1b// Haemostasis Flashcards
what is the purpose of haemostasis?
prevention of blood loss from intact vessels
arrest bleeding from injured vessels
enable tissue repair
what is haemostasis?
cellular and biochemical processes that enables both the specific and regulated cessation of bleeding in response to vascular insult
describe the mechanisms of haemostasis
vessel constriction
formulation of unstable platelet plug
stabilisation of plug with fibrin
vessel repair and dissolution of clot
what is primary haemostasis?
unstable platelet plug
platelet adhesion, aggregation to limit blood loss and provides surface for coagulation
what is secondary haemostasis?
stabilisation of platelet plug (fibrin)
blood coagulation to stop blood flow
what is fibrinolysis in haemostasis?
final stage of haemostasis - vessel repair and dissolution of clot
restores vessel integrity
what is the importance of understanding haemostasis?
diagnose/treat bleeding disorders control bleeding in normal individuals identify risk factors for fibrinolysis treat thrombotic disorders monitor treatment for bleeding/thrombotic disorders
how does platelet adhesion occur?
adheres to collagen in vessel wall
GlpIa receptor direct bonding
GlpIb receptor via Von Willebrand Factor
how does platelet aggregation occur?
platelets release ADP, fibrinogen and thromboxane A2 after they are activated
express GlpIIb/IIIa for adhesion of other platelets via fibrinogen and Ca2+
what conditions cause thrombocytopenia?
bone marrow failure (leukaemia, b12 deficiency) accelerated clearance (immune ITP, disseminated intravascular coagulation) pooling and destruction in splenomegaly
what conditions cause impaired platelet function?
hereditary absence of glycoproteins or storage granules
latrogenic - aspirin, NSAIDs, clopidogrel
what is immune thrombocytopenic purpura? ITP
antiplatelet autoantibodies bind to sensitised platelets
macrophages then bind to the platelets and destroy them (spleen)
this causes low platelet count
what are some hereditary platelet defects?
Glanzmanns thrombasthenia - absence of GlpIIb/IIIa
bernard soulier syndrome - absence of GlpIb
storage pool disease - absence of dense or alpha granules
what is aspirins MOA?
binds irreversibly to cyclooxygenase
inhibits thromboxane A2 synthesis
therefore prevents platelet aggregation
effects last around 7 days
what is clopidogrels MOA?
irreversibly blocks ADP receptor (P2Y12) on platelet cell membrane
therefore platelets cannot be activated to cause aggregation
what are the functions of von willebrand factor?
binding to collagen and capturing platelets
stabilising factor VIII
what is von willebrand disease?
hereditary autosomal dominant disease causing failure of primary haemostasis
deficiency of VWF (type 1&3)
VWF with abnormal function (type 2)
what are some causes of vessel wall disorders?
hereditary haemorrhagic telangiectasia ehlers danlos syndome steroid therapy ageing vasculitis scurvy
how does typical primary haemostasis bleeding present?
immediate prolonged bleeding from cuts prolonged nose bleeds, gum bleeding menorrhagia ecchymosis - easy and spontaneous bruises prolonged bleeds after trauma/surgery
what specific symptom occurs for thrombocytopenia?
petechiae - bleeding under skin
what disorders cause purpura as a symptom?
platelet or vascular disorders (thrombocytopenia pupura)
what tests are used in diagnosis of primary haemostasis disorders?
platelet count and morphology PFA100 (platelet function analysis - bleeding time) assays of VWF clinical observation PT and aPTT
what tests are usually normal in primary haemostasis disorders?
PT and aPTT
how do you treat failure of production/function platelet disorders?
replace missing platelets/factor e.g VWF prophylactically or therapeutically
stop aspirin/nsaids
how do you treat immune destruction of platelets?
immunosuppression
splenectomy for ITP
how do you treat increased consumption of platelets?
treat underlying cause
replacement
how can desmopressin be used to treat primary haemostatic abnormalities?
causes 2-5 fold increase of VWF and factor VIII
releases endogenous stores therefore only used in mild disorders
how is tranexamic acid used?
traumatic bleeds, strokes
antifibrinolytic
when are fibrin glues/sprays used?
during surgeries
what is the overall role/end goal of coagulation in haemostasis?
generate thrombin IIa to convert fibrinogen to fibrin
what are the acquired causes of factor deficiencies?
liver disease
anticoagulant drugs - warfarin, DOACs
what are the hereditary causes of factor deficiency?
haemophilia A/B (VIII/IX)
what are the causes of dilution coagulopathy?
blood transfusions
what are the causes for increased consumption coagulopathy?
disseminated intravascular coagulation DIC
immune autoantibodies
what is haemarthrosis?
spontaneous joint bleeding
causes long term chronic muscle wasting
prophylaxis from around 9mths age
what does a deficiency of factor II cause?
incompatibility with life - prothrombin is necessary
what does a deficiency of factor XI cause?
bleeds after trauma no spontaneous bleeding
what does a deficiency of factor XII cause?
no bleeding
what factors aren’t produced in the liver?
VWF (endothelium), factor V (platelets)
what is disseminated intravascular coagulation?
generalised activation of coagulation - tissue factor
consumes and depletes coagulation factors
platelets consumed - thrombocytopenia
fibrinolysis depletes fibrinogen causing raised D-dimer and red cell fragmentation
deposition of fibrin in vessels causes organ failure
risk of sepsis, cancer, obstetric disorders
different types of factor replacement therapy
Fresh Frozen Plasma
Cryoprecipitate
Factor Concentrates
Recombinate forms of FVIII and FIX
FFP
contains all Coagulation factors
cryoprecipitate
Fibrinogen, Factor VIII (8), XIII and VWF
factor concentrates
Concentrates available for all factors except factor V.
Prothrombin complex concentrates (PCCs) Factors II, VII, IX, X
whn are recombinant forms of FVIII and FIX used?
‘On Demand’ to treat bleeds
Prophylaxis to prevent bleeds
disorders of thrombosis present with
pulmonary embolism
deep vein thrombosis
pulmonary embolism symptoms
Tachycardia Hypoxia Shortness of breath Chest pain Haemoptysis Sudden death
features of DVT
Painful leg Swelling Red Warm May embolise to lungs Post thrombotic syndrome
What is thrombosis
inappropriate intravascular coagulation
Venous (or arterial)
Obstructs flow
May embolise to lungs
What is Virchow’s triad
Three contibutory factors to thrombosis Blood (dominant in venous) Vessel wall (dominant in arterial) Blood flow (both)
what is indicative of thrombosis
Thrombosis at young age
‘spontaneous thrombosis’
Multiple thromboses
Thrombosis whilst anti-coagulated
anticoagulant proteins
antithrombin
protein C
protein S
risk factors of venous thrombosis
age]
genetic
environmental
prevention of thrombosis
prophylactic anticoagulant therapy
acquired causes of coagulopathy
liver failure
anticoagulant drugs
dilution
increased consumption -DIC
blood test sign of DIC
raised D-dimer
red cell fragmentation
clinical features of coagulation disorders
superficial cuts dont bleed bruising common, nosebleeds rare spontaneous bleeds are deep - joints etc bleeding after trauma may be late and prolonged bleeding frewuently restarts
differences between platelet/vascular and coagulation disorders
platelet - superficial bleeds, immediate bleeds
coagulation - deep bleeds, prolonged but delayed
tests for coagulation disorders
clotting screen - APTT, PT, FBC
coagulation factor assays
tests for inhibitors
what does APTT measure
intrinsic pathway
what does PT measure
extrinsic factor VII via tissue factor pathway
prolonged APTT indicates
haemophilia A/B factor XI deficiency or XII (no bleeds)
prolonged PT indicates
factor VII deficiency
prolonged APTT and PT
liver disease anticoagulant drugs DIC dilution factor X, II, V (common pathway) deficiencies
treatments for failure of production
replaces as necessary
stop drugs e.g nsaids, aspirin
treatments for immune destruction
immunosuppresion - prednisolone
splenectomy - ITP
treatments for increased ocnsumption
treat cause
replace as necessary
how to reduce recurrence of thrombosis
lower procoagulants - DOACs, warfarin
increase anticoags - heparin
