YOU Should Be Concerned!

Are you or someone you love possibly at risk?

What was once believed to be mostly a post-op concern for surgical patients is now a serious issue for millions of Americans, many of which, have no idea they are at risk. Take this scenario for instance:

A seventy year old man returning from a vacation with his wife, experiences a longer than expected flight due to delays. It turns out to be about 7 hours on the plane. He sits in the window seat next to his wife but refuses to get up during the flight, the gentleman that he as, as to not disturb the woman holding a sleeping infant in the seat next to his wife. In the car ride home he mentions to his wife about soreness in his right leg, but gave no more attention to it thinking he probably bumped it on the crowded plane. Early the next morning he develops an uncomfortable shortness of breath followed closely by a persistent cough that begins to produce a small amount of blood. The blood finally causes a trip to the hospital where he was diagnosed with a venous thromboembolism(VTE) and treated for a pulmonary embolism(PE).

This man was treated and thankfully lived. However, thousands of people each year die from such an event, and it could be you or someone you know.

- Example of a VTE

- Example of a Pulmonary Embolus


What is a VTE?

Venous thromboembolism (VTE) is a possible life-threatening condition that arises from the development of a blood clot within a vein that is primarily associated with patient immobility, and vascular injury. Are you at high risk of experiencing a VTE? Your life style alone may have placed you within this category. Though there are numerous causes of VTEs, the most significant is the increased risks if you‘re physically inactive (immobile) for an extended length of time, if you’re over weight, if you smoke, and/or if you use birth control. VTEs are estimated to affect an average of two million people a year in the United States. Of these affected, Mary Ann E. Zagria, Pharm D, Senior Care Consultant Pharmacist and President of MZ Associates, attributes 200,000 deaths per year of pulmonary embolism as the result of such VTEs.

In general, blood clots are not uncommon and are repaired by the body naturally with a seal (platelet plug). Under normal circumstances, once the bleeding has stopped, the clot will slowly be eliminated (lysed) by plasmin. Under inadequate circumstances, the blood clot may develop into a life-threatening situation because the pressure created by the blood flow can cause the blood clot to dislodge from the venous wall (thromboembolism) and allow its migration through the bloodstream to eventually become embedded in an artery or a lung (pulmonary embolism). The lack of circulation beyond the clot eliminates oxygen and nutrients to the succeeding tissues leading to tissue death (necrosis). It's imperative to eliminate the clot rapidly to restore circulation. The sooner the clot is eliminated, the lesser the damage incurs and/or the less chance of death.

http://www.vteconsultant.com/vteconsultant/VTE-prevention-understanding-current-strategies-The-Anticoagulant-Timeline.html

How could this have been prevented?

There a are a few things that could have been done to prevent this man suffering from a VTE.
1) He could have been warned by his health care provider of his increased risk of a VTE due to his age and his survival from cancer for 20 years. Also, that these combined with sitting confined for such a long time made him a prime candidate for VTE. A complete list of risk factors can be found at the CDC website.
2) The health care provider, having assessed him correctly, could have had him on prophylaxis medication for a VTE such as daily aspirin therapy or possibly a warfarin regimen.
3) He could have been alerted by a friend or a family member who knew his condition and knew that he was at risk, and they possibly could have alerted him in time to take an active role in his own health care.

Where does he go from here?

Now that the VTE exists it has to be treated. There are several options and combinations of therapy used to treat this condition. The use of warfarin, unfractionated heparin, low molecular weight heparin, and fondaparinux are used to prevent further clotting. Then thrombolytic agents are used to break up the clot. All of which have there own complex methods of action. These as with all medications come with risks and complications. In fact, The Joint Commission's National Patient Safety Goal 3E states the need to "Reduce the likelihood of patient harm associated with the use of anticoagulation therapy". So it is important that prescribers and administrators as well as patients are aware of the risks of anticoagulation therapy.

American & American-Eagle Airlines.(2009, October 15). Onboard Our Flights [Special section]. American Way Magazine, 96-97.

Zagria, M.A.(2009, July). Raising awareness about Pulmonary Embolism. U.S.Pharmacist: The Journal for Pharmacists’ Education, 24-26.

History creating prophylaxis with coagulation modifiers

Anticoagulants

Medical procedures involving coagulation modifiers have occurred since ancient times. Hippocrates, an ancient Greek physician, noted surgical treatments with “oral blood thinners” in the 4th Century BC. Procedures known as “bloodletting” (removal of blood from the body) and Hirudotherapy that involve the use of were very common practices by Greek and Roman physician for over 4,000 years. Leeches, a hirudo species were used to treat an array of diseases but the therapeutic successes were later attributed to an anticoagulant compound within their saliva called hirudin. Medicinal accreditation for their use as an anticoagulant was proclaimed during the mid 1800’s. Despite that hirudin was found to be toxic when used as an extract in patients, the use of live leeches continues today in an array of therapies. A couple of major uses in surgical procedures are to restore blood flow to reconnected veins, and/or for the reattachment of body parts.

Treatments and surgeries for venous thromboembolism with anticoagulants date back to the late 1600’s. The first medically accredited anticoagulant was introduced in 1916. Jay McClean, a second-year medical student of Johns Hopkins University discovered the anticoagulant drug named Heparin which continues to be highly used today. The first oral anticoagulant termed dicoumarol (the predecessor to what is known today as Coumadin/warfarin) was introduced in 1939. The initial marketed use of warfarin was to exterminate rodents by causing profuse bleeding that resulted in the rodents death. The transition of warfarin from a poison to a therapeutic anticoagulant originated from an unsuccessful suicide attempt from its ingestion by a U.S. military soldier. Warfarin is now commonly prescribed to patients with elevated tendencies of developing thrombosis or as a prophylaxis for patients whom have already formed a clot to lessen their risks of VTEs.

http://www.leeches.biz/leech-approval.htm

http://www.vteconsultant.com/vteconsultant/VTE-prevention-understanding-current-strategies-The-Anticoagulant-Timeline.html


Antiplatelets

The use of antiplatelet therapy for VTE’s with aspirin transpired between the 1960s to the 1980s when it was clinically determined as having effective results in anti-clotting. Aspirin (acetylsalicicylic acid), the chemical result of a chemistry created reaction was officially discovered in 1853 by a French chemist named Charles Frederick Gerhardt. The history of aspirin dates back to 400 BC when Hippocrates was known to prescribe willow tree bark and leaves for the treatment of fever and pain. Through clinical studies, aspirin eventually acquired its name and was officially marketed by the Bayer drug and dye firm in 1899. The advancements in chemical technology led to the scientific discovery that aspirin also had an anti-clotting effectiveness on platelets in its inhibition of the prostaglandin thromboxane. The inhibiting of platelet aggregation has significantly reduced the risks of unwanted blood clots and moreover reduced the risks of life-threatening VTEs. The use of aspirin as a VTE prophylaxis following surgeries amplified dramatically from that point and continues today.

http://www.wonderdrug.com/pain/asp_history.htm


Thrombolytics

Procedures involving thrombolysis are the most modern in therapeutic care for patients that produce VTEs. The historical development of these medications originates from the 1930s when Tillett, and Garner at Johns Hopkins Medical School discovered thrombolytics ability to dissolve existing fibrin clots in Streptococcus bacteria. By 1956, E. E. Clifton from Cornell University Medical College in New York successfully treated numerous patients for blocked blood vessels, arteries, or veins (thrombi occlusions) with SK-plasminogen. This accomplishment lead to what we know as thrombolytic therapy today “clot busting” (to initiate the dissolution of blood clots) that legitimately began in the 1990s for conditions such as VTEs. The concern that arose with these medications was the extent of dissolution these drugs were capable of that could lead to hemorrhaging. Nevertheless, through years of research and trials these medications have proven that the efficacious use substantially outweighs the risk of ischemic deaths.

http://enth.allenpress.com/enthonline/?request=get-document&doi=10.1583%2F04-1340.1

An Aspirin A Day...

Depending on the source or who you ask the number of deaths attributed to VTEs can vary up to 100,000 one way or the other. However, one thing that everyone agrees on is that the number of deaths are far too many, and more importantly that a good portion of these deaths could be prevented. One of the most simple and cheapest means of preventing VTEs might be the use of antiplatelet therapy.

Anitplatelet drugs include the well known NSAID aspirin, as well as newer lesser known drugs such as clopidogrel, dipryidamole, pentoxifylline, and eptifibatide. For the purposes of my discussion, and to hopefully not put to sleep the majority of people who are going to read this, I'll stick to aspirin and clopiddogrel(Plavix).

How Do Antiplatelets Work?

Antiplatlet drugs by work by manipulating the cyclooxygenase(COX) pathway. Their action on this pathway prevents the aggregation, or clumping together, of platelets that is normally meant to be a protective measure by the body. Aspirin works by irreversibly inhibiting the production of prostaglandins and thromboxanes(TXA2). TXA2 is a substance that causes platelets to bind together and blood vessels to narrow. So conversely, it makes sense that taking aspirin would dilate blood vessels and work against the beginning of clot formation by platelets. Clopidogrel, on the other hand, works on the platelet membrane. It belongs to a class of antiplatelets referred to as ADP inhibitors. Its mode of action prevents the platelet from accepting a chemical message, called fibrinogen, that tells it to clot. Clopidogrel blocks this message by altering the GP IIb/IIIa receptor site on the platelet membrane. This is, of course, a simplified version of the mechanism of action for both drugs shown below.



Antiplatelet Administration

Again, it depends on who you ask. There is no accepted across the board dosage for antiplatelet drugs that is prescribed specifically for the prevention of VTEs. In fact, in regards to aspirin there is a prevailing school of thought that aspirin alone may a have little to no affect in preventing VTEs. Although, as recently as 2008 the U.S. Surgeon General has said that taking up to 150 mg of aspirin a day can be a good preventive measure for VTEs(Galson 2008). The same U.S. Surgeon General along with U.S. Department of Health & Human Services and several other leaders in the field have also called for the need of more research on the specific issue of aspirin's effectiveness in preventing VTEs. In the research I've done, the dosages for aspirin have ranged from as little as 30mg to over 325mg a day, but are usually accompanied by another form of anticoagulant when prescribed for VTE prophylaxis. Clopidogrel is usually started with a single 300-mg loading dose and then given at 75 mg once a day no matter what it is prescribed for. There seems to be more uniformity in the prescribed doses of clopidogrel vs. that of aspirin, as well as a belief that clopidogrel has a better success of preventing VTEs. However, these two drugs are often prescribed together in varying dosages. Once put on antiplatelets for the prevention of a VTE patients, especially those at high risk, may never stop taking them.

Are Antiplatelets Safe?

It is interesting that prostoglandin inhibition is what gives aspirin its beneficial as well as its undesirable effects. Of these undesirable-effects the most common are "gastrointestinal intolerance (including nausea, vomiting, indigestion, gastric ulceration and upper gastrointestinal bleeding), bleeding and renal dysfunction" (Mueller 2004). Another well know issue with aspirin therapy is the belief that children are more susceptible to Reye's syndrome when given aspirin while recovering from a virus. But they still call an 81mg dose "baby aspirin"? This is usually not an issue in regards to VTE prophylaxis, in that children are normally not at risk, and those who are do not receive aspirin. What needs to be the highest concern for those prescribing, administering, and taking aspirin and clopidogrel, as with any anticoagulant, is the increased risk of a bleeding episode (Liley, Harrington, Snyder 2007).


Chee,Y.L., & Watson,H.G. (2008). Aspirin and other antiplatelet drugs in the prevention of venous thromboembolism. Blood Reviews, 22(2), 107-116. doi:10.1016/j.blre.2007.11.001

Galson,S. (2008). Surgeon General’s Perspectives:Prevention of deep vein thrombosis and pulmonary embolism. Public Health Reports, 123, 420-421. Retrieved http://www.publichealthreports.org/

Lilliey, L. L., Harrington, S., & Snyder, J. S. (2007). Coagulation Modifier Drugs. In Pharmacology and the Nursing Process (pp. 417-439). Canada: Mosby, Inc.

Mueller, R. L. (2004). First-generation agents: aspirin, heparin. Best Practice & Research Clinical Haematology, 17(1), 23-53. doi:10.1016/j.beha.2004.03.003

Warfarin

How Warfarin Works

Warfarin sodium (Coumadin) is a pharmaceutical derivative of the natural plant anticoagulant known as coumarin. Warfarin, a vitamin K antagonist, is the most commonly prescribed oral (PO) anticoagulant that works by inhibiting the synthesis of Vitamin K dependent clotting factors (VII, IX, X, prothrombin) that are formed in liver. While warfarin works by preventing clots from forming, it does not work on existing clots. Warfarin is a highly protein bound drug with a low affinity for albumin; therefore, effortlessly resulting in increased free warfarin when in the presence of other high protein drugs with stronger affinities. This causes an increased anticoagulant effect potentially leading to toxicity. Warfarin is used for long term conditions such as stroke, cardiac dysrhythmias (Atrial Fibrillation), chronic heart failure, valve replacement treatment, immobility, and deep vein thrombosis. Warfarin requires careful monitoring of the prothrombin time/International Normalized Ratio (PT/INR), which is a standardized measure of the degree to which a patient’s blood coagulability has been reduced by the drug. A normal INR (without warfarin) is 1.0, whereas a therapeutic INR (with warfarin) ranges from 2 to 3.5, depending on the indication for use of the drug. Elderly patients older than 65 years may have a lower INR threshold and should be monitored accordingly.

http://www.mybloodthinner.org/research.html

Warfarin Administration

Because warfarin is used chronically to prevent clots, administration is not considered for an immediate effect. Warfarin is available in oral (PO) form only and the typical maintenance dosage is 2-10 mg/day as determined by PT/INR values. The onset of warfarin is 12 to 24 hours and therapeutic effect is typically reached in 3 to 5 days. Warfarin can be given with heparin to further its effect. Heparin therapy will destroy clots and the added use of warfarin will prevent further blood clots from forming. Before administering warfarin a nurse should assess for bleeding. Also, a nurse should know that the oral form must be started several days before heparin is discontinued, their patient should; be protected against injury and wear a medic alert device, avoid over the counter drugs containing aspirin, avoid Intramuscular injections if possible, and inform other healthcare providers before minor/major surgery. It is important to teach a patient receiving warfarin to be cautious of their alcohol intake, limiting it to 1-2 drinks per day, as it will affect their liver function. A consistent diet of vitamin K (avoiding a high intake) is also important as it affects the binding available effects INR levels. Also a diet high in protein must be monitored, the more proteins taken in result in higher amounts of warfarin binding resulting in lower free drug levels. Flavanoids (found in grapefruit and cranberries, etc.), inhibit warfarin metabolism causing the INR value to increase which may lead to warfarin toxicity.

http://www.drugs.com/warfarin.html

Is Warfarin Really Safe?

Potential side effects of warfarin therapy include hemorrhage, hematuria (blood in the urine), epistaxis (nose bleed), ecchymosis (bruising), tarry stools, bleeding gums, skin necrosis (indicates an allergic reaction), leukopenia (decrease in white blood cell count), and agranulocytosis (no white blood cell production).
Luckily, there is an antidote for the uncommon event of warfarin overdosing. Vitamin K (AquaMephyton) causes more vitamin K dependant clotting factors to be produced. Oral dosage is preferred, intramuscular (IM)/suncutaneous (SQ) available, and intravenous (IV) are to be used cautiously due to the high risk of allergic reactions. Procedures for overdoses can be determined by using the most recently high INR results as follows- If the INR is 3-9:hold Coumadin, if the INR is 9-20 & minor bleeding is occurring: administer vitamin K PO, if the INR is 20+ & acute active bleeding is occurring: administer vitamin K via IV.



Contraindications Of Warfarin

Warfarin is a category X drug, which means that its use is contraindicated in pregnancy. The use of warfarin is also contraindicated in the presence of an existing hemorrhaging; in which case heparin should be administered. IM dosing of warfarin is to be avoided because of risk of bleeding and bruising.
Warfarin’s effect can be increased by: highly protein bound drugs such as ASA (aspirin), Sulfa containing drugs (loop diuretics), antibiotics, NSAIDS and acetaminophen (in liver, also effects a Vit. K clotting factor). These drugs cause an increased potential for bleeding.
Warfarin’s effect is decreased by: Estrogen, Bile acid sequestrates, and antacids. These drugs reduce the absorption of warfarin at the stomach.

http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682277.html

Lilley, L. L., RN, PhD., Harrington, S., PharmD., & Snyder, J. S., MSN, RN, BC. (2007). Pharmacology and the Nursing Process (K. Geen & J. Horn, Eds., 5th ed.). St. Louis, MO: Mosby Elsevier

Heparin

How Heparin Works?

Heparin is the first choice anticoagulant in the treatment of Venous Thromboembolism because its onset of action is immediate. It is a heterogeneous mixture of branched glucosaminoglycans. It is produced naturally inside the human body by white blood cells and mast cells. Heparin combines at Arginine Reactive Centre of Anti-thrombin III (AT), a plasma cofactor, to form Heparin-Antithrombin complex. The Heparin-Antithrombin complex produces a conformational change in AT. AT then binds with the active serine centre of thrombin, a clotting enzyme, to inhibit its coagulation activity. Thus, Heparin works by converting AT from slow thrombin inhibitor to the rapid inhibitor.


Fig: action of Heparin to inactivate the clotting enzymes. Heparin reacts with slow inhibitor ATIII and converts it to active inhibitor by binding at its high affinity arginine reactive centre. Activated ATIII binds covalently to the clotting enzyme and inhibits the clotting of blood.

Heparin Administration

Treatment of VTE with Heparin is based on body weight, and the dosage is calculated based on Partial Thromboplastin Time (PTT) test. PTT test measures the time for anticoagulation (Guyton, & Hall, p. 464, 467). The normal range of PTT value is 60-80 seconds. If the PTT value is less than the normal range, Heparin dose is increased and vice versa. VTE patients are usually given 5,000 units/ml or less of low dose Heparin subcutaneously as a prevention. A 5-7 day course of low dose therapy is considered effective. It is also given in bolus (50-100 Units/kg) and infusion (15-25 Units/kg/hr) as high dose treatment for acute VTE. Application of Heparin is immediately stopped on the detection of any kind of bleeding, if severe Protamine sulfate is given to neutralize its anticoagulant effect.
Institute for safe medication practices has enlisted Heparin a high alert drug. It comes in different concentration and there are chances of wrong concentration being used in wrong patient.In order to reduce the risk s of Heparin, U.S Food and Drug Administration has changed the standard of Heparin. It will be 10% less potent than its normal dose.

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm184504.htm


Read the story( Actor Dennis Quaid’s newborn twins were given 1000 times greater dose of heparin)
http://www.kcby.com/news/entertainment/11697086.html

Is Heparin really safe?

There are several complications that can arise with the long term use of Heparin even if the drug dose is controlled. The U.S Food and Drug Administration released a warning regarding the use of this drug in 2008.

Heparin is a high risk drug which interacts with other drugs and further increases the complication. Aspirin, alcohol, and antibiotics increase the risk of bleeding with Heparin. Risks of hemorrhage, hypersensitivity, osteoporosis, alopecia are few of the side effects of using Heparin. It has been found that up to 10% of patients can develop major/minor bleeding which requires quick assessment of the patient and the contact with the physician. Bleeding due to injury or fall, bleeding from brain (hemorrhage), and any undiagnosed bleeding in digestive system are the side effects of Heparin.

HIT

Another major complication of Heparin is Heparin Induced Thrombocytopenia (HIT). About 3-30% of patients on Heparin Therapy have tendency to develop HIT after 3-4 days of medication. It is characterized when platelet count is less than 150 x 109/L or by 30% to 50% during treatment. It can result from any type of Heparin exposure, by any route of administration and from very tiny dose. Its detection is characterized by the formation of new emboli. Cessation of Heparin must be done after diagnosing HIT; however, it is not sufficient because it leaves patients in a hypercoagulable state. Therefore, anticoagulants argatroban and lepirudin are being used in the medical management of HIT. The best approach to prevent HIT is the regular monitoring of platelet count. Because HIT patients develop new clot rather than bleeding, platelet transfusion should not be done at once. It might increase the risk of bleeding.



Case study of HIT

Postoperative Stroke in a Young Man:

“A healthy 43 year old man underwent lumbar laminectomy and received postoperative prophylactic unfractionated heparin, 5,000 U subcutaneously every 8 hours. On the seventh postoperative day, he became hemiparetic and aphasic. On the 10th postoperative day, he was unresponsive. An angiogram showed left common and internal carotid occlusion. Postoperative blood work revealed that the platelet count, which had been normal preoperatively, was 32 × 109 cells/L. The vascular surgeon retrieved a “white clot” from the carotid artery as heparin and platelet transfusions were given during the patch angioplasty, and vascular catheters continued to be flushed with heparin postoperatively. The next morning, the platelet level remained at 45 × 109 cells/L, and the left leg was cold and pulse less. An emergency thrombectomy saved the leg. The hematology department was consulted, HIT was immediately diagnosed, and all heparin exposures stopped. A test for heparin-induced platelet antibodies was strongly positive (by an aggregation test). The platelet count normalized in few days. After 2 months in the hospital, the patient was transferred to a long-term care facility in a vegetative state” (Lawrence Rice).
Comment: The drop in the platelet count of the young man in this case indicates the development of HIT. The continuation of Heparin medication and platelet transfusion after the development of HIT increased the complication by forming more clots.

Contraindication in Heparin

Use of Heparin is risky for the patients with severe renal failure. Heparin can have teratogenic effect if taken during pregnancy. Similarly, heparin is contraindicated in patients with leukemia, gastrointestinal obstruction, serious inflammation, infection, recent surgery.

http://chestjournal.chestpubs.org/content/119/1_suppl/64S.full?ijkey=8afa523e49a5e53d211e584523e56396161df903&keytype2=tf_ipsecsha#sec-4

http://chestjournal.chestpubs.org/content/127/2_suppl/21S.full?sid=073d5472-76b2-4967-9a30-f2821dcda11d

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm184504.htm

Lovenox

Lovenox is an antithrombotic drug that alters the body’s ability to clot, preventing angerous clots from forming. The ability of Lovenox to prevent clotting is due to its ability to inhibit factor Xa resulting in decreased thrombin and ultimately the prevention of fibrin clot formation. Lovenox is used to treat unstable angina, Non-ST elevated myocardial infarction (NSTEMI) and ST elevated Myocardial Infarction (STEMI), Prophylactically following hip, knee or abdominal surgery or in those patients with severely restricted mobility in a hospital setting. It is also used to treat acute deep vein thrombosis (DVT) as inpatient for those with or without a pulmonary embolus.



Contraindications and Guidelines for Lovenox

Lovenox is contraindicated in patients with a history of aneurysm, cerebral vascular accident (CVA or stroke,) epidural punctures, uncontrolled hypertension, or women with a threatened abortion. Lovenox should be used cautiously in patients with a history of Heparin Induced thrombocytopenia (HIT). Dosing can be based on mg/Kg in patients with DVT, USA, or non-Q wave MI or a standard dose of 30 or 40mg subcutaneously every day for other indications. Dosages must be adjusted for patients with renal impairment. Side effects of Lovenox mainly relate to its inhibition of Xa resulting in spontaneous bleeding such as nosebleeds, bleeding gums coughing or vomiting blood or unexplained bruising. Other side effects include dizziness, rapid heart beat, chest pain shortness of breath, nausea,vomiting or confusion.

Is Death From A Pulomonary Embolus Preventable?

“Pulmonary embolism remains the most common preventable cause of death in hospitals.” (Morrell MT and Dunhill MS (1968) Br Surg 55, 347-352.)

It is estimated that 1 in every 100 patients will die from a pulmonary embolism (PE) giving prophylactic Lovenox could prevent many of these deaths. Patients taking a daily aspirin may not be completely safe from a dangerous blood clot while in the hospital. When patients are admitted they are evaluated based on their risk of developing a Deep vein thrombosis (DVT) or PE. Based on individual risk factors these patients are then placed on prophylactic Lovenox or Heparin subcutaneous (SQ). Patients who are at high risk for bleeding received sequential compression devices (SCD’s) or TED hose. Very high-risk patients, patients with multiple trauma, acute spinal cord injuries, or major hip, pelvis, or leg fractures. Patients admitted with myocardial infarction, congestive heart failure, severe lung disease, cancer, patients older than 75, or have a personal history of DVT are considered high risk. Moderate risk patients, are those with general medical illnesses, minor surgery, estrogen replacement therapy or pregnant women. These patients are then placed on Lovenox or Heparin based on hospital guidelines for prevention of DVT and PE’s. All low risk patients are encouraged to ambulate early and often and usually do not receive prophylactic anticoagulants. Of course there are also contraindications that the prescriber must also be careful of such as any bleeding disorder or HIT antibody positive.

The concern for patients devoloping a blood clot is not relagated to hospital stays only. This short video describes how lovenox is prescribed for high risk patients after their discharge from the hospital.

http://www.outcomes-umassmed.org/dvt/best_practice/

http://Lovenox.com/consumer/default.aspx

Galson,S. (2008). Surgeon General’s Perspectives:Prevention of deep vein thrombosis and pulmonary embolism. Public Health Reports, 123, 420-421. Retrieved http://www.publichealthreports.org/

Schilling McCaan, J.A. (2009) Nursing 2009 Drug handbook. New York: Wolters Kluwer/Lippincott Williams & Wilkins.

Tarrant County Hospital District (2008) DVT prophylaxis Order Set.

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.

COAGULATION MODIFIERS

In up to 25% of all hospitalized patients, there may be some form of Deep Vein Thrombosis, which often remains clinically unapparent.
That’s a lot! One in four hospitalized patients are likely to have a Deep Vein Thrombosis, so it is important that caregivers and patients be well informed of risk factors, signs, treatment, and prevention!

Our goal is that this site will help nurses and patients alike understand: the mechanism of action, indications, contraindications, adverse effects, and interactions involved with each of these drug classes in the treatment and prevention of Deep Vein Thrombosis (DVT) and other venous thromboembolic events (VTE).

We ask that you leave a comment or question on our postings, and enjoy reading in the hopes that we have helped to determine which coagulation modifying drug would be most beneficial in your situation.

Please keep in mind the following potential risk factors of major bleeding! BEWARE!

Hepatic or renal disease
Ethanol use (history of alcohol abuse, worsening liver disease)
Malignancy (recent metastic cancer)
Older (>75)
Reduced platelet count/function (<75,000)
Re-bleeding (prior hospitalized bleeding)
Hypertension (uncontrolled)
Anemia (hematocrit <30 or hemoglobin <10 g/dL)
Genetic factors
Elevated risk of fall (& neuropsychiatric disease)
Stroke



For further reading and information, we refer you to these sites:
Plavix
http://www.plavix.com/Index.aspx

Heparin
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM112597

Lovenox
http://www.lovenox.com/consumer/default.aspx

Warfarin
http://www.warfarindosing.orghttp://nlm.nih.gov/medlineplus/druginfo/meds/a682277http://mybloodthinner.org/research

Abbokinase
http://www.abbokinase.com/

Drugs.com sites for each coagulation modifier
http://www.drugs.com/warfarin , http://www.drugs.com/heparin.html , http://www.drugs.com/plavix.html , http://www.drugs.com/lovenox.html , http://www.drugs.com/mtm/urokinase.html