Session 5 Flashcards
Define thrombosis
Formation of a solid mass of blood within the circulatory system during life
In which vessels can thrombosis occur?
Any vessels - arteries or veins
What is the name given to the formation of solid mass of blood in a test tube/a cut?
Clotting
Thrombosis can occur due to abnormalities of… (3)
The vessel wall
Blood flow
Blood components
What three things can cause abnormalities of the vessel wall and therefore thrombosis?
Atheroma
Direct injury
Inflammation
What two abnormalities of blood flow can result in the formation of thrombi?
Stagnation
Turbulence
What three things can result in abnormalities of the components in blood that cause thrombosis?
Smoking
Pregnancy
Post-op
Name 4 features of arterial thrombi
Pale
Granular
Lines of Zahn
Lower cell content
Name 4 features of venous thrombi
Soft
Gelatinous
Deep red
Higher cell content
Name 5 outcomes of thrombosis
Lysis Propagation Organisation Recanalisation Embolism
What occurs in lysis of a thrombus? What happens to the blood flow? For which type of thrombi does this occur?
There is complete dissolution of the thrombus by the fibrinolytic system
Reestablished
When thrombi are small
What is propagation of a thrombus?
Progressive spread/enlargement of a thrombus in the direction of blood flow
In which direction does propagation occur in the arteries?
In which direction does propagation occur in the veins?
Propagates distally
Propagates proximally
What happens when there is organisation of a thrombus?
There is ingrowth of fibroblasts/capillaries to repair the vessel but the lumen remains obstructed
What happens during recanalisation of a thrombus? What happens to blood flow?
One or more channels is formed through the organising thrombus
Blood flow is reestablished but incompletely
In which direction do emboli travel in the arteries?
In which direction do emboli travel in the veins?
Away from the heart
Towards the heart
The effects of thrombosis in the arterial system depends on the __________ of the thrombus and the ________________ circulation
Site
Collateral
Name two effects of thrombosis in the arterial system
Ischaemia
Infarction
Name 4 effects of thrombosis in the venous system
Congestion
Oedema
Ischaemia
Infarction
Define embolism
The blockage of a blood vessel by solid, liquid or gas at a site distant from its origin
Over 90% of emboli are…
Thrombi-emboli
Name 5 other types of emboli excluding thrombo-emboli
Air Amniotic fluid Nitrogen Medical equipment Tumour cells
Roughly how much air is needed to cause an air embolism?
What effect does an air embolism have on the blood?
~150ml
Makes the blood ‘frothy’
When might nitrogen embolism occur? What happens in nitrogen embolism?
During decompression - e.g. Bends
Dissolved nitrogen becomes gaseous nitrogen
Where do thrombi-emboli from systemic veins end up?
In the lungs
Where do thrombi-emboli from the heart usually pass through?
The aorta to renal, mesenteric and other arteries
Thrombo-emboli from atheromatous carotid arteries pass to the…
Resulting in…
Brain
Stroke
Thrombo-emboli from atheromatous abdominal aorta pass to…
Resulting in…
The arteries of the legs
Ischaemic limbs
Thrombo-emboli that pass to the brain usually enter from which vessels?
Carotid arteries
Thrombo-emboli that end up in the arteries of the legs usually enter through which vessel?
Abdominal aorta
Name a few predisposing factors of deep vein thrombosis
The factors result in an increased risk of deep vein thrombosis and therefore…
Immobility/Bed Rest Post-Op Pregnancy Disseminated Cancer Cardiac Failure
Pulmonary embolism
Give an example of a preventative measure against DVT used in hospitals
Flowtron boots
How do Flowtron boots work?
Intermittently inflate mimicking the muscle pump of the calves and assisting venous return to the heart
Name two drugs that are used in the treatment of DVT
Do they dissolve the existing thrombus?
IV heparin type drugs
Oral warfarin
No, only prevent their propagation
What reduction in blood flow will be seen in a massive PE? What prognosis does this have for the patient?
> 60% reduction
Rapidly fatal
What blood vessels are blocked in a major PE? What symptoms may be seen in a patient?
Medium sized blood vessels are blocked
Shortness of breath
Cough
Blood stained sputum
Which vessels are blocked in a minor PE? What symptoms can this cause?
Small peripheral pulmonary arteries
Asymptomatic/Minor Shortness of Breath
Recurrent minor PEs can lead to…
Pulmonary hypertension
Fat embolism usually occurs as result of…
Long bone fracture
What happens in fat embolism?
There is the release of fat and marrow into the blood (usually as a result of a long bone fracture)
What is haemostasis?
Stopping of a flow of blood
What are the aims of haemostasis?
To prevent bleeding and prevent unnecessary coagulation to allow blood to flow
What cells are platelets produced from? Where in the body?
Megakaryocytes
Bone marrow
In which way are platelets produced from megakaryocytes?
They bud off their cytoplasm
What is the typical platelet count?
What is the typical platelet life span?
150-400
7-10 days
What causes platelet adhesion to take place? How do they adhere?
Damage to the vessel wall
Damage to the wall —> Exposure to underlying tissues. Platelets adhere to collagen via vWF receptor.
Which receptor do platelets bind to in their adherence to collagen?
vWF receptor
How do platelets activate other platelets and the clotting cascade to some extent after they adhere?
Secrete ADP, thromboxane and others to become activated and activate other platelets
What do platelets secrete to activate other platelets? What else do they secrete?
ADP, thromboxane etc.
Some coagulation factors from internal stores
How is a platelet plug formed?
There is aggregation and cross-linking of platelets to form a platelet plug
Describe the clotting cascade
Amplification activation of precursor proteins to generate thrombin
Thrombin converts soluble fibrinogen to insoluble fibrin
Strengthens initial platelet plug to make the stable clot
How is fibrin formed in the clotting cascade?
Thrombin converts fibrinogen to fibrin
What is the clotting cascade controlled by? (2)
Natural anticoagulants
Clot destroying proteins
Clotting factors are produced in which part of the body?
Liver
Give two examples of coagulation factors
Fibrinogen
Prothrombin
Give two examples of natural anticoagulants
Protein C
Protein S
What is used to measure the extrinsic pathway and common pathway?
What is used to measure the intrinsic and common pathway?
PT
APPT
What coagulation factors does PT mainly measure?
Factor VII
What coagulation factors does APPT mainly measure?
Factors VIII, IX, XI and XII
Which coagulation factors does both PT/APPT measure?
Factors V, X
Prothrombin
Fibrinogen
Name three functions of Von Willebrand Factor
Platelet adhesion
Platelet aggregation
Carries Factor VIII
What three things occur in the vessel wall during injury?
Vasoconstriction
Production of vWF
Exposure of collagen and tissue factor which initiates activation of clotting factors
What is fibrinolysis?
The process of breaking down a clot
Describe the process of fibrinolysis
Plasminogen activator converts plasminogen to plasmin which breaks down fibrin clot into D-dimers
What is the name of the molecule that converts plasminogen to plasmin?
Plasminogen Activator
What enzyme breaks down a fibrin clot to D-dimers?
Plasmin
What is the function of natural anticoagulants?
Stop further coagulation of blood
Give three examples of natural anticoagulants
Protein C
Protein S
Anti-thrombin
Bleeding disorders can be as a result of abnormalities in the… (3)
Vessel wall
Platelets
Coagulation factors
Give two examples of congenital coagulation factor disorders
Haemophilia A
Haemophilia B
Haemophilia A is as a result of which coagulation factor?
Deficiency of factor 8
Haemophilia B is as a result of which coagulation factor?
Deficiency of factor 9
Name three acquired conditions that can cause coagulation factor disorders
Liver disease
Vitamin K deficiency
Use of anticoagulants such as warfarin
How do anticoagulants such as warfarin act as anticoagulants?
Inhibit vitamin K
Clinical severity of coagulation factor disorder depends on…
The extent of the deficiency
In which way is haemophilia A inherited?
X-linked recessive
In haemophilia A there is a congenital lack of factor…
8
When is haemophilia A diagnosed if congenital?
Pre-natally or soon after birth
When is haemophilia A diagnosed if it as a result of a spontaneous mutation?
Infancy
What happens as a result of haemophilia A?
Bleeding into muscle and joints
Bleeding post-operatively
How is haemophilia A treated? (2)
Recombinant factor 8
DDAVP
How does haemophilia B present compared with haemophilia A?
Similar presentation
Which is rarer, haemophilia A or haemophilia B?
Haemophilia B
What is the cause of haemophilia B?
Congenital deficiency in factor IX
In which way is Von Willebrand’s disease inherited?
Autosomal dominant
What does Von Willebrand’s disease result in? (2)
Abnormal platelet adhesion to vessel wall
Reduced factor 8 amount/activity
Name two parts of the clotting cascade that will be seen at low levels in Von Willebrand’s disease
Factor 8
vWF
Name two clinical features of someone with Von Willebrand’s disease
Skin and mucous membrane bleeding
Prolonged bleeding after trauma
Give two examples of skin and mucous membrane bleeding which can take place as a result of Von Willebrand’s disease
Nosebleeds
Gum bleeding
How does the symptoms of Von Willebrand’s disease differ to haemophilia?
In haemophilia there is spontaneous joint/muscle bleeds. There is not in VW disease
Vessel wall abnormalities can cause bleeding disorders. What do they typically present with?
Easy bruising
Give two examples of congenital conditions that cause vessel wall abnormality
Hereditary Haemorrhage Telangiectasia (HHT)
Ehlers Danlos
In what way is HHT inherited?
Autosomal dominant
What happens in HHT?
There are dilated microvascular swellings that increase with time
Name 3 acquired causes of vessel wall abnormalities
Senile purpura
Steroids
Scurvy
Platelet disorders can be either qualitative or quantitative, what is meant by this?
Qualitative - abnormal platelet activity
Quantitative - thrombocytopenia
A low platelet count is either a result of…
Reduced production
Increased removal
What can be carried out to discover the cause of thrombocytopenia?
Bone marrow biopsy
Give an example of something that can result in increased removal of platelets
Splenic pooling
What is the most common way for the immune system to destroy platelets?
Immune thrombocytopenia purpura
What happens in immune thrombocytopenia purpura?
Autoantibodies are produced against the glycoproteins on platelets
How is immune thrombocytopenia purpura treated?
With immunosupression
Can platelet transfusions be given to a patient with immune thrombocytopenia purpura? Why?
No
These platelets also get destroyed
Give an example of a condition where there is non-immune destruction of platelets
Disseminated Intravascular Coagulopathy (DIC)
Name 4 factors that can result in reduced production of platelets in the bone marrow
B12/Folate Deficiency
Infiltration of bone marrow by cancer cells/fibrosis
Drugs
Viruses
Give two examples of drugs that can cause reduced production of platelets in the bone marrow
Chemotherapy
Antibiotics
Give two examples of viruses that can cause reduced production of platelets in the bone marrow
HIV
EBV
Patients with low platelets are generally asymptomatic until platelet count is less than…
30
Name 5 symptoms of severe thrombocytopenia
Easy bruising Mucosal bleeding Severe bleeding after trauma Intercranial haemorrhage Purpura
How common are hereditary disorders of platelet function? Give an example
Very rare
Bernard Soulier
What can cause acquired disorders of platelet function (3)
Aspirin
NSAIDS
Clopidogrel
Disseminated intravascular coagulapthy is a type of…
Microangiopathic haemolytic anaemia
What happens in DIC?
Numerous micro thrombi are formed. There is consumption of clotting factors, platelet and haemolytic anaemia.
How will PT, APPT, fibrinogen levels and D-dimer levels be affected by DIC?
Raised
Raised
Low
Raised
In which sorts of patients is DIC seen?
Severely ill patients - e.g. Cancer, burns, infections
How is DIC treated?
Treatment of the underlying cause
