Hemostasis Flashcards
Factor I
Fibrinogen
Factor II
Prothrombin
Factor III
Thromboplastin
Factor IV
Calcium
Factor V
Proccelerin
Factor VII
Proconvertin
Factor VIII
Antihemophilic factor
Factor IX
Christmas factor
Factor X
Stuart-Prower factor
Factor XI
Plasma thromboplastic antecedent (PTA)
Factor XII
Hageman factor
Factor XIII
Fibrin stabilizing factor
Fibrinolysis Fragments
D fragements double bond with each other, E single bonds
DD/E
DxD/DD
DY/YD
Primary Hemostasis
Involves the function of blood vessels and platelets in blood clot formation
Platelets
80% are in circulation, 20% are in the spleen
4-5 days to mature, 9-12 days in circulation
Activated by thrombin, PTA, lysophosphatidic acid, thromboxane A2, ADP, and serotonin
Peripheral Zone
Membrane: negatively charged phospholipids, GPIb bind vWF, GPIIIb/IIIa bind fibrinogen
Glycocalyx: gives a negative charge to platelets, provides a thick layer of glycoproteins/glycolipids/mucopolysaccharides where coagulation factors can bind (I, II, VII, vWF, IX, X)
Structural Zone
Microfilaments
Microtubules (actin and myosin)
Membrane Zone
Open canalicular system: channels leading from plt surface to interior, release granule content
Dense tubular system: smooth ER from megakaryocyte, acts as store of Ca2+
Organelle Zone
Mitochondria: 50% of ATP from respiration, glycolysis
Glycogen
Storage granules
Dense Granules
ADP, ATP, Ca2+, Serotonin
Alpha Granules
Hemostatic proteins (I, V, XI, XIII, vWF, plasminogen)
Protease Inhibitors
AAT, alpha 2macroglobulin, C1 esterase inhibitor, alpha2 antiplamin
Platelet Specific Proteins
PF4, B thromboglobulin, PDGF, thrombospondin
Platelet Adhesion vs Aggregation
Adhesion: plts adhere to exposed collagen/vWF through GPIb receptor, causes shape change, Ca2+ released from DTS
Aggregation: attachment of plts to each other, ATP dependent process, fibrinogen binds to the GPIIb/IIIa receptor
Granules Release
1st group: dense granules
2nd group: 1 release (alpha), 2 release (dense and lysosomes)
Secondary Hemostasis
Involves the coagulation cascade which forms a fibrin mesh around the platelet plug
Extrinsic Pathway
Activated by tissue damage/factor and trauma
Shorter pathway
Measured by PT
Vessel injury - TF and VII - TF and Ca++ and VIIa (Xase complex)
Intrinsic Pathway
Activated by negatively charged surface
Measures by PTT
Roles in fibrinolysis, inflammation, and complement activation
Contact - XII and XIIa - XI and XIa - Ca++ - IX - IXa and VIIIa and PL and Ca++ (Xase)
Factor VIII and vWF
Factor VIII: produced by liver, circulated bound to vWF to prevent degrading, activated by thrombin which releases it from vWF, binds to platelet phospholipid surface
vWF: made by endothelial cells, large glycoprotein cut by ADAMTS13, links platelets to collagen via the GPIb receptor
Xase
Extrinsic: TF, VIIa, X, IX (intrinsic IX to IXa, prothrombinase X to Xa)
Intrinsic: VIIIaH, VIIIaL, X, IXa (prothrombinase X to Xa)
Prothrombinase: VaH, VaL, II, Xa (protein case II to IIa)
Protein case: Tm, IIa, PC (PC to APC)
Common Pathway
Converts fibrinogen (factor I) into fibrin Also converts prothrombin (factor II) into thrombin X - Xa - Xa and Va and PL and Ca++ - Prothrombin to thrombin - XIII to XIIIa - Fibrin to cross-linked fibrin
Fibrinolysis
Degrades fibrin to keep vessels clear to carry blood
Inhibitors: a2-antiplasmin, TAFI, PAI1, PAI2, a2-macroglobulin
Plasminogen activators: tPA, urokinase, streptokinase, XII/HMWK/PK
Plasminogen is a zymogen and acute phase reactant protein
Called plasmin when it activates and degrades fibrin polymers
Intrinsic, Extrinsic, and Exogenous Pathway
Intrinsic: XII (contact HMWK) XIIA – Prekallikrain to Kallikrein
Extrinsic: tPA and urokinase
Exogenous: Plasminogen (streptokinase) plasmin – Fibrin to fibrin degradation products
Fibrin Digestion by Plasmin
X fragment: DED
Y fragment: DE
Plasmin can’t break crosslinked Ds (how we test for clots)
All act as competitive inhibitors of plasmin
Physiological Inhibition of Coagulation
Protein C system, TF pathway inhibitor, antithrombin
Protein C System
Protein C and S are vitamin K dependent
Protein C is activated by thrombin-thrombomodulin complex
Protein C-S complex degrades factors Va and VIIIa
Tissue Factor Pathway Inhibitor
Function enhanced by Protein S
Only inhibits extrinsic pathway after factor Xa has been made
Antithrombin
Can inhibit thrombin and any other serine proteases
IXa, Xa, XIa, XIIa, kallikrein, and plasmin