Coagulation Flashcards
Sonoclot ACT correlates with what on TEG
R time, K time, angle
CR on sonoclot correlates with what on TEG
all parameters
What does the Sonoclot do?
Measures changes in blood viscosity by detecting a change in mechanical impendance of a tubular, disposable, plastic probe oscillating vertically in a cuvette containing whole blood or plasma
How is platelet function determined on Sonoclot?
Not directly, calculated value based on both teh time it takes for the signature to peak, as well as degree of clot retraction
What 3 variables determined on Sonoclot
ACT, clot rate (CR), and platelet function (indirectly)
What does CR measure on Sonoclot?
rate of fibrin formation
Sonoclot correlated to several TEG parameters, platelet count, and fibrinogen, but not to other commonly used coagulation tests. T/F
T
MOA thrombomodulin
binds thrombin changing its substrate specificity and becomes an anticoagulant by activating protein C, with its cofactor, protein S, inactivates Va and VIIIa
thrombomodulin from endothelium
MOA TFPI
inhibits extrinsic pathway
TFPI from endothelium
What is the initiation stage of coagulation?
TF-VIIa makes a small amount of thrombin
What is the prothrombinase complex?
Va-Xa
What is the tenase complex?
VIIIa-IXa
Fxn: activates X to Xa which then binds with Va on platelet surface forming the prothrombinase complex to create thrombin burst
Antithrombin inhibits what factors?
2, 7, 9, 10, 11, 12
What dramatically increases AT activity?
heparan sulfate from endothelial cells (or heparin exogenously)
Effects of plasmin.
cleaves fibrin creating FDPs
inactivates 5, 8, 9, 11, cleaves complement C3, enhances conversion of 12 to 12a and conversion of prekallikrein to kallikrein
What are inhibitors of plasmin generation
a2-antiplasmin, a-2 macroglobulin
Heparin MOA
Facilitates AT-mediated inactivation of thrombin and factor Xa (also 7, 9, 11, 12)
Facilitates release of TFPI from endothelial cells
PS binds to heparin-binding domain of endothelial cell matrix protein, thrombospondin
Inhibits complement and hemolysis induced thrombin generation
How do you monitor heparin therapy?
anti-factor Xa (gold standard) or APTT (want 1.5-2.5 x normal)
What can affect APTT measurement with heparin therapy?
reagent used, high fibrinogen levels, antiphospholipid antibodies, increased circulating VIII, steroids, more low molecular weight multimers (can still have anti-factor Xa activity, but reduced ability to complex with thrombin, so APTT may appear subtherapeutic when it really is)
How do you monitor LMWH (enoxaparin, dalteparin)?
anti Xa only - b/c they are LMW do not complex to thrombin
What is the vWF platelet receptor?
Gb1b-IX-V
What’s the difference between platelet rich plasma and platelet concetrate?
PRP is made by a soft spin at 1000 x 4 min of FWB (200 mls). If you spin again (hard spin, 2000 x 10 min), get platelet concentrate (40-70 mls)
How many platelets are in PRP and PC?
> 100 x 10^9/L
Non immunologic complications of blood transfusion
pyrogen-mediated fever (most common), transmission of infectious agents, vomiting, mechanical hemolysis, CHF, hypothermia, citrate toxicity, pulmonary complications
Immunologic reactions to blood
acute and delayed hemolytic transfusion reactions manifesting as urticaria, anaphylaxis, graft vs host dz
Virchows triad
blood stasis, hypercoagulable state, endothelial damage
What coag factors increased in cushings?
5, 10, fibrinogen
What IL stimulates TF?
6 - predominantly
Where does heparan sulfate come from?
endothelial cells
When AT bound to heparan sulfate on endothelium, stimulates what factors regarding inflammation?
prostacyclin I2 and NF-kB
Negatively charged proteins on platelet surfaces when activated.
phosphatidylserine and phosphatidylethanolamine
What lives in Weibel Palade bodies
vWF, VIII, p-selectin, IL-8, TPA
What activates endothelial cells?
TNFa, bradykinin, thrombin, histamine, VEGF
What is the prothrombinase complex?
Va and Xa and prothrombin (II)
Feline platelet alpha granules have what that is special…
vWF (not in dog alpha granules)
What supports decrease in fibrinolysis?
decreased tPA, increased a2 antiplasmin, PAI-1, TAFI
What is MPC on Advia 120?
mean platelet component - granularity of platelets, activated platelets will have released their granules, so decreased MPC may indicate hypercoagulable state
G =
5000 x MA / (100-MA); higher = more hypercoagulable
Anticoagulant effects of aPC
inactivates Va and VIIIa
enhances fibrinolysis
Antiinflammatory effects of aPC
Inhibits apoptosis, decreases NF-kB, decreases inducible TF, decreases adhesion molecules
How does inflammation alter the protein C pathway?
Inhibits thrombomodulin and endothelial cell protein C receptor transcription resulting in a decreased ability to generated APC