Hypercoagulable states Flashcards
CCM 2nd Edition
Chapter 104 Hypercoagulable States
Do any inherited forms of hypercoagulability occur in vet med?
Not that we know
What is virchows triad?
endothelial injury or dysfunction, stasis and hypercoagulability
How does the endothelium exhibit an anti-coagulant phenotype when not activated?
the glycocalyx has 50-90% of GAGs made up of heparin sulfate which facilitates the binding of antithrombin. This enhances anti-thrombin mediated inhibition of thrombin
How does inflammation alter the anti-coagulant phenotype of the endothelium?
decreases GAG synthesis, shedding of the EG
Endothelial cells can be activated by tumor necrosis factor-α (TNF-α), bradykinin,
thrombin, histamine, and vascular endothelial growth factor
(VEGF)
This then results in release of ultralarge vWF - which causes binding to platelet GP Ib alpha and increases platelet activation.
How is ultralarge vWF delt with in health
broken down into small vWF by a disintegrin-like and metalloproteinase with thrombospondin type 1
This can be decreased during inflammation
What usually causes all coagulation?
through interactions of tissue factor with activated factor 7
What occurs during platelet activation?
Upon activation, platelets undergo shape change and shuffle negatively charged phospholipids to the surface. These provide a surface for the propagation phase of clot formation.
With activation, platelets greatly increase the number of copies of the active fibrinogen
receptor (glycoprotein IIbIIIa [GP IIbIIIa] on their surface.
Activated platelets will also release alpha and dense granules - that are procoagulant
What are microparticles and what do they do?
small vesicles released by activated or ruptured cells.
can express tissue factor and a phospholipid for thrombin generation
What are possible mechanisms of hypercoagulability?
Endothelial disturbances
Increased procoagulant elements
decreased endogenois anticoagulants
perturbaions in fibrinolysis
What are the three primary endogenous anticoagulants
AT, protein C and TFPI (tissue factor pathway inhibitor)
All are active within the endothelium
What is the action of antithrombin/
inhibit thrombin and factor Xa
most effective when bound to hepain sulfate
is decreased during systemic inflammation
Discuss fibrinolysis
plasminogen converts to plasmin via plasminogen activators. Plasmin then breaks down the fibrin meshwork of the clot
Activity decreased during inflammation
How can hypercoagulability be Dx?
viscoelastic testing
D-dimers
Decreased endogenous anti-coagulants.
How is systemic inflammation proposed to cause hypercoagulability?
complex process involving
increased expression of TF, activation of ECs and disruption of the
glycocalyx, impairment of anticoagulant systems, and abatement of
fibrinolysis
