Haemostasis Flashcards
What is haemostasis?
Tightly regulated process
Maintains fluid status while permitting rapid formation of haemostatic clot at site of vascular injury
3 components of haemostasis
Vascular wall
Platelets
Coagulation cascade (clotting factors and anticoagulant factors)
Aim of haemostasis
Stop bleeding following trauma to blood vessel
3 processes involved in haemostasis
Contraction of vessel wall
Form platelet plug at site
Form fibrin clot to stabilise (achieved by clotting cascade)
Importance of haemostasis
More important the larger the vessel is
Role of vessel wall
Damage to vessel exposes tissue factors and collagen (from tunica adventitia) to blood
Initiates clotting cascade
Basic principles platelets
Anucleate, disc shaped
Made from budding off of megakaryocytes
Life span 7-10 days
Normal platelet conc
150-400 x 10^9/ L
What do platelets do when vessel is damaged? (3)
Adhesion
Activation
Aggregation
Describe adhesion
Seconds
Damage to vessels means exposure of underlying tissues
Platelets adhere to collagen (vWF)
How do platelets adhere to collagen?
VWF (von willebrand receptor on platelets, factor is on collagen)
Describe platelet activation
Platelets secrete granules containing ADP, thromboxane and fibrinogen
Activate other platelets and clotting cascade
Describe platelet aggregation
Crosslinking of platelets to form platelet plug
Provides stability but still delicate
Mediating factors
Platelet receptors (glycoprotein binding sites for fibrinogen) Von willebrand receptor (platelets bind) Fibrinogen (links platelets) Collagen (binds platelets) ADP, Thromboxane Thrombin
Clotting cascade define
Steps activated in sequence
Conversion of zymogen to active enzyme
Amplification effects
How is clotting cascade controlled?
Natural anticoagulants
Clot destroying proteins activated by clotting cascade
Common pathway of clotting cascade
Intrinsic and extrinsic pathway result in:
Production of Factor 10
Prothrombin converted to thrombin
Thrombin converts fibrinogen to fibrin
Intrinsic pathway clotting factors
Contact activator 12 —> 12a 11–> 11a 9 —> 9a 8a (phospholipid and calcium)
(Then common pathway)
Intrinsic pathway activated by
Contact activator
Usually from trauma to internal vessel wall
Extrinsic pathway clotting factors
Tissue factor
7 —> 7a
Calcium
Then common pathway
Extrinsic pathway activated by
Tissue factor
Endothelial (blood vessel) damage that allows blood to escape circulation
What does APPT test?
Intrinsic pathway (and common)
What does PT test?
Extrinsic pathway (and common)
What does PT and APPT test?
Common pathway, extrinsic pathway and intrinsic pathway
Natural anticoagulants
Protein C
Protein S
Anti thrombin
Tissue factor pathway inhibitor
APTT
Activated partial thromboplastin time
Measures Intrinsic pathway
PT
Prothrombin time
Measures extrinsic pathway
TT
Thrombin time
Measures final step of pathway
Conversion of fibrinogen to fibrin via thrombin
Tests for clotting defects (3)
APPT (activated partial thromboplastin time)
PT (prothrombin time)
TT (thrombin time)
What type of blood are clotting tests done on?
Centrifuged
Platelet poor plasma (platelets removed)
Tests and what they measure
PT = extrinsic APPT = intrinsic
If APPT is prolonged…
Deficiency in intrinsic pathway
Factor 12, 11, 9, 8
If PT is prolonged…
Commonly due to factor 7 deficiency (extrinsic)
If APPT and PT are BOTH prolonged
Common pathway problem
Factor 5, 10, thrombin and fibrinogen deficiency
Vessel wall significance clotting cascade
Vasoconstriction
Production of vWF (platelet adherance)
Exposure of collagen and tissue factors initiates clotting cascade
What is vWF essential for?
Platelet adherance and protection of factor 8
How is protein C activated
when thrombin binds to thrombomodulin (endothelial cell receptor)
What does protein C do?
Inactivates factors 8a and 5a
Co factor for protein C
Protein s
Antithrombin 3 mechanism
Plasma protein inactivates thrombin
Prevents spread of clot by inactivating clotting factors that are carried away from site of clot
Antithrombin activated by…
Heparin on the surface of endothelial cells
What does tissue factor inhibitor do?
Acts in initiation phase (secreted by endothelial cells)
Binds to tissue factor-factor 7a complexes
Inhibits production of factor 10a
Thrombocytopenia pathology
Deficiency of platelets in blood
Bleeding into tissues, bruisng and slow clotting after injury
Thrombocytopenia signs/symptoms
Purpura petechiae mucosal bleeding nose bleeds (epistaxis) mennorrhagia (excessive menstrual bleeding)
Why can decreased platelets occur?
Decreased production Increased consumption (immune or non immune)
Reasons for decreased production of platelets
Marrow aplasia/infiltration
Megaloblastic anaemia
Sepsis
Systemic viral/bacterial infection
Immune reasons for low platelets
Immune thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Immune thrombocytopenic purpura
Isolated low platelet cound
Normal bone marrow (other cells normal)
Absence of any other cause
Thrombotic thrombocytopenic purpura
Blood clots forming in small vessels
Consumption of platelets and RBC
Non immune reasons for low platelets
Haemolytic-uraemic syndrome
Hypersplenism
Haemolytic uraemic syndrome
Low RBC’s and platelets
Actute kidney injury
Bloody diarrhoea, fever, vomitting, weakness
E-COLI main cause (effects children more)
Hyperspenism
Enlargement of spleen
Reduction in circulating blood cells (splenic pooling)
BM tries to compensate by proliferative
SPENECTOMY to treat
Coagulation factor disorders inherited
Haemophilia A/B
Von Williebrands disease
Aquired disorders of coagulation
Disseminated Intravascular Coagulation (DIC)
Liver disease
Vit K deficiency
Anticoagulants
Haemophlia signs/symptoms
Muscle haematomas
Haemarthroses (bleeding into joints)
Joint pain/deformity
Excessive Post op/trauma bleeding
Haemophilia A reason and test results
X linked recessive
Lack of factor 8
Prolonged APTT (normal PT)
Treatment Haemophilia A
Recombinant factor 8
DDAVP (Desmopressin)
Haemohphilia B
X linked recessive
Reduction of factor 9
Prolonged APTT and normal PT
Treatment haemophilia B
Infusions of recombinant factor 9
Von willebrand disease
Autosomal dominant
Abnormal platelet adhesion to vessel wall
Reduced factor 8 amount/activity
(Usually carries factor 8 and mediates platelet adhesion)
Von willebrand disease signs/symptoms
Unnoticed until additional stress
Spontaneous bleeding from mucous membranes (nosebleeds)
Excessive bleeding from wounds
Mennorhagia (heavy menstrual bleeding)
Tests results von willebrand
Prolonged bleeding time with normal platelet count
Hereditary haemorrhagic telangiectasia (HHT)
Autosomal dominant
Dilated microvascular swellings
GI haemmorhage = iron deficiency anaemia
Congenital vessel wall abnormalities
HHT
Connective tissue disorders (Ehlers Danlos)
Aquired vessel wall abnormalities
Senila purpura (bruising from age)
Steroids
Infections (measles, meningococcal)
Scurvy
Vessel wall abnormalities presentation
Rash
Easy bruising
Spontaneous bleeding from small vessels (mucous membranes/skin)
DIC
Disseminated intravascular coagulopathy
DIC what is it?
Microangiopathic haemolytic anaemia
What causes DIC
Pathological activation of coagulation
Malignancy, massive tissue injury, infections sepsis gram -ve, transfusion, haemorrhage
What does DIC lead to?
Microthrombi in circulation
Consumption of platelets
Haemolytic anaemia
Clotting tests DIC
Raised PT/INR, APTT, D dimers/fibrin degradation products
Low fibrinogen
Congenital thrombophilias
Deficiency in anticoagulants (protein C, S and antithrombin)
Abnormal factor 5 (resistance to protein C)
Aquired thrombophilias
Antiphospholipid syndrome (antiphospholipid antibodies)
Anticoagulant drugs
Vit K inhibitors
Oral anticoagulants
Low molecular weight Heparin
Heparin
Vit K inhibitors
Affects Vit K dependent factors (2, 7, 9, 20, protein C and protein S)
Monitor internal normalised ratio (PT time against normal)
Direct oral anticoagulants example
Dabigatran
Rivaroxaban
Apixaban
DOACS
Inhibit thrombin or factor 10a
No monitoring but careful if renal function is bad
Low molecular weight heparins
Makes antithrombin stronger
Dose by weight
Heparin monitor
APTT
Anitplatelet drugs
Asprirn
Clopidogrel/ticagrelor
Aspirin
Blocks formation of thromboxane A2 in platelets
Clopidogrel/ticagrelor
Block platelets ADP receptor
Complications with warfarin
Stop
Give Vit K
Prothrombin complex concentrate
Heparin complications
Stop
Give protamine sulphate IV if needed
Complications with anticoagulants =
EXCESSIVE BLEEDING
