Week 3 - D - Venous thrombosis - (touched on arterial) - Virchows triad, Thrombophilia (inherited and acquired conditions)

Question 1

Thrombotic events take place in arteries and veins. The more common abnormality in clotting is not bleeding problems but instead thrombosis What are the three main types of arterial thrombosis? and the 2 main types of venous thrombosis?

Answer 1

Arterial thrombosis - coronary, cerebral and peripheral thrombosis Venous - deep vein thrombosis (DVT) and pulmonary embolism (PE)

Question 2

What is the difference in how arteries and veins pump blood around the body? Which vessel out of the two contains valves?

Answer 2

Arteries are very high pressure vessels with thick muscular walls which contract to pump blood from the heart to cerebral and peripheral circulation Veins are low pressure and have thin muscular walls and it tends to be the muscular contraction (particularly the calf muscles) that pump blood in the veins back to the heart - veins have valves to prevent the back-flow of the blood

Question 3

What is the muscular layer present in arteries (thick) and veins (thin) known as?

Answer 3

This would be the tunica media - contains smooth muscle

Question 4

Arterial thrombosis is due to astherosclerosis mainly Name 4risk factors for arterial thrombosis? Is the clot described as platelet or fibrin rich ? Are platelet or fibrin thrombus described as a red or white thrombus?

Answer 4

Arterial thrombus - hypertension, hyperlipidaemia, smoking and diabetes mellitus All increase the risk of astherosclerotic plaque formation Described as platelet rich - white thrombus Venous thrombus is described as fibrin rich and is a red thrombus

Question 5

What is the mainstay of treatment for arterial thrombus?

Answer 5

Aspirin and other anti-platelet drugs Modify the risk factors for arterial thrombus also - ie treat HBP, stop smoking, lower cholesterol, treat diabetes

Question 6

What is the triad that sums up the main risk factors for venous thrombosis? (will ask about the risk factors soon)

Answer 6

This would be Virchow’s triad Damage to the vessel wall - ie valve damage Hypercoagulability Stasis of blood flow

Question 7

What are the two main things that cause valvular damage that can predispose to venous thrombosis? What are the treatment options for venous thrombosis?

Answer 7

Two main things - previous thrombosis causes damage to the venous valves and this is the single biggest risk factor for another thrombus Age also increase the risk of thrombosis as the valves degenerate Treatment options - LMWH, warfarin, new oral anticoagulants (NOAC) - thrombolysis is rarely used

Question 8

What are the symptoms of a deep vein thrombosis? What is the other differential for a DVT?

Answer 8

Symptoms o a DVT - usually unilateral swollen (tumor), hot (calor) red (rubor) leg that is often painful (dolor) The other differential would be cellultitis in someobody with these symptoms - swollen, red, hot, painful

Question 9

What are the symptoms/signs of a pulmonary embolism?

Answer 9

Pulmonary infarction HYpoxia Pleuritic chest pain Tachpnoea and tachycardia

Question 10

What may be seen on ABGs in pulmonary embolism? What may be seen on ECG in pulmonary embolism? It is very rare to see this

Answer 10

On ABGs - low PaO2 and low PaCO2 - person is usually in respiratory alkalosis On the ECG, typical to see a tachycardia Rarely see the callsical S1 QIII TIII pattern Deep S waves in 1, patholgical Q waves in III and Inverted T waves in III

Question 11

VTE (venous thromboembolism) risk increases with age with a lifetime risk of 2.5% (1in40) having a VTE What are the risk factors for VTE? Try name at least 8

Answer 11

* Age - Obesity -Immobility * Pregnancy - Oestrogen therapy ie combined pill * Previous DVT/PE -Trauma * Surgery -Malignancy * Paralysis - INfection * Thrombophilia

Question 12

For venous risk factors just thinking of things that cause any of virchows triads As you get old, valves don’t work as well and don’t move as much causing stasis Which of the risk factors increase the risk of stasis?

Answer 12

* Age * Marked obesity * Pregnancy * Previous DVT/PE * Trauma/surgery * Malignancy * Paralysis

Question 13

Which of the risk factors predispose to vessel wall damage? (this has already been discussed remember)

Answer 13

Age and Previous DVT/PE

Question 14

Which of the risk factors increase the risk of hypercoagulability?

Answer 14

* Age Pregnancy Peurperium * Oestorgen therapy * Trauma/surgery Malignancy * Infection Thrombophilia * Risk factors for arterial thrombosis - anything that increases astherosclerotic plaque formation * Risk factors for venous thrombosis - anything that contributes to virchows triad - stasis, vessel wall damage and hypercoaguability

Question 15

Thrombophilia was the other cause of hypercoagualbility. What is thrombophilia?

Answer 15

Thrombophilia is familial or acquired disorders of the haemostatic system which are likely to predispose to thrombosis.

Question 16

The mechanisms which can contribute to increased clotting can either be due to * Increased clotting activity * Platelets (eg essential thrombocythaemia) or * Increased fibrin clot formation Decreased fibrinolysis or Decreased anticoagulant activity Which of these mechanisms is the main cause usually of thrombophilia?

Answer 16

This would be due to decreased anticoagulant activity

Question 17

What are the main anticoagulants in the body? What is their function?

Answer 17

Serine protease inhibitors - ant thrombin Binds mainly to factors IIa and Xa and inactivates them as well as binding to other clotting factors Protein Cand S are activated by thrombin binding to thrombomoduin - a protein present on the endothelial surface and these inactivate mainly factors V and VIII

Question 18

Thrombophilias can be due to hereditary conditions or acquired What is the main familial (hereditary) cause of thrombophilias? Name all 5 inherited causes?

Answer 18

The main familial cause of thrombophilias is known as activated Protein C resistance (APC resistance) - better known as factor V leiden Other inherited causes Prothrombin gene mutation - Prothrombin G20210A mutation Anti-thrombin deficiency Protien C deficiency Protein S deficiency

Question 19

Factor V leiden is the chief cause of inherited thrombophilias What happens in factor V leiden disease?

Answer 19

There is a single point mutation in the factor V causing it to be resistant to protein C and is not broken down meaning anti-coagulation does not work properly

Question 20

What is the prothrombin gene mutation?

Answer 20

In this there is a specific gene mutation where guanine is changed to adenine at position 202010 of the DNA of the prothrombin gene causing high prothrombin levels in the circulation Hence the name Prothrombin G20210A

Question 21

Antithrombin and Protein C/S deficiencies simply mean there is less natural anti-coagulant in the body meaning the clotting factors are not inactivated and clotting continues State the 5 different inherited thrombophilias aain?

Answer 21

* Factor V leiden - single point mutation causes factor V to be resistant to activated Protein C * Prothrombin G20210A - guanine changes to adenine at position 20210 on the DNA of prothrombin - leads to an increase in prothrombin * Antithrombin deficiency * Protein C and S deficiency

Question 22

When is screening for thrombophilias considered?

Answer 22

Consider when venous thrombosis at less than 45 years old If there is recurrent venous thrombosis If there is unusual venous thrombosis - eg portal vein thrombosis If there is a family history of venous thrombosis or thrombophilia If there i recurrent foetal loss >/= 3

Question 23

What is the management of thrombophilias? (in the short and long term)

Answer 23

Avoid risk factors as best as you can eg COC Short term prophylaxis - given when eg pregnant or surgeries Short term acute management - give heparin (LMWH) and start warfarin at the same time and continue for at least 3 months (up to 6months) If the patient experiences recurrent thrombosis - then consider lifelong warfarin

Question 24

When is screening indicated for thrombophilia?

Answer 24

Screening * If patient has venous thrombosis at /=3

Question 25

What is the management of thrombophilia? * If pregnant * If short term prophylaxis eg surgery * If initial venous thromboembolic events * If recurrent thrombosis

Answer 25

Management * If pregnant - LMWH + aspirin If short term prophylaxis eg surgery - LMWH If initial venous thromboembolic events - start on LMWH and Warfarin and continue Warfarin for 3-6 months If recurrent thrombosis - lifelong warfarin if recurrent thrombosis

Question 26

If the patient as Protein C and S deficiency and they are on warfarin, what can this cause?

Answer 26

Skin necrosis can occur in patients with protein C or S deficiency - Warfarin puts people at a high risk of thombosis in the first few days of treatment and therefore if not recongised that they have this defieicny and not started with LMWH, can cause bad necrosis

Question 27

Some people with thrombophilias never actually suffer from thrombotic events Why is this? What is the usual inheritance of the thrombophilias?

Answer 27

This is because usually multiple risk factors are required before a thrombotic event actually occurs Usually the thrombophilias are autosomal dominant inheritance

Question 28

What is the main risk factor for acquired thrombophilia? it is a stronger risk factor for thrombosis than the thrombophilias

Answer 28

This would be anti-phospholipid syndrome

Question 29

What are the features of anti-phospholipid syndrome?

Answer 29

There is recurrent arterial and venous thrombosis As well as recurrent foetal loss (usually suspect if recurrent foetal loss >/= 3) And mild thrombocytopenia * Coag defects- arterial and venous thrombosis * Livedo reticularis * Obstetrics - recurrent miscarriages * Thrombocytopenia

Question 30

Antiphospholipid syndrome can be remembered by acronym CLOT

• Coagulation defects - recurrent arterial and venous thrombosis
• L - What is the condition that appears on the legs?
• Obstetrics - recurrent foetal loss
• Thrombyocytoepnia

What is antiphospholipid caused by?

Answer 30

It is caused by antibodies attacking B2 glycoprotein (unkown function in health) and this activates both primary & secondary haemostasis and vessel wall abnormalities leading to excessive clot formation in arteries and veins

Livedo reticularis on legs

• Mottled, reticulated vascular pattern on legs

Question 31

What are the antibodies that may be seen in anti-phospholipid syndrome? Why does the APTT increase in antiphospholipid syndrome?

Answer 31

Antibodies - Anti-B2 glycoprotein antibodies Anti-Lupus anticoagulant Anti-cardioplin antibodies In the condition there are autoantibodies - the lupus anticoaglants - which have specificity for anionic phosphopids and prolong phospholipid dependent coagulant tests

Question 32

Mostly anti-phospholipid syndrome is a primary disease and idiopathic for cause but what other autoimmune condition is it often associated with? Which antibodies are present in this condition?

Answer 32

It has an association with systemic lupus erythematous Antibodies here -Anti ANA antibodies (not specific), anti dsDNA antibodies, Anti Sm antibodies

Question 33

As antiphospholipid syndrome causes both arterial and venous thrombosis, what is its treatment?

Answer 33

Can treat dependent on the problem If an arterial event asprin, If venous event give LMWH + warfarin

Question 34

What is the score that is calculated when suspecting a DVT or PE?

Answer 34

This is Well’s score - will discuss in more depth in future lecture