Hematology Flashcards
(103 cards)
What two factors are necessary to maintain the circulation of blood in fluid state to blood vessels?
Fibrinolytic anticoagulant proteins
Coagulation factors, platelets
Describe the structure of platelets
Discoid
Non-nucleated
Granule-containing
Where and how are platelets formed?
Bone marrow by fragmentation of megakaryocytic cytoplasm from myeloid stem cells
Describe the Vasoconstriction stage of Primary Haemostasis
Nitric Oxide and prostacyclin concentrations are less than endothelin concentration
So vasoconstriction occurs to reduce the amount of blood being lost
Outline the process of Platelet Adhesion during Primary Haemostasis
VWF binds to collagen on the endothelium at the site of injury and then GPIb receptor on the platelet binds to VWF.
OR
platelets stick to collagen via the GPIa receptor.
What do the alpha granules contain?
VWF
Fibrinogen
What do dense granules contain?
Serotonin
ADP
Ca2+
How does the Activation and Degranulation of platelets occur in Primary Haemostasis?
Platelet and GPIb receptor change shape so that it can bind properly to the endothelium
The alpha and dense granules of platelets are released
The ADP in dense granules is what activates the GPIIIa receptors to bind to the fibrinogen
Describe the final step of platelet aggregation in Primary Haemostasis
Platelet releases Prostaglandin, Thromboxane A2, and ADP
Resulting in Positive feedback for more recruitment activation and aggregation as the platelet changes shape and many will bind to a single fibrinogen
Creating the platelet plug
How does Aspirin inhibit the activation of platelets?
Inhibits the production of thromboxane A2 by irreversibly blocking the action of cyclo-oxygenase (COX), resulting in a reduction in platelet aggregation.
How does the anti-platelet drug Clopidogrel work?
Irreversibly blocking ADP receptor (P2Y12) on the platelet cell membrane
What is the function of fibrin?
To reinforce the platelet plug at the site of injury and make it stronger
Describe what happens during the Initiation stage of Secondary Haemostasis
Extrinsic: Triggered by tissue factor (TF) on surface of endothelial cells binds to VIIa → X to Xa
Or
Intrisic: Triggered by Sub-endothelium collagen to convert XII to XIIa → XI to XIa → IX to IXa → VWF to VIIa → X to Xa
Xa leads to activation of prothrombin (Factor II) (inactive form) → Generation of small thrombin (active form)
What occurs in the Amplification stage of Secondary Haemostasis?
A small amount of thrombin mediates activation of co-factors V & VIII, zymogen (proenzyme) factor XI, and platelets
What is the purpose of thrombin?
To convert fibrinogen to fibrin
Outline the Propagation stage of Secondary Haemostasis
Factor XI converts more IX to IXa
With factor VIIIa, XIa will amplify conversion of factor X→Xa
Leading to a rapid burst in thrombin generation, which cleaves circulating fibrinogen to form insoluble clot
What is the function of Proteins C & S?
Protein C is activated when thrombin binds to thrombomodulin on endothelial cell surface
Activated protein C in the presence of protein S will inactivate factors Va and VIIIa
How do Antithrombin and Heparin promote anticoagulation?
Thrombin and factor Xa are inactivated by circulating inhibitor, antithrombin by the binding of antithrombin to endothelial cell-associated heparins.
Heparin enhances the binding capabilities of antithrombin to Factor II (prothrombin)
Inactivation of thrombin requires larger chains of heparin to wrap around both antithrombin and thrombin
How is Warfarin an anticoagulant?
It is a Vitamin K antagonist working by interfering with protein carboxylation
Therefore reduces synthesis of functional factors II, VII, IX and X by the liver
Takes several days to start working
What is meant by a zymogen?
A proenzyme = an enzyme that generates another enzyme
What is the function of the Fibrinolytic system?
To remove clot after vasculature is repaired
What is plasminogen?
The inactive zymogen form of plasmin
What does plasmin do?
Digests Fibrin into Fibrin Degradation Products - breaks down the clot
Digests Fibrinogen into Fibrinogen Degradation Products
Digests V & VII
Digests II & XII to prevent clot formation
Outline briefly the fibrinolytic system?
Tissue plasminogen activator (t-PA) converts plasminogen into plasmin to lyse the fibrin and fibrinogen to form degradation products. This activation will only happen if t-PA and plasminogen both bind to lysine residues in fibrin.
