• When vascular injury occurs, various mechanisms are available to stop the loss of blood
• The mechanism employed depends upon the extent of injury, but the end result of all is to produce strands of Fibrin to patch the hole; The difference in the various mechanisms is the speed and amount of Fibrin produced
When vascular endothelial tissue is damaged, a platelet plug can form, sealing the hole. If no deeper tissues are exposed, this may be the extent of the healing process. If damage is more extensive, platelets, as well as tissue exposure can initiate further coagulation. Platelet plug formation occurs in 4 steps (use pic to right of text as visual guide):
1) Adhesion: When subendothelial tissue is exposed, sticky proteins (Von Willebrand factor) are exposed to passing blood and act as magnets to passing platelets.
2) Aggregation: ADP, a breakdown product of ATP released from damaged cells, stimulates the production of receptors (GPIIb) on the platelets that bind a free floating soluble protein Fibrinogen.
Pharm Note: Plavix and Ticlid inhibit ADP, so platelets are not stimulated to produce fibrinogen receptors and clots are more difficult to produce
Pharm Note: Abciximab (Reopro) binds to the platelet GPIIb receptor and blocks fibrinogen from binding, and clots are more difficult to make
3) Secretion: Stimulated platelets release chemicals like Thromboxane, that attracts other platelets. Fibrinogen can bind two platelets, thus platelets begin to collect in mass.
4) Platelet Coagulation: Stimulated platelets now produce factor V, which leads to fibrinogen being transformed into Fibrin threads to incase the aggregated platelets
Pharm Note: Aspirin blocks the release of Thromboxane for the life of the platelet, so cell aggregation is made difficult. This is why aspirin is known to make platelets less sticky, and is so frequently given as prophylaxis against clot formation. Since platelets are still allowed to bind Von Willebrand, there is still some platelet plug action, meaning some bleeding is stopped. This is why Aspirin is not as powerful an antiplatelet drug as prescription drugs like Plavix and Reopro.
Pharm Note: Heparin inhibits the Intrinsic Factors, making them slower to respond, which makes clotting more difficult and less extensive
Lab Note: Partial Thromboplastin Time (PTT) measures the speed of collection of these factors, thereby measuring the effectiveness of Heparin. PTT, usually 30-40 seconds is the amount of time it takes all of the necessary factors to gather at site of need. Heparin binds these factors, slowing their collection, and lengthening PTT.
Pharm Note: Factor 7 is made in the liver from Vitamin K. Warfarin (Coumadin) blocks Vitamin K and thereby reduces the amount of Factor 7 made. Now it takes longer to collect enough Factor 7 to initiate this extrinsic clotting, and you have slower clotting that is less extensive. Since the medication effects future Factor 7 production and not that currently present in the blood, it takes a few days to see its effects.
Lab Note: Prothrombin Time (PT) measures the speed of collection of Factor 7, thereby measuring the effectiveness of Coumadin therapy. This value is converted to the INR. Think of this value as a stopwatch that starts timing as soon as injury occurs. PT, usually 10-12 seconds is the amount of time it takes factor 7 to reach the area of need.
Lab Note: Partial Thromboplastin Time (PTT) is not effected by Low Molecular weight heparins (Lovenox) because no Intrinsic factors are inhibited.