Introduction to haemostasis – a life-preserving process

Human blood: Red, white cells and platelets
Plasma (55%), contains clotting factors
Cellular component, 45%
Haemostasis – restore vascular integrity, limit infection.

Four key components to clotting:
Primary (the platelet plug), secondary haemostasis and fibrinolysis (the body’s hoovering process!)

Response to incision:
Vascular spasm – vasoconstriction, endothelium initiates
Fibrin mesh – strengthens clot, comes out of solution
Platelet adhesion and aggregation
Coagulation – stabilisation of clot
Fibrinolysis

Platelet life cycle: 7-10 days – fragments off megakaryocyte
Eventually removed by reticuloendothelial system
Platelets activated – increases surface area and becomes like putty.
Platelets recognise sub-endothelial tissue via Von Willebrand factor. v sticky (collagen,basement membrane etc). Platelets degranulate.
Von Willebrand factor – circulates and located in endothelial tissue. VW disease – clotting disorder, excessive bleeding
Tissue factor – thrombin. initiates development of fibrin. Stabilises platelets
Platelet science – v complicated. Lots of molecules they can release. Can remodel and change shape
Platelets adhere, activate and aggregate. Fibrin mesh stabilises.
Platelet acts as template to promote coagulation pathway, reactions leading to fibrin can take place on surface.

Exposure to sub endothelial tissue is required for platelet activation (extrinsic pathway).
Coagulation cascade tightly regulated. Factors turn system.
Fibrinolysis balances system.
13 clotting factors, mostly produced in liver. Named and numbered. Cascade of enzyme managed reactions

Tissue factor: Promotes clotting, by binding factor 7a recognising fibrin development
Tissue damage – thrombin (enzyme) and cascade of clotting: fibrinogen to insoluble fibrin

Extrinsic pathway – tissue factor outside of circulation
Intrinsic pathway – inherent coagulability of blood. Eg cut finger on bench. Blood on bench coagulates as a result of non-physiological contact. Contact coagulation
Coagulation pathway actually more complicated than just having these two arms.
Thrombin burst – tissue factor and 7a complex initiates thrombin enzyme and conversion of fibrinogen to fibrin.
Fibrinolysis: clot limiting, repair and healing mechanism (clot dissolution)
Plasminogen – enzyme, activated by another enzyme (tPA) to Plasmin. Eats clot.
The leftover part is D-Dimer, which can be measured clinically (eg in DVT).
tPA can be mimicked in clot busting medication

The body has natural anticoagulants eg.
Anti-thrombin inhibits thrombin.
Normal Clotting requires equilibrium of all of the above constituents
Can be disregulated by disease – eg infection, bone marrow insufficiency – thrombocytopenia – no platelets formed (results in non blanching rash)
Almost every inpatient takes some form of anticoagulant to prevent DVT

Thrombocytopenia – 450 hypercoagulability.
Bleeding disorders can be inherited (eg. Haemophilia) or acquired (liver disease)
Avoid intramuscular injections in these patients
Haemophilia – haemarthrosis v common. Patients become disabled with arthritis
Lab evaluations: FBC and film, coagulation tests, platelet function (inc VWF)
Blood incubated with reagents (eg calcium collater) until tests applied.
Clotting dependent upon calcium (as a co-factor), hence removal block coagulation
Calcium returned before test. Tissue factor can also be added to measure coagulation.
Prothrombin time (PT): measures extrinsic pathway. add tissue factor (also phospholipid and calcium), should take 11-13 seconds until fibrin forms. If around 20seconds, a clotting factor is lacking.
Activated partial thromboplastin time (APTT) – measures intrinsic clotting pathway. Normal time is 28-44 seconds
These tests don’t show which clotting factor is lacking
Thrombin time (TT): add thrombin. Tests final stage in clotting cascade.

In summary, haemostasis is tightly regulated and involves endothelium, platelets, clotting factors and fibrinolysis. Disregulation results in disease.

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