MoD S6 - Haemostasis, Thrombosis and Embolism

Question 1

What factors does successful haemostasis depend on?

Answer 1

Vessel wall contraction
Platelets
Coagulation system
Fibrinolytic system

Question 2

How do blood vessels limit blood loss upon being injured?

Answer 2

Constrict to limit blood loss:

• More effective if vessel fully severed, not just partially
• Mechanism not fully understood

Question 3

What are the major actions of platelets when a vessel is injured?

Answer 3

Adhere to damaged vessel wall and other platelets

Form a platelet plug

Platelet release reaction

Question 4

What is the platelet release reaction?

Answer 4

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

Question 5

Briefly describe the process of coagulation

Answer 5

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)

Question 6

Why must coagulation be tightly controlled?

Answer 6

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

Question 7

Give 5 examples of thrombin inhibitors

Which 2 are non specific antiproteases?

Which 3, when deficient lead to increased risk of thrombosis?

Answer 7

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

Question 8

Give a brief description of fibrinolysis

How is this process exploited therapeutically?

Answer 8

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

Question 9

How is the endothelium involved in haemostasis?

Answer 9

Produces anti-thrombotic factors such as:

• Plasminogen activators
• Prostacyclin
• Nitric oxide
• Thrombomodulin

Question 10

Define thrombosis

Answer 10

The formation of a solid mass of blood in the circulatory system during life

Question 11

Why does thrombosis occur?

Split the different reasons into 3 major categories

Answer 11

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

Question 12

Describe the appearance of an arterial thrombus

Answer 12

Paler
Granular
Lines of Zahn
Lower cell content

Question 13

What are lines of Zahn?

Answer 13

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

Question 14

Describe the appearance of a venous thrombus

Answer 14

Soft
Gelatinous
Deep red
Higher cell content

Question 15

What are the outcomes possible after thrombus formation?

Answer 15

Lysis
Propagation
Organisation
Recanalisation
Embolism

Question 16

Describe lysis of a thrombus

Answer 16

Complete dissolution of the thrombus

The fibrinolytic system is activated and bloodflow re-established

This is most likely when thrombi are small

Question 17

Describe propagation of a thrombus

Answer 17

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

Question 18

Describe organisation of a thrombus

Answer 18

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

Question 19

Describe recanalisation of a thrombus

Answer 19

Similar to organisation however one or more channels are developed in the organising tissue to partially re-establish bloodflow

Question 20

Describe embolism of a thrombus

Answer 20

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

Question 21

What are the effects of an arterial thrombosis?

What effects do site and collateral circulation have on the effects of a thrombus?

Answer 21

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

Question 22

What are the effects of a venous thrombosis?

Answer 22

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

Question 23

Define embolism

Answer 23

The blockage of a blood vessel by a solid, liquid or gas at a site distant to its origin

Question 24

What are some of the different types of embolism?

Answer 24

Thrombo-embolism (90%)
Air
Amniotic fluid
Gaseous nitrogen (the bends)
Medical equipment
Tumour cells
Septic tissue

Question 25

Give 4 common locations for thrombus formation and where any emboli from these thrombi would travel

Answer 25

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

Question 26

What are the pre-disposing factors to deep vein thrombosis?

Answer 26

``` Immobility/bed rest Post-op Pregnancy and post-partum Oral contraceptives Severe burns Cardiac failure Disseminated cancer ```

Question 27

How can risk of deep vein thrombosis be reduced?

Answer 27

High risk patients are identified and then: - Heparin can be given subcutaneously - Leg compression before and after surgury (thrombo-embolic deterrent stocking)

Question 28

How can deep vein thrombosis be treated?

Answer 28

Intravenous heparin Oral warfarin Filter can be placed in the inferior vena cavae

Question 29

Give the effects of a massive pulmonary embolism and how 'massive' is defined

Answer 29

Massive defined by reduction of >60% of blood flow Rapidly fatal

Question 30

Give the effects of a major and minor pulmonary embolism

Answer 30

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

Question 31

What is the effect of recurrent minor pulmonary emboli?

Answer 31

Can lead to pulmonary hypertension as progressively more and more of the pulmonary circulation is blocked

Question 32

What is a common cause of fat embolism? Where might this embolism end up?

Answer 32

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)

Question 33

What is the effect of Disseminated intravascular coagulation on the body? Explain how these seemingly opposite effects occur as a result of this condition

Answer 33

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

Question 34

How can disseminated intravascular coagulation be treated?

Answer 34

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

Question 35

Give examples of conditions that may cause disseminated intravascular coagulation This card lists only a few examples, there are others

Answer 35

Cancers (particularly lung, prostate, stomach) Massive tissue injury (trauma, burns, hypothermia) Bacterial, fungal or protozoal infections Liver disease Obstetric complications

Question 36

What is the inheritance pattern of Haemophilia?

Answer 36

X-linked recessive

Question 37

What are the main clinical features of Haemophilia ?

Answer 37

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

Question 38

What are the laboratory findings of someone with Haemophilia A?

Answer 38

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

Question 39

How is Haemophilia A treated?

Answer 39

Best treated through injection of additional clotting factor

Question 40

Give a complication of Heamophilia A treatment

Answer 40

Immune rejection of the injected clotting factors may occur

Question 41

What is thrombocytopenia? What are some of the possible causes?

Answer 41

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

Question 42

How is thrombocytopenia treated?

Answer 42

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

Question 43

What are some of the common symptoms of thrombocytopenia?

Answer 43

Mild to serious internal and external bleeding Purpura (bruises) and petechiae (red or purple dots on the skin)

Question 44

How might a cerebral embolism come about? What conditions may result?

Answer 44

Atrial fibrillation causing blood stasis and thrombus formation Thrombus embolises to the cerebral circulation Can cause stroke or transient ischaemic attacks

Question 45

What is an iatrogenic embolism?

Answer 45

Embolism due to medical treatment E.g. Medical equipment or injection of air