Disorders of homeostasis Flashcards
What does healthy endothelium express which blocks platelet adhesion?
ecto-ADPase (CD39)
prostacyclin (PGI²)
nitric oxide (NO)
How are platelet disorders organised?
Acquired (drugs etc)
Qualitative (functional defect, inherited/acquired)
Quantitative (thrombocytopenia or thrombocytosis)
Outline thrombocytopenia
- Deficiency of platelets in blood
- Mild = 50-150
- Moderate = 20-50
- Severe = <20
What is a normal platelet count?
150-359 x10⁹/L
What is thrombotic microangiopathies?
A pattern of damage that can occur inside the smallest blood vessels in vital organs, often kidney or brain
Very briefly outline haemostasis
Results in platelet plug formation
Does NOT involve coagulation pathways
Includes disorders of platelet numbers/size/functionality
Briefly outline secondary homeostasis
Formation of an insoluble fibrin clot after coagulation cascade
Fibrinolysis occurS
Common, Intrinsic, and extrinsic pathways
Which pathway is the main initiation for coagulation?
Extrinsic
Outline the extrinsic pathway
Exposure of transmembrane receptor tissue factor (TF) to plasma factor VII, activating factor X.
Prothrombinase complex activates thrombin (from prothrombin), activating FXI
Outline the intrinsic pathway
Amplifies the coagulation cascade
Tenase complex amplifies activation of FX, large amount of thrombin generated.
Thrombin cleaves fibrinogen to form soluble fibrin monomers, which polymerise to form a polymer.
Thrombin activates FXII to cross link calcium (stabilises polymer)
what does a deficiency of protein C or S lead to?
Thrombin spread into vasculature due to prevention of cleavage and inactivation of FV
What happens after an injury is healed?
Plasminogen begins to dissolve the fibrin clot.
Plasmin cleaves the network and releases FDP, and cleaves fibrinogen. It also inactivates Fva and FVIIa
State two fibrinolysis defects
Hyperfibrinolysis (bleeding snd thrombosis)
Hypofibrinolysis (thromboembolic disease associations)
What are the inhibitors in coagulation?
TFPI, Antithrombin, Protein C, Thrombomodulin
What are the intrinsic and extrinsic tenases?
Extrinsic = TF-VIIa
Intrinsic = IXa VIIIa
What does a congenital deficit of factor VIII cause?
Haemophilia A
What does a deficiency of combined FV and FVIII cause?
Rare autosomal recessive bleeding disorder. Normally due to a mutation in transport protein.
Treat sith FVIII concentrate.
What does a deficiency of factor IX lead to?
Haemophilia B
What does a deficiency in factor XI lead to?
Haemophilia C
3 mutations, majority type II or III
Which factors can become an acquired deficiency?
Factor II - antibody due to lupus
Factor V - after surgery/transfusion
Factor VII - very rare
Factor IX - rare, associated with postpartum
Factor X - amyloidosis
How does liver disease affect haemostasis?
Increased prothrombin time due to a decrease of extrinsic coagulation factors synthesized in the liver
What else can increase prothrombin time?
Vitamin K deficiency (due to vit k dependant factors)
What is prothrombin time?
A measure of efficiency of the extrinsic clotting system
What is activated partial thromboplastin time?
Same as PT but with an added activator to speed the process up, resulting in a narrower reference range
What agents are used in anticoagulant therapy?
Aspirin (platelet function inhibition)
Warfarin (for vit. K dependant factors)
Heparin (inhibits thrombin)
Thrombin inhibitors
FXa inhibitors
Thrombolytic agents (e.g., streptokinase)
Natural coagulation inhibitors
Which factors are vitamin K dependent?
- FII
- FVII
- FIX
- FX
- Protein C
- Protein S
What is international normalised ratio?
A blood test telling you how long it takes for you blood to clot.
Calculated by: INR = PR*(ISI)
PR = prothrombin rate
ISI = international sensitivity index
