Chapter 6 Flashcards
What are the initiators of haemostasis?
Tissue factor (FIII)
Extracellular matrix proteins (collagen)
What are the 3 stages of haemostasis and what do they involve?
Primary - platelet plug
Secondary - formation of fibrin
Tertiary - fibrinolysis
What are the main cells, facilitators and inhibitors of primary haemostasis?
Platelets
F - vWF, collagen, fibrinogen
I - ADPase, prostacyclin, NO
What are the main cells, facilitators and inhibitors (initiation and progression) of secondary haemostasis?
Initiation
Fibroblasts
F - tissue factor, FVII
I - tissue factor pathway inhibitor
Progression
Platelets
F - Thrombin, intrinsic and common pathway factors
I - Antithrombin, protein C, protein S
What are the main cells, facilitators and inhibitors of tertiary haemostasis?
Endothelial cells
F - plasminogen, tissue plasminogen activator
I - TAFI, antiplasmin, plasminogen activator inhibitor-1
Where is vWF produced/stored?
Endothelial cells, stored in Weibel-palade bodies
Explain primary haemostasis
BSAVA Clin Path pg 95
What are the tests of primary haemostasis?
Platelet count, BMBT, PFA
Explain secondary haemostasis
BSAVA Clin path pg 98
What are the 3 stages of secondary haemostasis?
What cells are responsible for each step?
Initiation (fibroblasts), amplification (platelets), propagation (platelets)
What activates the extrinsic pathway?
TF - binds FVII (requires Ca and PS)
What activates the intrinsic pathway?
Surface contact - activates FXII
What activates the common pathway?
Intrinsic tenase - FIXa-FVIIIa-PS-Ca
Extrinsic tenase - TF-VIIa-PS-Ca
What is the prothrombinase complex?
FXa-FVa-PS-Ca
What is FXIII? What activates it?
Cross links fibrin
Activated by thrombin
What are the vit K - dependent coagulation factors?
FII, VII, IX, X
Protein C+S
What is the ‘alternative’ pathway
TF-FVII complex of extrinsic pathway can activate FIX of intrinsic pathway
What are the roles of thrombin in coagulation?
Fibrin formation
Amplification - activates FXI and intrinsic pathway
Activates FXIII and cross linking of fibrin
Activates TAFI - prevents fibrinolysis
What are the anti-platelet medications and their mechanisms of action?
Aspirin/NSAIDs - inhibit COX - prevents thromboxane A2 production
Clopidogrel - ADP receptor antagonist
What are the major physiological inhibitors of secondary haemostasis?
AT and protein C (intrinsic and common)
TFPI (extrinsic)
What are antithrombins targets?
FXa and thrombin
What activates protein C?
Thrombin binding to thombomodulin
What is protein S role in coagulation?
Cofactor - supports protein C and TFPI
Where are AT, protein C, protein S and TFPI produced?
Liver
What are the pharmacological inhibitors of secondary haemostasis and how do they act?
Heparin - potentiates AT activity
Warfarin - inhibits vitK recycling
Describe fibrinolysis
BSAVA Clin Path pg 100
Where is plasminogen produced?
Liver
What is the most potent activator of TPA and where is it produced?
FXIIa/kallikrein complex - weak plasminogen activators
- cleaves HMW kinogen => bradykinin
What is the main physiological inhibitor of fibrinolysis?
Thrombin-activated fibrinolytic inhibitor (TAFI)
Plasminogen activator inhibitor-1
Antiplasmin
What changes are seen on a CBC during active thrombopoeisis?
^ MPV
What factors can cause an elevated MPV?
Storage (particularly at 4oC)
Clumping
Can be normal in cats
Inherited - CKCS, Norfolk Terrier, Cairn Terrier
BM neoplasia
How if vWF:Ag interpreted?
> 70% - vWD unlikely
50-70% - vWD possible, bleeding unlikely
<50% - vWD likely
<35% - vWD likely, bleeding likely
What are the normal BMBT ranges?
D - 1.7-3.3 mins (4.2 minutes if sedated or GA)
C - <3.3 mins
What can lead to elevated BMBT?
Thrombocytopenia (inherited or acquired - aspirin/azotaemia), vWD, thrombopathia
What can lead to an elevated closure time on a PFA-100?
Thrombocytopenia (weak correlation with plt count)
Drug - associated thrombopathia (not reliable)
vWD - severe only
Thrombopathia
What factors can interfere with PFA-100 results?
Low hct - prolong
High hct - shorten
Citrate concentration
What is assessed by the ACT?
How does it work?
What causes it to be elevated?
Intrinsic and common pathways
Contact with negatively charged surface activates FXII
Rodenticide, DIC, inherited defects (haemophilia A/B), severe thrombocytopenia (mild)
What is assessed by the PT?
How does it work?
What causes it to be elevated?
Extrinsic and common pathways
Exogenous TF
Rodenticide, heparin, DIC, (angiostrongylus), liver failure, hypofibrinogenaemia (DIC/liver failure)
Activation of clotting during sampling
What is assessed by the aPTT?
How does it work?
What causes it to be elevated?
Intrinsic and common pathways
Contact activators
Rodenticide, heparin, DIC, (angiostrongylus), liver failure, hypofibrinogenaemia (DIC/liver failure)
Activation of clotting during sampling
What is assessed by the TCT?
How does it work?
What causes it to be elevated?
Fibrinogen => Fibrin
Thrombin
Hypofibrinogenaemia/afibrinogenaemia - DIC, liver failure
Dysfibrinogenaemia - reported with liver disease
Heparin
Elevated FDPs, monoclonal gammopathy
Which test becomes abnormal first in rodenticide toxicity?
PT
What can lead to reduced AT levels?
Liver failure
DIC
PLE/PLN
Inflammation (negative APP)
L-asparaginase
Heparin
What is the action of protein C?
Inhibits the intrinsic tenase complex
What can lead to low protein C?
Liver disease (failure, EHBO, PSS)
DIC
Vit K deficiency
Inflammation
How is D-dimer interpreted?
Produced by cross-linked fibrin
Elevated levels = increased thrombin = hyper coagulability
What can lead to increased D-dimer?
Pathological
- internal haemorrhage
- hepatopathies, EHBDO
- many diseases
- DIC, thrombosis, hyper coagulability
Physiological
- post surgery
False
- haemolysis
Draw a normal TEG trace with parameters measured included
BSAVA Clin Path pg 111
Should include R time, K time, Alpha angle, MA, LY30, LY60
What changes would be seen on a hypocoagulable TEG trace?
^ R, K
v alpha, MA
What changes would be seen on a hypercoagulable TEG trace?
v R, K
^ alpha, MA
What changes would be seen on a hyperfibrinolytic TEG trace?
^ LY30/60
What can interfere with TEG?
Time to analysis
HCT - low = hypercoagulable, high = hypo
High blood viscosity = hypercoagulable
What drives platelet production?
Thrombopoietin
Produced in liver, kidney and BM
What are the possible causes of thrombocytosis?
Drugs - adrenaline/vinc/steroids
Reactive - inflammatory cytokines (IL-1/6/11)
Iron deficiency
Megakaryocytic neoplasia
What are the features of type I vWD?
Which breeds are predisposed?
Decreased quantity, normal structure
Dobermans, Manchester Terriers, Airedales, Rottweilers
What are the features of type II vWD?
Which breeds are predisposed?
Decreased quantity, abnormal structure
Pointers
What are the features of type III vWD?
Which breeds are predisposed?
Absolute vWF deficiency
Scottish Terriers, Shetland Sheepdogs, Chesapeake Bay Retrievers, Dutch Kooiker Dogs
What is the most common inherited disorder of secondary haemostasis in dogs and cats?
D - Haemophilia A
C - Hageman trait (FXII)
Which factors are deficient in Haemophilia A and B?
A - VIII
B - IX
What coagulation testing abnormalities are seen with Haemophilia A and B?
Prolonged aPTT
How do rodenticide anticoagulants work?
Inhibit vitamin K epoxide reductase
Prevents recycling of Vit K - vit K epoxide accumulates => relative vit K deficiency
What coagulation tests are abnormal with rodenticide anticoagulants?
PT - increases first
aPTT and ACT also elevated
What confirmatory tests are available for rodenticide anticoagulant toxicity?
Toxicology
Vit K epoxide:it K ratio
What is the mechanism of vitamin K deficiency in liver disease?
Vit K fat soluble - bile needed tor absorption, absent in cholestatic liver disease
What is the abnormality in Scott syndrome?
How is it diagnosed?
How is it treated?
Inability to exteriorise PS
Flow cytometry for surface PS
Transfusion therapy
