S5: haemostasis & thombosis + embolism

Question 1

What are the three steps in haemostasis?

Answer 1

1) Severed artery contracts, not enough to stop the bleeding but enough to decrease pressure downwards
2) Primary haemostatic plug of activated platelets forms at the hole in the vessel (fragile but may control the bleeding)
3) Secondary haemostatic plug forms as fibrin stabilises the friable platelet plug into a blood clot

Question 2

Name some things platelets are activated by

Answer 2

Collagen surfaces
ADP (released by activated platelets)
Thromboxane A2 (powerful platelet aggregator)
Thrombin

Question 3

What happens after platelets are activated?

Answer 3

1) Stick to the exposed subendothelium specifically to vWf
2) Aggregate with other platelets (this is how platelet plugs grow), fibrinogen binds to platelets and sticks them together
3) Swell and change shape into sticky, spiny sphere
4) Secrete factors that help the platelet plug to grow and aid clotting eg. ADP, thromboxane A2

Question 4

Briefly outline why the clotting cascade exists

Answer 4

Thrombin (enzyme that cleaves the circulating plasma fibrinogen into fibrin which is the endpoint)
Thrombin can’t circulate in the blood freely (blood would be solid then)
Therefore, thrombin is activated by a group of clotting factors

Question 5

Which molecules require vitamin K for their synthesis?

Answer 5

Factors II, VII, IX and X

Anticoagulants protein C and protein S

Question 6

What are the two pathways in the clotting cascade?

Answer 6

1) Intrinsic pathway = all the factors involved are contained within the blood, triggered by a negatively charged surface & no vessel wall needs to be broken for it to occur
2) Extrinsic pathway = needs a tissue factor (thromboplastin) which is present outside of the blood (pathway triggered by this released from damaged cells adjacent to the area of haemorrhage)

Question 7

Detail the importance of the vascular wall in haemostasis

Answer 7

Arterial media contracts when the artery is damaged

Opposes and favours clotting by secreting different substances

Question 8

Name some factors which oppose clotting

Answer 8

Dilution of clotting factors by blood flow and natural anticoagulants
Natural coagulants = antithrombin III, protein C & protein S
Fibrin degradation products

Question 9

Describe fibrinolysis

Answer 9

Blood clot is dissolved by fibrinolysis (enzyme is plasmin)
Plasminogen is activated by TPA which also circulates in the blood to form plasmin
Other plasminogen activators = urokinase (in the urine) & streptokinase
Side effects of giving these therapeutically is bleeding (commonly gums or nose)

Question 10

Describe haemophilia A and its test results

Answer 10

Deficiency of factor VIII
X-linked recessive
Symptoms: easy bruising and massive haemorrhage after trauma & surgery
Normal platelet count, bleeding time, PT but prolonged APTT
Treatment: recombinant factor VIII

Question 11

Describe haemophilia B and its test results

Answer 11

Factor IX deficiency
Clinically indistinguishable from haemophilia A (also X-linked recessive)
Normal platelet count, bleeding time, PT but prolonged APTT

Question 12

Describe Von Willebrand disease and its test results

Answer 12

Deficiency/abnormality in vWf

Bleeding time, APTT both raised, normal platelets and PT

Question 13

Describe thrombocytopenia and its test results

Answer 13

Count of less than 100 x 109/L (spontaneous bleeding = 20 x 109/L)
Low platelet count, prolonged bleeding time and normal APTT & PT

Question 14

Describe DIC, causes and treatment

Answer 14

Disseminated intravascular coagulation (DIC) is a thrombohaemorrhagic disorder occurring as a secondary complication in a variety of conditions
An activator of clotting gets into the blood and microthrombi are formed through the circulation (consumes platelets, fibrin, coagulation factors and activates fibrinolysis)
Treatment: treat the underlying cause of DIC (eg. sepsis, trauma), transfusions of platelets, fresh frozen plasma, RBCs etc

Question 15

Define thrombus and embolus

Answer 15

Thrombus = a solid mass formed from the constituents of the blood within the heart of vessels during life
Embolus = sudden blocking of an artery by a thrombus or foreign material which has been brought to its site of lodgement by the blood current

Question 16

Describe Virchow’s triad

Answer 16

1) Changes in the vascular wall (endothelial damage)
2) Changes in blood flow (slow or turbulent flow)
3) Changes in the blood (hypercoagulability)
Thrombosis depends on these three things (two of the three are usually enough to form a thrombus)

Question 17

List the outcomes of thrombosis

Answer 17

Resolution = complete dissolution 
Propagation = grows bigger
Organisation = becomes a fibrous scar
Recanalisation = new channels lined with endothelium run through thrombus 
Embolisation = part breaks off

Question 18

List the clinical effects of thrombosis

Answer 18

Occlusion of an artery resulting in ischaemia and infarction
Congestion and oedema in the venous bed
Repeated miscarriages due to thrombosis of the uteroplacental vasculature

Question 19

What is a thromboembolism?

Answer 19

Embolism that arises from a thrombus

Cannot occur in veins as blood flow is from smaller to larger veins (embolise in the pulmonary artery)

Question 20

What are pulmonary emboli?

Answer 20

Most arise from the deep veins of the thigh and popliteal vein
Large pulmonary emboli cause sudden death
Saddle emboli = large emboli that become lodged astride the bifurcation of an artery thus blocking both branches

Question 21

What are paradoxical emboli?

Answer 21

Thromboemboli that form in the systemic veins but embolise to the systemic arteries
Can bypass the lungs in two ways:
1) Small emboli can pass through arterio-venous anastomoses in the pulmonary circulation
2) Larger emboli can only enter by passing through defects in IV septum/patent foramen ovale

Question 22

What are TIAs?

Answer 22

Transient ischaemia attacks are episodes of neurological dysfunction that appear suddenly, last minutes to hours and then disappear
Result of microemboli, usually atheroemboli, to the brain

Question 23

What are other types of emboli?

Answer 23

Fat and bone marrow emboli
Gas emboli (air embolism, nitrogen in divers)
Amniotic fluid embolism
Talcum embolism (found in lungs of IV drug users)

Question 24

What are the different types of treatment for thromboembolic disease?

Answer 24

General prophylaxis = achieved by either preventing venous stasis or by preventing hypercoagulability
Aspirin = antithrombogenic -> irreversibly acetylates cyclooxygenase and this means that platelets can’t produce thromboxane A2 which is a powerful platelet aggregator
Heparin = forms irreversible complexes with antithrombin III resulting in its activation (used as prophylaxis and treatment)
Warfarin = oral medication which interferes with vitamin K metabolism
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