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1

2 stages of hemostasis

1. primary hemostasis--platelet plug2. secondary hemostasis--proteolytic clotting cascade; fibrin clot/mature thrombus

2

platelet characteristics

anucleatemegakaryocyte precursorlife span 6-8 days

3

prostaglandin responsible for platelet aggregation/activation

thromboxane (TxA2)made from AA-->cox 1 pathway

4

platelet MOA after endothelial injury

1. adhere to exposed endothelial collagen via vWF2. activation which leads to granular release (TXA2, ADP) and conformational change exposing binding domains for fibrinogen3. recruitment4. aggregation

5

cascade model of coagulation INTRINSIC

XII converts XI activeXI with VIII, PL, Ca activate IXCOMMONIX activates X X with V, PL, Ca activate THROMBINthrombin converts fibrinogen to fibrinaPTT

6

cascade model of coagulation

TF +PL, Ca activate VIICOMMONVII activates XX with V, PL, Ca activate THROMBINthrombin converts fibrinogen to fibrinPT

7

clotting number of thrombin

II

8

theory behind cell based model of coagulation

1. TF is primary physiologic activator/initiator2. coagulation is localized to and controlled by cell surfacesinitiation, amplification, propagation

9

normal inhibitors of platelet reactivity

Prostacyclin (PGI2)NOectoadenosine diphosphatase

10

Three natural anticoagulant pathways

antithrombin IIIactivated protein CTF inhibitor

11

MOA of antithrombin III

AT III binds and inactivates factor 10 of the common pathwayalso neutralizes other clotting factors, antiinflammatoryactivity of AT III is increased with the presence of heparin

12

MOA of activated protein C

activated protein C inhibits VII, Vdecreases thrombin formationenhances fibrinolysis

13

MOA TF inhibitor

inhibits TF of extrinsic pathway

14

fibrinolysis

dissolution of fibrin clotmain proteolytic enzyme = plasminogen -->plasmindegrades fibrin to FDP, FSPother enzyme: tissue type and urokinase type plasminogen activators

15

how is fibrinolysis controlled

plasminogen activator inhibitorsalpha antiplasminthrombin activator fibrinolysis inhibitor

16

cause of pseudothrombocytopenia

falsely low due to platelet aggregation and mis countingreported in 71% of feline blood samples

17

estimate of average platelet count on blood smear

# platelets/HPF x 15,000

18

BMBT

buccal mucosal bleeding time--tests platelet fx/primary hemostasisN dog 1.7-4.2 minN cat 1.4-2.4 mininter/intraoperative variability up to 2 min

19

BMBT is prolonged with what diseases

thrombocytopeniathrombocytopathia (vWF disease)vasculopathy

20

what % of coagulation factors must be decr to have prolonged PT/aPTT

25-30% decreased prior to prolongation

21

vitamin K dependent coagulation factors

2, 7, 9, 107 has the shortest half life

22

what coagulation test to examine for bit K deficient animals

PT7 because of very short half life 4-6 hr

23

PT tests...

extrinsic + common pathwayTF, 7less sensitive to heparin affects than aPTT

24

aPTT tests...

intrinsic + common12, 11, 9

25

activated clotting times ACT

whole blood + diatomaceous earth (contact factor for XII)tests INTRINSIC and common pathN dog < 110 sN cat < 75 sless sensitive than aPTT

26

FDP/FSP

degradation products of fibrin/fibrinogenmarkers of fibrinolysisusually cleared via livercan lead to dysfx in platelets/inhibit coagulationMay be a marker DIC

27

D dimers

indicate activation of thrombin and plasminspecific for activation of coagulation and fibrinolysissensitive marker for DIC, thromboembolism with excellent negative predictive valueNOT specific

28

fibrinogen deficiency in relation to thrombin clot time

TCT is prolonged and clot formation decreased with 1. hypofibrinogenemia2. dysfibrinogenemia3. presence of factors inhibiting fibrin polymerization (heparin, FDPs)

29

list coagulation testing

platelet number and blood smear reviewPT/PTTBMBTACTFDPs/FSPsDDimersFibrinogenTEG

30

Thromboelastography

TEG evaluations clot initiation, formation, propagation to fibrinolysisstrength and stability of clotdynamics of its formation and breakdown