Help: Thrombolytic agents and Heparin

Daytonite, BSN, RN · Aug 10, 2008

Heparin is almost always given immediately after a specific level of a thrombolytic has been achieved in order to maintain anticoagulation. Oral anticoagulation agents such as warfarin (Coumadin) which are long acting and take several days to build up in the blood are also started. When enough oral agent is present the IV heparin will be discontinued. The thrombolytic agent dissolves the clot; the anticoagulant prevents any more clots from forming. There are long acting and short acting thrombolytics now. Anticoagulants are contraindicated when there is known active bleeding which is what a hemorrhagic stroke is. Hemorrhage is not the same as a clot.

Thrombolytics are proteins also called thrombolytic enzymes or clotbusters. They stimulate the synthesis of fibrinolysin which is what breaks apart or dissolves a blood clot. The textbook I have, Pharmacology: An Introduction, 5th Edition, by Henry Hitner and Barbara, says: "At the end of the streptokinase or urokinase infusion, treatment usually continues with heparin infusion. Heparin is begun only after the thrombin time (PT, PTT) has decreased to less than 2 times the normal control (usually 3 to 4 hours after completion of urokinase infusion). . .Alteplase (tPA) is rapidly cleared from the blood within 5 to 10 minutes after [its] infusion is terminated. . .Thrombolytic enzymes are approved for use in the management of acute myocardial infarction, acute ischemic stroke, and pulmonary embolism. Streptokinase is also approved for lysis of deep vein thrombi." (page 299)

There are also different drugs used here and some act faster than others.

tPA (alteplase) - short acting - Onset of action is immediate; cleared from the blood plasma by the liver within 5-10 minutes after the infusion is stopped and effects may linger up to 4 hours after the infusion
streptokinase - long acting (compared to alteplase) - onset of action is immediate; duration is about 12 hours, but can be as long as 24 hours
urokinase - same as streptokinase

Thought you might have gotten caught up on the statement about the anticoagulants not being given for the 24 to 48 hours after the administration of a thrombolytic agent. That would be for streptokinase or urokinase because their effects last for 12 hours and sometimes as long as 24 hours according to one of my IV books. The reason the heparin isn't started for 24 to 48 hours with it is because the docs are waiting for the patient's PTT levels to come down to less than 2 times the normal control which is the accepted therapeutic goal for anticoagulation. If they start the heparin infusion before that they run the risk of the patient developing unwanted hemorrhaging. Keep in mind that the goal of thrombolysis is to bust up the clot, so let's do that safely first, then anticoagulate the guy--safely--next. tPA, on the other hand, is a short acting thrombolytic that has a super short half life and is out of the person's system in 10 minutes to 4 hours. To determine how soon the heparin infusion is started, PTTs are also done. Again, you don't want to start heparin too early and have the patient bleeding out on you until their PTT levels decrease to a safe level. When patients are getting these thrombolytic agents, PTT levels are being drawn almost minute-by-minute (well, not that much, but maybe hourly) and monitored very, very closely.

You do know the difference between a hemorrhagic stroke and an ischemic stroke, right?

Strokes are classified as ischemic or hemorrhagic. There are three types of ischemia strokes: thrombotic, embolic and lacunar.

(1) Cerebral thrombosis.

Thrombosis of the cerebral arteries supplying the brain or of the intracranial vessels occluding blood flow is the most common cause of strokes in middle-aged and elderly people. It is commonly the result of atherosclerosis, but also associated with hypertension, smoking and diabetes. A thrombus in an extracranial or intracranial vessel blocks blood flow to the cerebral cortex. The carotid artery is the most commonly affected extracranial vessel. Common intracranial sites include the bifurcation of the carotid arteries, distal intracranial portion of vertebral arteries, and proximal basilar arteries. Thrombotic stokes commonly occur during sleep or shortly after awakening, during surgery, or after a myocardial infarction.

(2) Cerebral embolism.

An embolism from outside the brain, such as in the heart, aorta, or common carotid artery can occur at any age, especially among patients with a history of rheumatic heart disease, endocarditis, posttraumatic valvular disease, myocardial fibrillation and other cardiac arrhythmias, or after open heart surgery. These embolisms float into the cerebral bloodstream and lodge in the middle cerebral artery or one of its branches. It is the second most common type of stroke. These types of strokes typically occur during activity and develop rapidly. These emboli commonly originate during atrial fibrillation.

(3) Cerebral Lacunar stroke.

This is a type of thrombotic stroke. Hypertension creates cavities deep in the white matter of the brain which affects the internal capsule, basal ganglia, thalamus and pons. The lipid coat lining the small penetrating arteries thickens and weakens the walls of these blood vessels causing microaneurysms and dissections.

Hemorrhagic stroke.

This is the third most common type of stroke. A rupture occurs in an intracranial artery or vein as a result of hypertension, aneurysm, arteriovenous malformations, trauma, hemorrhagic disorders or a septic embolism. Hypertension and ruptured aneurysms are the most common causes. It can occur at any age. As a result there is diminished blood supplied to the tissues fed by the ruptured artery and compression of the brain cells by accumulated blood. When hemorrhage has occurred the blood that has spilled among the brain cells acts as a space-occupying mass that exerts pressure on the brain tissue. At first, ruptured cerebral blood vessels may constrict to limit blood loss which further restricts blood flow to the area of stroke and promotes ischemia. Blood cells can also migrate into the spaces where cerebral spinal fluid circulates and cause blockages of this fluid circulation resulting in hydocephalus.

When any type of stroke occurs, there is deprivation of oxygen and nutrients to the affected area of the brain. When blood flow in a blood vessel remains blocked for more than a few minutes, oxygen deprivation leads to infarction of brain tissue. The brain cells cease to function because they can neither store glucose or glycogen for use nor engage in anaerobic metabolism.

Hope all the above helped unconfuse you.

justme1972 · Aug 10, 2008

Thought you might have gotten caught up on the statement about the anticoagulants not being given for the 24 to 48 hours after the administration of a thrombolytic agent. That would be for streptokinase or urokinase because their effects last for 12 hours and sometimes as long as 24 hours according to one of my IV books.

....and you would be correct!!!!

That was why I got confused.

THANK YOU! THANK YOU!

:bow:

Daytonite, BSN, RN · Aug 10, 2008

I halted at that statement too and kept going back to it. I wasn't sure if your confusion was because of the difference between the length of action of the tPA and the streptokinase or the hemorrhagic stroke. Did my explanation make sense? I re-wrote it several times.

Dianacabana · Aug 10, 2008

Daytonite, I'm always amazed by your knowledge! Terrific information.

Thanks!

Daytonite, BSN, RN · Aug 10, 2008

actually, this one probably would make a lot more sense if you saw a patient in a clinical situation getting these drugs and lab tests so you could make the correlation with what was being said on paper. when i started thinking about what i saw as a nurse (we had to put 4 iv lines in these people before they started the tpa [#1 for the tpa, #2 for the heparin, #3 for blood draws and #4 for the nitroglycerin drip if they were having an mi] because of the danger of them hemorrhaging because we couldn't stick them once the tpa was started. the drugs are amazing through. when these people come in with an mi and get tpa you can see the blood clot melt away and their cardiac function improve right on the ekg monitor. it is so amazing! it actually saves their heart muscle from ischemic death.

justme1972 · Aug 11, 2008

actually, this one probably would make a lot more sense if you saw a patient in a clinical situation getting these drugs and lab tests so you could make the correlation with what was being said on paper. when i started thinking about what i saw as a nurse (we had to put 4 iv lines in these people before they started the tpa [#1 for the tpa, #2 for the heparin, #3 for blood draws and #4 for the nitroglycerin drip if they were having an mi] because of the danger of them hemorrhaging because we couldn't stick them once the tpa was started. the drugs are amazing through. when these people come in with an mi and get tpa you can see the blood clot melt away and their cardiac function improve right on the ekg monitor. it is so amazing! it actually saves their heart muscle from ischemic death.

which is another good thing to know :)

thanks again...i'll let you know how i do on my exam.

this is pharm iii (i have one more left)...i overloaded myself this semester with that class and my externship, so i haven't done too hot in this one. i have to get a 31 out of 50 to pass the class, and the scores so far have been running about 41/42..so i'm hopeful.

thank god it's only a one hour course...if it was 3 semester hour course, i would be flipping out.

we had a cardiac exam that i really bombed on, and that killed my average and put me behind.

i'm used to being ahead!!!

justme1972 · Aug 13, 2008

I did very well on my exam :)

I thought I was going to end up with a C but ended up with a B!!!!

Our Pharm is broke down into 4 semesters, at one semester hour each, so I wasn't going to flip out if I got a C (b/c so far, I haven't got one yet in school).

But it sure helps to know that I did better than that!

Thanks to everyone who helped and asked :)

:bow:

Editorial Team / Admin · Aug 13, 2008

congrats, hopefull2009

misswoosie · Jun 19, 2009

Sorry, just cam across this post and had to say that there is a BIG difference depending who you are thrombolysing. I have little experience with MI thrombolysis but a considerable amount with stroke.

1. 80% of strokes are infarcts (ie a blockage) whilst only 20% are haemaorrhages.

2. Clearly, you don't give thrombolytics, anticoagulants or antiplatelet agents to a haemorrhagic stroke (need CT to diagnose)

3. If a stroke patient is thrombolysed the agent will be rTpa -only one licensed.

4. Heparin is rarely given to any stroke patients because of the increased risk of haemorrhagic transformation in the brain infarct over the potential benefits of preventing further clots. This includes prophylactic doses.

5.Heparin is used for Cerebral Venous Thrombosis and may be used in patients that have carotid artery disection that causes stroke.