Lecture 9 - HAEM 6 Flashcards
What are the factors that are involved in secondary haemostasis?
Activation of the coagulation cascade with the formation of insoluble fibrin
What is involved in secondary haemostasis?
Coagulation factors: enzymes and cofactors
Platelet phosphatidyserine (PS)
Calcium
What are the clinical signs seen in secondary haemostasis?
Ecchymosis, haematomas, intracavity haemorrhage
Where are the coagulation factors produced and what are the Vitamin K dependant one’s?
They are produced in hepatocytes. The production of factors II, VII, IX and X are vitamin K dependant. Vitamin K is ingested and also produced by intestinal bacteria
What is the half life of the coagulation factors?
Range from a few hours (>5h for factor VII) to several days (factor II, XIII) with most around 1-2 days
Briefly explain the cell based model of secondary haemostasis:
Initiation: Extrinsic pathway with tissue factor and on the cell surface of fibroblasts
Amplification: Intrinsic pathway with thrombin and cell surface platelets
What is disseminated intravascular coagulation?
Coagulation gone crazy. Systemic - not restricted to site of injury, Consumptive - platelets and coagulation factors
What causes DIC and what are some examples?
They are always secondary to an underlying disease:
Severe inflammation: Sepsis, heat stroke, pancreatitis, viral infections, immune-mediated hemolytic anemia
Neoplasia: snake venoms
How are coagulation disorders initiated?
Always initiated by the release of tissue factor:
Widespread/severe endothelial injury - exposes TF
Severe organ injury - releases TF or cytokine storm
Inflammatory cytokines - induce TF expression on monocytes and endothelial cells (no endothelial injury)
Cancer - aberrant TF expression
What is non-overt DIC?
DIC is contained or compensated by inhibitors. Antithrombin (ATIII) = bind to thrombin forming a complex and preventing the converting of fibrinogen to fibrin Protein C (PC) = vitamin K-dependant anticoagulant and pro-fibrinolytic protein (activated by thrombin) --> inactivates factors Va and VIIIa
What occurs in the process of overt DIC?
widespread exposure of phosphatidylserine by activated or by injured cell types - by microparticles - loss of inhibitors (AT or PC). DIC dysregulated or uncompensated = Overt DIC
What is thrombosis?
partial or complete obstruction of a blood vessel by a thrombus
What is a thrombus?
a solid aggregate of fibrin, platelets and other blood elements on the wall of blood or lymphatic vessel
What are the three factors that lead to thrombosis?
Endothelial injury and exposure of tissue factor and sub-endothelial matrix
Abnormal blood flow (slow and/or turbulent) increases the risk of thrombosis = more frequent in veins than artery due to lower rated
Increased coagulability of blood reflects increased activation of coagulation factors
What is the effect of a vitamin K deficiency on clotting factors and what scenarios could potentially cause this?
Vitamin K is essential in the synthesis of factors II, VI, IX and X as well as protein C. Examples of scenarios that could cause Vitamin K deficiency rodenticide toxicity, sweet clover and sweet vernal grass, decreased absorption
