Haemostasis and Coagulation
- Haemostasis means the arrest of bleeding. Platelets are activated and aggregate together. However this is weak. if the platelet plug breaks up again, you will begin bleeding again
- So the coagulation cascade produces fibrin cross-links (reinforces) platelets to allow them to bind to each other more strongly, thus decreasing the risk of re-bleeding
The Vascular Phase
- Blood vessel tries to maintain blood flow but also respond to breaches. The inner layer is a single layer of endothelial cells on a basement membrane. The cells secrete von Willebrand factor (VWF) into the plasma and subendothelium.
- Below the basement membrane is a subendothelium rich in collagen, elastin, fibronectin, tissue factor (TF), VWF etc. Below this lies smooth muscle layer. Below the smooth muscle layer is the adventitial layer.
- Endothelium has a negative charge and repels platelets,
produces prostacyclin and degrades ADP. Heparan sulphate and antithrombin III inhibit clotting factor activation. The endothelium also causes intrinsic fibrinolysis with a plasminogen activator.
- Smooth muscle can dilate and constricts in response to local NO production and so regulates blood flow
and dilatation
- The VWF binds to platelet GPIb-IX and GPIIbIIIa and mediates platelet adhesion to the vessel wall. Also carries FVIII and prevents its early degradation so prothrombotic
- The subendothelial Collagen, elastin if exposed will activate platelets tissues VWF etc and lead to thrombus formation
Platelets
- Platelets are formed from megakaryocytes in the bone marrow. The normal platelet count is 150- 450 x109/l. The life span of the platelet is 8 - 9 days.
- The platelet has a phospholipid cell membrane
into which are inserted glycoproteins (GP) which act as major cell receptors and
antigens of the platelets.
- Platelet Adhesion: if endothelium breached then platelets contact subendothelial tissues and GPIb-IX and VWF form a complex and platelets adhesion occurs.
- Aggregation: Platelets then stick to one another to form the primary platelet plug. Normal platelet number, presence of GPIIb-IIIa complex on the platelet surface (receptor for fibrinogen), plasma fibrinogen and calcium ions are necessary for platelet aggregation. As platelets aggregate they release their a and d granule contents which further sustain the aggregation response.
The Coagulation Phase
- In this phase liquid blood coagulates into a stable jelly-like clot. Blood coagulation takes in a cascade of enzyme reactions, each successive
step being catalysed by the active enzyme formed in the previous step.
- The process soon "snowballs" and gathers speed and force. Complexes are formed by Vitamin K dependent factors that help to localise the process. These factors are produced in the liver in their precursor form.
- They bear glutamic (Gla) residues at the amino-terminal end of the molecule which undergoes carboxylation of the Gla residues in the presence of a carboxylase, vitamin K, carbon dioxide and oxygen. These bind calcium ions which
then serve as a bridge to bind the proteins to phospholipid surfaces
Investigations
- Extrinsic and common pathway is tested by Prothrombin Time (PT)
- Intrinsic and common pathway is tested by Activated Thromboplastin Time
(APTT)
- Bleeding time measures platelet vessel wall interaction and is a poor predictor of abnormal surgical bleeding
- Thrombin time (TT) measures clottable fibrinogen and normal TT is 12-14 seconds
Bleeding
- Vascular/Platelet defect: skin petechiae and mucosal
surfaces ? bruising, epistaxis, gum bleeding, menorrhagia
- Coagulation defect: Bleeding into subcutaneous tissues, haematoma formation and haemarthrosis
