Haemostasis, Thrombosis And Atheroma Flashcards
Define haemostasis
The body’s response to stop bleeding and loss of blood
What does successful haemostasis depend on?
Vessel walls
Platelets
Coagulation system
Fibrinolytic system
How do the blood vessels aid haemostasis?
They constrict to limit blood loss
How do platelets aid haemostasis?
They adhere to damaged vessel walls and to eachother to form a platelet plug
How does the coagulation system aid haemostasis?
The cascade reaction converts prothrombin to thrombin and fibrinogen to fibrin.
Requires tight regulation, maintained by balance of procoagulant and anticoagulant (eg thrombin inhibitors).
How does the fibrinolytic system aid haemostasis?
Breaks down clots by releasing anti-thrombotic factors from endothelium.
Plasminogen converted to plasmin to break down fibrin
How is the coagulation system regulated?
Thrombin positively feeds back on factors V, VIII, XI
Thrombin Inhibitors: anti-thrombin III, alpha 1 anti-trypsin, alpha 2 macroglobulin, protein C/S
What is thrombophilia?
Inherited deficiency of antithrombin III or protein C/S
Give 2 examples of fibrinolytic therapy
Streptokinase and Tissue plasminogen activators both activate plasminogen = ‘clot busters’.
Define thrombosis
The formation of a solid mass of blood within the circulatory system during life.
What three things lead to thrombosis formation and what is the collective name for these?
Vessel wall abnormalities
Blood flow abnormalities
Blood component abnormalities
= Virchow’s Triad
Give some examples of vessel wall abnormalities that can lead to thrombosis formation
Atherosclerosis
Direct injury
Inflammation
Give some examples of blood flow abnormalities that can lead to thrombosis formation
Turbulence
Stagnation
Give some examples of blood component abnormalities that can lead to thrombosis formation
In smokers
Pregnancy
Post-op, leads to hypercoaguable blood
How does the appearance of arterial and venous thrombi differ?
Arterial = pale, granular, lower cell content, show lines of Zahn (red and yellow lines of RBCs and fibrin)
Venous = deep red, soft, higher cell content, gelatinous
What are the possible effects of arterial thrombi?
Ischaemia
Infarction
(Depends on site and collateral circulation)
What are the possible effects of venous thrombi?
Congestion
Odema
Ischaemia (if tissue pressure > arterial pressure due to odema)
Infarction
What are the five possible outcomes of thrombosis?
Lysis Propagation Organisation Recanalisation Thrombo-embolism
What occurs in lysis of a thrombus?
Complete dissolution of the thrombus, the fibrinolytic system activates and breaks down clot.
Blood flow is re-established.
What occurs in propagation of a thrombus?
Progressive spread of the thrombus (distally in arteries, proximal in veins)
What is organisation of a thrombus?
A reparative process with ingrowth of fibroblasts and capillaries into the thrombus.
Lumen remains obstructed.
What occurs in recanalisation of a thrombus?
One or more channels forms through organising thrombus.
Blood flow is re-established (usually incompletely).
How can a thrombus lead to an embolism?
Part of the thrombus breaks off, travels through the blood stream and lodges at a distant site eg. coronary artery
Define embolism
The blockage of a blood vessel by a solid, liquid or gas at a site distant from its origin.
List types of embolism
Thrombi-embolism Air Amniotic fluid Nitrogen Medical equipment Tumour cells
Where do thromboembolisms from the heart pass to?
Pass via aorta to renal/mesenteric arteries etc
Where do thromboembolisms from atheromatous carotid arteries pass to?
The brain (stroke)
Where do thromboembolisms from an atheromatous abdominal aorta pass to?
To the arteries of the legs
Where do thromboembolisms from the systemic veins pass to?
The lungs (pulmonary embolism) as they will not get stuck in the large veins near the heart.
What’s the difference between massive, major and minor pulmonary emboli?
Massive PE = >60% reduction in blood flow, rapidly fatal
Major PE = blockage of medium sized vessels, leads to shortness of breath, cough, blood stained sputum.
Minor PE = blockage of small peripheral arteries, can be asymptomatic or cause shortness of breath.
What do recurrent pulmonary emboli lead to?
Pulmonary hypertension
List possible causes of a deep vein thrombosis
Immobility/bed rest Post-operative Pregnancy and post-partum Oral contraceptives Severe burns Cardiac failure Disseminated cancer
How would you treat a DVT?
Intravenous heparin = an anticoagulant and a cofactor for anti-thrombin III
Oral warfarin = interferes with synthesis of vitamin K dependent clotting factors (slower effect)
When might a fat embolism occur and what symptoms can it have?
After long bone fractures/ lacerations of adipose tissue.
Rash, shortness of breath, confusion
When might a cerebral embolism occur and what symptoms can it have?
In atrial fibrillation (as this causes stasis of blood leading to thrombus formation, if this is in the left heart it goes to the brain)
Can cause stroke or transient ischaemic attack
When might an iatrogenic embolism occur?
Due to medical treatment eg. an air embolism from an injection.
How does a nitrogenic embolism occur?
Nitrogen bubbles form in the blood with rapid decompression. Commonly called “the bends”, common in divers due to rapid changes of pressure.
What is Disseminated Intravascular Coagulation (DIC)?
Pathological activation of coagulation mechanisms in response to diseases.
Small clots form throughout the body, disrupt normal coagulation and use up clotting factors, so abnormal bleeding occurs from the skin.
What can trigger Disseminated Intravascular Coagulation?
Infection
Trauma
Liver disease
Obstetric complications
What’s the difference between haemophilia A and haemophilia B?
A = deficiency of factor VIII B = deficiency of factor IX
What causes haemophilia?
Deficiency of clotting factor due to a nonsense point mutation.
X-linked recessive.
What can haemophilia lead to?
Haemorrhage into major joints, synovial hypertrophy, pain
Haemorrhage into retroperitoneum/urinary tract
Muscle bleeding causes increased pressure/necrosis of nerves (painful)
How do you treat haemophilia?
Factor replacement therapy (self-administered)
What is thrombocytopenia?
Platelet count well below reference range, usually accompanied by a bone marrow dysfunction eg. leukaemia, anaemia.
What can cause thrombocytopenia?
Failure of platelet production
Increased platelet destruction
Sequestering of platelets (cause may be DIC)
Define atheroma
The accumulation of intracellular and extracellular lipid in the intima and media of large or medium sized arteries
Define atherosclerosis
The thickening and hardening of arterial walls as a consequence of atheroma
Define arteriosclerosis
The thickening and hardening of arteries and arterioles as a result of hypertension/diabetes mellitus.
Describe the macroscopic appearance of an atheroma
Fatty streak: lipid deposits in the intima are yellow and slightly raised.
Simple plaque: raised, yellow/white, irregular, widely distributed, enlarge and coalesce.
Complicated plaque: leads too thrombus, haemorrhage into plaque, calcification and aneurysm formation.
Describe the microscopic appearance of atheroma
Early changes: proliferation of SMCs, foam cells, extracellular lipid
Later changes: fibrosis, necrosis, cholesterol clefts, inflammatory cells.
Summarise the unifying hypothesis of atherogenesis
Endothelial damage
Platelet adhesion: PDGF release, SMC proliferation & migration, insudation of lipids, uptake of lipids by SMCs & macrophages producing FOAM CELLS.
Stimulates SMCs produce matrix material.
Foam cells secrete cytokines causing further SMC stimulation & recruitment of other inflammatory cells.
What can cause endothelial damage (leading to atheroma formation)?
Increased LDLs
Toxins eg. from smoking
Hypertension
Haemodynamic stress
What are possible effects of severe atherosclerosis?
Ischaemic heart disease
Cerebral Ischaemia
Mesenteric Ischaemia
Peripheral vascular disease
What can ischaemic heart disease lead to?
MI
Angina
Arrhythmias
Cardiac failure
How can atherosclerosis lead to ischaemic heart disease?
If atheroma forms in a coronary artery and blocks it
What can cerebral ischaemia lead to?
Cerebral infarction (stroke)
Transient ischaemic attack
Multi-infarct dementia
What can mesenteric ischaemia lead to?
Ischaemia colitis
Malabsorption
Intestinal infarction
Aneurysm (due to increased pressure leading to hardening and weakening)
What can peripheral vascular disease lead to?
Intermittent claudication
Leriche syndrome (atheroma in bifurcation of abdominal aorta), leading to ischaemic rest pain
Gangrene
List some risk factors for atheroma
Age Gender (women have hormonal protection before menopause) Hyperlipidaemia (familial lead ps to corneal arcus & xanthalasma) Smoking Hypertension Diabetes Alcohol Infection Obesity Oral contraceptives Stress
How can you prevent atheroma formation?
Stop smoking
Modify diet
Treat hypertension & diabetes
Lipid lowering drugs
What affects susceptibility to coronary heart disease?
Genetic eg. disorders such as familial hypercholesteraemia increase risk
Geographical, less common in the Mediterranean
Ethnicity, common in Asians
