Haemostasis

Question 1

Define haemostasis

Answer 1

Stoppage of haemorrhage

Question 2

Provide an overview of the three steps of haemostasis

Answer 2

1. Vasoconstriction - decrease blood pressure downstream
2. Temporary blockage of a break by a platelet plug
3. Blood coagulation, or formation of a fibrin clot through clotting cascade which stabilises the friable platelet plug into a stable clot

Question 3

What happens when platelets are activated

Answer 3

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

Question 4

What does aspirin target

Answer 4

Inactivates cyclooxygenase, one of the enzymes responsible for production of thromboxane A2 to decrease platelet aggregation

Question 5

What are platelets activated by

Answer 5

Collagen, ADP, thomboxane A2, thrombin

Question 6

What is the role of Vitamin K in the clotting cascade

Answer 6

Gamma carboxylation in formation of factor II, VII, IX, X and protein C and protein S

Question 7

What is the intrinsic pathway and how is it begun

Answer 7

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

Question 8

What is the extrinsic pathway and how is it begun

Answer 8

Triggered by thromboplastin released from damaged cells

Thromboplastin/tissue factor/ factor III converts factor VII to X

Question 9

What is the role of the vessel wall in clotting

Answer 9

Vasoconstriction to reduce blood flow and amount of haemorrhage
Production of vWF
Exposure of collagen and tissue factor which initiates activation of clotting factors

Question 10

What are factors that oppose clotting

Answer 10

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

Question 11

What is the role of protein C and protein S

Answer 11

Protein S activates protein C which inactivates factor V and VIII, reduces clotting

Question 12

Describe the common pathway of clotting

Answer 12

Precursor proteins in intrinsic or extrinsic pathway generate thrombin
Thrombin converts soluble fibrinogen into insoluble fibrin which reinforces platelet plug

Question 13

Describe fibrinolysis

Answer 13

Plasminogen activators (tPA, urokinase, streptokinase) convert plasminogen into plasmin
Macrophages recognize fibrin end point and break it down
Plasmin breaks down fibrin clot remains

Question 14

Why is streptokinase used in treating blood clots in the heart instead of heparin or warfarin

Answer 14

Immediately break down clot

Can have side effects including internal bleeding around the body

Question 15

What do warfarin and heparin target

Answer 15

Warfarin inhibits vitamin K and heparin inhibits factor II and X (low-molecular heparin)
Both reduce clotting cascade to allow fibrinolysis

Question 16

What is the role of von Willebrand factor

Answer 16

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

Question 17

How is blood clotting measured

Answer 17

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

Question 18

What do APTT and PT test for

Answer 18

Activated partial thromboplastin time (APTT) measures time of intrinsic + common pathway 
Prothrombin time (PT) measures time of extrinsic + common pathway

Question 19

Haemophillia A description, presentation, laboratory abnormalities

Answer 19

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

Question 20

Haemophillia B description, presentation, laboratory abnormalities

Answer 20

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

Question 21

Von Willebrand’s disease description, presentation, laboratory abnormalities

Answer 21

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

Question 22

Thrombocytopenia description, presentation, laboratory abnormalities

Answer 22

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

Question 23

Immune thrombocytopenic purpura description, presentation, laboratory abnormalities

Answer 23

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

Question 24

Thrombophilia types, pathophysiology, presentation

Answer 24

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

Question 25

Disseminated intravascular coagulation (DIC) causes, pathophysiology, diagnosis, treatment

Answer 25

Activator of clotting gets into blood and microthrombi are formed throughout circulation
Process consumes platelets, fibrin, coagulation factors and stimulates fibrinolysis
Patient may experience haemorrhage, neurological impairment, gangrene of skin, renal failure
Haemolytic anaemia - consumption of clotting factors and platelets
Occurs as a secondary complication to another disease - eg. sepsis, severe trauma, extensive burns, infection, childbirth problems, snake bite
Treatment - treat underlying cause, platelet transfusion, red blood cell transfusion, anticoagulants
Fibrin degradation product such as D-dimers released in large quantities due to fibronolysis