Secondary Haemostasis Flashcards
Difference in cell based model compared to traditional coag cascade
Takes into account tissue factor and platelet involvement as well as interactions of the extrinsic and intrinsic coagulation pathways
Steps of secondary haemostasis
- Initiation - TF activates extrinsic path generating low amounts of thrombin and activatic F9 on platelet surface
- Amplification - Thrombin activates F11 on platelet surface which combined with F9 activation starts the intrinsic cascade generating larger amounts of Thrombin
- Propagation - cofactor 8 amplify the extrinsic activation of Factor 10; and cofactor 5 amplifies conversion of prothrombin to thrombin. Both released from platelet alkpha granules. Formation of prothrombinase complex.
Activation of TAFI fibrinolysis inhibitor - Fibrin Formation - generated by thrombin/prothrombinase complex converting fibrinogen to fibirin which binds to plt surface GP IIb/IIIa R and crosslinks
Physiological inhibitors of secondary haemostasis
TF Pathway inhibitor - inhibits extrinsic pathway activation. enhanced by heparin
Protein C - vit K dependent protein from liver in circulation. Inhibits cofactors 8 and 5 thus reducing thrombin generation. Enhanced by thrombin and endothelial cell factors
Protein S - in circulation, enhances protein C activity
Antithrombin - also produced in liver, is in circulation. Enhanced activity by heparins released from damaged endothelial cells.
Plasmin - inactivates cofactor 13 which crosslinks Fibrin
What is Hageman factor deficiency
Factor 12 deficiency
Common in cats but does not result in clinical bleeding as intrinsic cascade is not reliant on F12 and will proceed without it - however in vitro this is what is activated to assess intrinsic path so APTT is prolonged.
Steps of Fibrinolysis and fibrinolysis inhibitors
Plasminogen from liver binds to activated platelet surface
Converted to plasmin by tPA, urokinase from damaged endothelium and F11/12
Promoted by Fibrin
Plasmin cleaves cross-linked fibrin generating fibrin degradation products
tPA and urokinase are inhibited by PAIs from platelet granules
Plasmin is inhibited by TAFI, macroglobulins and antiplasmin
Fibrinolysis is inhibited by presence of DNA/RBC in fibrin clot or polyphosphate dense fibrin
What are alpha-macroglobulins
they are non-specific protease inhibitors produced by the liver and in circulation. They can inhibit coagulation factor activity as well as plasmin mediated fibrinolysis
What does prothrombin time measure
EXTRINSIC path - FVII
and common path
Needs >30% reduction in one or more of the evaluated factors
What does activated partial thromboplastin time (APTT) measure
INTRINSIC path - activation of F12 but subsequent activation of F11 and F9. and common path.
(similar mechanism for ACT test but more sensitive for deficiency)
Prolonged with Hagemann F12 deficiency in cats.
Requires >30% reduction in any of the factors in this path
What are common causes of APTT prolongation
Haemophilia A - F8 deficiency
Haemophilia B - F9 deficiency
Haemophilia C - F11 deficiency
Hageman factor deficiency
Also prolonged from heparin tx, DIC (and liver disease but not without PT prolongation)
Prolonged by underfilling of tubes or by prolonged storage of sample
If PT normal then common path is not affected
What causes PT prolongation
Factor 7 deficiency from liver disease or vit K antagonists, inherited deficiency, warfarin tx or DIC.
May be prolonged if underfilled tubes
Not affected by thrombocytopenia
Can also be prolonged by low fibrinogen - interpret in light of APTT (if latter normal then common pathway defect is unlikely)
When are specific factor levels measured
For diagnosis of Haemophilia A/B/C which all cause prolonged APTT with normal PT
Factor deficiencies of <30% normal are associated with clinical bleeding
What are tests for fibrinolysis
Fibrin levels - can be quantitative or qualitative. Can be helpful in identification of dysfibrinogenemia. Tru deficiency causes prolongation of PT, APTT and TCT
Thrombin Clot time - direct measure of fibrinogen conversion to fibrin
FDPs - not specific for clot lysis just plasmin activity (so b/d of any fibrin in blood).
Ddimers - specific FDP that comes only from clot lysis. Increase is much greater in DIC but also seen in other inflammatory or systemic diseases. Though increase is not always present
TEG - not perfect for measurement, can improve sensitivity by adding tPA so that fibrinolysis starts before clot dries out (fibrinolysis inhibitors in blood may prevent lysis occurring in vitro)
What does PIVKA measure
Non-activated Vit K dependent clotting factors.
Increase in Vit K deficiency or antagonism
What is viscoelastic testing or TEG
Thromboelastography - Test performed on whole blood that measures time to clot formation, strength of clot and time to fibrinolysis
Provides a closer representation of invivo haemostasis cell based model.
Platelet # and function are major determinants of overall function.
TEG and ROTEM are available for use in vet med but limited.
TEG there is rotation of the cup to detect torque, ROTEM it is a pin rotating. Changes in clot strength are graphed against time.
Different clot activators are used to evaluate different pathways
What factors can confound TEG results
Low Hct - hyper
High Hct - hypo
Type of activator used - different activators are not directly comparable
Different analyser or changes in analyser environment can alter results –> not directly comparable
Delay in processing results in hypocoagulability
