Haemostasis Flashcards
Process of clot formation
I dunno look it up
Where are platelets produced and by what?
Megakaryocytes produce platelets in the bone marrow
Normal platelet count
150-400 x10^9/L
Normal lifespan of platelets
7-10 days
What do platelets adhere to collagen via?
von Willebrand factor receptor
Platelet activation
- Secrete ADP, thromboxane and other substances to become activated and activate other platelets
- Involved in activation of the clotting cascade
What is the function of thromboxane?
- Vasoconstrictor
- Hypertensive agent
- Facilitates platelet aggregation
Clotting cascade mediating factors
- Glycoprotein complexes on platelets e.g. GPIIb-IIIa
- Von Willebrands factor (binds to factor VIII)
- Fibrinogen (forms bridges between platelets by binding to their GPIIb-IIIa receptors)
- Collagen
- ADP
- Thromboxane/arachidonic acid
- Thrombin
Initiation and activation of the clotting cascade
- Tissue factor exposure activates FVII
- Prothrombin –> Thrombin
- Clotting factors activated
- Thrombin IIa positive feedback??
- Fibrinogen –> Fibrin clot (cleaved by thrombin)
Fibrinolysis
- Plasminogen –> Plasmin
- Breaks up fibrin clot
Natural anticoagulants
- Protein C
- Protein S
- Anti thrombin
What can bleeding disorders be due to?
Abnormalities in the vessel wall, platelets or coagulation factors
Congenital coagulation factor disorders
- Haemophilia A (factor 8)
- Haemophilia B (factor 9, rarer)
Acquired coagulation factor disorders
- Liver disease (produce coagulation factors)
- Vitamin K deficiency
- Anticoagulants including warfarin
Haemophilia A
- X linked recessive
- Bleeding into muscles and joints
- Treated with recombinant factor VIII or desmopressin
Von Willebrand’s disease
- Autosomal dominant
- Abnormal platelet adhesion to vessel wall
- Reduced FVIII amount/activity
- Either not enough vWF produced or reduced activity
Clinical presentation of vWD
- Skin and mucous membrane bleeding (epistaxis, bruising)
- Prolonged bleeding from trauma (heavy periods, post surgery)
- Spontaneous joint or muscle bleeds are rare
Vessel wall abnormalities presentation
- Easy bruising
- Spontaneous bleeding from small vessels
- Skin mainly
- Can be mucous membranes
Congenital problems with vessels
- Hereditary Haemorrhagic Telangiectasia (HHT)
- Connective tissues disorders e.g. Ehlers Danlos
Hereditary Haemorrhagic Telangiectasia (HHT)
- Autosomal dominant
- Dilated microvascular swellings increase with time
- GI haemorrhage can lead to iron deficiency anaemia
Acquired problems with vessels
- Senile purpura (vessel walls become thin)
- Steroids
- Infection e.g. measles, meningoccocal infection
- Scurvy (vit C def causing defective collagen production)
Immune destruction of platelets
- Immune thromocytopenic purpura (autoantibodies against GP IIb/IIIa and GPIb/IX)
- Can be secondary to autoimmune disease
- Treated with immunosupression (cordicosteroids or IVIg first line)
- Platelet transfusions do not work (why? Haemostasis slide 39)
Reduced production of platelets
- B12/folate deficiency
- Infiltration of bone marrow by cancer cells or fibrosis
- Drugs e.g. chloramphenicol and co-trimaxazole
- Vituses e.g. HIV, EBV
When do patients become symptomatic in severe thrombocytopenia?
When the platelet count is less than 30
