Hemostasis/Coagulation. Gregory S. Travlos, DVM, DACVP National Institute of Environmental Health Sciences Research Triangle Park, NC 27709 919-541-0653 [email protected] Hemostasis. The process by which bleeding is arrested.
The process by which bleeding is arrested.
Intact endothelium forms a thromboresistant surface
Proteoglycan matrix of the vessel wall influences thrombogenicity.
Besides their role in thromboresistance, endothelial cells have additional synthetic functions.
Adhere to exposed collagen (platelet plug)
Secretory functions; mediators of coagulation and fibrinolysis
mitochodrionPlatelet - TEM
The role of platelets in hemostasis is as important as the coagulation mechanism.
Platelets promote hemostasis by:
When a vessel is injured or severed a brief, local, reflex vasoconstriction occurs.
Passing platelets adhere to exposed collagen.
The adhered platelets undergo a conformational change.
Platelets - unstimulated
Addition of ADP
Addition of thrombin
(strong stimulation )
Characteristic discoid shape
Shape change (elongation and crescents) and filaform process formation (arrows)
Increased spreading, filaform process extension (arrows) and aggregate formation (stars)
Activated platelets release their a-granule and dense body contents inducing additional platelet recruitment.
The agonists accelerate the development of an irreversible platelet aggregate (platelet plug).
More about agonists.
In real life, however, platelets are exposed to multiple agonists from platelets and other cells (e.g., red cells, ADP; white cells, PAF).
& Muggli, 1980
Consists of a cascading system of proteins
The coagulation system consists of three pathways (intrinsic, extrinsic and common)
But, his feathered companion does notDoes this turkey have factor XII?
The activity of coagulation system must be attenuated.
Coagulation is controlled by three types of actions.
AT IIIProposed Mechanism of AT III-Heparin System
Method for removing clots and maintenance of a patent vascular system and fibrin deposited during inflammation and tissue injury must be removed.
InhibitionFibrinolytic System and Factors Regulating Fibrinolysis (Fibrinogenolysis)
Plasminogen activator inhibitor
FV, FVIII, FIX, FXI
Fibrinogen or Fibrin Activity
Small PeptidesDegradation of Fibrin/Fibrinogen
Fundamental physiology and pathophysiology of hemostasis is similar in mammalian species.
Collect sample from an endothelial-lined vessel and careful venipuncture
Plasma samples separated from cells within 30 minutes
Citrate (trisodium salt) is the anticoagulant of choice.
Activated Coagulation Time (ACT) - in vivo test
Activated Partial Thromboplastin Time (APTT)
One-Stage Prothrombin Time (OSPT, PT)
Russel’s Viper Venom Time (RVVT)
Thrombin Clotting Time (TCT)
Fibrinogen Concentration (factor I)
Fibrin-Fibrinogen Degradation Products (FDP)
Acute oral study in dogs
Animals given 3 X LD50 in food