A Bloody Good System

Water Explosion by David R./flickr

Fixing problems

You work as a field engineer for a very large factory, and your job is to traverse the entire facility each day and ensure the water pipes are not leaking.

Fortunately, the factory invested in some nifty sensors that can notice a small break when it happens. Your job is just to apply a quick fix. If you don’t do your job, then the leak continues. If you do your job too enthusiastically (i.e. responding to false alarms), then you are wasting time and money. After you apply your quick fix, you have to alert your supervisor to implement a permanent one.

Now, you’re in a big bureaucracy. So to actually get that fix, your supervisor needs to initiate a whole cascade of phone calls. He calls some guy in one department and convinces him there’s a problem. That guy calls another guy in another department and convinces him there’s a problem. And so on…

Finally, after many phone calls, the head operations guy hires a contractor to seal the leak for good. If any part of this chain of events falls through, then the contractor doesn’t come in and the leak doesn’t get fixed.

Normally, after the problem is fixed, the contractor is paid, everyone else is called off and things go back to normal. But sometimes the contractor’s payment is delayed or the other people in the chain of events aren’t notified that the problem has been solved, and everyone remains in a state of alert.

This is pretty much how blood clotting works.

Blood vessels are our body’s internal plumbing system. They carry water, oxygen, nutrients, and other important things all around the body. They’re fairly sturdy, but they can get damaged (i.e. when we cut ourselves and start bleeding).

When blood vessels break, the layer that touches blood sends out an alarm that attracts special cells called platelets. The first platelet swoops in, binds to the injury, and sends a signal to its friends to band together. The binding can hold for a bit but is still rather loose - a temporary solution. The components on the platelets that assist in this process are like the field engineer we talked about earlier. They supply a quick fix, but a more permanent solution is needed.

To strengthen the binding between platelets, chemical signals are released into the blood to attract the attention of a set of proteins called clotting factors. There are 12 different factors, but the key is they are part of what’s known as the coagulation cascade. That is, much like the bureaucrats and their phone sequence, the factors are activated by other factors in a very regulated order (i.e. Factor 12 activates Factor 11 which activates Factor 9, etc., etc.).

Finally, you get to the head operations guy who calls in the contractor (known as thrombin). The contractor fixes the problem by making the binding agent between platelets super strong (converts to something called fibrin). After that happens, all the factors get deactivated and the alarm signals turn off.

Disorderly conduct

There are a few things that can screw us up: (a) the platelets aren’t doing their job properly (short-term solution), (b) the coagulation cascade isn’t doing its job properly (long-term solution), or (c) the process isn’t being turned off.

Depending on the error, we can get two different outcomes. If the system is too passive and doesn’t respond with haste, then we get a bleeding disorder. Many are genetic - the most famous example is Hemophilia, which has afflicted several members of the British royal family. These patients are missing Factor 8, so the coagulation cascade doesn’t work without external replacement of the missing factor.

Now, a more interesting outcome is the opposite of that. If the system is working more than it ought to, or if it doesn’t turn itself off, we get more clotting than we want. This can eventually block off the blood vessel and lead to things like heart attacks and stroke.

Getting back to normal

Thankfully, we can treat excessive blood clotting! We use pretty well-known drugs to do this, so now you’ll finally know what all those drugs you see on TV, in movies and in advertisements actually do.

(A) Block the short-term fix: You might have heard that Aspirin can be helpful to people who are prone to heart attacks. Aspirin blocks the chemical signals that attract platelets to bind to other platelets. While it can’t break up a clot that blocks a blood vessel, it can help prevent it from getting worse or new clots from forming. Plavix, another common drug, achieves a similar result.

(B) Block the long-term fix: We use a drug called Warfarin to block the production of coagulation factors needed to start the long-term fix. As you can imagine, taking too much of this can lead to the opposite problem (excessive bleeding) - which is why high levels of warfarin are used in rat poisons.

(C) Accelerate the inactivation of the system: We can stop excessive clotting by accelerating the stoppage of the system. One well-known drug that does this is Heparin.

(D) Break up the clot: In an absolute emergency situation (like a serious stroke or heart attack), we can give drugs, such as tPA, that break up the clot entirely. It activates a specific protein that can dissolve the contractor’s really strong binding agent. We do this only after all other options have been exhausted because it can dissolve EVERY clot (even ones that are fine).

Blood disorders are complicated and have an entire medical speciality, hematology, all to themselves. But hopefully this simple illustration gives some context behind how our body heals itself and how we can treat very common problems clinically. Or at the very least, when a TV doctor tells his nurse to give the patient warfarin, you’ll know why.

Vinayak Venkataraman is a rising second-year medical student at Duke University School of Medicine. He graduated from Princeton in 2011 with a degree in Electrical Engineering and certificate in Bioengineering. After graduating, he worked with Dr. Ray Dorsey at Johns Hopkins, researching the feasibility and value of using web-based videoconferencing (i.e. telemedicine) to expand access to care for patients with Parkinson disease. Outside of medicine, Vinayak is the author of an awesome novella and loves Indian cooking, tennis, and coffee.

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