Flashcards in Haemostasis and Thrombosis and Embolism Deck (59):
What exactly is haemostasis
blood stopping process
maintain blood in a fluid state in normal vessels
Clotting (thrombosis) --- Bleeding (Haemorrhage)
What's the difference between a thrombus and clot?
thrombus formed WITHIN the cardiovascular whereas clot formed OUTSIDE or post mortem
Order of haemostasis process
What happen at step 1, transient vasoconstriction, in haemostasis?
- reflex vasoconstriction by endothelin from endothelial cells
- temporarily slows bleeding
What happen at step 2, primary haemostasis?
- expose thrombogenic subendothelial ECM
- platelets adhere, activate and release granules to recruit more platelet => platelet plug
note: involve vWF, ADP and Thromboxane A2
What happen at step 3, secondary haemostasis?
- tissue factor (thromboplastin) released
- tissue factor + factor VII activate coagulation cascade (extrinsic)
- generate thrombin
- thrombin convert fibrinogen to insoluble fibrin => fibrin polymerisation
What happen at step 4, anti-thrombotic mechanism, in haemostasis?
- t-PA = fibrinolysis
- thrombomodulin = block coagulation cascade
both t-PA and thrombomodulin limit platelet plug.
What are the 3 main ingredients of haemostasis?
1. ENDOTHELIUM (vasoconstriction)
2. PLATELET (platelet plug)
3. COAGULATION (fibrin formation)
3 roles of a normal endothelium can do
1. anti-platelet : have prostacyclin, NO and ADPase to prevent adhesion and activation
2. anti-coagulant : anti-thrombin, thrombomodulin, protein C and S, tissue factor inhibitor
3. Fibrinolysis: t-PA
What is the normal INTACT endothelium's behaviour?
An injured endothelium promotes____?
- by trauma, cytokines, infectious agents, haemodynamic F, p/m mediators
What effects does injured endothelium produce?
- platelet : adhesion via vWF
- pro-coagulant : tissue factor
- anti-fibrinolytic : plasminogen activator inhibitors
What are some main things that platelets contain?
alpha-granules (fibrinogen, vWF)
dense granules (ATP, ADP, serotonin, adrenaline)
dense tubular system
What makes platelet adhere to site of injury?
glycoprotein von Willebrand factor (vWF)
(bind to subendothelial collagen)
What does platelet secrete?
- dense granules: ADP and serotonin
- alpha granules: vWF, FV, PF4, Fibrinogen
What does ACTIVATED platelets secrete more?
Thromboxane A2, vWF
=> activate more platelets
What is the aggregation receptor for platelet?
Gp IIb/IIIa : binds to fibrinogen
What does Thromboxane A2 (TXA2) do? (4)
- it comes from cyclo-oxygenase pathways
- amplifies aggregation
- activates more platelets
- constricts vessels
What can coagulation cascade do?
- enzyme rx occurs on the surface of activated platelets
- to stabilize the platelet plug
- here, RBC, WBC trapped make the plug even bigger
What does EXTRINSIC coagulation pathway require?
- Tissue factor
- Factor VII-a
What does INTRINSIC coagulation pathway require?
- Hageman factor
- Factor VIII, IX, XI, XII (8,9, 11, 12)
What does COMMON coagulation pathway require?
- Factor II (thrombin)
- Factor I (fibrinogen
What does it mean by 'stable meshwork' in coagulation?
cross-linked fibrin that stabilize the platelet plug
What are ways to investigate coagulation?
Platelet count (~150-400 x 10^9)
Platelet function : PFA, bleeding time
Coagulation studies : APTT, PT/INR
What are the 2 main inhibitors of coagulation cascade (physiological)?
- Anti-thrombin : enhance by heparin (endothelium)
- protein C and S : stop cascade! (activated by thrombin & thrombomodulin)
- tissue factor inhibitor : block binding of factor VII-a in extrinsic pathway
What is the main inhibitor of fibrin forming (physiological)?
- t-PA : activate plasminogen to break down fibrin
What is the process of fibrinolysis (counter mechanism)?
t-PA (tissue plasminogen activator)
- started by the activation of coagulation cascade
- plasminogen cleaved to plasmin
- plasmin breaks down fibrin : D-dimers
What pharmaceutical products block platelet R binding?
- monoclonal aB
What pharmaceutical product inhibit TXA2 product?
What pharmaceutical products 'block' coagulation cascade?
What pharmaceutical products 'block' the cleaving of plasminogen to plasmin?
What are the main problems with bleeding disorder?
- fragile endothelium or blood vessels
- defective/deficient platelet
- defective/deficient coagulation factors
Common causes of blood vessel wall abnormalities?
- petechiae < purpura < ecchymoses in skin and mucous membrane
What are causes of abnormal blood vessel wall?
Drug Rx (immune)
Vitamin C deficiency
What is thrombocytopenia?
Deficient platelet = 'Low platelet count'
What are the causes of thrombocytopenia? (4)
- Reduced platelet function : bone marrow failure and liver disease (reduce thrombopoietin)
- Reduced platelet survivals
- Sequestration in hyper-splenism
What makes platelet function defects?
- inherited defects of adhesion, aggregation or secretion
- acquired cause (uremia, drugs and food)
What are the inherited cause of abnormal clotting/coagulation factor? (2)
von Willebrand disease
haemophilia A and B
What is von Willebrand disaese
Bleeding disorder that reduce platelet function
familial defective vWF (autosomal dominant)
What are the consequences of vWD?
prolonged bleeding time
What is haemophilia A and B?
Bleeding disorder at joints and m/s with causative mutation
- Haemoph A : factor VIII deficiency
- Haemoph B : factor IX deficiency
How to treat haemophilia A and B?
IV clotting factor
- usually as prophylaxis regularly
- before surgery or dental treatment
What are the acquired causes of abnormal clotting factors, thus result in bleeding?
- vitamin K deficiency
- Severe liver disease
What is Warfarin?
Vitamin K antagonist
- inhibit carboxylation of clotting factors II, VII, IX and X
- to reduce risk of thrombosis
What is vitamin K?
It's a biological redox reagent to regulate coagulation factor
What does Vitamin K-deficiency result in?
- decrease carboxylation of Vit.K
- thus coagulation factors (2, 7, 9, 10) is non-functional
What can Vit K limited to?
new born infants (as no transfer across placenta)
intestinal malabsorption (lack of bile salts)
What is haemorrhage?
leakage of blood from vessels into extravascular space
- result in external bleeding or accumulation of blood within tissue (hematoma)
What are 3 ranges of haematoma?
- petechia : dot hemorrhage
- purpura : small hemorrhage (2-5mm)
- ecchymoses : bruises (1-2cm and larger)
What haematoma associated with thrombocytopenia, defective platelet function and increased intravascular pressure?
- purpura (also increase vascular fragility, inflammation and trauma)
What is the process of ecchymoses?
RBCs leaked and being phagocytosed by Mø
Hb (red-blue) ---> bilirubin (green-yellow) ---> hemosiderin (yellow brown)
What is Virchow's triad?
Pathogenesis of Thrombosis
- Endothelial injury
- Abnormal blood flow
What are the 4 possible outcomes after a thrombus formed
- resolution : fibrinolysis
- embolisation to lungs : cause PE
- organisation and recanalisation : reestablish blood flow
- propagation : thrombus occluded vessels (to heart)
What is thromboemolism?
thrombus travel through the blood and lodge in narrow vessels.
result in vascular occlusion
What is pulmonary embolism (PE)?
Thrombi from deep leg veins (DVT) travel to Right side of heart then block at pulmonary trunk.
Where does ARTERIAL thromboemboli originate from?
intracardiac mural thrombi
- aortic aneurysms
- ulcerated atheroscelrotic plaques
- valvular vegetations
What does arterial emboli result in?
What is another name of large emboli that occlude in the pulmonary trunk centre?
Saddle embolus in PE