Haemostasis Flashcards
role of haemostasis
- Prevents bleeding
- Prevents unnecessary coagulation allowing blood to flow
main principls of haemostasis
1) Make clot
2) Control clotting
3) Break it down
what are essential for haemostasis?
- Movement of blood
- Heart
- Venous valves
- Calf pump
- Platelets
- Coagulation factors
- Anticoagulant factors
Haemostasis pathway
-
Clot initiation
- Platelet aggregation at site of damage
- Activation of coagulation
-
Clot formation
- Activation of prothrombin to thrombin
- Thrombin converts fibrinogen to fibrin
- Fibrin polymers form
- Retraction
-
Fibrinolysis (during tissue repair)
- Fibrin fragments
how are platelets produced
by megakaryocytes- bud from cytoplasm
normal platelet count
150-400 x10^9/l
lifespan of a platelet
- Lifespan 7-10 days
what does a platelet look like
what happens to the vessel wall after famage
vasoconstriction and production of von willebrand factor
von willebrand factor
- Involved in platelet adhesion to the vessel wall,
- platelet aggregation
- and also carries and protects Factor VIII
otulien the steps involvinf platelets
1) Platelet adhesion
2) Platelet activation
3) Platelet aggregation
1) Platelet adhesion
- *
- Damage to vessel wall
- Exposure of underlying tissues
- Platelets adhere to collagen via vWF/receptors
2) Platelet activation
- Secrete ADP, thromboxane and other substances to become activated and activate other platelets
- Involved in activation of clotting cascade
- Provide some coagulation factors by secretion from internal stores
3) Platelet aggregation
Cross linking of platelets to form platelet plug
mediating factors of platelets role in haemostasis
- Von Willebrand’s factors
- Fibrinogen
- Collagen
- ADP
- Thromboxane
- Thrombin
the clotting cascade is an
amplficiation system
the clotting cascade activates preucrosor molecules to generate
IIa (thrombin)
Thrombin converts
- Fibrinogen to fibrin
- Enmeshes initial platelet plug to make a stable clot
how is the clotting cascade controlled
- Natural anticoagulates that inhibits activation
- Also clot destroying proteins
both the intrinsic and extrinsic pathwya lead to the activation of
Xa which actives prothrombin to thrombin (IIa)
The intrinsic pathway is activated through
exposed endothelial collagen
The extrinsic pathway is activated through
tissue factor released by endothelial cells after external damage.
Coagulation factors and natural anticoagulants are made in the
liver
coagulation factors
- Fibrinogen
- Prothrombin
- Factors5,7,8,9,10,11,12,13, tissue factor
natural anticoagulants
- Protein C
- Protein S
- Antithrombin
- Tissue factor pathway inhibitor
how do we measure coagulation
Extrinsic/ PT (prothrombin time) test
- VII
Intrinsic/ APTT (activated partial thromboplastin time) test
- VIII, IX,XI, XII
V,X, prothrombin and fibrinogen can be done for both x
Fibrinolysis
- Plasminogen is activated by tissue plasminogen activator to form plasmin (e.g. T-PA, alteplase)
- Plasmin breaks down the fibrin clot
- Forms D-dimers- broken down by proteases in the blood
clinical relevance of haemostasis
- Bleeding disorders
- Arterial thrombotic disorders
- Venous thrombotic disorders
- Abnormal blood test results
- Drug therapy for pro-antithrombotic purposes
bleeding disorders can be due to
abnormalities in the vessel wall, platelts or coagulation factors
bleeding disorders can be
congenital or acquired
congenital bleeding disroders
- Haemophilia A (factor 8)
- Haemophilia B (Factor 9)
acquired bleeding disorders
- Liver disease
- Vit K deficiency
- Anticoagulants including warfarin (inhibit Vit K)
vessel wall abnormalities
- Easy bruising
- Spontaneous bleeding from small vessels
- Skin mainly
- Can be mucous membranes
congenital vessel wall abnormalities
- Hereditary haemorrhagic telangiectasia (HHT)
- Connective tissue disorders- Ehlers Danlos
Hereditary haemorrhagic telangiectasia (HHT)
- Autosomal dominant
- Dilated microvascular swellings increase with time
- GI haemorrhage can lead to iron deficiency anaemia
acquired vessel wall abnormalities
- Senile purpura
- Steroids
- Infection e.g. measles, meningococcal infections
- Scurvy-Vit C def causing defective collagen production (cant be hydroxylated)
Coagulation factor disorders
Clinical severity correlates with extent of deficiency
- Muscle haematomas
- Recurrent hemarthroses
- Joint pain and deformity
- Prolonged bleeding post dental extraction
- Life threatening post op and post traumatic bleeding
- Intracerebral haemorrhage
haemophilia A is an
x-linked recessive disease which causes lack factor VII (8)
severity of haemophilia A depends on
amount of VIII present
when is haemophilia A diagnoseed
pre-natally or soon after birth if family history or usually in infancy if new spontaneous mutation
where can bleeding occur with Haemophilia A
- Bleeding into muscle and joints, and post-operatively
treatment of haemophilia A
recombiannt factor VIII/ DDAVP
which test will show an abnormality with haemophilia A
intrinsic/ APTT test
haemophilia B has a
similar presentation to hameophilia A
what causes haemophilia B
congenital reduction in factor IX
Von Willebrand’s disease
- Relatively common
- Autosomal dominant, affects males and females
role of VWF
carries factor VIII and mediates platelet adhesion to the endothelium
von willebrand diseases causes abnormal
- Causes abnormal platelet adhesion to the vessel wall
- Reduced factor VIII amount/activity
- Factor 8 can be low in addition to low VWF levels
what causes VWD?
several genetic defects
symptoms of coagulation factor disorders
- Skin and mucous membrane bleeding
- Epistaxis
- Gum bleeding
- Bruising
- Prolonged bleeding after trauma
Disseminated intravascular coagulopathy (DIC)
- Type of microangiopathic haemolytic anaemia
- Pathological activation of coagulation
- Numerous microthrombi are formed in the circulation
- Leads to consumption of clotting factors and platelets and a haemolytic anaemia
- Clotting tests are affected- raised PT, raised APTT, low fibrinogen and raised D-dimers (fibrin degradation products)
disseminated intravascular coagulopathy (DIC)
- Type of microangiopathic haemolytic anaemia
- Pathological activation of coagulation
- Numerous microthrombi are formed in the circulation
- Leads to consumption of clotting factors and platelets and a haemolytic anaemia
*
test results for DIC
Clotting tests are affected- raised PT, raised APTT, low fibrinogen and raised D-dimers (fibrin degradation products)
triggers for DIC (always a trigger)
- Malignancy
- Massive tissue injury e.g. burns
- Infection
- Massive haemorrhage and transfusion
- ABO transfusion reaction
- Obstetric causes- placental abruption, pre-eclampsia, amniotic fluid embolism
Thrombophilias
- Acquired or congenital defects of haemostasis which cause increased risk of thrombosis
congenital causes of thrombophilia
- include deficiency in natural anticoagulants (protein C, protein S and antithrombin) and an abnormal factor V (factor V Leiden)
acquired thrombophilia
Acquired causes include antiphosphopholipid syndrome
thrombophilias are a relatively
rare conditions and many patients with them do not develop clots unless they have additional risk factors
