Haemostasis Flashcards
What are the essntials for haemostasis?
Essentials for haemostasis • Keep blood moving – heart, venous valves, calf pump • Blood vessels are important • Platelets • Coagulation factors • Anticoagulant factors
What are platelets produced from and what is the normal platelet count?
- Megakaryocytes produce platelets in the bone marrow
- Platelets ‘bud’ from cytoplasm
- Normal platelet count is 150-400 x 109/L (dont tend to get much bleeding until platelet count is below 20-30)
- Normal life span 7-10 days
What is platelet adhesion?
- Damage to vessel wall
- Exposure of underlying tissues
- Platelets adhere to collagen via vWF/receptor
What is platelet activation?
• Secrete ADP, thromboxane and other substances
to become activated and activate other platelets
• Involved in activation of the clotting cascade
• Provide some coagulation factors by secretion from internal stores
What is platelet aggregation?
Cross liking o platelets to form a platelet plug
What are the medicating factors of haemostasis?
• Plt receptors – glycoprotein complexes e.g. GP1b-V-IX, GPIIb-IIIa
P• Von willebrands factor
• Fibrinogen
• Collagen
• ADP
• Thromboxane/arachidonic acid (aspirin inhibits thromboxane)
• Thrombin
What is the clotting cascade?
• Amplification system activation of precursor proteins to generate thrombin (IIa)
• Thrombin converts soluble fibrinogen into insoluble fibrin which strengthens the clot
• Enmeshes initial platelet plug to make stable clot
• ……controlled
– Natural anticoagulants to inhibit activation
– Clot destroying proteins which are activated by the clotting
cascade (carefully balanced!) - dont want coagulation to occur abnormally
How is coagulation measured?
Extrinsic and intrinsic join to form a common pathway
tissue factor activates factor 7
intrinsic pathway - different factors activate each tother
Can measure aptt (intrinsic pathway) - measures the amount of time that takes for clot to be made - rewatch
Can measure appt (extrinsic pathway)
low in factor 7 - pt prolonged
low in factor 9 - aptt prolonged
if deficient in smth in common fpathway both prolonged
What is PT?
Prothrombin time - measures extrinsic an common pathway, INR is derived/calculated from this and is used in measuring warfarin
Deficiency of which factors leads to an increase in PT (prothrombin time)?
VII (extrinsic)
V, X,prothrombin, fibrinogen (common)
What is APTT?
Activated partial thromboplastin time - measures intrinsic and common pathway
Deficiency of which factors leads to an increase in APTT?
VII, IX, XI, XII (intrinsic)
V, X, prothrombin, fibrinogen (common)
What is Von willer and factor?
• Involved in platelet adhesion to the vessel
wall, platelet aggregation, and also carries (stabilises) FVIII
What occurs in the vessel wall in haemostasis?
• Vasoconstriction
• Production of Von Willebrands factor (vWF)
– Essential for plt adhesion
– Carrier and ‘protector’ of Factor 8
(clotting protein)
• Exposure of collagen and Tissue factor
which initiates activation of clotting factors (proteins)
What are natural anticoagulants?
• Stop further coagulation - control mechanisms of haemostasis
– Protein C
– Protein S
– Anti-Thrombin
What is fibrinolysis
When clot no longer needed
plasminogen converted to plasmin
clot dissolved
plasminogen activator activates the process
we can make recombinant plasminogen activators
dugs break down the clots
patienst that have had an acute stroke - recombinant plasminogen activator - thrombolysis durg - breaks down cult
What are fibrinogen count and D diners used to measure?
Fibrinogen count measures the amount of fibrinogen
D dimers measures fibrin degradation products
What is the clinical relevance of haemostasis?
• Bleeding disorders • Arterial thrombotic disorders • Venous thrombotic disorders • Abnormal blood test results • Drug therapy for pro- or anti-thrombotic
purposes
What are bleeding disorders?
- Due to abnormality in the vessel wall, platelets or coagulation factors
- Inherited and acquired
What are coagulation factor disorders?
Congenital
Haemophilia A (congenital reduction in Factor 8)
Haemophilia B (congenital reaction in Factor 9) etc
Acquired
Liver disease Vit K deficiency Anticoagulants (factors II, VII, IX and X dependednt on Vit K) including Warfarin (inhibits Vit K)
Describe coagulation factor disorders?
Clinical severity correlates with extent of deficiency
• Muscle haematomas with very little trauma
• Recurrent haemarthroses
• Joint pain and deformity
• Prolonged bleeding post dental extraction
• Life threatening post op and post traumatic bleeding
• Intracerebral haemorrhage
What is haemophilia A?
• Haemophilia A
– X-linked recessive
– Congenital lack of factor VIII
– Mild/moderate/severe depending on amount of factor VIII
present
– Diagnosed pre-natally or soon after birth if family history, or usually in infancy if new spontaneous mutation
– Bleeding into muscles and joints, and post-operatively
– Treated with recombinant factor VIII or DDAVP
– What abnormalities would you expect to see in the blood
results of a patient with haemophilia A?
What is haemophilia b?
Haemophilia B
– Similar presentation to haemophilia A
– Congenital reduction in factor IX
What is Von Willebrands disease?
- Relatively common
- Usually autosomal dominant, affects males and females
- VWF carries factor VIII and mediates platelet adhesion to the endothelium
- Abnormal platelet adhesion to vessel wall
- Reduced FVIII amount/activity
- Factor VIII levels can be low in addition to low VWF levels
• Several genetic defects cause this condition
• Main type due to a reduction in vWF
production ie not enough
• (others where activity reduced)
