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Our two main players in coagulation are platelets and clotting factors. To help make things clear we can split up these two agents into separate categories even though the work in concert.
Primary hemostasis
When a blood vessel is damaged, the subendothelium spaces are exposed to blood. This triggers a number of events designed to prevent bleeding. Platelets bind directly to the collagen in the subendothelium space. vWF increases the binding between the platelets and the collagen. Platelets become activated and release vWF and platelet activating factor (PAF) as well as thrombin and a number of other proteins into the bloodstream which attract more platelets and boost the clotting cascade. These platelets are crosslinked by a protein called fibrinogen (factor II).
Secondary hemostasis
The clotting cascade is a series of chemical reactions where an enzyme acts on a protein thereby activating it and turning into an enzyme that will act on another protein and so on and so on until we get to the production of fibrin from fibrinogen. The clotting cascade leads to the creation of fibrin. A tough, stringy protein that forms a web or mesh and holds the platelets in place.
The clotting cascade can be described as having two different pathways depending on which proteins are activated first. These are called the intrinsic and extrinsic pathways.
Towards the end of the clotting cascade, regardless of which pathway is used, factor X activates prothrombin ( factor II) creating thrombin (factor IIa). Thrombin then in turn acts on fibrinogen (factor I) creating fibrin (factor Ia).
A Few More Things to Know
- Heparin
- Thrombin inhibitor. Thrombin changes fibrinogen into fibrin.
- Faster onset and shorter half life than warfarin
- Preferred to warfarin during pregnancy
- IV or IM
- Monitored with PTT or aPTT
- Normal PTT range is 30-40 seconds
- Therapeutic range is 60-80 seconds
- Warfarin
- Vitamin K antagonist
- Vitamin K is necessary for the production of clotting factors
- It takes about three days to get an anticoagulation effect with warfarin
- Oral
- Monitored with PT/INR
- Normal PT/INR 0.75-1.25
- Therapeutic range is 2-3
- NSAIDS and Aspirin
- Blocks thromboxane A2 which would normally stimulate platelet activation and platelet binding.
– Tissue plasminogen activator (tPA)
– Activates plasminogen
– Plasminogen is the precursor to plasmin which will perform fibrinolysis and dissolve blood clots.
- Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT)
- Used to assess the intrinsic and common coagulation pathways
- Normal range is 30-40 seconds
- Causes of a delayed PTT include
- Heparin use – therapeutic range is 60-80
- Hemophilia
- Missing coagulation factors
- Sepsis – secondary to coagulation factor consumption
- Prothrombin time (PT) and International normalized ratio (INR)
- INR is a method to normalize data across different labs
- Used to assess the extrinsic pathway and common coagulation pathways
- Normal range is 0.75-1.25
- Causes of a delayed PT/INR include
- Warfarin use – therapeutic levels are 2-3
- Liver damage
- Bleeding time
- Used to assess platelet function
- The patient is cut under standard conditions and is observed until bleeding stops
- D-Dimer
- D-dimer is a byproduct of blood clots being broken down in the body. Elevated levels may indicate a large amount of clot within the vascular system.
