Coagulation Lecture 1 - Primary and Secondary Haemostasis Flashcards
What is Haemostasis?
The process/es that prevent excess blood loss after tissue injury
Maintains an equilibrium between bleeding and clotting (thrombosis)
Thrombosis - the formation of a blood clot
Roles of Haemostatic System
Keep blood fluid
Confine circulating blood to vasculature
Prevent excessive blood loss if damage occurs
Confine blood coagulation to the site of injury
Lyse and/or remove fibrin clots
Elements involved in Haemostasis
Vascular - endothelial cells - smooth muscle cells and fibroblasts Circulatory - platelets - leukocytes - plasma proteins - lipoproteins
Primary and Secondary Haemostasis - Introduction
Two stages of haemostasis:
- primary and secondary
Primary
- involves platelets
- platelets become activated
- formation of the primary haemostatic plug
Secondary
- involves the plasma coagulation factors
- complex series of reactions that results in the formation of fibrin
- stabilises primary haemostatic plug
- prevents ongoing loss of blood from the vasculature
- clot must (eventually) be removed/dissolved to allow vessel to resume/normal function
Overview of Primary Haemostasis
Endothelial damage => platelet activation
- adhesion
- shape change
- aggregation
- secretion
The platelet plasma membrane is the focus of interactions between extra and intracellular environments
Platelet Agonists
Substances that activates platelets
- ADP (nucleotide)
- thromboxane A2, platelet activating factor (lipids)
- collagen (protein)
- thrombin (enzyme)
Primary Haemostasis - Platelet Adhesion
Vascular injury exposes subendothelial collagen to blood
Platelets adhere to this collagen
Occurs quickly
Platelets bind to collagen-bound vWF in subendothelium via Gp 1b-V-IX
Collagen binding induces platelet activation which causes changes in platelet biochemistry and shape
Exposure of GP IIb-IIIa
Flip-flopping of membrane PL
von Willebrand Factor (vWF)
Protein Variably sized units 'multimers' Produced by ECs and megakaryocytes Storage - platelet alpha granules - Weibel-Palade bodies in ECs Released after - platelet activation - damage to endothelial cells - therapeutic treatments Also circulates as complex with factor VIII
Platelet Aggregation
Fibrinogen binds to GP IIb-IIIa on adjacent platelets
Measurement of platelet aggregation is the gold standard test to determine platelet activation
Laboratory Assays for Primary Haemostasis
Platelet concentration
Bleeding time
Platelet function analyser (PFA-100)
vWF
Laboratory Assays for Primary Haemostasis - Platelet Function Analysers
Mimics platelet adhesion and aggregation at a site of vessel injury - high shear rates - collagen exposure Membrane coating - collagen - agonist Time to membrane occlusion recorder Sensitive to platelet adhesion, aggregation deficiencies
Basic Concepts of Blood Coagulation
Its a sequential process of chemical reactions involving
- plasma proteins
- phospholipids
- calcium ions
Inactive forms of enzymatic factors are called ‘zymogens’
Active forms of enzymatic factors are called ‘serine proteases’
Clotting Factors I, II, III and IV
I - fibrinogen - function: thrombin substrate II - prothrombin - function: serine protease III - tissue factor - function: co-factor IV - calcium - function: mineral
Common Characteristics of Coagulation Factors - Proteins
Proteins that are clotting factors have four characteristics in common:
- a deficiency in the factor generally produces a bleeding tendency disorder
- the physical and chemical characteristics of the factor are known
- the synthesis of the factor is independent of other proteins
- the factor can be assayed in the lab
Common Characteristics of Coagulation Factors - Fibrinogen Group
Factors I, V, VIII and XIII
Factors V and VIII decrease during blood storage in vitro
Increase during pregnancy, inflammation, OC use
