Venous Thromboembolism

Question 1

What is arterial thrombosis?

Answer 1

A blood clot that forms in an artery

Question 2

What happens when the endothelium is damaged in arteries?

Answer 2

Recruitment of cholesterol-rich macrophages (foamy macrophages) leads to plaque formation

Question 3

What is the difference between stable and unstable plaques?

Answer 3

Stable plaques cause stable angina and intermittent claudication

Unstable plaques can rupture, causing stroke, unstable angina, or myocardial infarction

Question 4

What triggers platelet adhesion in arterial thrombosis?

Answer 4

Exposed endothelium and release of Von Willebrand factor and other proteins

Question 5

Name three substances released by platelets that promote clot formation

Answer 5

ADP, thrombin, and thromboxane A2

Question 6

Which glycoprotein receptors mediate platelet aggregation?

Answer 6

GPIIb/IIIa receptors and fibrinogen

Question 7

What is the main type of drug used to treat arterial thrombosis?

Answer 7

Antiplatelet drugs
= eg, aspirin

Question 8

How does arterial thrombosis typically present clinically?

Answer 8

As a stroke or acute coronary syndrome (ACS)

Question 9

What is venous thrombosis?

Answer 9

A blood clot that forms in a vein

Question 10

What are the three factors in Virchow’s triad that contribute to venous thrombosis?

Answer 10

(1) Hypercoagulable state
(2) Endothelial injury
(3) Circulatory stasis

Question 11

How does a venous thrombus differ from an arterial thrombus in composition?

Answer 11

Venous thrombi are rich in fibrin, while arterial thrombi are platelet-rich

Question 12

Where do deep vein thromboses (DVTs) predominantly form?

Answer 12

In venous valve pockets and other sites of venous stasis

Question 13

What is the difference between distal and proximal DVTs?

Answer 13

Distal DVT
= in the calves.

Proximal DVT
= In the popliteal or femoral veins, it is more likely to embolise.

Question 14

What are the key diagnostic tests for a DVT?

Answer 14

D-dimer
=rule-out test in low Wells score

1. US Doppler leg scan
   =diagnostic test

Question 15

When is a Doppler leg scan indicated?

Answer 15

If the patient has raised D-dimers or a high Wells score

Question 16

What is the first-line imaging for suspected PE?

Answer 16

CT Pulmonary Angiography

Question 17

When would a V/Q scan be used instead of a CTPA?

Answer 17

In patients with renal impairment, contrast allergies, or pregnancy

Question 18

What ECG finding is suggestive of PE?

Answer 18

Sinus tachycardia or the S1Q3T3 pattern (right heart strain)

Question 19

What is the first-line treatment for DVT or PE?

Answer 19

Anticoagulation with apixaban or rivaroxaban

Question 20

What are the anticoagulation options for the long-term prevention of venous thrombosis?

Answer 20

Warfarin, DOACs, or LMWH

Question 21

What anticoagulant is preferred in pregnancy?

Answer 21

Low molecular weight heparin

Question 22

What is the anticoagulant of choice for antiphospholipid syndrome?

Answer 22

Warfarin

Question 23

What are genetic defects that increase the tendency for premature, unusual, and recurrent thromboses called?

Answer 23

They are conditions associated with increased blood clotting factors and hypercoagulability

Question 24

What is the most common genetic defect leading to decreased anticoagulant activity?

Answer 24

Factor V Leiden

Question 25

How does Factor V Leiden increase the risk of thrombosis?

Answer 25

It causes resistance to activated protein C

Question 26

Name four other genetic causes of decreased anticoagulant activity.

Answer 26

1. Prothrombin 20210 mutation 2. Antithrombin deficiency 3. Protein C deficiency 4. Protein S deficiency

Question 27

What non-hereditary factors are associated with hypercoagulability?

Answer 27

Pregnancy Oestrogen therapy

Question 28

What are the symptoms of hereditary thrombophilia?

Answer 28

Usually asymptomatic until the patient develops a thrombosis

Question 29

At what age should venous thrombosis trigger consideration of hereditary thrombophilia screening?

Answer 29

Before age of 45

Question 30

How many occurrences of venous thrombosis would prompt hereditary thrombophilia screening?

Answer 30

Recurrent

Question 31

What type of venous thrombosis might suggest hereditary thrombophilia?

Answer 31

Unusual venous thrombosis

Question 32

When should hereditary thrombophilia screening be considered?

Answer 32

(1) Venous thrombosis <45 years old (2) Recurrent venous thrombosis (3) Unusual venous thrombosis (4) Family history of venous thrombosis (5) Family history of thrombophilia

Question 33

What is the clinical manifestation of autoimmune disorder APS (Antiphospholipid Syndrome) ?

Answer 33

APS manifests as recurrent venous or arterial thrombosis and/or fetal loss

Question 34

What is the genetic predisposition for APS?

Answer 34

(1) APS is more common in young females (2) Some patients may have no associated disease (primary APS) (3) have it with SLE or another autoimmune disorder (secondary APS)

Question 35

How does APS affect β2 glycoprotein 1 in the pathophysiology?

Answer 35

Antibodies lead to a conformational change in β2 glycoprotein 1, activating both primary and secondary haemostasis and causing vessel wall abnormalities

Question 36

What effect does APS have on coagulation tests?

Answer 36

an increase in phospholipid-dependent coagulation tests

Question 37

What are the venous clinical manifestations of APS?

Answer 37

(1) DVT (2) PE (3) Recurrent pulmonary emboli (4) Thrombus-induced life-threatening pulmonary hypertension. (5) Livedo reticularis may also occur

Question 38

What are the arterial clinical manifestations of APS?

Answer 38

(1) increased stroke or MI frequency (2) often in younger individuals,

Question 39

What is the relationship between APS and pregnancy?

Answer 39

APS is associated with (1) recurrent pregnancy loss (2) Late spontaneous fetal loss (second or third trimester) (3) possible early fetal loss (< 10 weeks gestation) (4) Many patients also experience migraine

Question 40

What is the management for APS?

Answer 40

(1) Aspirin and warfarin for primary and secondary haemostasis, thrombosis, and stroke prevention. (2) Anticoagulation with LMWH then warfarin or aspirin is used after a thrombosis episode. (3) Patients without a thrombosis history but positive antibodies do not require anticoagulation. (4) During pregnancy, LMWH and aspirin are used for recurrent pregnancy loss

Question 41

What tests should be done in suspected antiphospholipid syndrome?

Answer 41

Anticardiolipin antibodies Lupus anticoagulant

Question 42

How is antiphospholipid syndrome diagnosed?

Answer 42

One or more of the following positive blood tests are needed on 2 occasions, 12 weeks apart to diagnose APS: (1) Anti-cardiolipin antibodies. (2) Anti-beta2-GPI antibodies. (3) Positive lupus anticoagulant assay. Note - syphilis can cause false positive tests for the above, and so should be excluded with with treponemal serology.

Question 43

What is the first line treatment in anti-phospholipid syndrome?

Answer 43

Low dose aspirin

Question 44

What are the clinical features of antiphospholipid syndrome?

Answer 44

CLOT C- Clots (Usually venous thromboembolism (eg. deep venous thrombosis or pulmonary embolism), but arterial embolism (eg. myocardial infarction or stroke) can also occur) L- Livedo reticularis O-Obstetric loss (Recurrent miscarriages + premature births) T-Thrombocytopenia

Question 45

A 31-year-old Caucasian female patient presents to the emergency department with sudden onset shortness of breath and pleuritic chest pain. The patient is hypoxic and tachycardic, but physical examination is otherwise normal. The patient has no past medical or surgical history of note. She works as a fitness instructor. There is no recent travel history. She reports that her sister recently suffered from an unprovoked deep vein thrombosis (DVT) What mutation would be consistent with the most likely diagnosis?

Answer 45

Factor V = The patient presents with clinical features consistent with an unprovoked pulmonary embolism. Patients presenting with unprovoked venous thromboembolism (VTE), particularly those under the age of 50, require workup for inherited causes of thrombophilia. The most common inherited thrombophilia is factor V Leiden, caused by a mutation in factor V

Question 46

A 46-year-old female presents to the emergency department with a painful calf. She is diagnosed with a deep vein thrombosis (DVT). There does not appear to be any risk factors and so this appears to be an unprovoked venous thromboembolism (VTE). She is otherwise well and does not take any medication. She reports that her mother and sister have both had unprovoked pulmonary embolisms in the past. Aside from the DVT, there are no abnormal findings on examination. What is the most likely underlying diagnosis that made her more susceptible to developing DVT?

Answer 46

Factor V Leiden

Question 47

A 30-year-old female is seen in the anticoagulation clinic. She has had 4 episodes of venous thromboembolism (VTE). Two of these episodes occurred during pregnancy. All of her three pregnancies have survived to term. She has a family history of recurrent VTE on her maternal side although not all family members are affected. She is currently on long-term warfarin and her INR is currently in range. What is the most likely cause of her venous thromboembolism?

Answer 47

Factor V Leiden/ Activated Protein C resistance

Question 48

Antiphospholipid syndrome is associated with an increased risk of what disease?

Answer 48

Pulmonary embolism

Question 49

When could an answer be Protein C deficiency for the most likely underlying diagnosis rather than Factor V Leiden

Answer 49

When warfarin is mentioned Protein C deficiency is a hereditary thrombophilia associated with low levels of protein C, a serum anticoagulant. Warfarin reduces production of factor II, VII, IX, X, protein C and protein S. As protein C and S have a shorter half-life than most of the procoagulant clotting factors, there is a period around 1 to 2 days after initiation of warfarin therapy where patients become procoagulable, particularly if they have an underlying protein C or S deficiency.

Question 50

When should thrombophilia testing be considered?

Answer 50

In people who have had an unprovoked DVT or PE

Question 51

A 36-year-old female patient presents to the emergency department with shortness of breath and pleuritic chest pain CT pulmonary angiogram confirms the likely diagnosis. She has a past medical history of antiphospholipid syndrome and a deep vein thrombosis 10 months ago, for which she is receiving warfarin What is the most appropriate long-term anticoagulation plan?

Answer 51

Warfarin for life, target INR 3-4