MoD S6 - Haemostasis, Thrombosis and Embolism Flashcards
What factors does successful haemostasis depend on?
Vessel wall contraction
Platelets
Coagulation system
Fibrinolytic system
How do blood vessels limit blood loss upon being injured?
Constrict to limit blood loss:
- More effective if vessel fully severed, not just partially
- Mechanism not fully understood
What are the major actions of platelets when a vessel is injured?
Adhere to damaged vessel wall and other platelets
Form a platelet plug
Platelet release reaction
What is the platelet release reaction?
ATP —> ADP
ADP and thromboxane A2 cause platelet aggregation
5-HT and platelet factor 3 released
PF3 important in coagulation cascade (extrinsic pathway)
Platelets coalesce after aggregation
Briefly describe the process of coagulation
MGD S3
Coagulation cascade converts a series of inactive components to active components
Prothrombin is proteolytically cleaved to form thrombin which in turn catalyses the fibrinogen to fibrin reaction
Fibrin then goes on to form the clot (along with RBCs and platelets)
Why must coagulation be tightly controlled?
1ml of blood can generate enough thrombin to convert all the fibrinogen in the body to fibrin
Therefore a delicate balance of procoagulant and anticoagulant factors must be maintained
Give 5 examples of thrombin inhibitors
Which 2 are non specific antiproteases?
Which 3, when deficient lead to increased risk of thrombosis?
Anti-thrombin III and Proteins C and S:
- Inherited deficiency of these can lead to increased risk of thrombosis
Alpha 1 anti-trypsin, Alpha 2 macroglobulin:
- Wandering non-specific anti-proteases
Give a brief description of fibrinolysis
How is this process exploited therapeutically?
Breakdown of fibrin is performed by plasmin, which is converted from plasminogen by plasminogen activators
Fibrinolytic therapy with drugs such as t-PA and streptokinase can be used to breakdown a clot and restore bloodflow during a stroke or MI
How is the endothelium involved in haemostasis?
Produces anti-thrombotic factors such as:
- Plasminogen activators
- Prostacyclin
- Nitric oxide
- Thrombomodulin
Define thrombosis
The formation of a solid mass of blood in the circulatory system during life
Why does thrombosis occur?
Split the different reasons into 3 major categories
Virchow’s Triad
Abnormalities of the vessel wall:
- Atheroma
- Direct injury
- Inflammation (E.g. Vasculitis)
Abnormal blood flow:
- Stagnation
- Turbulence
Abnormalities of blood components:
- Smokers
- Post partum
- Post op
Describe the appearance of an arterial thrombus
Paler
Granular
Lines of Zahn
Lower cell content
What are lines of Zahn?
Appear in an arterial thrombus
Fast flowing blood produces a laminar structure in the thrombus
Lighter areas have lower red cell content
Darker areas have picked up more red cells
Describe the appearance of a venous thrombus
Soft
Gelatinous
Deep red
Higher cell content
What are the outcomes possible after thrombus formation?
Lysis Propagation Organisation Recanalisation Embolism
Describe lysis of a thrombus
Complete dissolution of the thrombus
The fibrinolytic system is activated and bloodflow re-established
This is most likely when thrombi are small
Describe propagation of a thrombus
Stagnant blood present around the thrombus (distally in arteries and proximal in veins) can lead to the formation of a new thrombus
Tributaries into veins proximal to a thrombus create turbulent blood flow which is also at risk of thrombus formation
Describe organisation of a thrombus
A reparative process comprising of the ingrowth of fibroblasts and capillaries (similar to granulation tissue) into the lumen of the occluded vessel where the thrombus is present
Lumen remains obstructed after this process occurs
Describe recanalisation of a thrombus
Similar to organisation however one or more channels are developed in the organising tissue to partially re-establish bloodflow
Describe embolism of a thrombus
Thrombo-embolisms are formed when part of the thrombus breaks off to form an embolism
This travels in the bloodstream and lodges at a different site
What are the effects of an arterial thrombosis?
What effects do site and collateral circulation have on the effects of a thrombus?
Can cause Ischaemia or infarction
Site:
- If the thrombus is in an end artery such as the retinal artery, bloodflow to the tissues supplied is completely blocked and more severe effects are seen
Collateral circulation:
- Lesser effect present if there is more collateral circulation
What are the effects of a venous thrombosis?
Will cause congestion as blood can enter the tissue but not leave, raising tissue pressure
This may lead to oedema as fluid is forced into the interstium
Further raising pressure may lead to tissue pressure equalling arterial pressure at which point blood flow stops
This can lead to ischaemia and infarction
Define embolism
The blockage of a blood vessel by a solid, liquid or gas at a site distant to its origin
What are some of the different types of embolism?
Thrombo-embolism (90%) Air Amniotic fluid Gaseous nitrogen (the bends) Medical equipment Tumour cells Septic tissue
Give 4 common locations for thrombus formation and where any emboli from these thrombi would travel
Thrombus in the systemic veins will give off emboli that will lodge in the lungs (pulmonary emboli)
Thrombus in the heart will pass via the aorta into the systemic arteries (renal, mesenteric etc)
Thrombus in the atheromatous carotid will pass into the cerebral arteries (TIA or stroke)
Thrombus from the atheromatous abdominal aorta will pass into arteries in the legs
What are the pre-disposing factors to deep vein thrombosis?
Immobility/bed rest Post-op Pregnancy and post-partum Oral contraceptives Severe burns Cardiac failure Disseminated cancer
How can risk of deep vein thrombosis be reduced?
High risk patients are identified and then:
- Heparin can be given subcutaneously
- Leg compression before and after surgury (thrombo-embolic deterrent stocking)
How can deep vein thrombosis be treated?
Intravenous heparin
Oral warfarin
Filter can be placed in the inferior vena cavae
Give the effects of a massive pulmonary embolism and how ‘massive’ is defined
Massive defined by reduction of >60% of blood flow
Rapidly fatal
Give the effects of a major and minor pulmonary embolism
Major:
- Medium sized vessel occluded
- Patients short of breath and may cough up blood stained sputum
Minor:
- Small peripheral pulmonary artery blockage
- Often asymptomatic or minor shortness of breath
What is the effect of recurrent minor pulmonary emboli?
Can lead to pulmonary hypertension as progressively more and more of the pulmonary circulation is blocked
What is a common cause of fat embolism?
Where might this embolism end up?
Breakage of a bone, where fat leaks from a bone into the bloodstream
Commonly ends up in the cerebral circulation (can cause confusion) or lungs (can cause shortness of breath)
What is the effect of Disseminated intravascular coagulation on the body?
Explain how these seemingly opposite effects occur as a result of this condition
DIC disregulates coagulation and fibrinolysis causing widespread clotting and bleeding
The excessive clotting that occurs depletes thrombin, raising prothrombin time and activated partial thromboplastin time
Platelets and plasma fibrinogen are also depleted
This in turn raises clotting time and leads to bleeding
How can disseminated intravascular coagulation be treated?
Treatment of the underlying cause is the only effective treatment
However, to manage the patient short term:
- Anti-coagulants can be given in acutely ill patients
- Platelets and plasma can be transfused to replenish platelets and clotting factors
Give examples of conditions that may cause disseminated intravascular coagulation
This card lists only a few examples, there are others
Cancers (particularly lung, prostate, stomach)
Massive tissue injury (trauma, burns, hypothermia)
Bacterial, fungal or protozoal infections
Liver disease
Obstetric complications
What is the inheritance pattern of Haemophilia?
X-linked recessive
What are the main clinical features of Haemophilia ?
Due to nonsense point mutations
Can be mild, moderate or severe depending on mutation
Deficiency in clotting factor VIII (type A) or IX (type B)
Leads to increased clotting time and hence excessive bleeding
Internal and external bleeding episodes can occur after trauma or surgery
Haemorrhage into the joints can also occur (painful)
Muscle bleeding can cause pressure and necrosis of nerves (painful)
Can haemorrhage into the retroperitoneum/urinary tract
What are the laboratory findings of someone with Haemophilia A?
Complete blood count is normal (may be lowered if patient has experienced excessive bleeding)
Activated partial thromboplastin time is increased (reflects the lower level of Factor VIII)
Prothrombin time is normal
Fibrinogen test is normal
Levels of factor VIII will be lower than 50% when assayed
How is Haemophilia A treated?
Best treated through injection of additional clotting factor
Give a complication of Heamophilia A treatment
Immune rejection of the injected clotting factors may occur
What is thrombocytopenia?
What are some of the possible causes?
A condition in which platelet count is lowered in the blood
Bone marrow doesn’t make enough platelets:
- Cancer (E.g. leukaemia)
- Chemotherapy
- Viral infection
- Toxic chemicals
- Alcohol
Body destroys platelets:
- Autoimmune disease (Immune thrombocytopenia)
- Medicines
- Infections
- Surgery
- Disseminated intravascular coagulation
Splenic sequestration:
- Enlarged spleen due to cancer or serious liver disease (E.g. Cirrhosis) can lead to an increased proportion of platelets being stored in the spleen and hence lowering intravascular levels
How is thrombocytopenia treated?
Often resolved when underlying cause is treated (E.g. The causative infection being treated)
If Severe:
- Medicines such as corticosteroids may slow platelet destruction
- Blood or platelet transfusions can be used to treat those actively bleeding or at high risk of bleeding
- Splenectomy in worst case scenario to prevent platelets being stored in the spleen
What are some of the common symptoms of thrombocytopenia?
Mild to serious internal and external bleeding
Purpura (bruises) and petechiae (red or purple dots on the skin)
How might a cerebral embolism come about?
What conditions may result?
Atrial fibrillation causing blood stasis and thrombus formation
Thrombus embolises to the cerebral circulation
Can cause stroke or transient ischaemic attacks
What is an iatrogenic embolism?
Embolism due to medical treatment E.g. Medical equipment or injection of air
