MoD session 5: haemostasis and thrombosis

Question 1

What is haemostasis?

Answer 1

Physiological host defence response to blood vessel injury and bleeding-to stop blood loss

Question 2

What factors determine successful haemostasis?

Answer 2

Vessel wall-constricts to limit blood loss
Platelets-form a platelet plug
Coagulation cascade-ends in formation of fibrin
Fibrinolysis-to break down fibrin so not excess clotting. Plasminogen activators convert plasminogen to plasmin
Endothelium-produces anti-thrombotic factors (plasminogen activators, prostacyclin, nitric oxide, thrombomodulin)

Question 3

What is the platelet release reaction?

Answer 3

Once stuck, platelets release molecules to expand the plug and activate coagulation
ADP and thromboxane A2 cause platelet aggregation. 5HT and PF3 are also released

Question 4

What are platelets?

Answer 4

Subcellular fragments of megakaryocytes that are made in the bone marrow

Question 5

Outline the coagulation cascade

Answer 5

Extrinsic and intrinsic pathways
Prothrombin–>thrombin so thombin can convert fibrinogen–>fibrin
Tightly regulated to balance pro- and anti-coagulants
Review MGD

Question 6

What is thrombosis?

Answer 6

The formation of a solid mass of blood within the circulatory system/heart DURING LIFE (if after death isn’t a thrombus)

Question 7

Describe Virchow’s triad, which explains the causes of thrombosis

Answer 7

1. ABNORMAL VESSEL WALL: atheroma/direct injury/inflammation
2. ABNORMAL BLOOD FLOW: stagnation/turbulence
3. ABNORMAL BLOOD COMPONENTS: smokers/post partum/post operative (more coagulants to prevent bleeding in latter two is natural)

Question 8

Appearance of arterial thrombi?

Answer 8

Pale, granular, lines of Zahn (alternating pale pink bands with fibrin, and red bands of RBCs), low cell content

Question 9

Appearance of venous thrombi?

Answer 9

Soft, gelatinous, deep red colour, high cell content

Question 10

Describe the possible outcomes of thrombosis

Answer 10

LYSIS: complete dissolution more likely if small, by fibrinolytic system

PROPAGATION: spread of thrombus in direction of blood flow (i.e. distally in arteries and proximally in veins); veins get bigger towards heart so thrombus starting in small vein gets bigger

ORGANISATION: reparative ingrowth of fibroblasts and capillaries, lumen remains obstructed and connective tissue becomes more scar-like

RECANALISATION: mix of fibrinolysis and organisation. Blood flow incompletely reestablished, 1 or more channels formed through organising thrombus

EMBOLISM: part of thrombus breaks off, travels through bloodstream and lodges at a distant site

Question 11

Effects of an arterial thrombus?

Answer 11

Ischaemia
Infarction
(depends on site and collateral circulation)

Question 12

Effects of a venous thrombus?

Answer 12

Congestion and oedema (as veins can’t drain tissue, so increase in hydrostatic pressure so poor flow. Tissue pressure can eventually reach arterial pressure so no flow–> infarction)
Ischaemia
Infarction

Question 13

Define embolism

Answer 13

Blockage of a blood vessel by solid, liquid or gas at a site distant from its origin

Question 14

Name the different types of embolism

Answer 14

Thrombo-emobili (>90%)
Air
Amniotic fluid 
Nitrogen (decompression sickness when gaseous nitrogen leaves blood; can lead to avascular necrosis)
Medical equipment
Tumour cells

Question 15

Where can thrombo-emoboli travel to and from?

Answer 15

Systemic veins to lungs (pulmonary emboli)
Heart via aorta to renal, mesenteric and other arteries
Atheromatous carotid arteries to brain
Atheromatous abdominal aorta to arteries of legs

Question 16

Risk factors for deep vein thrombosis?

Answer 16

Immobility
Long journey where legs compressed
Surgery
Pregnancy and post-partum
Oral contraceptives
Severe burns
Cardiac failure
Disseminated cancer

Question 17

Prevention and treatment of DVT?

Answer 17

Prevention: subcutaneous heparin-based drug, leg compression during surgery to expel blood from venous circulation back to the heard to prevent stagnation
Treatment: IV heparin and oral warfarin. Stop thrombus getting bigger but don’t directly dissolve

Question 18

Pulmonary embolism?

Answer 18

Minor PE: small peripheral pulmonary arteries blocked. Asymptomatic or minor sob, particularly in young fit people. Multiple minor PEs can lead to pulmonary hypertension
Major PE: medium-sized pulmonary vessels blocked. SOB, cough, bloody sputum
Massive PE: >60% reduction in blood flow, rapidly fatal

Question 19

Cerebral embolism?

Answer 19

Thrombus passes through cerebral supply, causes TIA, “messenger” that there might be a stroke

Question 20

Iatrogenic embolism?

Answer 20

Due to medical treatment

Question 21

Fat embolism-from a long bone fracture?

Answer 21

Fat and bone marrow from site of fracture gets into circulation and stops somewhere, causing ischaemic problems.
Can cause neurological symptoms e.g. confusion in #NoF patients

Question 22

Haemophilia?

Answer 22

X-linked recessive disorder affecting mainly males.
Haemophilia A: deficiency in factor VIII
Haemophilia B: deficiency in factor IX

Both cause spontaneous haemorrhage into joints and soft tissues, bleeding after trauma, bruising. Need treatment with clotting factor replacement therapy

Question 23

Disseminated intravascular coagulation? (acquired)

Answer 23

Physiological generation of thrombin is unregulated, so when coagulation is activated thrombin is released into the circulation so microthrombi form in numerous organs
Fibrinolytic system is activated but unregulated, leading to haemorrhagic consequences-plasmin released into circulation
so
combination of thrombosis and haemorrhage. Consumption of clotting factors and platelets in the process of clot formation

Question 24

Thrombocytopenia

Answer 24

Deficiency of platelets, so bleeding into tissues, bruising and slow blood clotting after injury
Causes:
-leukaemia: not enough platelets made in the bone marrow
-DIC or hypersplenism: increased breakdown of platelets in blood/spleen

Question 25

Thrombophilia

Answer 25

Blood has increased tendency to form clots
Presentation: history of venous thromboembolism, or strong family history (can be heritable)
Other causes: heart failure, haemolytic anaemia
Predisposes to thromboembolism, may need thromboprophylaxis

Question 26

Amniotic fluid embolism

Answer 26

A rare and severe consequence of pregnancy
Entry of amniotic fluid/hair/foetal cells into the maternal circulation via uterine veins in placental bed of uterus. Causes heart and lung collapse and massive haemorrhage
Very rare, no specific treatment

Question 27

Bowel infarction

Answer 27

Often due to bowel obstruction or occlusion of one of the mesenteric arteries

Question 28

Define aneurysm

Answer 28

A permanent and irreversible dilatation of a blood vessel by at least 50% of the normal diamter. Aortic aneurysms are abdominal (majority) or thoracic

Question 29

How are aneurysms caused?

Answer 29

Degradation of the elastic lamellae, a leukocytic infiltrate, enhanced proteolysis and smooth muscle cell loss. The dilatation affects all 3 layers of the arterial wall

Question 30

What is a pseudoaneurysm?

Answer 30

Blood leaks through arterial wall but is contained by the adventitia or surrounding perivascular structure

Question 31

Seqeunce of events leading to DVT after long flight?

Answer 31

Immobility and compression causes stagnated flow
Thrombus forms in vein of lower limb
Clot increases venous pressure so increases hydrostatic pressure
Water leaks into vein–>oedema
Venous return in legs driving force reduced even more than usual
Symptoms often not until late as collateral venous supplies initially available to bypass clot

Question 32

Why are those who have had surgery, burns or trauma particularly susceptible to DVT?

Answer 32

Hypercoagulative state of healing-release of procoagulant substances e.g. tissue factor
Increased hepatic synthesis of coagulation factors
Decreased tissue plasminogen activation
More platelets

Question 33

What is Trousseau syndrome?

Answer 33

Migratory inflammation of a vein, due to an imbalance in the clotting cascade that is induced by an underlying malignancy-tumours produce clotting factors
Common in lung and pancreas adenocarcinomas. Palpable lumps in superficial veins

Question 34

What is a saddle embolus?

Answer 34

A large PE straddling where the pulmonary artery bifurcates and extends into both the left and right pulmonary arteries (very serious as blocks both lungs)

Question 35

What is a paradoxical embolus?

Answer 35

Venous embolus that causes systemic artery infarction by passing through an interatrial or interventricular defect
Paradox as formed in vein but goes into an artery