Thrombolytics

How Thrombolytics work?

The significance for utilizing thrombolytics in the treatment of VTEs is primarily due to their ability to rapidly dissolve massive blood clots and due to their compatible use with anticoagulant therapy such as Heparin (prevent clot formation). Immense blood clots (pulmonary emboli) are typically treated aggressively with thrombolytic medications such as: Abbokinase (urokinase), Activase (alteplase), or Retavase (reteplase). These medications vary in half-life (time of drug extent to decrease by one-half) and in their binding affinity (attraction) to plasmin considerably, however they all infiltrate the thrombus at alarming rates (Guton, & Hall, 464-467).


Animation: http://www.si.mahidol.ac.th/department/biochemistry/home/md/courseware_202/animation/Fibrinolysis.swf

http://www.aafp.org/afp/20020315/1097.html

Thrombolytic therapy is successful because these medications rapidly activate plasminogen, a plasma protein that becomes trapped within blood clots and activate/accelerate its transformation into plasmin(Lilly, Harrington, & Snyder, p.430-437). Plasmin, a proteolytic enzyme in turn causes the break down of fibrin fibers and numerous clotting factors responsible for clot formation. The defining factor for the use of this class of drugs for the treatment of VTEs is their speed of action, and their hinderance of blood coagulation. Abbott Laboratories, the manufacturer of Abbokinase (urokinase), indicate that treatment with their medication demonstrates improved treatments on pulmonary blood clots (embolus) and the restoring of lung blood flow (perfusion). According to the American Academy of Family Physicians, thrombolytics are classified as the most effective medications to prevent and eliminate the source of clot formations. In result of the clot dissolutions and source eliminations, the reoccurrence of such complications are dramatically reduced.



Fig: Fibrinolysis (simplified). Blue arrows: stimulation, Red arrows: inhibition.

http://en.wikipedia.org/wiki/Alteplase

http://en.wikipedia.org/wiki/Thrombolytic_drug


Thrombolytic Administration

Due to the extensive risks involved in the use of thrombolytics and based on the extent of severity of the patient’s condition, prompt detection of a venous thromboembolism is crucial. Venography is a highly used method to determine if patients have acquired a deep vein thrombosis (DVT). If the condition has negatively progressed and suspected as a pulmonary embolism (PE), a pulmonary angiography that measures ventilation perfusion is ensued. The dilemma with these procedures is their cost, the distressfulness on the patient, and that the procedure itself (venography) may cause a DVT. The determining factor with the use of thrombolytics is time, and the urgency of treatment.

Thrombolytics are utilized in an array of methods, however the method most common is when administered by infusion in conjunction with heparin. When administered by infusion, thrombolytics require partial thromboplastin time (PTT) monitoring to prevent excessive anticoagulant therapy. Therapeutically, the PTT levels should be 1.25 to 2.5 times the normal range within 21 to 35 seconds. Heparin is also administered if the PTT level is below this range. If the patients PTT base line level (level taken prior to medication administering) is initially over the normal range their PTT level should be monitored every 4 hours. Khalid Almoosa, M.D., clinical fellow in pulmonary/critical care medicine at the University of Cincinnati Medical Center, indicates 86% of patient’s in his care that received this treatment within 24 hours of diagnosis with pulmonary embolism improved dramatically.

http://www.medscape.com/viewarticle/487577_2

http://www.medscape.com/viewarticle/487577_4

Are Thrombolytics safe?

Khalid Almoosa, M.D., expresses concern with the use of thrombolytics to eradicate blood clots because they also have a systemic effect in the activation of plasminogen. This effect leads to increased incidence of bleeding, which is the most common side effect. The most severe case in this event of bleeding includes intracranial bleeding that may lead to hemorrhagic stroke and/or even death. For patients receiving thrombolytic treatment, it is essential to be monitored closely for bleeding.

Although the risks in the use of thrombolytics are substantial, physicians will only utilize therapeutic treatments with thrombolytics if the benefits surpass the risks. Life Site News published a real-life incident of a potentially serious blood clot (deep vein thrombosis, DVT) that formed in a woman's vein. The blood clot was attributed to the increased levels of estrogen as a side effect from her birth control. The Federal Drug Administration (FDA) states that all birth control medications have this risk but for women who use the patch formulation the risks are significantly higher because they are exposed to 60 percent more estrogen than the women on the birth control pill.





A factor that must be considered in this case is that some women are more susceptible to blood clots and being on birth control will only increase their risks. Using birth control may be an effective way to prevent a pregnancy but the increased risk of blood clots that endanger your life may change your mind.

http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm095628.htm

Contraindication in Thrombolytics

The determinant factor if whether patients are eligible for thrombolytic treatment is acquired through exceptional communication between the patient and their healthcare provider. The most critical contraindications that exclude patients from this type of treatment include: current or recent bleeding/hemorrhaging (excluding menses), recent trauma, recent surgery, brain disease, and pregnancy.
The reason for their exclusion as previously mentioned is due to the thrombolytics indiscriminative lysing of all blood clots with no regard if they are beneficial or life-threatening. The utilization of these medications in such patients could result in severe bleeding (hemorrhaging) and perhaps death, so extreme caution is essential for proper patient care under these circumstances.

http://archinte.highwire.org/cgi/content/abstract/152/6/1265

http://www.medscape.com/viewarticle/423479_3

Guyton, A. C., & Hall, J. E. (2006). Blood Cells, Immunity, and Blood Clotting. Textbook of Medical Physiology (5th ed.), Philadelphia : Elsevier Saunders.

Lilley, L. L., Harrington, S.,& Snyder, J. S.(2007). Coagulation Modifier Drugs. In Pharmacology and the Nursing Process. Canada: Mosby Elsevier.