Platelets Average platelet count- 150,000 TO 400,000 per cubic Rec enone mm Lifespan- 10 days Site of formation- bone marrow PHSC > CFU-S > CFU- megakaryocyte > megakaryoblast > promegakarycyte > megakaryocyte > platelets Primary regulator-_thrombopoietin (produced primarily in liver, kidney and bone marrow)AMLEX 00 @ © eal Morphology @© Oo a . + Minute discs 1-4um in diameter 2 oO nae nO + Anucleate + Cell membrane- rich in phospholipids, coated with a layer of glycoproteins + Present in the cytoplasm are the following:- Actin and myosin Thrombosthenin Tgp Remnants of endoplasmic reticulum and golel apparatus (storehouse of calcium) Mitochondria 2 Prostaglandins ZA Fin stabilizing factor CA Granules‘ALLEN Hemostasis RO + Hemostasis = prevention of blood loss + 3 steps Vasoconstriction um Damage to vessel wall > local myogenic contraction 1 Trauma to tissues and platelets > release of local autocoid factors (e.g., thromboxane A2 from damaged platelets) -> vasoconstriction = Trauma ~ pain > reflex vasospasm Formation of platelet plug © Formation of blood clotALLEM Platelet plug formation + Endothelial injury + Exposure + Adhesion, activation, aggregation eae eee + Adhesion- to collagen and von Willebrand factor + Activation- secretion of ADP and thromboxane A2; Gpllbilla receptor attaches strongly to fibrinogen and von Willebrand factor + Aggregation forms a platelet plugALLEN‘ALLEN Thrombocytopenia % P4A7R CRI coun eet ae endenentab eedironeneltentlesenctesn lanes » Punctata hemorthages (thrombocytopenic purpura)Blood coagulation G aio0on earl -nG Meese LeRupture of a vessel or damage to the blood -> formation of prothrombin activator Prothrombin Prothrombin cate activator ~— Thrombin Fibrinogen _t, Fibrinogen monomer a Cross-linked fibrin fibers ‘Thrombin — Activated fibrin-stabilizng factorClot retraction- role of platelets + Platelets trapped in a clot bind fibrin fibers + Platelets release procoagulant substances- fibrin stabilizing factor + Activation of platelet thrombosthenin, actin and Coe ee ew myosin cause clot contraction + Thrombin and calcium from mitochondria, golgi Re ree eo apparatus, endoplasmic reticulum of platelets accelerate clot retractionCoagulation factors £oolish people try climbing Jong slopes gfter Christmas some people have fallen Factor f: Fibrinogen Factor II: Prothrombin. Factor Ill: Tissue thromboplastin or Tissue factor Factor IV: Calcium Factor V: fabile factor, Proaccelerin JactorVirneccionn Factor VII 2 Stable factor, Proconvertin Factor VIII: Anti-hemophilic factor A Factor IX: Christmas factor, Anti-hemophilic factor 8 Factor X: Sart power factor, Autoprothrombin Ill Factor XI: Plasma Thromboplastin Antecedent or PTA Factor XII" Hageman factor, Glass or contact factor Factor XIII: Fibrin stabilizing factor or Fibrinase r ALLEWExtrinsic pathway @ Tissue trauma 2) vii vii) SAS activated x (xa) t cai ZV Cate 8) Prothrombi \ Sectwator ) Pateet a) phosphalbids | / Prothrombin —+ $+ rrombin cate ‘Mnemonic TENE 5 10-5-2-1 Intrinsic pathway- twelve, eleven, nine, eight (TENE) Extrinsic pathway- seven Common pathway 1Intrinsic pathway Intrinsic pathways slower! Usually requires 1 to 6 minutes for clot formation Fone nT TENE S “Intrinsic pathway- twelve, leven, nine, eight (TENE) Extrinsic pathway- seven Common pathway 10-5-2-1ao m 2 ALLEN INTAI NSIC EXTRINSIC - T Ika, Tae s E£ Na ne 9 i\e. at a 19 100 Sa at a aa ) lo Fipnin MONOMERALLEN Intravascular anticoagulants Smoothness of endothelial surface Layer of glyocalyx on the endothelium which repels clotting factors and platelets Thrombomodulin which binds thrombin hrombomodulin- thrombin complex activates protein C, which inactivates activated factor V and VIII Antithrombin action of fibrin and antithrombin-tIl Heparin © Produced by mast cells © Antithrombin-heparin complex removes thrombin, activated factors XII, XI, X, IX eeALLEN Role of plasmin in lysis of blood clots —S wa & ee aera . MpcWvator |. ee Junomen &meduler PAI-1 Cleave canes, | meine pe Ye Plasminogen ==> Plasmin. a,-antiplasmin Dogrades (Ghee nore ferme eet ee eee corel ebitecrodrg hope oes paste) teres Fibrin degradation fbn => —— products a F D)ALLEN Role of Vitamin K «GQplus 7 equals 9 not 107) itamin K Is an essential factor to carboxylase in the liver that adds carboxyl group to glutamic acid residues in © Prothrombin Factor VII ° © Factor IX o Factor X © Protein CPUL. A RMbouiem fi Dv7T = E&P rely 7HADMBISHL i AUT COA GUEAUES WARE HAIN Ants vil %- 7 71Rechy mMosKS XX eine, / EAS TAME re “ Ox Pag oY @% \ woe & HEME posh ralALLEN Anticoagulants for clinical use PT itech Heparin (including low Inactivates thrombin _Intravenous immediate molecular weight factorXa action heparin) pt Warfarin Inhibits vitamin Oral; takes 4-5 days for caine Teas complete reponse Direct thrombin Inhibt Intravenous and oral inhibitors (Hirudin) = ———— Factor Xa inhibitors Inhibits factor XAntiplatelets for clinical use EEE Usage Aspirin Inhibits platelet Oral- used in low doses aaa cyclooxygenase, “synthesis of thromboxane A2, platelet aggregation Dipyridamole “Tnhibit platelet ——— Oral a phosphodiesterase Ticlopidine Inhibits platelet Oral —"~~— aggregation; prevents Gp lib-Iila expressionAuLEW ~ fi Bleeding time by Duke’s method ——— + Patient is pricked with a special needle or lancet , preferably on the earlobe or fingertip, after having been swabbed with alcohol + Prick is about 3-4 mm deep oP. .en wipes the blood every 30 seconds with a filter paper e test ends when bleeding sto} + Usual bleeding time is about 2-6 minutes‘ALLER Bleeding time by Ivy method * Blood pressure cuff is used to maintain constant pressure within the capillaries to help standardize the procedure. + Cuff is inflated to 40 mm Hg on the upper arm to control capillary tone and to e ity and reproducibility. + Sterile, disposable blood lancet is used, and the length of time required for bleeding = to cease is recorded. » The greatest source of 40mm Ma variation in this test is largely due to difficulty in performing a standardized puncture, leading to erroneously low results.ALLE Clotting time by capillary glass tube method ——Clotting time by Lee & White method N:5-11 minALLEW Prothrombin time + Blood withdrawn from patient is immediatel + Excess calcium (to nullify effects of oxalate) and tissue factor (to activate prothrombin-to-thrombin reaction) mixed with oxalated blood Time taken for coagulation k/a prothrombin time + Normal PT- 12 secondsInternational normalized ratio (INR) + INR is the ratio of patient’s PT to PT ofa normal, control sample raised to the power of ISI (internatio + Normal range for INR in a healthy person is 0.9- 1.3 + Pateints undergoing warfarin therapy usually have an INR of 2.0- 3.0