MoD Session 5 Flashcards
What does the success of haemostasis depend on?
Vessel wall
Platelets
Coagulation system
Fibrinolytic system
What is haemostasis?
Stopping of haemorrhage within seconds to prevent blood loss
What does a severed artery do in haemostasis?
Contracts to decrease pressure downstream
What happens after 5 minutes of an artery being severed?
Fragile primary haemostatic plug of platelets has formed at mouth of vessel to control bleeding
What happens ~30 minutes after an artery is severed?
Secondary haemostatic plug forms w/fibrin which becomes organised forming granulation tissue which develops into a tiny scar
What do all vessels do to limit blood loss?
Constrict their vessel walls
How is a platelet plug formed?
Platelets adhere to the damaged vessel wall and each other
What is the platelet release reaction?
ATP –> ADP
ADP and thromboxane A2 cause platelet aggregation
5HT and platelet factor 3 released
Which molecules are important in platelet coagulation?
5HT
Platelet factor 3
What do platelets do after aggregation?
Coalesce
Where are the factors used in the intrinsic coagulation system found?
Within BV
What is needed to activate the extrinsic coagulation system?
Exo-BV factors
Which factors are activated in the intrinsic coagulation system?
12a –> 11a –> 9a –> 10a
Which factors are activated in the extrinsic coagulation system?
3a –> 7a –> 10a
How does activation of factor 10a by both the extrinsic and intrinsic coagulation systems cause fibrin formation?
10a –> thrombinogen –> thrombin –> fibrinogen –> fibrin
Why does the coagulation system have to be tightly regulated?
There is enough thrombin in 1 ml of blood to convert all the fibrinogen in the body to fibrin
How is the coagulation system tightly regulated?
Balance procoagulant and anticoagulant forces
What can inhibit the activation of fibrinogen by thrombin?
Anti-thrombin III
Alpha 1 antitrypsin
Alpha 2 macroglobin
Protein C and S
What are the effects of inherited antithrombin III or protein C and S deficiencies?
Thrombosis (thrombophilia)
What is the fibrinolytic system?
Conversion of plasminogen to plasmin which can dissolve fibrin
Give two examples of widely used fibrinolytic therapies.
Streptokinase A
Tissue plasminogen activator (tPA)
What is needed for the fibrinolytic system to function?
Plasminogen activators
What is activated partial thromboplastin time (aPTT)?
Time taken to generate fibrin from initiation of the intrinsic pathway
When is aPTT long?
Haemophilia A and B
Factor deficiencies
How do you test aPTT?
Activate factor XII w/out activating factor VII in phospholipid emulsion
What is prothrombin time (PT)?
Time taken to generate fibrin from factor VII
How do you test PT?
Add thromboplastin, recalcify and wait for fibrin filaments to form
When is PT long?
Inherited factor VII deficiency
Liver disease
Warfarin treatment
Sever bleeding/massive transfusion
How is a long PT rectified in severe bleeding/massive transfusion?
1:1 mix w/normal plasma
What is thrombin time (TT)?
Time taken for fibrinogen –> fibrin in the presence of thrombin
How is TT measured?
Add thrombin and calcium and wait for fibrin filaments to form
When is a long TT seen?
Deficient fibrinogen
Abnormal fibrinogen
Presence of inhibitor to reaction
What does the endothelium secrete?
Anti-thrombotic molecules e.g. Plasminogen activators, prostacyclin, nitric oxide and thrombomodulin
What is thrombosis?
Formation of a solid mass of blood w/in circulatory system
What does thrombosis occur due to?
Virchow’s triad
What is Virchow’s triad?
Abnormalities of:
Vessel wall
Blood flow
Blood components
What can cause abnormalities of the vessel wall?
Atheroma
Direct injury
Inflammation
What can cause abnormalities of blood flow?
Stagnation
Turbulence
In what circumstances might a patient be hyper-coaguable?
Smoker
Post-partum
Post-op
Why can patients who are post-partum have abnormalities of blood components?
Due to over-enthusiastic response to blood loss from childbirth
What is given post-op to reduce the risk of abnormalities of blood components causing hyper-coaguability?
Prophylactic treatment
How do arterial thrombi appear?
Granular
Pale
Low cell content
Lines of Zahn due to bloodflow - yellow = fibrinous, red = RBCs
How do venous thrombi appear?
High cell content
Gelatinous
Deep red
Soft
What are the possible outcomes of thrombosis?
Lysis Propagation Organisation Recanalisation Embolism
Why is lysis the best outcome of thrombosis?
Fibrinolytic system is active so can completely dissolute thrombus to re-establish blood flow
When is lysis the most likely outcome of thrombosis?
When thrombi are small
What can aid lysis of a thrombus and help return bloodflow to an ischaemic area?
Streptokinase A
Why is propagation when an outcome of thrombosis?
Progressive spread of thrombosis which is distal in arteries and proximal in veins
How does a thrombus change as it moves during propagation?
Increases in size with increasing venous diameter
What is organisation as an outcome of thrombosis?
Reparative process where ingrowth of fibroblasts and capillaries keep lumen unobstructed
What process is organisation as a result of thrombosis like?
Formation of granulation tissue
What is recanalisation?
One or more channels formed through organising thrombus which re-establish blood flow
Is previous bloodflow usually matched after recanalisation?
No, recanalisation is usually incomplete
What is embolism as an outcome of thrombosis?
Where part of the thrombus breaks off and travels through bloodstream to a distant site
What is the passage of an embolism in a vein?
Encounters larger vessels until it reaches the heart where it passes through to pulmonary circulation and becomes trapped
What is the passage of an embolism in an artery?
Encounters smaller vessels until it becomes trapped
What origin does pulmonary embolism always have?
Venous
What are the effects of arterial thrombosis?
Ischaemia
Infarction
What do the effects of arterial thrombosis depend on?
Site and collateral circulation
What are the effects of venous thrombosis?
Congestion
Oedema from obstruction causing high hydrostatic pressure
Ischaemia
Infarction if tissue pressure is high enough to occlude artery
What is an embolism?
Blockage of a BV by solid, liquid or gas at a site distant from its origin
> 90% of emboli are what type?
Thrombo-emboli
How do thrombo-emboli from the heart enter renal, mesentric and other arteries?
Via the aorta
Where do thrombo-emboli in the brain originate from?
Atheromatous carotid arteries
Where do thrombo-emboli caused by an atheromatous abdominal aorta end up?
Arteries of the legs
What types of emboli are there apart from thrombo-emboli?
Air Amniotic fluid Nitrogen Medical equipment Tumour cells
What can embolism lead to which requires amputation?
Coagulation necrosis
Why can an amputation due to embolism have to be more proximal than the necrotic tissue?
Remaining tissue has increased metabolic demand which the blood supply cannot support
What can cause the formation of a thrombo-emboli in the heart?
MI
AF
How can carotid endarctorectomies decease the risk of cerebral embolism?
Strip carotid arteries of atheroma so decrease risk of thrombus formation
Why must a patient who has presented with a fracture who then goes on to develop SoB and neurological symptoms be treated quickly?
They have a fat embolism which has blocked vessels in the brain causing small haemorrhages
How does fracture of a long bone cause fat embolism?
2-6 days after break bone marrow cells die and release fat into the surrounding broken BV
Why does fat embolism cause neurological symptoms?
The fat can squeeze through arterial-venous anastomoses in the lungs and therefore enter the arterial system where it is most noticeable in the brain as it causes small haemorrhages
What two causes other than long bone fracture can cause fat embolism?
Adipose tissue damage
Biochemical disturbance
What type of embolism would injection of an oily drug into a vein cause?
Iatrogenic
What are the predisposing factors for DVT?
Immobility - lack of calf muscle pumping Post-op Pregnancy and post-partum High oestrogen type contraceptives Severe burns Cardiac failure Disseminated cancer
What is Trossaeu syndrome?
Where tumour cells secrete coagulation factors
Can DVT be prevented?
No, you can only reduce the risk in identified high-risk patients
What is used for prophylaxis in patients with a high risk of DVT?
SC heparin
Heparin derivatives w/low molecular weight
ED stockings
Inflatable boots in surgery
What treatment is given for DVT?
IV heparin followed by oral warfarin
What does IV heparin followed by warfarin take a few days to act?
Have to irreversibly inhibit all enzyme molecules
What method does DVT treatment usually follow?
Prevention of thrombus propagation, not breaking it down
What determines the outcome of pulmonary embolism?
Size of embolism
What are the effects of a massive pulmonary embolism?
If it causes >60% decrease in bloodflow it is rapidly fatal as it often completely blocks the pulmonary trunk
What are the effects of a medium sized pulmonary embolism?
Medium sized BV are blocked causing SoB with or without a cough
Blood stained sputum can be caused due to development of a pulmonary infarct
What effects does a minor pulmonary embolism cause?
Asymptomatic or minor SoB due to peripheral pulmonary artery blocking
What do recurrent pulmonary emboli cause?
Pulmonary hypertension
How fast does the fibrinolytic system destroy blood clots?
At the same rate at which they are formed
Why does it not matter that a severed vein will not contract as a severed artery does in haemostasis?
Pressure in them is already low
Which step of haemostasis do patients with a platelet count of <1x10^9/L lack?
Formation of a primary haemostatic plug
Which step of haemostasis do haemophiliacs lack?
Secondary haemostatic plug formation as they have normal platelets but can’t produce fibrin
What are the five platelet activators?
Collagen surfaces within extravascular areas
Thrombin
ADP released by activated platelets and injured RBC
Adrenaline
Some prostaglandins
What do activates platelets do?
Swell into sticky spiny spheres and die
How do platelets adhere to other surfaces?
Stick to von Willebrand factor which is concentrated on the subendothelial basement membrane
What is the subendothelium?
The basement membrane or collagen where the endothelium is removed
What acts as glue between platelets in aggregation?
Fibrinogen
What factors do platelets secrete to help the platelet plug to grow?
Fibrinogen
ADP
Thromboxane A2 - powerful platelet aggregator
What are most of the circulating molecules which act to activate thrombin?
Proenzymes
Give two examples of cofactors used in blood clotting.
Phospholipids
Calcium
What is clot retraction?
When platelets cling to fibrin filaments and pull by their actin-myosin system as they die
What is the purpose of clot retraction?
Toughen clot by squeezing out fluid?
Helps to pull sides of small wounds together
What happens to fibrinolytic activity after surgery?
Drops for 7-10 days
What is urokinase?
A plasminogen activator found in urine
Why is the vascular wall not passive?
The arterial media contracts and the subendothelium traps platelets
Why does smoking cause hypercoaguability of blood?
Activates Hageman factor (factor XII)
Why are platelets in the veins more concentrated along the endothelium?
They are the smallest formed elements in the blood
How does a parietal thrombus compare to an occlusive thrombus?
Parietal - restricts lumen of vessel
Occlusive - fills and obstructs lumen
What is the most important mechanism for limiting spread of thrombus?
Blood flow
How do thrombi form in a vein?
Platelets catch in an eddy behind a valve, form an aggregate, settle on the wall and stick to other platelets as they pass by
What do arterial thrombi tend to remain?
Parietal
When do occlusive arterial thrombi tend to occur?
Over an atherosclerotic plaque that has cracked open
How can thrombi and post-mortem clots be distinguished?
Thrombi = laminated w/lines of Zahn, opposed to intimal surface Clots = rubbery and shiny, not laminated, not attached to intima
What is a vegetation?
2-3 cm long thrombus on a cardiac valve
Why do vegetations usually occur on the valves of the left heart?
Exposed to greater pressure and therefore microtrauma so exposed subendothelial tissue is thrombogenic
What can happen the vegetations?
They can become infected
How does aspirin work as an antithrombogenic?
Irreversibly acetylates an enzyme of prostaglandin metabolism in platelets so they cannot produce thromboxane A2, inhibiting haemostatic plug formation
What is a saddle emboli?
Large emboli that becomes lodged astride the bifurcation of the pulmonary artery
Where do approximately 80% of pulmonary emboli arise?
In thrombi in the deep veins of the thigh and popliteal vein
How does atrial fibrillation lead to thrombi formation?
Decreased atrial contraction –> dilatation of the left atrium –> stagnation of blood in atrium –> thrombus
How do paradoxical emboli bypass the lungs?
Small emboli pass through arterio-venous anastomoses in the pulmonary circulation
Larger emboli pass through defects in the IV septum or formaen ovale during straining which increases pressure in right side of heart
What is a paradoxical embolus?
Arise in systemic veins but embolism in systemic arteries
What is atheroma?
Gruel-like necrotic material in atherosclerotic plaques released into the blood when the plaque breaks open
When might an atherosclerotic plaque break open?
Spontaneously
During surgery
During catheterisation
Why do patients with emboli of atheroma present with abdominal pain?
The intestine is often affected
How does air embolism arise after trauma or the neck and chest?
During inspiration in the upright position veins draw in air due to their negative pressure
What approximate amount of air will cause a fatal air embolus?
100 ml
How can air embolism arise in labour?
Enter uterus and be forced into veins open during uterine contraction
What happens to air emboli from the lungs when they reach the heart?
Gather in right heart as a frothy mass that stops circulation
Why is nitrogen a particular problem when a diver resurfaces too quickly and releases dissolved gases into the body as bubble?
It is fat soluble and can result in persistent bubbles in lipid-risk tissues e.g. CNS
How is the bends treated?
Prompt recompression
How does amniotic fluid cause embolism?
Enters circulation through a tear in amniotic membranes
What can amniotic fluid embolism cause?
Sudden respiratory distress and collapse
What is amniotic fluid embolism a complication of?
Labour and Caesarean section
Why can emoblisation not occur in veins?
Blood runs from smaller to larger vessels so injects will o through heart and embolism pulmonary arteries
Why does venous flow favour stenosis?
It is slow
What can be seen in the lungs of IV drug abusers?
Microscopic foreign bodies e.g. talcum
