Bleeding and Thrombosis Flashcards by Scott Mcildowie

List causes of failure of platelet plug formation (failure of primary haemostasis)

Vascular disease
Low platelet count (thrombocytopenia)
Impaired platelet function
Von Willbrand Factor disease

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What is the main vascular cause of failed primary haemostasis?

Vasculitis e.g. Henoch-Schonlein purpura

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Thrombocytopenia can be due to what 2 factors?

Reduced platelet production (marrow disorder)

Increased platelet destruction

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List the main causes of platelet destruction

Coagulopathy (DIC)
Autoimmunity
Hypersplenism

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Von Willebrand Factor deficiency is mainly hereditary and follows what inheritance pattern?

Autosomal dominant

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List causes of failure of fibrin clot formation (failure of secondary haemostasis)

Multiple clotting factor deficiency

Single clotting factor deficiency

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List causes of multiple clotting factor deficiency

DIC
Liver failure
Vitamin K deficiency
Warfarin therapy

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What is the main cause of single clotting factor deficiency?

Haemophilia

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Which clotting factors are carboxylated (activated) by vitamin K?

II
VII
IX
X

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List causes of vitamin K deficiency

Poor dietary intake
Malabsorption
Obstructive jaundice
Antagonists (warfarin)
Haemorrhagic disease of newborn

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What is disseminated intravascular coagulation (DIC)?

Excessive activation of the haemostatic system, causing depletion of all clotting factors

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What are the main signs of DIC?

Abdominal bruising/purpura

Generalised bleeding

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What are the main screening tests/investigations for haemostasis?

Platelet count
Prothrombin time
APT time

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List the main causes of DIC

Sepsis
Obstetric emergencies
Malignancy
Hypovolaemic shock

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How is DIC treated?

Treat underlying cause

Replace clotting factors

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What pattern of inheritance does haemophilia follow?

X-linked

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What are the two types of haemophilia? Which is more common?

Haemophilia A (VIII deficiency)
Haemophilia B (IX deficiency)
A is more common than B

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Where does bleeding usually occur in haemophilia?

Ankles
Knees
(haemarthroses)

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Is haemophilia a disorder of primary or secondary haemostasis?

Secondary haemostasis

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Prothrombin time is usually normal in a haemophiliac. True/False?

True

Isolated prolonged APT time

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What is the main cause of arterial thrombosis?

Atherosclerosis

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How is atherosclerosis treated?

Antiplatelet (aspirin)

Venous thrombosis is caused by Virchow’s triad. List the components of this triad

Hypercoagulability
Vessel wall damage
Stasis of blood flow

What is the risk of a deep vein thrombosis in the leg?

Clot can form and end up in pulmonary circulation, causing pulmonary embolism

List risk factors for venous thromboembolism

``` Age Obesity Pregnancy Oestrogen therapy (OCP) Trauma/surgery Infection Paralysis Thrombophilia Previous DVT/PE ```

What are the main mechanisms of thrombophilia?

Increased coagulation activity Decreased fibrinolytic activity Decreased anticoagulant activity

What are the main naturally occuring anticoagulants?

Serine protease inhibitors (antithrombin) | Protein C and S

What is Factor V Leiden?

Variant of factor V that cannot be inhibited as effectively - increases risk of venous thrombosis due to less anticoagulation

List the main hereditary thrombophilias

Factor V Leiden Antithrombin deficiency Protein C and S deficiency Prothrombin mutation

What is the main acquired thrombophilia?

Antiphospholipid syndrome

How does atherosclerosis form?

Foamy macrophages rich in cholesterol are attracted to damaged arterial endothelium, forming atherosclerotic plaques

What are the consequences of unstable atherosclerotic plaques?

Can rupture and cause arterial thrombosis/embolism (resulting in unstable angina/MI/stroke)

Which chemicals released by platelets encourage platelet aggregation?

``` Thromboxane A2 (TXA2) ADP ```

List risk factors for arterial thrombosis

Hypertension Smoking High cholesterol Diabetes

How does aspirin work?

Inhibit COX enzyme causing decreased TXA2 production and thus reduced platelet aggregation

List some side effects of aspirin

Bleeding GI ulceration Bronchospasm

How does clopidogrel work?

ADP receptor antagonist (blocks P2Y1) to reduce platelet aggregation

Through which receptors do platelets bind together?

GP IIb/IIIa

How does atrial fibrillation increase the risk of stroke?

Stasis of blood flow (due to irregular heartbeat) causes congealing and clot formation in atrium, which may travel and lodge in the brain

Which factors do protein C and S inhibit in the clotting cascade?

V VIII IX Xa

How does heparin work?

Potentiates action of antithrombin (inhibitor of thrombin) to reduce clotting

Which factors are inhibited by unfractionated heparin?

Thrombin | Xa

Which factors are inhibited by LMW heparin?

Xa only (indirectly inhibits thrombin since X is higher in the cascade)

Which coagulation test is used to monitor heparin?

APT time for unfractionated heparin | Anti-Xa assay for LMW heparin

List some side effects of heparin

Bleeding Thrombocytopenia, causing thrombosis Osteoporosis long-term

How can the effects of heparin be reversed?

``` Stop heparin Protamine sulphate (reverses AT so complete reversal for unfractionated heparin) ```

How does warfarin work?

Inhibits vitamin K to cause reduced clotting factor activation

What is required for vitamin K absorption?

Bile salts

Which factors are vitamin K -dependent?

``` II VII IX X Protein C and S ```

How is acute thrombosis in hospital treated - heparin or warfarin?

Heparin (works immediately)

What is the equation for calculating a patient's INR?

(PT time / mean normal PT time)^ISI

How can the effects of warfarin be reversed?

Omit warfarin dose Oral vitamin K Administer clotting factors

Give an example of a direct thrombin inhibitor

Dabigatran

Give an example of an oral Xa inhibitor

Rivaroxaban