StreptokinaseDissolves

Blood Clots

Ananya Agrawal

StreptokinaseDissolves ThrombusThrombus, a common cause of heart attacks, can be dissolved using a cheap drug. A cheap drug with one crucial ingredient it owes its name to. Streptokinase-an enzyme that converts a blood protein called Plasminogen into the enzyme Plasmin-is that ingredient.

Streptokinase is far from the only enzyme used for a medical purpose. Erythropoietin is given to anaemic patients to make more red blood cells. Asparaginase is another enzyme that is used to aid in treatment of Acute Childhood Leukemia. Even Cystic Fibrosis can be treated using deoxyribonuclease, or DNAʼase breaks down extra DNA in the mucous. Penicillin, the first antibiotic, can be enhanced using an Enzyme Inhibitor. Bacteria can develop immunity to Penicillin using enzymes called beta lacatamase which break down penicillin. The active site of beta lactamase can be blocked using an antibiotic called Augmentin which uses certain enzymes in it. Thus, enzymes have started to play an integral role in medical treatment and with the boom in biotech industries and research, this is sure to increase to greater heights.

Streptokinase is administered to a patient intravenously, as soon as possible, after a heart attack starts. It dissolves clots in the arteries of the heart wall and this aids in the restoring of normal blood circulation. The product of its substrate, plasmin, is an enzyme which digests fibrin, one of the main components of blood clots. Drugs like streptokinase are placed under the category of “Thrombolytic agents” or drugs used to dissolve a clot. They are also colloquially known as clot-busters.

Streptokinase has one major limitation which increases the time it requires to act. It can only perform this chemical conversion in a fluid. This means that instead of being injected into the thrombus-agents like tissue plasminogen activator(tPA)can-it has to be injected into the blood stream. This increases the time it takes to have an effect.

However, thrombolytic agents cannot be used by all patients. Patients prone to internal bleeding can suffer from a possibly fatal internal hemorrhage as the plasmin will interfere with the bodies natural blood clotting for healing. However, in the case that the patient is prone to internal bleeding, there are methods to solve the problem. Drugs that strengthen the heart are given to the patient. Even then, this can lead to arrhythmias (irregular and possibly fatal heart beat rhythms)

Along with this, if a dose of streptokinase is administered within 2 hours of the heart attack, the thrombus can be cleared with a change of no permanent damage to the circulatory system. However, if it is administered between 2 and 4 hours of the heart attacks commencement, myocytes (muscle cells) start to get destroyed but the damage will be less severe than otherwise.

Plasminogen Streptokinase Plasmin

ISIS 3 Debacle: Cheaper can be BetterIn the 1990s, a medical comparison covering over 42,000 heart patients in over 20 countries found that from three “clot-busters” or thrombolytic agents, the cheapest is as good as, if not far better than its competitors.

Said to be the largest medical comparison ever, the “3rd international study of Infarct survival” compared the drugs

• Streptokinase• tPA

Both these drugs are commonly used enzyme based Thrombolytic agents and are fairly successful at their job, with varying side effects.

Other studies have proven that tPA, much more expensive, is marginally more fast and effective, for the time-being, saving an extra one patient for every hundred treated. However, it cost ten times as much, leaving doctors in a dilemma. Should they use a drug that is only marginally more effective with a far greater cost, or use the cheaper drug, bringing up the question for the cardiologist, “which 1% of their patients should the cardiologist sacrifice to save money?”

As seen on the right, tPA is much more aggressive in combating the clotting, yet, due to its side effect, more deadly. It can cause a brain hemorrhage, leading to a deadly stroke. Thus, eventually the patient can die. Does this cancel out its 1% gain on streptokinase?

A c c o r d i n g t o t h e Genentech, a manufacturer of tPA, based in San Francisco, the entire comparison is very unfair. Quoting its official statement: “The trial used duteplase, a form of tPA made be Wellcome but which is no longer manufactured. Gentech makes alteplase, which is a single chain molecule; duteplase, is a double-chain. Because duteplase is not clinically equivalent to alteplase, ISIS-3 results cannot be applied to alteplase.”

So what can be done about t h i s t P A v e r s u s Streptokinase problem?Some people in the United States of America think there is another way, a more natural route to health. Following a large influx of FDA approved drugs which have been fatal in their side effects, consumers there, have lost trust and are now looking for natural alternatives.

However, Streptokinase is just one of its victims. Nitroglycerin, often used to dilate blood vessels, is starting to be replaced by Resveratrol.

Nattokinase, an enzyme extracted from a Japanese dish consisting of fermented soybeans, is often used as a natural replacement for the clot-busting and blood thinning treatment of Aspirin and Streptokinase that it commonly administered. However, it is not recommended as it has never showed a sign of being preventive of any form of cardiovascular disease. In fact, when combined with Aspirin, it greatly raises the risk of a cranial hemorrhage(right).

This leaves patients nowhere. The most feasible option seems to be the much debated Streptokinase. Abandon the use of tPA and 400 strokes, half of which are fatal, donʼt occur. Using streptokinase, $100million is saved in drug costs and the patient has equal chances of surviving the heart attack. And this is only for the USA, imagine the impact elsewhere in the world.

At present, in the United States of America, over half the heart patients are treated using tPA. This is far more than in Britain, another country where tPA is commonly administered.

Poor Testing, Making a Profit and Human NatureHumans have always been entranced by the pursuit of money and power. It fills pirates and vikings with bloodlust, innocent men into thieves, rulers into ruthless invaders and toddlers into bawling banshees when they do not get a lollipop.

Now it seems that doctors, the once clean practice, is going this way too. The once compulsory Hippocrates Oath, has now been send into the recesses, hidden behind a lust for money. The oath states:

“I swear by Apollo the Physician and Asclepius and Hygieia and Panaceia and all the gods, and goddesses, making them my witnesses, that I will fulfill according to my ability and judgment this oath and this covenant:To hold him who has taught me this art as equal to my parents and to live my life in partnership with him, and if he is in need of money to give him a share of mine, and to regard his offspring as equal to my brothers in

male lineage and to teach them this art–if they desire to learn it–without fee and covenant; to give a share of precepts and oral instruction and all the other learning to my sons and to the sons of him who has instructed me and to pupils who have signed the covenant and have taken the oath according to medical law, but to no

one else.I will apply dietic measures for the benefit of the sick according to my ability and judgment; I will keep them

from harm and injustice.I will neither give a deadly drug to anybody if asked for it, nor will I make a suggestion to this effect. Similarly

I will not give to a woman an abortive remedy. In purity and holiness I will guard my life and my art.I will not use the knife, not even on sufferers from stone, but will withdraw in favor of such men as are

engaged in this work.Whatever houses I may visit, I will come for the benefit of the sick, remaining free of all intentional injustice,

of all mischief and in particular of sexual relations with both female and male persons, be they free or slaves.What I may see or hear in the course of treatment or even outside of the treatment in regard to the life of men, which on no account one must spread abroad, I will keep myself holding such things shameful to be

spoken about.If I fulfill this oath and do not violate it, may it be granted to me to enjoy life and art, being honoured with

fame among all men for all time to come; if I transgress it and swear falsely, may the opposite of all this be my lot”

One line from this traditional oath sticks out, “I will neither give a deadly drug to anybody if asked for it, nor will I make a suggestion to this effect”

In one aspect, this has already been broken by the FDA. Between 1985 and 1986, almost 22,000 people died in the United States of America only because of unnecessary testing when it had already been allowed and administered in a country like France.

In the age of WikiLeaks, lawsuits, health boards and massive press scandals, it is surprising that the quagmire of unnecessary testing and retesting still exists.

These tests, known as randomized controlled trials (RCTs), are known as one of the best ways to test the effectiveness of new treatments. However, the problem doesnʼt lie with the RCT itself. Infact, over the years, theyʼve identified countless life saving therapies, like new surgical techniques to cancer drugs. The patients who volunteer are randomly sorted into two or more groups that are prescribed the different treatments. By comparing the success rates, as shown on the right, doctors can gauge the effectiveness of a new treatment.

No one doubts these results. No one, except the many researchers, who unconvinced, insist on carrying out RCTs for proven therapies. In dividing their patients, they are denying have of the patients access to the already proven theory. At best, the patients health is unjustifiably jeopardized. At worst, they are dead and the researcher is at the mercy of a lawsuit. One line from the Hippocrates oath sticks out, “I will neither give a deadly drug to anybody if asked for it, nor will I make a suggestion to this effect.” This very practice, or malpractice rather, goes against the very lines of the oath and yet, happens regularly.

RCTs of clot busters like streptokinase have been showing that they can saw the lives of heart attack patients since the mid 1970s. Even then, the researchers have doggedly gone on with the trials till the 1990s, denying treatment to tens of thousand patients

Its not always patients who have the tried and tested route who suffer. In the trials in the 70s, the harmful drugs were also re-tested over and over again, only to make money for the researchers, the drug companies and the doctors. It is one of the main reasons why alternatives like tPA are still so widely used and preferred over safer Streptokinase, for money.

Bibliography [all accessed on 2/1/2011]1. http://www.bbc.co.uk/dna/h2g2/A33283552. http://en.wikipedia.org/wiki/Streptokinase3. http://en.wikipedia.org/wiki/Nattokinase4. http://heart.bmj.com/content/88/3/298/F2.large.jpg5. Edelstein, Ludwig; Owsei Temkin, C. Lilian Temkin (1987). Owsei Temkin, C. Lilian

Temkin. ed. Ancient Medicine. Johns Hopkins University Press. pp. 6. ISBN 0801834910.

6. http://www.livescience.com/php/multimedia/imagedisplay/img_display.php?s=health&c=technovelgy&l=on&pic=061106_blood_clot_02.jpg&cap=Clotting+occurs+on+a+large+damaged+area,+but+not+small+areas.+Credit:+Nicolle+Rager+Fuller,+National+Science+Foundation&title=

7. http://www.bjwinslow.com/albums/heartsurgery/open_heart_surgery_1.jpg8. http://www.newscientist.com/data/images/archive/1673/16735601.jpg9. http://drsvenkatesan.files.wordpress.com/2010/02/stemi-coroanry-care-tnk-tpa-tnktpa-

streptokinase-bolus-tpa-gusto-4-assent-4-assent-2-drip-irrigation-tnk-pulmonary-embolismthrombolysis.jpg?w=500&h=299

10.http://www.neuropathologyweb.org/chapter2/images2/2-23l.jpg11.http://www.newscientist.com/article/mg13818777.500-heart-attacks.html?

full=true&print=true12.http://www.newscientist.com/article/mg18725075.300-stop-withholding-tried-and-

tested-treatments.html?full=true&print=true13.http://www.newscientist.com/article/mg13418151.300-cheap-heart-drug-safter-than-

modern-substitute.html?full=true&print=true14.http://www.newscientist.com/article/mg12917593.400-cheap-drug-is-best.html?

full=true&print=true15.http://www.lewrockwell.com/sardi/sardi169.html16.http://reason.com/archives/1995/05/01/clinical-trials17.http://www.aei.org/article/25967