haemostasis Flashcards
(30 cards)
give an overview of the response to vessel injury
- vessel constricts
2.primary haemostasis- formation of an unstable platelet plug (platelet adhesion and aggregation)
3.secondary haemostasis- formation of a stable plus (stabilisation with fibrin) (blood coagulation)
4-dissolution of the clot (via fibrinolysis) and vessel repair
describe primary haemostasis
Platelet adhesion- von willebrand factor (vWF) binds to the exposed collagen –> Glycoprotein 1-b on platelets bind to vWF
OR
Platelet directly binds to exposed collagen via Glycoprotein 1-a
Platelet aggregation: binding of platelets activates them–> they release ADP and THROMBOXANE—> +ve feedback activates platelets more–> activates glp-IIb/IIIa on platelet surface–> binds to circulating fibrinogen–> forms platelet aggregate
describe secondary haemostasis
intrinsic pathway:XII-XIIa–>XI-XIa–>IX-IXa (tissue factor acts here-activates VII-VIIa) +VIIIa—> X-Xa(where the pathways converge)–> prothrombin-thrombin–>fibrinogen-fibrin+XIIIa–>cross linked fibrin
Extrinsic pathway: tissue factor activates VII-VIIa—>X-Xa—>then same as intrinsic pathway
describe fibrinolysis
Plasminogen—(tissue plasminogen activator, tPA)—> plasmin—> fibrin degradation
describe prostacyclin synthesis + location + function
membrane phospholipid–> Arachidonic acid—COX–> endoperoxides (PGG2, PGH2)—> PGI2 aka prostacyclin
endothelialial cells
potent inhibitor of platelet function
describe thromboxane synthesis + location + function
membrane phospholipid–> Arachidonic acid—COX–> endoperoxides (PGG2, PGH2)—> Thromboxane A2
platelet
endoperoxidases and thromboxane are potent inducers of platelet aggregation
what are the main anti platelet therapies
COX-1 inhibitor - aspirin (irreversible)
ADP receptor antagonist - prasugrel
Glp-IIb/IIIa antagonist - abciximab
what are the uses of anti-platelet drugs
angina, post-myocardial infarction
mechanism of action of heparin + indications for use
it accelerates the action of a natural plasma inhibitor, antithrombin (ie inhibits: thrombin (IIa), F10a, F9a, F11a by forming irreversible complexes with them–> inactivation)
indications: used for immediate anticoagulation in venous thrombosis and pulmonary embolism
mechanism of action of warfarin + indication for use
WARFARIN antagonises the action of vitamin K, so warfarin blocks the assembly of the coagulation factors on the platelet surface. (as coagulation factors synthesis is vital-K dependant)
enzyme that is inhibited is a complex called vitamin-K epoxide reductase
indications:Venous thrombosis: warfarin treatment for 6 months. Atrial fibrillation: warfarin treatment is life long.
what are the different lab tests for coagulation
Activated partial thromboplastin time (APTT): activated coagulation through FXII and therefore detects abnormalities in intrinsic and common pathways
Prothrombin time (PT): initiates coagulation through tissue factor and therefore detects abnormalities in the extrinsic and common pathways.
Thrombin clotting time (TCT): add thrombin- shows abnormalities in conversion of fibrinogen to fibrin.
Factor assays (for Factor VIII etc.) In haemophilia, the APTT is prolonged because you are not making factor 8 or 9
- PT will be normal (extrinsic pathway not affected) – TYPICAL CLOTTING SCREEN FOR HAEMOPHILIA
uses of coagulation tests
- APTT and PT are used together for screening for causes of bleeding disorders
- APTT is used to monitor heparin therapy in thrombosis
- PT is used for monitoring warfarin treatment in thrombosis
what are the platelet function tests
Bleeding time, 2-9 minutes–indicates that the platelets are acting abnormally with the vessel wall
Platelet count, 150-400 x10^9/L
Platelet aggregation—It is used in inherited platelet abnormalities, and von Willebrand Disease
what are the clinical features of people with primary haemostasis
problem with platelets- no formation of unstable plug:
- Immediate
- Prolonged bleeding from cuts
- Epistaxes (nose bleed>10 mins)
- Gum bleeding (areas of high shear without functioning vWF)
- Menorrhagia (heavy + prolonged menstrual bleeding)
- Easy bruising
- Prolonged bleeding after trauma or surgery
- Thrombocytopenia > petechiae (small dotted bruising)
what are the clinical features of people with secondary haemostasis
problem with stabilisation of platelet plug:
- Spontaneous bleeding is deep, into muscles and joints (HAEMARTHRITIS)
- Bleeding after trauma may be delayed and is prolonged
- Superficial cuts do not bleed (platelets)
- Bruising is common,
- Nosebleeds are rare
- Frequently restarts after stopping
causes of primary haemostasis disorders
Platelets:
-Thrombocytopenia: eg Bone marrow failure (leukaemia), DIC (disseminated…)
-Von Willebrand Disease (deficient or impaired)
-Impaired function: Acquired due to drugs, eg aspirin, NSAIDs,
The vessel wall: -
hereditary vascular disorders (Hereditary haemorrhagic telangiectasia),
-scurvy,
-steroids,
-age
causes of secondary haemostasis disorders
hereditary: Haemophilia A (FVIII) & B (FIX) – X linked,
acquired: liver disease (most cf made in liver), dilution, anticoagulation
Disseminated intravascular coagulation (DIC)
fibrinolysis defects:
Hereditary
Antiplasmin deficiency
Acquired
Drugs that enhance tPA (tissue plasminogen activator)
Disseminated intravascular coagulation
treatment of abnormal haemostasis
Failure of production/function
o Replace missing factor/platelets (Prophylactic or ' Therapeutic)
o Stop drugs causing this
oDDAVP (desmopressin) – release the body’s own ' stores of VWF and F8
- Immune destruction (e.g. immune thrombocytopenia)
o Immunosuppression (e.g. prednisolone) o Splenectomy for ITP (Idiopathic thrombocytopenic ' purpura)
- Increased consumption
o Treat the cause of the DIC o Replace what is missing as necessary oTranexamic acid – anti-fibrinolytic (competitively inhibits binding of tPA to fibrin)
name the 3 different treatment you can give to replace factors
Replace Factors:
Plasma: Contains all coagulation factors
Cryoprecipitate: Rich in Fibrinogen, FVIII, VWF, Factor XIII
Factor concentrates: Concentrates available for all factors except factor V.
Prothrombin complex concentrates (PCCs) Factors II, VII, IX, X
Recombinant forms of FVIII and FIX are available.
what are the major ABO blood groups
A, B, AB, O
A adds N-acetyl galactosamine
B adds galactose
what antigens/antibodies would people in the ABO blood group types have
A- A antigens and Anti-B antibodies B- B antigens and Anti-A antibodies AB- A and B antigens, no antibodies O- no antigens, Anti-A and Anti-B antibodies IgM
what are the major Rh blood groups
RhD positive
RhD negative
IgG
what antigens/antibodies would people in the Rh blood group types have
RhD+ would have Rhd antigens and no antibodies
RhD- would have no antigens but Anti-RhD antibodies(after previous exposure to RhD+ blood or fetus can make it)
