plasminogen to plasmin by tissue plasminogen activator (tPA).
Plasmin cleaves fibrin into soluble Fibrin Degradation Products (FDPs), such as D-dimer.
Significance:
Limits the size of the clot, restores blood flow after tissue repair, and prevents permanent vascular occlusion.
5. Common Bleeding and Clotting Disorders
Thrombocytopenia:
Etiology: Bone marrow failure, autoimmune destruction (ITP), or splenic sequestration.
Pathogenesis: Low platelet count (< 150,000/\mu L) leading to failure of the primary platelet plug.
Clinical Presentation: Petechiae, purpura, and mucosal bleeding (e.g., epistaxis).
Thrombocytosis:
Etiology: Myeloproliferative disorders or reactive states (inflammation/iron deficiency).
Pathogenesis: Elevated platelet count (> 450,000/\mu L) promoting arterial or venous thrombosis.
Clinical Presentation: Increased risk of DVT, stroke, or myocardial infarction; headaches.
Von Willebrand Disease (vWD):
Etiology: Inherited deficiency or defect in vWF.
Pathogenesis: Impaired platelet adhesion and reduced stabilization of Factor VIII.
Clinical Presentation: Easy bruising, heavy menses, and prolonged bleeding from minor cuts.
Hemophilia (A and B):
Etiology: X-linked recessive genetic deficiency. Hemophilia A (VIII) and Hemophilia B (IX).
Pathogenesis: Dysfunction in the intrinsic pathway preventing stable fibrin formation.
Clinical Presentation: Deep tissue bleeding and hemarthrosis (joint bleeding).
Liver Disease:
Etiology: Cirrhosis or severe hepatitis.
Pathogenesis: Decreased synthesis of clotting factors and TPO.
Clinical Presentation: Prolonged PT/PTT and high risk of life-threatening variceal bleeding.