Haemostasis Flashcards
What is haemostasis?
the cellular and biochemical processes that enable both the specific and regulated cessation of bleeding in response to vascular insult
What is the purpose of haemostasis?
- prevention of blood loss from intact vessels
- arrest bleeding from injured vessels
- enable tissue repair
What is the overall mechanism of haemostasis?
- vessel constriction–> vascular smooth muscle cells contract locally to limit blood flow to injured vessel
- 1y- formation of unstable platelet plug w/ platelet adhesion+aggregation to limit blood loss+provide surface for coagulation
- 2y- stabilisation of plug w/ fibrin–> blood coagulation to stop blood loss
- fibrinolysis- vessel repair+dissolution of clot to restore vessel integrity
What is thrombocytopenia and what are its causes?
low numbers of platelets
- reduction in production by bone marrow e.g. leukaemia, vitamin B12 deficiency
- accelerated clearance of platelets e.g. immune thrombocytopenia (ITP) (common cause), or disseminated intravascular coagulation (DIC)
- pooling and destruction in enlarged spleen
What are the causes of impaired function of platelets?
- -> hereditary absence of glycoproteins or storage granules (rare)
e. g. - Glanzmann’s thrombasthenia- absence of GPIIbIIIa receptor on platelets - Bernard Soulier syndrome- absence of GPIb receptors
- Storage pool disease: reduction in granular contents of platelets
–> acquired due to drugs e.g. aspirin (irreversibly blocks COX), NSAIDs, clopidogrel (irreversibly blocks ADP receptor on platelets) (common)
What is Von Willebrand disease?
- hereditary (common): autosomal inheritance- deficiency (type 1 or 3) or abnormal function (type 2)
- acquired due to antibody (rare)
What are the causes of vessel wall disorders?
- inherited (rare) e.g. Ehlers-Danlos syndrome (abnormalities in collagen)
- acquired (common) e.g. steroids, age (senile purpura), vasculitis, scurvy (vitamin C deficiency)
What are the clinical features of primary haemostatic disorders?
- immediate
- prolonged bleeding from cuts
- prolonged nose bleeds/epistaxis (>20min)
- prolonged gum bleeding
- heavy menstrual bleeding (menorrhagia)
- sponaneous/easy bruising (ecchymosis)
- prolonged bleeding after trauma or surgery
N.B. petechiae common of thrombocytopenia
N.B. purpura- platelet or vascular disorders- do not blanch when pressure is applied (and bigger than petechiae)
How do you test for primary haemostatic disorders?
- platelet count, platelet morphology
- bleeding time (PFA100 in lab)
- assays of von Willebrand Factor
- clinical observation
N.B. coagulation screen (PT, APTT) usually normal except in severe VWD cases where FVIII is low
How do we treat primary haemostatic disorders?
- replace missing factor/platelets e.g. VWF containing concentrates, or platelets–> either prophylactic (before surgery) or therapeutic (following bleeding)
- stop drugs e.g. aspirin/NSAIDs
- immunosuppression e.g. prednisolone
- splenectomy for ITP
- desmopressin (DDAVP) for releasing endogenous stores of VWF in mild disorders
- tranexamic acid (antifibrinolytic)
- fibrin glue/spray during surgery
- other approaches e.g. COCP for menorrhagia
treat underlying cause + replace as necessary
What is the role of coagulation?
to generate thrombin (factor IIa), which will convert fibrinogen to fibrin
What are the 3 broad causes of coagulation factor disorders?
- deficiency of coagulation factor production:
- hereditary: factor VIII/IV (haemophilia A/B)
- acquired: liver disease, anticoagulant drugs (warfarin, DOACs) - dilution: acquired- blood transfusion (inadequate replacement of plasma)
- increased consumption: acquired- DIC (common), autoantibodies (rare)
What is the hallmark of haemophilia?
- haemarthrosis: spontaneous joint bleeding
- chronic haemarthrosis–> joint deformity and muscle wasting
- seen in patients who come from other parts of the world who haven’t had access to care
Why does liver failure result in decreased production of coagulation factors?
because most coagulation factors are synthesised in liver (except VWF and factor V)
Why does major haemorrhage require transfusion of plasma as well as red cells and platelets?
to avoid a dilution effect with reduction in coagulation factors
What is disseminated intravascular coagulation?
- generalised, unregulated activation of coagulation (tissue factor)
- triggered by sepsis, cancer, major tissue damage, inflammation, severe pre-eclampsia
- widespread consumption and depletion of coagulation factors
- platelets consumed–> thrombocytopenia
- activation of fibrinolysis depletes fibrinogen–> raised D-dimer (breakdown product of fibrin)
- deposition of fibrin in vessels causes organ failure and receiving cell fragmentation
What are the clinical features/ bleeding pattern of coagulation disorders?
- superficial cuts do not bleeds (as platelet plug is sufficient)
- bruising is common, but nosebleeds are rare
- spontaneous bleeding is deep, into muscles and joints
- bleeding after trauma may be delayed and prolonged
- bleeding frequently restarts after stopping
