Bleeding and Thrombosis Flashcards
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
What is the main vascular cause of failed primary haemostasis?
Vasculitis e.g. Henoch-Schonlein purpura
Thrombocytopenia can be due to what 2 factors?
Reduced platelet production (marrow disorder)
Increased platelet destruction
List the main causes of platelet destruction
Coagulopathy (DIC)
Autoimmunity
Hypersplenism
Von Willebrand Factor deficiency is mainly hereditary and follows what inheritance pattern?
Autosomal dominant
List causes of failure of fibrin clot formation (failure of secondary haemostasis)
Multiple clotting factor deficiency
Single clotting factor deficiency
List causes of multiple clotting factor deficiency
DIC
Liver failure
Vitamin K deficiency
Warfarin therapy
What is the main cause of single clotting factor deficiency?
Haemophilia
Which clotting factors are carboxylated (activated) by vitamin K?
II
VII
IX
X
List causes of vitamin K deficiency
Poor dietary intake Malabsorption Obstructive jaundice Antagonists (warfarin) Haemorrhagic disease of newborn
What is disseminated intravascular coagulation (DIC)?
Excessive activation of the haemostatic system, causing depletion of all clotting factors
What are the main signs of DIC?
Abdominal bruising/purpura
Generalised bleeding
What are the main screening tests/investigations for haemostasis?
Platelet count
Prothrombin time
APT time
List the main causes of DIC
Sepsis
Obstetric emergencies
Malignancy
Hypovolaemic shock
How is DIC treated?
Treat underlying cause
Replace clotting factors
What pattern of inheritance does haemophilia follow?
X-linked
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
Where does bleeding usually occur in haemophilia?
Ankles
Knees
(haemarthroses)
Is haemophilia a disorder of primary or secondary haemostasis?
Secondary haemostasis
Prothrombin time is usually normal in a haemophiliac. True/False?
True
Isolated prolonged APT time
What is the main cause of arterial thrombosis?
Atherosclerosis
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
