Clotting Flashcards
What does the endothelium excrete?
Prostacyclin
Nitric oxide
What dies the endothelium secrete?
Mediators like prostaglandins and nitric oxide which prevent platelet adhesion
How doe platelet adhesion occur?
Leads to degranulation of the platelets, releasing ADP
ADP stimulates further platelet aggregation at the site
Platelets synthesise prostaglandin thromboxane A, which causes both vasoconstriction and further aggregation
Receptors on the platelet surface then activate the coagulation cascade, which generates fibrin/platelet thrombus
This is known as primary haemostasis
What occurs after intake of aspirin?
Nuclei of endothelial cells are quickly able to secrete mRNA for the PGI2 production
The enucleate platelets cannot from TXA2, so levels decrease until new platelets are formed in approximately 7 days
How does clopidogrel work?
Works as an ADP receptor antagonist, thus preventing glycoprotein expression and platelet aggregation
What are the causes of reduced platelet production in thrombocytopenia?
Reduced production: Anaplastic anaemia Marrow infiltration Marrow suppression Excess destruction: Immune thrombocytopenia purapura: ITP Other autoimmune causes: SLE, CLL, viruses Thrombotic thrombocytopenia purapura: TTP Haemolytic uraemia syndrome: HUS Sequestration: hyperthyroidism
What is the presentation of thrombocytopenia?
Mucocutaneous bleeding
Bruising/purapura of the skin
Epistaxis/menorrhagia
What is prothrombin time?
Tests the extrinsic pathway, by addition of a tissue factor substitute tot he patient’s plasma
It is prolonged in liver disease, or if the patient is on warfarin
What is international normalised ratio?
Ratio of patient’s PT to a normal control whilst using an international reference preparation (standardises laboratories worldwide)
0.9-1.1 is the normal range
Used for warfarin dosing
What is activated partial thromboplastin time (APTT)?
Addition of a surface activator to the plasma
Tests for intrinsic (contact) pathway
It is the monitoring required for unfractionated heparin (not required for LMWH)
What is thrombin time?
Addition of thrombin to the patient’s plasma
Prolonged with fibrinogen deficiency or abnormal function, or inhibitors such as heparin
What is the coagulation cascade?
Clotting factors are primarily synthesised in the liver and many act as serine proteases to activate other factors
Fibrinogen is factor I
Prothrombin is factor II (thrombin is IIa)
Extrinsic and intrinsic pathway activate a final common pathway that leads to production of fibrin and thus. a thrombus can be formed
At the same time, thrombin, in the presence of calcium ions, activates factor VIII, which stabilises the fibrin clot by cross-linking fibrin molecules
Where is vitamin K found?
leafy green vegetables, dairy products and soya beans
Interstitial flora can also synthesise many forms of vitamin K
It is a cofactor necessary for the production of blood clotting factors:
Factor II, VII, IX, X
What can vitamin K deficiency cause?
Leads to deficiency in clotting factors, leading to an increased PT and haemorrhage
Can arise form malabsorption conditions (fat soluble), cholestatic jaundice (no bile salts), or antibiotics (gut flora disturbances)
What are inhibitors of coagulation?
Anti-thrombin III: serine protease inhibitor, potentiated by heparin
Activated protein C (APC): also generated by vitamin K and activated by thrombin
APC acts with the co-factor protein S to induce fibrinolysis
It destroys factor V and VIII, reducing further thrombin generation and also inhibits stabilisation of the fibrin clot
What is fibrinolysis?
Plasminogen is converted to plasmin by tissue plasminogen activator (t-PA), produced by endothelium
Many mediators, including thrombin and APC stimulate the release of t-PA
Plasmin is a serine protease that breaks down fibrinogen and fibrin into fibrin degradation (FDPs) e.g D-dimer
D-dimer presence in the plasma thus indicates that the coagulation mechanism has been activated
What is the ABO system?
Red cells can be A, B, AB or O: named accordingly to their surface antigens
They will carry IgM antibodies against any antigen that they do not carry
O group blood will carry anti-A and anti-B antigens
AB group blood will not carry any anti-A or anti-B antigen
What is Rhesus system?
Blood class can either show the rhesus D antigen (rhesus positive) or not (rhesus negative)
If a rhesus negative individual is exposed to rhesus positive blood products, they can then develop IgG antibodies directed against the rhesus D antigen
If exposed to rhesus positive blood products again, there will be haemolysis
This is the pathology behind haemolytic disease of the newborn, as well as transfusion reactions
What is blood grouping and antibody screening?
Blood grouping: ABO and RhD groups of the patient are determined
Antibody screening: patient serum/plasma screened for atypical antibodies that would cause significant hameolysis of transfused cells
Tested using at least 2 group O donors expressing a wide range of antigens
What occurs in cross-matching?
Indirect agglutination test: donor RBCs added to patients serum, then Coomb’s reagent is added, agglutination indicates that the patient’s serum has antibodies for the donor RBCs. This test is always performed pre-transfusion
Direct agglutination: patients’s washed RBCs are added to Coomb’s reagent and if they agglutinate that indicates that there is an autoimmune haemolytic process occurring, with the RBCs coated with immunoglobulins. Rarely required pre-transfusion (Coomb’s test)
Which blood products need to be cross-matched?
All of them except platelets
What occurs in a group & save?
antibody screen performed to confirm if it’s negative, so that appropriate blood can quickly be made available if required
If the antibody screen is positive, compatible blood should always be reserved in advance
What is the massive transfusion protocol?
2 units of O negative blood to be made available immediately
Blood of the same ABO/rhesus group will be available in 10-15 mins
Fully cross-matched blood will be available within 45 minutes
What occurs in endothelium damage?
There is exposed collagen and von Willebrand factor, which leads to platelet adhesion