CVR - Haemostasis Flashcards
What is haemostasis?
The cellular and biochemical process that enables both the specific and regulated cessation of bleeding in response to vascular insult
State the 3 functions of haemostasis
- Prevent blood loss from intact vessels
- Arrest bleeding from injured vessels
- Enable tissue repair
What occurs in primary haemostasis?
- Platelet adhesion
- Platelet aggregation
What is the function of primary haemostasis?
Formation of a unstable platelet plug:
- Limit blood loss and provide a surface for coagulation
What occurs in secondary haemostasis?
- Blood coagulation
What is the main function of secondary haemostasis?
Stabilisation of the platelet plug with fibrin
What is fibrinolysis?
Vessel repair and dissolution of clot
What is normal haemostasis maintaining a balance between?
Bleeding and thrombosis
What factor(s) cause platelet aggregations and adhesion?
VWF via the Gp1b or Glp1a (GLycoprotein 1a)
What is ITP?
Idiopathic thrombocytopenia purpura:
The presence of antiplatelet antibodies within the body which result in platelets being destroyed by macrophages
What are the potential causes for thrombocytopoenia?
- Bone marrow failure
- Accelerated clearance
- Pooling and destruction in an enlarged spleen
What can cause imparied function of platelets?
- Hereditary absence of glycoproteins or storage granules
- Acquired due to drugs
State the functions of VWF in haemostasis?
Binding to collagen and capturing platelets
Stabilising factor VIII:
- Factor VIII may be low if VWF is low
What inherited diseases can cause vessel wall damage ?
- Hereditary haemorrhagic telangiectasia
- Ehlers-Danlos syndrome
What acquired factors/diseases can cause vessel wall damage ?
- Steroid therapy
- Ageing
- Vasculitis
- Scurvy (vitamin C deficiency)
What are some typical symptoms of primary haemostasic bleeding disorders?
- Immediate
- Prolonged bleeding
- Nose bleeds: prolonged >20mins
- Gum bleeding: prolonged
- Heavy menstrual bleeding
- Bruising: easy or spontaneous
- Prolonged bleeding after trauma or surgery
What physical symptom is characteristic of thrombocytopoeania?
Petechiae - marks from bleeding under skin
State the tests for primary haemostatic disorders
- Platelet count
- Bleeding time
- Assays of von Willebrand Factor
- Clinical observation - petechiae or purpura?
What are the treatment options for abnormal haemostasis?
- Failure of production /function:
- Replace missing factor/platelets
i) Prophylactic
ii) Therapeutic - Stop drugs that impair platelet function; sucha as aspirin
- Replace missing factor/platelets
- Immune destruction
- Immunosuppression
- Splenectomy for ITP
- Increased consumption of platelets:
- Treat cause
- Replace as necessary
What is the function of desmopressin?
Vasopressin analogue:
Leads to 2-5 fold increase in VWF (and VIII)
It also releases endogenous stores (so only useful in mild disorders)
What type of drug is tranexamic acid?
Antifibrinolytic
What is the role of coagulation?
To produce factor IIa which converts fibrinogen into fibrin
What can cause disorders of coagulation?
- Deficiency of coagulation factor production:
- Hereditary
- Factor VII/IX: haemophilia A/B
- Acquired:
- Liver disease
- Anticoagulant drugs
- Hereditary
- Dilution:
- Acquired
- Blood transfusion
- Acquired
- Increased consumption:
- Disseminated intravascular coagulation
Which factor is deficient in haemophilia A?
Factor VIII
Which factor is deficient in haemophilia B?
Factor IX
What is the hallmark of haemophilia?
Haemarthrosis - bleeding in joints
Can lead to muscle wasting
What is the effect of prothrombin (Factor II) deficiency?
Death - very lethal
What is the effect of Factor XI deficiency?
Bleed after trauma but not spontaneously
What is the effect of Factor XII deficiency?
No bleeding at all
Why does liver failure result in coagulation disorders?
Most coagulation factors are synthesised in the liver
How does dilution of coagulation factors occur?
Red cell transfusions no longer contain plasma, which contains the coagulation factors - blood volume increase but coagulation factor number remains same, so concentration decreases
What occurs in disseminated intravascular coagulation?
- A generalised activation of coagulation occurs which uses up platelets and clotting factors around the body
- This means there are little to no platelets or clotting factors left for coagulation elsewhere to occur
- Deposition of fibrin in vessels an cause organ failure
What can cause disseminated intravascular coagulation?
Associated with :
- Sepsis
- Major tissue damage
- Inflammation
- Cancer
What are the clinical features of coagulation disorders?
- Superficial cuts do not bleed
- Bruising is common, nosebleeds are rare
- Spontaneous bleeding is deep, into muscles and joints
- Bleeding after trauma may be delayed and is prolonged
- Bleeding frequently restarts after stopping
What is the clinical distinction between bleeding due to platelet and coagulation defects?
Platelet: - Superficial bleeding into skin - Bleeding immediately after injury Coagulation: - Bleeding deep - Bleeding delayed but severe bleeding after injury
What are the tests for coagulation disorders?
Screening tests: - Prothrombin time - Activated partial thromboplastin time - Full blood count (platelets) Coagulation factor assays (for Factor VIII etc) Test for inhibitors
What pathway does the prothrombin time test measure?
The ‘extrinsic’ pathway
What pathway does the partial thromboplastin time measure?
The ‘intrinsic’ pathway
By what methods can missing coagulation factors be replaced?
Plasma (fresh frozen plasma)
- contains all coagulation factors
Cryoprecipitate
- rich in fibrinogen, factor VIII, VWF, factor XIII
Factor concentrates
- Concentrates available for all factors except factor V
- Prothrombin complex concentrates; factors II, VII, IX, X
Recombinant forms of Factor VIII AND Factor IX are available
- ‘On demand’ to treat bleeds
- Prophylaxis to prevent bleeds
What novel treatments are there for haemophilia?
- Gene therapy (Haem A and B)
- Bispecific antibodies:
- Emicizumab
- Binds to factor IXa and X
- This mimics the procoagulant function of Factor VIII
What are the associated symptoms of a pulmonary embolism?
- Tachycardia
- Hypoxia
- Shortness of breath
- Chest pain
- Haemoptysis - coughing up blood
- Can lead to sudden death
What are the associated symptoms of a deep vein thrombosis?
- Painful leg
- Swelling
- Red
- Warm
- May embolise to lungs
- Post thrombotic syndrome
What is Virchow’s triad?
The three contributory factors to thrombosis:
- Blood
- Vessel wall
- Blood flow
What is meant by thrombophilia?
Increased chance of venous thrombosis
What factors do protein C and S activate?
Factor VIIIa and Va
What type of cells produce heparin?
Mast cells
What affect does the difference in heparin chain length cause?
Long chain: - Intravenous - Short half life Low molecular weight: - Subcutaneous
What are the target proteases of antithrombin?
- Factor Xa
- Thrombin
Why does low molecular weight (Short chain) heparin not affect thrombin?
The heparin chain has to wrap around the thrombin to have its desired affect however the LMW heparin is too short to do so
Still affects Xa
How does warfarin work?
It prevents vitamin K from being recycled into it’s hyroquinone state, required for the activation of factors II, VII, IX, X, Protein C and S
What are the side-effects of the warfarin?
- Bleeding:
- Ranges from minor to fatal
- Skin necrosis
- Purple toe syndrome
- Embryopathy - Chrondodysplasia punctata
What is chrondodysplasia punctata?
Early fusion of the epiphyses
What can cause resistance to warfarin?
- Diet: if they intake too much vitamin K
- Increased metabolism
- Reduced binding
