Tuesday, February 12, 2008

It's Always about the Blood

It's always about the blood. – Spike, from Buffy the Vampire Slayer

Bone marrow makes blood cells. More specifically, it contains various "uncommitted" stem cells that remain in the marrow while splitting off cells that then are "committed" to maturing into cells that circulate in the blood.

The biggie is the red blood cells, without which you and I would die in seconds, since they are what convey oxygen from the lungs to everywhere else. The fancy term for red blood cells is erythrocytes, which has the interesting characteristic of being not only less informative than "red blood cells" but also has more syllables.

The lab measurement for red blood cells is called "hematocrit," and 35% to 55% is considered normal. Less, and you have anemia. More, and you may have a blood disease, live at a high altitude, have dengue fever, or are taking a performance enhancing drug, like EPO.

White blood cells are "leukocytes," or ""lymphocytes" (hooray! same number of syllables, plus there's a differentiation in kind. That's what technical terms should be about). There's an entire menagerie of white blood cells, having to do with which part of the immune system is in play.

Then there are platelets, aka thrombocytes, which aren't exactly cells, but I'll get to that. A normal platelet count is between 150,000 and 400,000 per cubic millimeter of blood, but the ",000" is usually dropped in reporting, so a person with a platelet count of 200,000 is usually said to have a platelet count of 200. A low platelet count is called thrombocytopenia, and may create problems with bruising, bleeding, etc. although there are other factors involved. A count of 120, for example, is not considered that big a deal, but if the count drops below 20, the risk of spontaneous bleeding becomes very high.

Platelets aren't cells, per se; they are more akin to cell walls, hence the "plate" part of the name. Platelets are formed in the cytoplasm of a very large cell, the megakaryocyte. Megakaryocytes mature in about 10 days, from a large stem cell, the megakaryoblast. The cytoplasm of the megakaryocyte fragments at the edge of the cell. This is called platelet budding. The spleen serves as a holding tank for platelets, and contains about a third of the blood's platelets at any given time. Platelets are destroyed by macrophages, and have a lifetime of between 8 and 12 days in the blood, so the full life cycle of a platelet is on the order of about 20 days.

Platelets are necessary but not sufficient for blood clotting. A blood clot consists of a mass of platelets enmeshed in a lattice of insoluble fibrin molecules. Platelet aggregation and fibrin formation both require the proteolytic enzyme thrombin, plus calcium ions and about a dozen other protein clotting factors. Most of these circulate in the blood as inactive precursors until they are activated by trigger enzymes that form when blood vessels are ruptured or something else unpleasant happens.

So, basically, platelets are the bricks and the aggregation factors are the mortar, glue, etc, that hold them together to form blood clots. This entire process is pretty much unique to mammals, incidentally.

There are a number of drugs that will reduce platelet count, including the aspirin-like drugs, ibuprofen and naproxen. I was taking prescription-level amounts of naproxen until recently, owing to the practice of Aikido, and this did lower my platelet levels to somewhat below the lower level of normal, which is to say 100-150, but I did not seem to have any clotting problems, so big deal, was my opinion. However, a few months ago, I began a series of encounters with a fine (intentional irony here) drug called Temodar, which really slams the platelet count, so I had to give up the naproxen. I now report that this made me feel roughly 10-15 years older on the Aikido mat.

A fellow Aikido student recently underwent a root planing, a dental procedure that removes accumulated plaque from below the gum line. After finishing one side, the dentists said, "There's too much bleeding here. I'm not going to do the other side without a doctor's release." So, said student went to his doctor, who sent him to get the requisite blood test.

Upon receipt of the results, the doctor called and told him, "I want you to immediately go to the nearest hospital and check yourself in." The student then called a friend of his, also a physician, for advice. Upon reading his friend the blood test results over the phone, the friend said, "What are you doing talking to me? Go to the nearest hospital and check yourself in immediately."

Our boy did not quite follow the advice. He first wrote up a list of things that needed doing at his job, then he went, not to the nearest hospital, but to San Francisco General. This was actually a good move, because they immediately sent him over to UCSF Hospital, where they could make a proper diagnosis, and where he is now just about done with the chemotherapy for the rare (and, fingers crossed for the happy ending) and very curable form of leukemia that he had developed. Upon admission, he was immediately given a transfusion, and has since had 6-8 "platelet packs," which consist of platelets that have been centrifuged out of whole blood.

He is 36.

His blood test platelet count was 11.

3 comments:

black dog barking said...

Most of these circulate in the blood as inactive precursors until they are activated by trigger enzymes that form when blood vessels are ruptured or something else unpleasant happens.


From time to time I design information input systems that require a level of foresight and planning to deal with unexpected consequences. Compared to physical processes exchanging information in a living organism this is completely trivial stuff. But it seems complicated to me until I get the flow worked out.

The point here is I can't even begin to imagine a system that required me to include chemical precursors that would react with enzymes in emergency situations. Nor can I begin to imagine debugging such a system.

James Killus said...

Many years ago, at a company lunch, I was talking to one of the software guys, or, more accurately, he was holding forth for the benefit of the secretary who was (I later came to learn) his girlfriend. In other words, he was talking to me but showing off for her.

During the course of it all, he mentioned that it's often the case that the body's immune response was often responsible for most of the damage from an illness, that someone who was quite sick often had already killed off the pathogens, but their immune system was still hammering at them long afterwards.

I commented that this was to be expected; pathogens show an exponential growth curve generally, so any control system that has to deal with exponentially growing inputs is bound to have some overshoot in it.

He stared back at me blankly, and it was at that moment that I realized that he wasn't nearly as smart as he was pretending to be. Later events proved that spot judgement to be spot on.

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