Plasma Coagulation Factors PDF

72 3. Fibrinogen proteins a. Factors I, V , VIII , XIII b...

72 3. Fibrinogen proteins a. Factors I, V , VIII , XIII b. Consumed during clotting (therefore not in serum) c. ,t- in acute phase (pregnancy and Steps in Formation of inflammation) Platelet Plug Plasma Coagulation Factors FUNCTIONS 1. Substrate - Factor I (fibrinogen) Characteristics of Coagulation Proteins 2. Cofactors - accelerate enzymatic reactions a. Factors III, V and VIII FACTOR NAMES b. Factor HMWK (high molecular weight kininogen ) 1. Noted by Roman numerals 3. Enzymes 2. Exceptions: a. Serine protea ses - cleave peptide a. Prekallik:rein bonds (Factors II, VII, IX, X , XI b. High molecular weight kininogen and XII) STABILIZED CROSSLINKED FIBRIN b. Transamidase - XIII only 1. Turn it on CHARACTERISTICS OF COAGULATION PROTEINS a. Activated intrinsically by the collagen ( via Factor XII) contact Coagulation Groups system b. Activated extrinsically by disrupted GROUP CONTACT PROTHROMBIN FIBRINOGEN endothelial cell membrane ( tissue fa ctor or tissue thromboplasti.n) Factors XI, XII, PK, 11, VII, IX, X i, V, VIII, XIII complex with Factor VII to directly HMWK activate F actor X Vitamin K No Yes No 2. Cofactors Dependent a. Factor VIII is bound with a ctivated Consumed in No No (except for II) Yes F actor IX b y calcium to the platelet Clotting phospholipid membrane (PL) b. Together these factors activate Factor X (in the comJnon pathway 1. Contact proteins Factor Vis the cofactor to Factor a. Factors XII , XI, P K (prekallikrein) and HMWK (high molecular weight X a in a similar arrangement with calcium and PL) kininogen) c. This prothrombinase complex b. Participate in the initial phase of converts prothrombin to the active the intrinsic system thrombin c. NOT consumed during clotting (found in both serum and plasma) 3. Thrombin d. NOT Vitamin K dependent a. Cleaves peptides off of the fibrinogen molecule to form fibrin 2. Prothrombin proteins which polymerizes to form insoluble a. Factors II, VII, IX, X fibrin strands b. Vitamin K dependent b. Thrombin also activates Factor XIII c. NOT con sumed during clotting which crosslinks the fibrin strands (ex cept II) at the " D" region (birth of the D- d. Present in fresh and stored plasma dimer) and serum  73 Coagulation Cascade Intrinsic Extrinsic (APTT) (PT) Collagen Tissue Factor HMWK Kallikrein t ca++ X11t ----- Xlla VII xr- Xia ~ FIBRINOLYTIC SYSTEM 1. Turn it on Monitors IX ~ ~ / Monitors Oral a. Activated intrinsically by collagen Heparin Therapy C ++ a j Anticoagulants (Coumarin) via the Factor XII / contact pathway that initiates intrinsic clotting or extrinsically by tissue plasm.inogen activator ( TPA)........... _ ':_ft P_"°_'_P,;,f; ______ pcmm~ f iliw Y... b. Activators convert the precursor x--► Xa plasminogen to plasmin ca++ V 2. What does it do? ca++ a. Plasmin cleaves fibrin strands to Pit. Phospholipid soluble fragments of fibrin (fibrin Prothrombin ca++ Thrombin - I XIII ca++ degradation products are X, Y, D orE) b. Can come from fibrin clot (fibrinolysis) or from unclotted Fibrinogen - - - ~Fibrin - --- -- - --Xllla fibrinogen (fibrinogenolysis) ! Stabilized Cross/inked Fibrin c. D-dimer comes from crosslinked clot (clo t specific) 3. Turn it off Other functions of thrombin a. TPA inactivated by tissue plasminogen activator inhibitor Feeds back to "potentiate" factors (TPAI) - stops activation V and VII I b. Active plasmin inhihited by Alpha-2 Recruits and aggregates platelets Plasmin Inhibitor if it escapes the area of the clot. This prevents Turns on endothelial cell thrombomoduliA fibrinogenolysis (receptor/activator for Protein C and Protein S system) to inactivate Factors V and VIII Excessive and inappropriate fibrinolysis 4. Turn it off Major feature of disseminated intravascular a. Heparan sulfate on the endothelial coagulation {DIC); response to excessive cell binds antithrombin (AT) which clotting inactivates the activated serine proteases (heparin works this way, Also seen in liver disease (activators too!) are not cleared and the inhibitors are b. Activated Protein C and its cofactor diminished) Protein S ( when bound to its receptur/1:1(.:Livutur tl1rumhuL11udulin) Complications of cancer or surgery inactivates Factors VIII and V of the prostate or urinary tract where urokinase can leak into the circulation