Thursday, May 22, 2008

Cardiovascular Drugs made EZ: Part 2

One subject that often confuses nursing students preparing for the NCLEX exam and practitioners alike, is that of clotting and anticoagulants. The problem with this, is these medications are extremely common in both inpatient and outpatient populations, so this knowledge is imperative for those in the healthcare industry to have. Lets take a look together and see if we can make it a bit more simple, in case your NCLEX exam decides to drill you on this point. We will go step by step through the clotting process, taking small sidetracks to look at specific medications.


• 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
1.Platelet Plug
2.Intrinsic Coagulation
3.Extrinsic Coagulation

Platelet Plug

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.

(platelet aggregation)

(fibrin threads creating plug)

Intrinsic Coagulation
When the insult is deeper, collagen may be exposed, initiating the intrinsic coagulation cascade. Collagen activates factor 12 then 11 then 8 + 9 then 10. 10 converts Prothrombin into Thrombin, which then converts Fibrinogen to Fibrin. This process is faster than a platelet plug as you don’t need to wait for platelets to collect, and it forms more extensive Fibrin patches.

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.

Extrinsic Coagulation
When deep injury occurs, tissue is exposed to blood, initiating the extrinsic coagulation cascade. Tissue factor activates factor 7 then 10. 10 then follows same route as above. With fewer steps this cascade is faster than the intrinsic and develops more extensive Fibrin patch. Of importance to note is just as Ca makes muscle contract stronger, its presence also makes clots stronger.

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.
(extensive fibrin patch)
Regulation of Coagulation
To assure coagulation does not go too far, 2 specific mechanisms inhibit or reverse the process:
1) Antithrombin III (AT III): AT III inhibits the production of Thrombin by blocking Prothrombin, thereby reducing the amount of Fibrin formed. Healthy endothelial cells produce this, thereby quarantining off the damaged area so clotting does not extend beyond where it is needed.
Pharm Note: Lovenox (Enoxaparin) enhances the activity of AT III, thereby slowing clot formation. The low molecular portion of heparin is the active part here, so regular Heparin partially works here in addition to Intrinsic factor inhibition.
Lab Note: Partial Thromboplastin Time (PTT) is not effected by Low Molecular weight heparins (Lovenox) because no Intrinsic factors are inhibited.
2) Tissue Plasminogen Activator (TPA): Injured cells also release TPA, which converts free floating Plasminogen to Plasmin. Plasmin degrades Fibrin, so clots are constantly broken down, even as they are built. The more active system wins, depending upon how much clotting is actually needed.
Pharm Note: TPA (Alteplase) can be synthetically injected to actively break down clots, such as in the case of a Stroke or Myocardial Infarction. Great caution should be used when administering this as massive, even fatal bleeds are possible. (Streptokinase and Urokinase are alternatives that work by same method)


NurseReview.Org said...

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Nov 2008 NLE Results said...
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Manjot kaur said...

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