Coagulation Phys Flashcards
What is the difference between the cell based model and the traditional model?
Traditional: two pathways operate semi-independent distinct, redunt interactions between factors and cells are limited
Cell based model: Plasma does not clot therefore cells invovled
What is the extrinsic pathway of coagulation
Tissue Damage —> Tissue factor + Ca –> FVIIa with Ca + Phospholipid –> FXa
What is the intrinsic pathway of coagulation
Damaged vessel –> FXII —> FXI + Ca —-> FIX w/ FVIII + Ca + plt phospholipid —> FX
What are the Vitamin K factors and why is one more likely decreased?
Thrombin (II), FVII, IX, X
FVII shortest 1/2 life 4-6 hrs
What Coagulation factors are tested in PT
Extrinsic and common pathway
Added to TF, phospholipid, and Ca
What coagulation factors are tested in PTT
Intrinsic and common
Added to contact activator and phospholipid and Ca
In the cell based model of coagulation what is the initiation phase:
‘Spark’ Tissue factor exposed to endothelium to circulating FVII forms complex with Ca
Extrinsic factor tenase complex activates FXa w/ FV get thrombin formation
Tissue factor inhibitor inhibits Extrinsic factor tenase complex
In the cell based model of coagulation what is the amplification phase
Thrombin burst: Activation and aggregation of platelets
Thrombin activates FVIII which binds with FIX to make intrinsic factor tenase complex—> FX with Ca
50-100 times more thrombin
In the cell based model of coagulation what is the propagation phase
Dependent on platelets: Leads to fibrin deposition
What are the procoagulation effects of thrombin
FV, Fibrin, FXI, FXIII, TAFI
What are the anticoagulation effects of thrombin
Plasmin, Protien C (by binding with thrombomodulin)
How does uremeic thrombocytopathy affect coagulation
Increased thrombosis, increased fibrin activation of P-selectin, abnormal release of microparticles
What is the pathway of fibrinolysis
tPA (tissue plasminogen activator) Released from vascular endothelial cells binds and activates plasminogen to plasmin
Plasmin molecules bineds to lysine residues on fibrin
What is the difference in FDPs and D-dimers
FDPs- are fibrin and cross-linked fibrin
D-Dimers- only cross-linked
What are the regulators of fibrinolysis
Plasminogen activator inhibitor-1 (PAI-1)
Alpha 2 Antiplasmin
Thrombin-activated Fibrionlysis inhibitor (TAFI)
What does Plasminogen activator inhibitor 1 do
inhibits tPA and uPa
What does alpha 2 antiplasmin do
Forms complex with plasmin
Prevents plasminogen into active clot
What does Thrombin-activated fibrinolysis inhibitor do
Down regulates fibrinolysis prevents palsmin from binding fibrin
What is the difference between primary and secondary hyperfibrinolysis
Primary: quantitative /qualitative abnormalities in regulation of fibrionlysis
Secondary: hyperactivity of normal fibrinolysis due to other coagulation abnormaliteies
What is the difference in TEG versus Rotem
TEG: Cup moves around stationary pin
ROTEM: Pin moves around stationary cup
What is the treatment for low fibrin
cyroprecipitate
How is hyperfibrinolysis develop with cavitary effusions
Anticoagulant environment, mesothelial cells secrete tPA and uPA, increase local expression of Protien C
Systemic due to reabsorption of hyperfib fluid via thoracic duct
How does hyperfibrinolysis develop with hepatic failure?
decreased hepatic production of alpha 2 atniplasmin
decreased clearance of plasminogen activators and plasmin
What is the MOA of EACA and TXA
Lysine analogues competitively bind c-terminal lysine sties on plasminogen
Plasmin formation is inhibited
What are platelets, how long til mature
anucleate cytoplasmic fagments from megakaryocytes
Mature in 3-5 days, life span 5-7 days
What are 4 key features of platelets for coagulation
Phospholipd membraned with high density regulated adhesive receptors
Cytoskeleton with contractile proteins
dense tubular system equest/release Ca
Secretory granules
What are the types of platelet secretory granules and what is included
Alpha granules: fibrinogen, P-selectin, Factor V, FXI, growth factors, VWF
Dense granules: released for mass platelet attraction
ADP, Epiniphrine, serotonion, histamine, calcium
How does platelet adhesion occur
Subendothelial collagen exposed with vascular injury
GPV1 or GP1b-IX-V receptor w/ VWF
alpha 2b Beta 2 (GP2B3A) intrigren with VWF
Where is VWF produced and stored
Produced by endothelial or megakaryocytes
Stored in weibel-palade bodies
Also prevents degredation of FVII
Which VWF has the higher affinitiy for platelets
Larger
What occurs in activation to lead to increased platelet binding
Adhesion triggers intracellular signaling to
alpha 2bB3 to high affinity for further adhesioin
membrane flipping exposing phosphaltidylserine creating a neg charge (scrambalase)
Contractile protein change shape to incrase surface area
Dense granules
TXA2 Potent platelet agonist stimulated by AA and Cox
What occurs in platelet aggregation
Adhesion of activated platelets to each other using receptor bound fibrinogen
What are the normal inhibitory mechanism of platelet activation and aggregation
Endothelial cells relase ADPase, prostacyclins: inhibit platelet activation
Negatively charged glycocosaminoglycans release nitric oxide to inhibit aggregation
What are the three types of VW disease
1: low multimers of all sizes
2: variable concentrations, absence of large size
3: marked reduction/absence of all sizes
What are three tests of platelet function
PFA-200: adhesion under shear stress Light transmission aggegometry Electrical impedance (muultiplate):
What is the MOA of coagulapothay with rattle snake envenomation
Local: Metalloprotienases damage extracellular matrix proteins mostly collagen
Phospholipase A2, protein C, antithrombin, and FV denaturation
Leads to decreased platelets, consumptive coagulatoapthy
What is the MOA of uremic bleeding
Primary hemostasis
Platelet secretion defects abnormal vessel wall interaction
Increase platelet inhibitors, uremic toxins
How does anemia result in hypercoagulable viscoelastic testing
Increase of clotting factors per volume of RBCs
What is the MOA of Rivaroxabain
Directly inhibits factors Xa
Renal and biliary excretion
What is the MOA of Warfarin
Vitamin K antagonist
FII, VII, IX, X
What is the MOA of unfractionanted heparin
Increase activity of antithrombin 3
Inhibit Xa and IIa (thrombinogen)
Inhibits thrombin formation
What is the MOA of LMWH
Binds AT3, Higher impact on Xa vs. IIa
What is the MOA of daltparin
Binds AT3, Higher impact on Xa vs. IIa
What is the MOA of Enoxaparin
Binds AT3, Higher impact on Xa vs. IIa
What is the MOA of protamine
Postive cationic that forms a salt with heparin
What is the MOA of clopidogrel
ADP irreversible P2Y12 inhibitor
Platelet activation inhibitior
What is the MOA of Aspirin
Irreversible inhibition of TXA2 formation
Inhibits platelet activation
What is the MOA of NSAID in coagulation
Reversible inhibition of TXA 2 Formation inhibits platelet activation
What is the proposed MOA of Yunnan biayo
enhanced expression of surface glycoprotiens on platelets under condition of stimulation
What are the eitologies of aortic thrombosis in dogs
Disregulation mechanisms– Increase generation of prothombotic elements
Inhibition of anticoagulation mechanisms
Inhbition of thrombolysis via fibrinolytic system
What is virchawos triad in aortic thrombosis in dogs
alterations in flow
endothelial damage
Hypercoagulable states
Name 10 underlying disease process that have been reported with ATE
PLN, PLE, HypoT4, Hypo adrenal, hyperadrenal, Immune mediated disease, DM, neoplasia, steroid administration, endocardiosis, PDA endocarditis, Spiroceria
What is the difference between arterial and venous clots
Arterial: high shear, VWF, Platelet rich, Tx with platelet inhibitors
Venous: low shear, fibrinogen, RBCs, WBCs, Fibrin, anticogulants
How does PLN lead to ATE in dogs
Loss of antithrombin 3 in kidneys
How does TRALI occur after blood transfusion
antibiodies in donor plasma agains antigens present in reciepnt leukocytes (why leukoreduction might not help)
What are 7 factors that make IMHA patients hypercoagulable
excessive platelet activation
TF expression of microparticles
Sequestation of nitric oxide
Cytokine induce endothelial TF expression
Monocyte activation of TF expession
TF expressing microparticles derived from monocytes bind to endothelium
Phosphatidylserine exposing particles released from platelets
How does oxidative hemolysis lead to anemia
denaturation of hemoglobin leads to heinz body formation
Methehemoglobinemia
Felines more susceptible due to sulfhydroxyl groups
How does Zinc lead to anemia
Intravascular hemolysis
Pennies after 1982, bolts, screws, skin products
How does endogenous heparin sulfate work and where is it found
On glycocalyx. Works with antithrombin to inhibit II and X
What are eicosanoids
Signaling molecules generated following release of arachadonic acid from phospholipid bilayers of cells especially platelets and immune cells
What are the canine dog blood types
DEA 1.1, 1.2, 1.3, 3, 4, 5, 7
Dahl
Which blood type is most common and which is most immunogenic in dogs
1.1 most immunogenic
Alloantibiotied against 7 highest
What is leukoreduction
Filter the blood to remove WBCs (platelets) prior to storage
What is cryopriciptate
Contains FVIII, VWF, Fibrinogen, and FXIII
What disease processes if cryopreciptate used for and what is it better than FFP for
VWD and hemophillia
More effective at increasing BMBT in VWD
Define Massive transfusion- at least three
1 blood volume in 24 hrs
50% of blood volume in 3 hrs
150% of blood volume regardless of time
1.5 ml/kg/min of blood products for 20 minutes
What shock index in dogs is likely to result in transfusion after blunt trauma
SI > 1.43
71% resulted in transfusions
Define the blood vicious cycle of ATC
bleeding –> resuscitation –> dilutional and hypothermia –> coagulopathy —> bleeding
What are complications of massive transfusions
Transfusion reactions
Hypocalcemia (citrate from blood or failure of liver to break down citrate)
Hypomagnesemia
HyperK (increase K in RBC supernate
Hypothermia
metabolic alkalosis— citrate broken down to bicarb
Metabolic acidosis— units have low pH
Name immunologic transfusion reactions state if delayed or acute
Hemolytic -acute
Fever- acute
Uticareia - acute
Transfusion realted immunomodulation (TRIM) - delayed
Name acute non immunologic transfusion reactions (9)
TACO Vomiting ARDS Infectious disease citrate toxicity TRALI Dilutional thrombocytopenia embolism Hemosiderosis (iron overloade
In hemolytic transfusion reactions what is the mechanism
Type II hypersenstivity
Steroids/antihistamines won’t prevent
In febrile non hemolytic reactions what is the mechanism
cytokines and WBCs in donor unit
Steroids and antihistamines won’t prevent
