Haemostasis Flashcards
What is haemostasis for?
To prevent bleeding and to prevent unnecessary coagulation, allow blood to flow
Principles of haemostasis
Make a clot
Control clotting
Break it down
What is essential for haemostasis?
Keep blood moving - heart, venous valves, calf pump
Blood vessels
Platelets
Coagulation factors
Anticoagulant factors
What are platelets?
Megakaryocytes produce platelets in the bone marrow
Platelets ‘bud’ from cytoplasm
Normal platelet count is 150-400 109/L
Normal lifespan 7-10day
Platelet adhesion?
Damage to vessel wall
Exposure of underlying tissues
Platelets adhere to collagen via vWF / receptor
Platelet activation…
Secrete ADP, thromboxane and other substaces to become activated and activated other platelets
Involved in activation of the clotting cascade
Provide some coagulation factors by secretion from internal stores
Platelet aggregation
Cross linking of platelets to form a platelet plug
What does the clotting cascade mean?
Amplification system activation of precursor proteins to generate thrombin (IIa)
Thrombin converts voluble fibrinogen to insoluble fibrin.
Enmeshes initial platelet plug to make stable clot
…Controlled
Natural anticoagulants to inhibit activation
Cot destroying proteins which are activated by thr clotting cascade (carefully balanced).
Where are coagulation factors made?
They are made in the liver
What is the clotting cascade?
PT - extrinsic pathway. VII
APTT - Intrinsic. VIII IX XI XII
Commo pathway - V, X, Prothrombin, Fibrinogen
Lab tests?
PT - measures extrinsic and common pathway. INR is derived from this and it used to measure warfrin.
APTT measured intrinsic and common pathway
Fibrinogen count measues the amount of fibrinogen
VonWillebrand Factor?
Involved in platelet adhesion to the vessel wall, platelet aggregation. And also carries factor VIII
Vessel Wall?
Vasoconstriction
Production of Von Willebrands Factor (vWF)
- -Essential for plt adhesion
- -Carrier and ‘protector’ of Factor 8 (clotting protein).
Exposure of Collagen and Tissue factor which initiates activation of clotting factors (proteins).
Natural anticoagulants?
Stop further coagulation
- Protein C
- Protein S
- Anti-Thrombin
Fibrinolysis?
Plasminogen to Plasmin which break down clots. This is activated by plasminogen activator.
D Dimers?
D-dimer is a fibrin degradation product (or FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis.
Clinical relevance of haemostasis
Bleeding disorders
Arterial rhomboid disorders
Venous thrombotic disorders
Abnormal blood test results
Drug therapy for pro- or anti- thrombotic purposes
Coagulation Factor disorders?
Congenital : haemophilia A (F8) Haemophilia B (F9)
Acquired: Liver disease, Vitamin K (F2,7,9,10) Anticoagulants including Warfrin (inhibits Vit K - reduction in 2,7,9,10)
Clinical symptoms of coagulation factor disorders?
Clinical severity correlates with extent of deficiency
Muscle haematomas
Recurrent haemarthroses
Joint pain and deformity
Prolonged bleeding post dental extraction
Life threatening post op and post traumatic bleeding
Intracerebral haemorrhage
Haemophilia A?
X-linked recessive
Congenital lack of factor VIII
Mild/moderate/severe depending on amount of factor VIII present
Diagnosed pre-nasally or soon after birth if family history, to usually in infancy if new spontaneous mutations
Bleeding into muscles/and joints and post-operatively
Treated with recombinant factor VIII or DDAVP
See in blood results?
Prolonged APTT as less factor 8
Haemophilia B?
Similar presentation to haemophilia A
Congenital reduction in factor IX
Von Willebrands Disease?
Relatively common
- Usually autosomal dominant, affects makes and females
- vWF carried Factor VIII and mediates platelet adhesion tot he endothelium
Abnormal platelet adhesion to vessle wall
Reduced FVIII amount / activity (FVIII can be low in addition to low VWF levels)
Several genetic defects cause this condition
Main type due to a reduction in vWF production ie not enough
(others where activity reduced)
Symptoms of vWD?
Skin and mucous membrane bleeding
- Epistaxis
- Gum bleeding
- Bruising
Prolonged bleeding
- Heavy periods
- Post surgery
- Post dental extraction
Vessel wall abnormalities?
Easy bruising
Spontaneous bleeding from small vessels
Skin mainly
Can be mucous membranes
Problems with Vessles?
Congenital
- -Hereditary Haemorrhagc Telangiectasia (HHT)
- -Autosomal Dominant
- -Dilated microvascular swellings increase with time
- -GI haemorrhage can lead to iron deficiency anaemia
- Connective tissue disorders - Ehlers Danlos
Acquired
- Senile purpura
- Steroids
- Infection
- Scurvy
Disseminated Intravascuar Coagulopathy?
Type of microangiopathic haemolytic anaemia
Pathological activation of coagulation
Numerous microthrombi are formed in the circulation
This leads to consumption of clotting factors and platelets and a haemolytic anaemia
Clotting tests are affected - usually raised PT / INR, low fibrinogen and raised D dimers / fibrin degradation products
Triggers of disseminated intravascular coagulopathy?
Malignancy
Massive tissue injury eg burns
Infections - usually gran negative sepsis
Massive haemorrhage and transfusion
ABO transfusion reaction
Obstetric causes - placental abruptly, pre-eclampsia, amniotic fluid embolism.
Only way to treat it is to treat underlying cause
Thrombophilias?
These are acquired or congenital defects of haemostasis which can increase a patient’s risk of thrombosis
Congenital causes include deficiency on natural anticoagulants (Protein C, Protein S and antithrombin) and an abnormal factor V (factor V Leiden - relatively common)
Acquired causes include antiphospholipid syndrome
These are relatively rare conditions and many patients with them do not develop clots unless they have additional risk factors.
