Haemostasis Flashcards
What is Haemostasis?
the cellular and biochemical processes that enables both the specific and regulated cessation of bleeding in response to vascular insult
What is the aim of haemostasis?
- prevention of blood loss from intact vessels
- arrest bleeding from injured vessels
- enable tissue repair
What are the mechanisms of Haemostasis?
- vessel constriction
- formation of an unstable platelet plug
- stabilisation of the plug with fibrin
- vessel repair and dissolution of clot
What happens when vessel constriction occurs?
- vascular smooth muscle cells contract locally
- limits blood flow to injured vessel
What happens during primary haemostasis?
formation of an unstable platelet plug
- platelet adhesion
- platelet aggregation
- limits blood loss and provides surface for coagulation
What happens during secondary haemostasis?
stabilisation of the plug with fibrin
- blood coagulation
- stops blood loss
What happens during fibrinolysis?
vessel repair and dissolution of the clot
- cell migration/proliferation and fibrinolysis
- restores vessel integrity
Why is understanding of haemostatic mechanisms important?
- diagnose and treat bleeding disorders
- control bleeding
- identify thrombosis risk factors
- treat thrombotic disorders
- monitor drugs used to treat bleeding/thrombotic disorders
What is balanced in normal haemostasis?
- fibrinolytic factors and anticoagulant proteins
AND - coagulant factors
- platelets
What can cause the lack of a specific factor?
- failure of production (congenital and acquired)
- increased consumption and clearance
What can cause defective function of a specific factor?
- genetic
- acquired: drugs, synthetic defect and inhibition
What are the 3 main components of primary haemostasis?
- platelets
- Von Willebrand factor
- Vessel wall
What do platelets adhere to in platelet adhesion?
- collagen revealed in wall damage
- direct via Glp1a receptor
- VWfactor GlP1b
What activates platelets?
thromboxane
What does Thrombocytopenia mean?
low number of platelets
What are the 2 causes of Thrombocytopenia?
- bone marrow failure
- Accelerated clearance
- Pooling and destruction in an enlarged spleen
What can cause bone marrow failure?
- leukaemia
- B12 deficiency
What causes accelerated platelet clearance?
- immune (ITP)
- Disseminated Intravascular Coagulation (DIC)
(cleared in the peripheral system)
What happens in Immune Thrombocytopenic Purpura (ITP)?
- anti-platlet antibodies
- attach to sensitised platlets
- cleared by macrophages of the reticula endothelial system of the spleen
(COMMON)
What causes the impaired function of platelets?
- Hereditary absence of glycoproteins or storage granules (rare)
- Acquired due to drugs
What is an example of hereditary impaired platelet function?
Glanzmann’s thrombasthenia
- problem with: GP2a
What causes Bernard Souller syndrome?
absence of GP1b
What causes storage pool disease?
Reduction in the granular contents of platlets
What drugs are associated with causing impaired platelet function?
- aspirin
- NSAIDs
- clopidogral (common)
When are anti-platelet drugs used?
in the prevention and treatment of cardiovascular and cerebrovascular disease
How does aspirin have an anti-platelet effect?
aspirin prevents the production of Thromboxane A2 by irreversibly blocking COX causing reduced platelet aggregation
How does aspirin have an clopidogrel effect?
irreversibly blocks the ADP receptor on platelets
What can cause Von Willebrand disease?
- Hereditary: decrease of quantity +/ function (COMMON)
- Acquired: antibody (rare)
What is the effect of Von Willebrand disease?
reduced or defective Von Willebrand factor
What are the roles of Von Willebrand factor in Haemostasis?
- binding to collagen and capturing platelets
- stabilising factor VIII
What is the relationship between Von Willebrand Factor and Factor VIII?
VWF is needed for Factor VIII, so if VWF is low, so is Factor VIII
What are the 2 different types of Von Willebrand factor?
Type 1/3: deficiency of VWF
Type 2: VWF with abnormal function
What is the inheritance pattern in VWD?
autosomal basis
What can cause inherited problems with the vessel wall?
RARE
- Haemorrhagic telangiectasia
- Ehlers-Danlos syndrome
(other connective tissue disorders)
What can cause acquired problems with the vessel wall?
COMMON
- steroid therapy
- Ageing (senile purpura)
- Vasculitis
- Scurvy
What VWF to unfold/uncoil?
shear force
What does VWD impact in haemostasis?
primary haemostasis
What are the clinical features of primary haemostasis disorders?
- immediate bleeding
- prolonged bleeding from cuts/trauma/surgery
- nose bleeds (epistaxis) >20mins
- prolonged gum bleeding
- heavy menstrual bleeding (menorrhagia)
- bruising (ecchymosis), spontaneous/easy
What are the visible signs seen in primary haemostasis disorders?
Petechiae and Purpura (do not blanch under pressure)(bleeding under the skin)
What is a key symptom of thrombocytopenia?
Petechiae
When are purpura seen?
- platelet disorders (thrombocytopenic purpura)
- vascular disorders
What is a key clinic feature of severe VWD?
haemophilia-like bleeding (due to low FVIII)
What is a key symptom of immune thrombocytopenia?
ecchymosis
What are symptoms are there of Ehlers-Danlos syndrome?
- increase skin elasticity
- blue sclera
- nose abnormalities
- abnormal hypermobility
What are tests are done for primary haemostasis disorders?
- platelet count/morphology (electron)
- bleeding time (PFA100)
- VWF assays
- clinical observation
- coagulation screen
What should be the expected results from the coagulation screen?
normal (PT, APTT)
UNLESS
severe VWD cases where factor VIII
What happens when platelet count <100x109?
- no spontaneous bleeding
- bleeding with trauma
What happens when platelet count <40x109?
common spontaneous bleeding
What happens when platelet count <10x109?
severe spontaneous bleeding
How would you treat the failure of production/function in primary haemostasis disorders?
replace missing factor/platelets
- prophylactic
- therapeutic
STOP drugs (aspirin, NSAIDs)
How would you treat the immune destruction in primary haemostasis disorders?
- immunosuppression (prednisolone)
- splenectomy for ITP
How would you treat the increased consumption/clearance in primary haemostasis disorders?
- treat cause
- replace as necessary
What additional treatments can be used to support haemostasis?
- Desmopressin
- Tranexamic acid (antifibrinolytic)
- Fibrin glu/spray
- other approaches ( eg: OCP for menorrhagia)
What is Desmopressin?
Vasopressin analogue
What does Desmopressin do?
- 2-5 fold increase in VWF (+ Factor VIII)
- releases endogenous stores (only used in mild disorders)
What is another name for secondary haemostasis?
coagulation
What is the role of coagulation?
generate thrombin (Factor IIa) - which converts fibrinogen to fibrin