Haemostasis - 1 Flashcards by Sara Russell

Describe the three main factors involved in haemostasis.

Vessel Constriction
Platelets - activation, adhesion, platelet plug
Coagulation cascade activated = fibrin

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When would increased bleeding or thrombosis occur?

Vessel wall disease
Abnormal numbers of functions of platelets
Reduced or abnormal coagulation proteins or inhibitors of coagulation

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Purpura

Bleeding into the skin due to reduced platelet count

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Ecchymoses

Large purpura

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Petechiae

Small pinpoint sites of bleeding from capillaries

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What is needed for normal homeostasis?

Normal blood vessel walls
Normal endothelium
Normal platelet numbers and function
Normal amounts of functionally normal coagulation proteins
Normal blood flow and normal inhibitors of platelet activation and coagulation

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Name the platelet activation receptors.

Collagen - GpIa
vWF - GpIb 
Thromboxane A2 
Adrenaline
ADP 
Thrombin 
Serotonin

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Name the steps of platelets involved in bleeding.

Adhesion
Activation
Platelet plug formation

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What happens in platelet adhesion?

GPIV/GPIa binds to collagen

GPIb binds to vWF

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Describe the events occurring in platelet activation.

Shape change - more spherical and pseudopods extended
Secretion of granules - alpha and dense to recruit and activate more platelets
Production of thromboxane A2 (TXA2) via COX pathway - more platelets activated by TXA2
GpIIa and GPIIb activated - Fibrinogen or vWF binds to GpIIa/GpIIb and platelets aggregate
Microvesicles budded off platelet cell membrane

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What effect does shearing stress from turbulent blood flow have on platelet activation?

May partially activate platelets

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What are dense granules formed of?

Ca
ADP
Serotonin - vasoconstriction and platelet activation

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What are alpha granules formed of?

Fibrinogen, vWF, Factor V, Factor VII

Platelet specific: platelet factor 4 (anti-heparin)

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Why is the platelet plug essential for stopping bleeding?

Ensures activating coagulation factors are not washed away

Activated coagulation factor concentrations increase to the levels needed for a fibrin clot to be produced

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What is the bleeding time test?

Standardized assessment of microvascular bleeding

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When is the bleeding time test not undertaken?

Uncooperative px (children)
Elderly px with thin skin
Abnormal skin
Taking anti-platelet meds

What is the PFA-100 test?

Tests platelet function, replaces bleeding time test

What affects the PFA-100 results?

Platelet numbers, platelet function abnormalities

What factors affect both the bleeding time test and PFA-100 test?

Diet factors - garlic, ginger, chocolate, alcohol

What are important questions to ask before surgeries?

Do you bleed from small cuts for longer than other people? (significant if >5min)
Do you get spontaneous nosebleeds? - how long and how often
Do you bruise more easily than others - how often do you get a bruise? (monthly or more)
How large are the bruises (significant if often >2.5cm)

NB: these questions are not reliable for carrier states,

Where are platelets produced?

In the bone marrow by megakaryocytes

What is the process of platelet production called? Describe this process.

Thrombopoiesis
Megakaryoblast –> megakaryocyte –> platelets
25% of platelets are kept in the spleen, after splenectomy, platelet count increases by 20%

What is thrombocytopenia?

Reduced platelet count

Name the features of mild thrombocytopenia.

Platelet count: 50-100
Increased bleeding with trauma or surgery if below 100
Slow oozing from cut surface

Name the features of moderate thrombocytopenia.

Platelet count: 20-50 | Bruising more common

Name the features of severe thrombocytopenia.

Platelet count: less than 20 Bruising with minimal trauma, petechiae, may be spontaneous Life threating bleeding into brain, from gut, retroperitoneal

What is the effect of aspirin on bleeding time in thrombocytopenia?

Prolongs bleeding time by 3 min. | However hype responders and non-responders exist.

Name the causes of thrombocytopenia.

Reduced production of platelets Shortened survival of platelets Dilutional Sequestration in spleen

What causes a reduction in the number of platelets?

Marrow depression: chemo, radiotherapy, drugs/chemicals Marrow failure due to marrow replacement: cancer of bone marrow, secondary marrow infiltration Selective depression of megakaryocytes: viral infections, drugs and chemicals Aplastic anaemia (rare) Hereditary (rare)

What is responsible for shortened platelet survival?

Increased destruction of platelets - autoimmune, drug-induced antibody Activation/Consumption of platelets - immune, disseminated intravascular coagulation (gram negative septicaemia)

Describe the dilutional cause for thrombocytopenia.

Bleeding followed by massive transfusion

Describe how sequestration in the spleen causes thrombocytopenia.

Pooling of 30-80% of platelets in an enlarged spleen (splenomegaly)

Name factors causing acquired platelet function defects.

Anti-platelet drugs - aspirin, clopidogrel | Other drugs - NSAIDs

How else might a person have a platelet function defect?

From inheritance | Severe Inherited Platelet Function Defects are rare.

Describe the relationship between platelets and endothelium in normal blood flow.

Platelets do no normally adhere to the endothelium. This is because the endothelium secretes NO and prostacyclin which dilates the blood vessels and inhibits platelet activation.

Describe the flow of normal blood.

Velocity of flow is faster in the centre of blood vessels Lower shear stress at endothelial cell surface Central red cell rich zone Peripheral plasma and platelet rich zone

What do endothelial cells do?

Clear ADP released by activated platelets

What happens hen the endothelium is activated?

P-selectin expressed - platelets may adhere | Endothelin is produced - enhances vasoconstriction

What happens when endothelial cells are lost?

Vessel constriction - nerve reflexes Platelets adhere to connective tissue - collage and subendothelial vWF Platelet activation and release reaction - release of ADP, release of serotonin (vessel constriction), TXA2 synthesized More platelets activated and aggregated - plug forms, bleeding from small vessels stops