Venous Thromboembolism Flashcards
Arterial Thrombosis, Venous Thrombosis, Hereditary Thrombophilias, Antiphospholipid Syndrome
What is arterial thrombosis?
A blood clot that forms in an artery
Name four key risk factors for arterial thrombosis
Hypertension
Smoking
High cholesterol
Diabetes mellitus
What happens when the endothelium is damaged in arteries?
Recruitment of cholesterol-rich macrophages (foamy macrophages) leads to plaque formation
What is the difference between stable and unstable plaques?
Stable plaques cause stable angina and intermittent claudication
Unstable plaques can rupture, causing stroke, unstable angina, or myocardial infarction
What is the sequence of events following plaque rupture in arterial thrombosis?
(1) Plaque rupture → platelets adhere to the exposed endothelium
(2) Platelets activate and release granules to recruit more platelets
(3) Platelets aggregate via glycoproteins (GPIIb/IIIa and fibrinogen)
(4) Acute thrombosis → organ ischaemia and infarction.
What triggers platelet adhesion in arterial thrombosis?
Exposed endothelium and release of Von Willebrand factor and other proteins
Name three substances released by platelets that promote clot formation
ADP, thrombin, and thromboxane A2
Which glycoprotein receptors mediate platelet aggregation?
GPIIb/IIIa receptors and fibrinogen
What is the main type of drug used to treat arterial thrombosis?
Antiplatelet drugs, e.g., aspirin
How does arterial thrombosis typically present clinically?
As a stroke or acute coronary syndrome (ACS)
What is venous thrombosis?
A blood clot that forms in a vein
What are the three factors in Virchow’s triad that contribute to venous thrombosis?
(1) Hypercoagulable state
(2) Endothelial injury
(3) Circulatory stasis
How does a venous thrombus differ from an arterial thrombus in composition?
Venous thrombi are rich in fibrin, while arterial thrombi are platelet-rich
Where do deep vein thromboses (DVTs) predominantly form?
In venous valve pockets and other sites of venous stasis
What is the difference between distal and proximal DVTs?
Distal DVT: In the calves.
Proximal DVT: In the popliteal or femoral veins, more likely to embolise.
What are the key diagnostic tests for a DVT?
D-dimer (rule-out test in low Wells score)
US Doppler leg scan (diagnostic test)
When is a Doppler leg scan indicated?
If the patient has raised D-dimers or a high Wells score
What is the first-line imaging for suspected PE?
CT Pulmonary Angiography
When would a V/Q scan be used instead of a CTPA?
In patients with renal impairment, contrast allergies, or pregnancy
What ECG finding is suggestive of PE?
Sinus tachycardia or the S1Q3T3 pattern (right heart strain)
What is the first-line treatment for DVT or PE?
Anticoagulation with apixaban or rivaroxaban
What are the anticoagulation options for the long-term prevention of venous thrombosis?
Warfarin, DOACs, or LMWH
What anticoagulant is preferred in pregnancy?
Low molecular weight heparin
What is the anticoagulant of choice for antiphospholipid syndrome?
Warfarin
What are genetic defects that increase the tendency for premature, unusual, and recurrent thromboses called?
They are conditions associated with increased blood clotting factors and hypercoagulability
What is the most common genetic defect leading to decreased anticoagulant activity?
Factor V Leiden
How does Factor V Leiden increase the risk of thrombosis?
It causes resistance to activated protein C
Name four other genetic causes of decreased anticoagulant activity.
- Prothrombin 20210 mutation
- Antithrombin deficiency
- Protein C deficiency
- Protein S deficiency
What non-hereditary factors are associated with hypercoagulability?
Pregnancy
Oestrogen therapy
What are the symptoms of hereditary thrombophilia?
Usually asymptomatic until the patient develops a thrombosis
At what age should venous thrombosis trigger consideration of hereditary thrombophilia screening?
Before age of 45
How many occurrences of venous thrombosis would prompt hereditary thrombophilia screening?
Recurrent
What type of venous thrombosis might suggest hereditary thrombophilia?
Unusual venous thrombosis
When should hereditary thrombophilia screening be considered?
(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
What is the clinical manifestation of autoimmune disorder APS (Antiphospholipid Syndrome) ?
APS manifests as recurrent venous or arterial thrombosis and/or fetal loss
What is the genetic predisposition for APS?
(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)
How does APS affect β2 glycoprotein 1 in the pathophysiology?
Antibodies lead to a conformational change in β2 glycoprotein 1, activating both primary and secondary haemostasis and causing vessel wall abnormalities
What effect does APS have on coagulation tests?
an increase in phospholipid-dependent coagulation tests
What are the venous clinical manifestations of APS?
(1) DVT
(2) PE
(3) Recurrent pulmonary emboli
(4) Thrombus-induced life-threatening pulmonary hypertension.
(5) Livedo reticularis may also occur
What are the arterial clinical manifestations of APS?
(1) increased stroke or MI frequency
(2) often in younger individuals,
What is the relationship between APS and pregnancy?
APS is associated with recurrent pregnancy loss, late spontaneous fetal loss (second or third trimester), and possible early fetal loss (< 10 weeks’ gestation). Many patients also experience migraine
What is the management for APS?
(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
What tests should be done in suspected antiphospholipid syndrome?
Anticardiolipin antibodies
Lupus anticoagulant
How is antiphospholipid syndrome diagnosed?
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.
What is the first line treatment in anti-phospholipid syndrome?
Low dose aspirin
What are the clinical features of antiphospholipid syndrome?
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
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?
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
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?
Factor V Leiden
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?
Factor V Leiden/ Activated Protein C resistance
Antiphospholipid syndrome is associated with an increased risk of what disease?
Pulmonary embolism
When could an answer be Protein C deficiency for the most likely underlying diagnosis rather than Factor V Leiden
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.
When should thrombophilia testing be considered?
In people who have had an unprovoked DVT or PE
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?
Warfarin for life, target INR 3-4
