Haemostasis Flashcards
Define haemostasis
Stoppage of haemorrhage
Provide an overview of the three steps of haemostasis
- Vasoconstriction - decrease blood pressure downstream
- Temporary blockage of a break by a platelet plug
- Blood coagulation, or formation of a fibrin clot through clotting cascade which stabilises the friable platelet plug into a stable clot
What happens when platelets are activated
Platelet binds to vWF which causes platelet release
Undergoes conformation change to release ADP and exposes GP IIb/IIIa which exposes fibrinogen which cross links with other platelets to form platelet plug
Thromboxane A2 stimulates vasoconstriction
Swell and change shape into sticky, spiny spheres
What does aspirin target
Inactivates cyclooxygenase, one of the enzymes responsible for production of thromboxane A2 to decrease platelet aggregation
What are platelets activated by
Collagen, ADP, thomboxane A2, thrombin
What is the role of Vitamin K in the clotting cascade
Gamma carboxylation in formation of factor II, VII, IX, X and protein C and protein S
What is the intrinsic pathway and how is it begun
Involves factors all of which are in the blood
Triggered when blood comes into contact with collagen
Promotes binding of factor XII to begin pathway
What is the extrinsic pathway and how is it begun
Triggered by thromboplastin released from damaged cells
Thromboplastin/tissue factor/ factor III converts factor VII to X
What is the role of the vessel wall in clotting
Vasoconstriction to reduce blood flow and amount of haemorrhage
Production of vWF
Exposure of collagen and tissue factor which initiates activation of clotting factors
What are factors that oppose clotting
Dilution of clotting factors by blood flow and natural coagulants
Natural coagulants include antithrombin III, protein C and protein S - a person lacking these experience thrombosis
Fibrin degradation products inhibit clotting
What is the role of protein C and protein S
Protein S activates protein C which inactivates factor V and VIII, reduces clotting
Describe the common pathway of clotting
Precursor proteins in intrinsic or extrinsic pathway generate thrombin
Thrombin converts soluble fibrinogen into insoluble fibrin which reinforces platelet plug
Describe fibrinolysis
Plasminogen activators (tPA, urokinase, streptokinase) convert plasminogen into plasmin Macrophages recognize fibrin end point and break it down Plasmin breaks down fibrin clot remains
Why is streptokinase used in treating blood clots in the heart instead of heparin or warfarin
Immediately break down clot
Can have side effects including internal bleeding around the body
What do warfarin and heparin target
Warfarin inhibits vitamin K and heparin inhibits factor II and X (low-molecular heparin)
Both reduce clotting cascade to allow fibrinolysis
What is the role of von Willebrand factor
Involved in platelet adhesion to the vessel wall, platelet aggregation and carries factor VIII
Assists in platelet plug formation by attracting circulating platelets to sites of damage
Acts as an anchor for platelets
Stabilises factor VIII protecting it from premature destruction
How is blood clotting measured
When too much fibrin is made, there will be high amounts of fibrin degradation product (FDP)
Detect thrombosis
De-dimer test more specific - fibrin constantly formed and degraded
Only in thrombus is there crosslinking fibrin
De-dimer is degradation product of cross linked fibrin, FDP is degradation product of fibrin
What do APTT and PT test for
Activated partial thromboplastin time (APTT) measures time of intrinsic + common pathway Prothrombin time (PT) measures time of extrinsic + common pathway
Haemophillia A description, presentation, laboratory abnormalities
X-linked recessive
Congenital lack of factor VIII - affects mainly intrinsic pathway
Diagnosed pre-natally or soon after birth if family history, or usually in infancy if new spontaneous mutation
Bleeding into muscles and joints with minor trauma, post-operative bruising and haemorrhage
Lab tests - normal platelet count, bleeding time and PT
Prolonged APTT, low factor VII assay
Treated with recombinant factor VIII or DDAVP
Haemophillia B description, presentation, laboratory abnormalities
Also known as Christmas disease
Deficiency in factor IX
X-linked recessive
Bleeding into muscles and joints with minor trauma, post-operative bruising and haemorrhage
Lab tests - normal platelet count, bleeding time and PT
Prolonged APTT, low factor IX assay
Treated with recombinant factor VIII or DDAVP
Von Willebrand’s disease description, presentation, laboratory abnormalities
vWF production inhibited leading to abnormal platelet adhesion to vessel wall
Reduced factor VIII amount/activity
Several genetic defects cause this condition
Skin and mucous membrane bleeding, mucosal bleeding
Prolonged bleeding after trauma - post surgery, heavy periods, post dental extraction
APTT and bleeding time both prolonged
Thrombocytopenia description, presentation, laboratory abnormalities
Low platelet count
Due to decreased platelet production, decreased platelet survival, sequestration, dilutional (blood transfusion)
Mucosal bleeding, severe bleeding after trauma
Prolonged bleeding time but normal APTT and PT
Immune thrombocytopenic purpura description, presentation, laboratory abnormalities
Low platelet count
Causes purpuric rash and increased tendency to bleed
Antibody targets own platelet - problem with immune system
Lab tests - low platelet count, abnormal bleeding time
Thrombophilia types, pathophysiology, presentation
Inherited or acquired defects of haemostasis resulting in predisposition to thrombosis
Eg. factor V Leiden (in which there is an abnormal factor V which isn’t deactivated resulting in thrombosis), antithrombin deficiency, protein C or protein S deficiency and antiphospholipid syndrome
Abnormalities in clotting factors results in excessive or decreased clotting
Presentation - warning signs of DVT: leg swelling, heavy ache, redness
