Haemostasis and Thrombosis Flashcards
what does the HEALTH of tissues depend on
INTACT circulation to deliver oxygen and remove wastes
what structures are involved in normal haemostasis
- vessel wall
- coagulation system
- platelet
characteristics of Normal Haemostasis
- Maintains blood in a fluid state in NORMAL VESSELS
- Rapid formation of a LOCALISED haemostatic plug at site of VASCULAR INJURY
- Tightly regulated
Primary Haemostasis (first series of events after vascular injury)
- Transient Vasoconstriction
2. Formation of Platelet Plug
Secondary Haemostasis
3.Formation of Fibrin Meshwork –> activates the Clotting System
PRIMARY HAEMOSTASIS: What causes the initial vasoconstriction
Neurogenic REFLEX mechanisms
PRIMARY HAEMOSTASIS: What augments the vasoconstriction
Locally released ENDOTHELIN
PRIMARY HAEMOSTASIS: Function of exposed Subendothelial ECM
Allows platelets to adhere and become activated
PRIMARY HAEMOSTASIS: Activated platelets do…
recruit additional platelets to form a HAEMOSTATIC PLUG
SECONDARY HAEMOSTASIS:
What substance is released at injury site and responsible for activation of Clotting Cascade?
Tissue Factor. Activates Clotting Cascade in conjunction w secreted PLATELET FACTORS
SECONDARY HAEMOSTASIS:
Clotting Cascade ultimate goals.
- Activation of THROMBIN
2. Conversion of FIBRINOGEN to FIBRIN
List of substances involved in Control of Haemostasis
- tPA (Tissue Plasminogen Activator)
- Antithrombin III
- Protein C, Protein S and THROMBOMODULIN
- Tissue Factor Pathway inhibitor
Role of tPA (Tissue Plasminogen Activator)
- Converts PLASMINOGEN into Plasmin
2. This degrades fibrin strands (Fibrinolysis)
Role of Antithrombin III
Binds & INactivates Thrombin and Other Clotting Factors
Role of Protein C, Protein S and THROMBOMODULIN
- Binding of Thrombin to Thrombomodulin activates protein C
- Protein S augments activity of Protein C
- Jointly they INACTIVATE Clotting Factors
Definitions of Thrombosis
a. Blood clot* formation in UNINJURED vessels
b. Thrombotic OCCLUSION of vessel following minor injury
* aka Thrombus
Define Virchow’s Triad
The predisposing factors to Thrombosis
List Virchow’s Triad
Predisposing Factors for Thrombosis
- Endothelial injury
- Stasis OR Turbulent flow
- Hypercoagulability
What properties does normal endothelium have
Both:
- Antithrombotic properties
- Prothrombotic properties
effect of endothelial damage
shifts balance in favour of thrombosis (prothrombotic properties)
Normal blood flow is
Laminar (platelets do not come in contact w endothelium). Turbulence and Stasis causes these to come in contact –> activate Clotting System
define Hypercoagulability
alteration in the Coagulation Pathways predisposing to Thrombosis. Can be Primary (genetic) or Secondary (acquired)
Primary Hypercoagulable States
- Mutation Factor V Leiden
- Antithrombin III deficiency
- Prothrombin gene mutation
- Protein C deficiency
- Protein S deficiency
- Others
Secondary Hypercoagulable States (Acquired) - High Risk Acquired Factors for Thrombosis
- Prolonged bed rest OR immobilization
- Myocardial infarction
- Atrial fibrillation
- Prosthetic cardiac valves
- Tissue damage (surgery, fracture, burns)
- Cancer
Lower risk acquired factors for thrombosis
- Oral contraceptives
- Hyperestrogenic states (eg. pregnancy)
- Cardiomyopathy
- Smoking
- Sickle Cell Anaemia
Define Vegetations
Thrombi occurring on heart VALVES
usually in cases of infective endocarditis/rheumatic carditis
Define Mural Thrombi
Thrombi occurring in heart CHAMBERS OR aortic LUMEN
Fate of the thrombi: a combination of the following 4 events can happen…
- Propagation - thrombi accumulate platelets + fibrin causing vessel obstruction
- Embolisation - thrombi are transported elsewhere in the vasculature
- Dissolution - thrombi removed by fibrinolytic activity
- Organization and Recanalization
Explain 4.Organization and Recanalization
- thrombi induce inflammation AND fibrosis (organization)
- they can recanalize OR
- they can be incorporated into a thickened vessel wall
Possible complications of Venous Thrombi
- can cause congestion
- oedema
- can embolize lungs and cause death if massive
Possible complications of Arterial Thrombi
- can embolize and cause Tissue Infarction
- can cause vascular obstruction at CRITICAL sites (cerebral vessels; coronary)
Risks of Deep Venous Thrombosis AT/ABOVE KNEE LEVEL
- they can embolize to the lung
- asymptomatic in 50% cases
- may cause local PAIN and OEDEMA
Which organs are prime targets for embolism and why
- Brain
- Kidneys
- Spleen
* due to large volume of blood flow
Embolus
- a DETACHED intravascular solid
- liquid or gaseous mass
- carried by the blood
- to a site DISTANT from its origin
Common and uncommon emboli?
- 95% Thromboemboli
- Rare: large fat droplets, bubbles of air, nitrogen, atherosclerotic debris, tumor fragments, bits of bone marrow, foreign bodies
action of emboli
lodge in vessels
results in partial OR complete vascular obstruction –> ischaemic necrosis (infarction)
what determines whether an embolus will lodge in the Pulmonary or Systemic Circulation
its site of origin
Causative agent for Pulmonary Thromboembolism
95% - Deep Vein Thrombosis originating ABOVE KNEE LEVEL
Pathway travelled
depends on size;
- pass through right side of heart
- enter pulmonary vasculature
- may obstruct MAIN PULMONARY VEIN
- may obstruct SMALLER ARTERIOLES
- may impact across the BIFURCATION
Consequences of Pulmonary Thromboembolism
-sudden death
-right ventricular failure
-cardiovascular collapse
medium sized vessel obstruction –> PULMONARY HAEMORRHAGE
What do multiple small emboli in the lung cause
Pulmonary Hypertension
Most frequent cause for SYSTEMIC (Arteriolar) Thromboembolism
Intracardiac Mural Thrombi (80%)
Remainder: thrombi on atherosclerotic plaques, fragmentation of valvular vegetations etc.
Major sites for Arteriolar Thromboembolism
-Lower Extremities (75%)
-The Brain (10%)
Intestines, kidneys and spleen affected to a lesser extent.
Consequence of Arteriolar Embolisation
Infarction of affected tissues
Fat Embolism
usually after bone trauma (fractures; orthopaedic operations)
Air Embolism
after instrumentation of neck veins, obstetric procedures or as a consequence of chest wall injury. Also after sudden changes in atmospheric pressure (decompression sickness)
Decompression Sickness
Gases dissolve in blood at high pressure
- come out as bubbles during rapid decompression
- affects muscles, lungs, brain and heart
Amniotic Fluid Embolism
A complication of labour and the immediate postpartum period
Other types of emboli
Septic (infective endocarditis)
Tumour
Foreign material
Cholesterol emboli
