Bleeding and Thrombosis Flashcards by Maris Cawthorn

What factors help to forma clot?

Platelets
Von Willebrand Factor
Coagulation Factors

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What causes the clot to remain within the confines of the injury?

Natural anticoagulants

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What causes the clot to disappear?

Fibrinolytic System

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What features of the endothelium also aid flow?

Non-stick surface cells

Produces nitric oxide, heparins, TFPI, Thrombomodulin and prostaglandins which also stop stuff sticking to it.

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What causes clotting factors to become activated?

Abnormal surface

Physiological activator

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What is the first step of Clot formation?

Platelets recognise the abnormal surface and bind to it via receptors.
VWF and tissue factor are also produced to add platelet adhesion.

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Which parts of the platelet bind to endothelium and which to the clotting factors?

Glycoproteins on surface bind to substances to you want to stick to the platelets.
Receptors on their surface bind to molecules that are released due to damage. This triggers signalling so substances can find site to clot.

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What are the substances that can cause granules within the platelet to be released onto the surface of the platelet?

Alpha granules:
VWF
Thrombin

Dense granule:
ADP/ATP
Calcium
Serotonin

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What is the function of platelets in haemostats?

Adhere
Activation
Aggregation

Provide phospholipid surface for coagulation.

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What does collagen bind to on a platelet?

GP1a

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What does vWF bind to on a platelet?

GP1b

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What is the function of Thromboxane?

Allows platelets to shrink down and clump together (aggregate).

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What is required for the activation of coagulation factors?

Need scramblase to flip phospholipid membrane to surface of platelet.

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What binding sites are contained within a molecule of vWF?

Collagen
Platelets
Factor 8

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What attaches to the initial platelet plug?

Fibrinogen bind to 2b3a receptor on platelet.

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What causes fibrinogen to become fibrin?

Activation of coagulation factors. When it becomes fibrin it is a solid clot.

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What is the mechanism of the coagulation pathway.

Zymogens are activated by serum activates.
Factor 12, Factor 11, Factor 9, Factor 8, factor 10, Prothrombin and then Fibrinogen all need to be activated appropriately, in that order for coagulation to occur.

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What is the cause of Haemophilia B?

Factor IX deficiency

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What is the cause of Haemophilia A?

Factor VIII deficiency

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What is the extrinsic pathway?

Factor 7 and tissue factor bind together to activate Factor 10.
Factor 10 then activates prothrombin to change int o thrombin.
Thrombin then activates fibrinogen to change into fibrin.

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What is the Intrinsic pathway?

Thrombin from extrinsic activates intrinsic.

Factor 11 activates Factor 9, Factor 9 and 8 then activate factor 10 to increase thrombin production.

What are some examples of natural anticoagulants?

Tissue factor pathway inhibitor (TFPI)
Antithrombin
Activated Protein C and Protein S.

What is the mechanism of action of TFPI?

Binds to activated factor 10 and 7 and deactivates them.

What is the mechanism of action of Activated protein C and protein S?

Co-factor that binds to Factor 8 and factor 5 and switches them off.

What is the mechanism of action of Antithrombin?

serum protease inhibitor that switches off thrombin, factor 10, factor 11, factor 9 and factor 8.

What are activators of plasminogen and where are they released from?

t-PA and u-PA are activators of plasminogen that are released by the endothelium.

What is the function of t-PA?

Cleaves plasminogen into molecules of plasmin. Plasmin then starts to attack the clot and breaks it into fragments. D-dimer is one of these fragments.

What are some inhibitors of plasmin?

PA1-1 PA1-2 alpha-2-antiplasmin alpha-2-macroglobulin

What drugs acts on the P2y12 pathway?

(ADP pathway) Clopidogrel Prasugrel Ticagrelor

What drugs work on the GP2b/3a pathway?

Abciximab Tirofiban Eptifibatide

What drug works on the COX pathway to produce thromboxane?

Aspirin

What coagulation factors does warfarin work on?

Factors 2, 7, 9, 10. | Post translational modification to prevent them being activated.

What coagulation factors does Heparins work on?

Bind to antithrombin to kill these proteases. Also factor 10

What drugs are direct inhibitors of factor 10?

Rivaroxaban Edoxaban Apixaban

What drugs are direct inhibitors of thrombin?

Dabigatran Bivalirudin Argatroban

What is a thrombus?

Clot arising in the wrong place.

What is a thromboembolism?

Movement of a clot along a vessel.

What is Virchow's triad of thrombosis?

Stasis Hypercoagulability Vessel damage

What are some features of an arterial thrombus?

White clot - platelets and fibrin. Results in ischaemia and infarction. Principally secondary to atherosclerosis.

What are some examples of arterial thromboembolism?

Coronary - MI, Unstable angina. Cerebrovascular - stroke, transient ischaemia. Peripheral - limb ischaemia.

What are the risk factors for arterial thrombosis?

``` Age Smoking Sedentary lifestyle Hypertension Diabetes mellitus Obesity Hypercholesterolaemia ```

What is the management of arterial thrombosis?

Primary prevention - lifestyle modification, treat vascular risk factors. Acute presentation - thrombolysis, anti platelet/anticoagulant drugs. Secondary prevention.

What are the features of venous thrombus?

Red thrombus - fibrin and red cells. Results in back pressure. Principally due to stasis and hyper coagulability.

What are some examples of venous thromboembolism?

``` Limb deep vein thrombosis Pulmonary embolism Visceral venous thrombosis Intracranial venous thrombosis Superficial thrombophlebitis. ```

What are the risk factors for venous thrombosis?

``` Stasis and hyper coagulability Increasing age Pregnancy Surgery Obesity Systemic disease Fam hx Immobility Tissue trauma Hormonal therapy. ```

What are some common systemic diseases that are associated with venous thrombosis?

Cancer Myeloproliferative neoplasm (MPNs). Autoimmune disease - IBD, Connective tissues disease e.g. SLE, Antiphospholipid syndrome (arterial and venous).

How is venous thrombosis diagnosed?

Pretest probability scoring - wells score, geneva score. Lab testing if probability low - D-dimer. Imaging - doppler US, ventilation perfusion scan, CT angiogram.

What drugs are used to treat venous thrombosis?

Anticoagulants - low molecular weight heparin, coumarins (warfarin), DOACs. Thrombolysis in selected cases - massive PE.

What is heritable thrombophilia?

Inherited predisposition to venous thrombosis.

What are some causes of heritable thrombophilia?

``` Factor 5 leiden Prothrombin G20210A Antithrombin deficiency Protein C deficiency Protein S deficiency ```

What are the features of microvascular thrombus?

Platelets and/or fibrin Results in diffuse ischaemia Principally in disseminated intravascular coagulation (DIC).

What are some features of DIC?

Occurs in septicaemia, malignancy, eclampsia. Causes tissue ischaemia - gangrene, organ failure. Consumption of platelets and clotting factors leading to bleeding.