Haemostasis And Thrombosis

Question 0

Discuss the regulation of the coagulation system

Answer 0

Thrombin positively feeds back on factors V, VIII, XI.
Thrombin inhibits antithrombin 3, a1 antitrypsin, a2 macroglobulin.
Fibrinolysis - the breakdown of fibrin by plasmin e.g. Streptokinase which activates plasminogen.

Question 1

Define and discuss the term ‘haemostasis’

Answer 1

Haemostasis - the body’s response to stop bleeding and loss of blood
Depends on vessel wall, platelets, coagulation system, fibrinolytic system.
Blood vessels - constrict to limit blood loss
Platelets - adhere to damaged vessel wall and to each other, form a platelet plug
Coagulation - cascade, series of inactive components –> active components, requires tight regulation, balance of procoagulant and anticoagulant forces

Question 2

Define and discuss the term ‘thrombosis’

Answer 2

Thrombosis - the formation of a solid mass of blood within the circulatory system during life
Virchow’s triad:
1. Changes in blood flow (stagmentation, turbulence)
2. Changes in vessel wall (atheroma, injury, inflammation)
3. Changes in blood components (smokers, pregnancy)
Arterial thrombus - pale, granular, lines of Zahn, low cell content
Venous thrombus - deep red, soft, gelatinous, high cell content

Question 3

Discuss the effects of thrombosis

Answer 3

Arterial - ischaemia, infarction

Venous - congestion, oedema, ischaemia, infarction

Question 4

Discuss the outcomes of thrombosis

Answer 4

Lysis - complete dissolution of thrombus, fibrinolytic system active, blood flow re-established
Propagation - progressive spread of thrombosis, distally in arteries, proximally in veins
Organisation - reparative process, ingrowth of fibroblasts and capillaries, lumen remains obstructed
Recanalisation - blood flow re-established but usually incompletely, one or more channels formed through thrombus
Embolism - part of thrombus breaks off, travels in bloodstream, lodges at distant site

Question 5

Define and discuss the term ‘embolism’

Answer 5

Embolism - the blockage of a blood vessel by solid, liquid or gas at a site distant from its origin
90% are thrombo-emboli, others include air, amniotic fluid, nitrogen, medical equipment, tumour cells.

Question 6

Describe possible pathways of a thrombo-emboli

Answer 6

Systemic veins –> lungs = pulmonary embolism
Heart –> aorta –> renal, mesenteric etc.
Atheromatous carotid arteries –> brain = stroke
Atheromatous abdominal aorta –> arteries of the legs

Question 7

Discuss pulmonary embolisms

Answer 7

Massive PE - >60% reduction in blood flow, rapidly fatal
Major PE - medium sized vessels blocked, shortness of breath, cough, blood stained sputum
Minor PE - small peripheral pulmonary arteries blocked, asymptomatic or minor shortness of breath
Recurrent PE –> pulmonary hypertension

Question 8

Discuss deep vein thrombosis

Answer 8

Predisposing factors - immobility/bed rest, post operative, oral contraceptives, severe burns, cardiac failure, disseminated cancer
Prevention - heparin subcutaneously, leg compressions, TED stockings,
Treatment - intravenous heparin (anticoagulant, cofactor for anti thrombin 3), oral warfarin (interferes with synthesis of vit. K dependent clotting factors, slow effect)

Question 9

List other types of embolism

Answer 9

Cerebral embolism - wedge shaped cerebral infarct, atrial fibrillation –> stasis –> thrombus, lead to stroke or transient ischaemic attack
Iatrogenic embolism - air embolism from injection
Fat embolism - after a long bone fracture, lacerations of adipose tissue, rash, shortness of breath, confusion
Nitrogen embolism - nitrogen bubbles form in the blood with rapid decompression

Question 10

Discuss disorders of coagulation including disseminated intravascular coagulation, thrombocytopenia and haemophilia

Answer 10

Disseminated intravascular coagulation (DIC) - pathological activation of coagulation mechanism, small clots form throughout body, disrupting normal coagulation by using up all clotting factors –> abnormal bleeding from skin
Treatment: transfusion of platelets
Thrombocytopenia - low platelet count due to either failure of platelet production, increased platelet destruction or sequestering of platelets. Usually accompanied by bone marrow dysfunction e.g. leukaemia
Haemophilia A - deficiency in factor VIII
Haemophilia B - deficiency in factor IX
X linked recessive, nonsense point mutation, can be mild, moderate or severe, haemorrhage into major joints –> synovial hypertrophy, pain, muscle bleeding –> pressure and necrosis of nerves.
Treatment: self administered factor replacement therapy.