platelets

The Professors' Posts

Platelets

SUSAN LECLAIR

Karin - you sort of have the idea. Platelets do have markers on them which are activated in the course of constructing a blood clot. In situations such as MPD, and ET in particular, these platelets may have their markers already activated so they are much more likely to clot - especially in small blood vessels . What aspirin does is prevent the platelets from making one of the compounds that activate platelets so that the platelet looks ok but simply cannot become active under any circumstances.
Because blood clots are a combination of platelets stuck together (platelet aggregation) and fibrin, another way to prevent/slow down/lessen a blood clotting episode is to block the creation of fibrin. The most common way to do this is with an anticoagulant. Cureently there are two major ones on the market: heparin and coumadin. Heparin interferes with the ability of 2 enzymes that are needed to make fibrin while Coumadin lessens the production of 4 other enzymes involved in the same process.
Plavix is quite new and works on the platelet side of the blood clot process by preventing them from adhering to each other.
You are correct - it is the balance that is the key. Aspirin and Plavix will both cause petechiae. Coumadin will cause much more extensive bleeding since it is the fibrin that actually "makes" the blood clot.
Lots of other folks have bruising with plenty of platelets. It is called a qualitative platelet defect. Some of these are hereditary; some acquired. Almost none of them are primary disease states in that something else always causes the platelets to go out of whack . Medications are a very common culprit. Some people can get black eyes - just be bending over and allow blood to pool in the delicate capillaries around the eyes! We don't have many other alternatives so I am sure that you and your physician will have a loooooong conversation about how to protect yourself from potentially serious bleeding situations.

SUSAN LECLAIR

Denise, for platelet counts of below 20 there are only 3 choices = holding your breath and waiting, platelet transfusions or a synthetic platelet stimulating hormone similar to EPO for red cells.
If reverse order - platelet hormone can work wonders on some people. However, there have been a lot of reports of people's platelet counts going through the roof (2-3 million) when using the standard dosage so it apparently does not work well on everyone and you simply don't know which one you are going to be until after you have tried it.
Platelet transfusions can get you through short time issues but should not be used for prolonged correction since 1) you get antibodies to platelets making future use problematic and 2) you can get blood borne diseases such as hepatitis so transfusions are only done when there really isn't another choice.
Waiting - especially if you are going to use neupogen - is the conservative approach unless you are bleeding somewhere. Not only will your WBC count go up, there is a boost to the platelet producing cells as well. Making sure that you are eating a balanced diet also helps, since you will have to make a lot of platelets to catch up and they will need nutrients such as iron, B12, folate, etc.
In the meantime - don't shave! ;-)

SUSAN LECLAIR

It is true that Fludara will definitely drop his platelets. Having said that - it is also equally true that all oncologists already know this and frequently use platelet transfusions in situations in which there is a suspicion of bleeding.
As to the postponed surgery, did the surgeon know of his CLL? I find it amazing but it is true that in many situations physicians don't talk to each other (at all or well enough). While low platelets is a concern for any surgery, platelet transfusions might just get him through this.

SUSAN LECLAIR

One of the functions of the lymphocytes is to produce agents that stimulate other cells to divide or mature or function in some ways. When they are all taken out by immunologic therapy, their production of interleukins will obviously drop as well. Then, when the interleukins start being produced, one of the cells which will be targeted is the progenitor cells for red cells, granulocytes, monocytes, and platelets. Increases in each of those in the blood stream will occur depending on the time it takes them to mature and platelet mature more slowly than the others.

Second - if you have ITP, then all bets are off on normal recovery. ITP is caused by an antibody which you form against platelets. Any additional platelet that you get from a transfusion will be coated by the same antibody and removed from the system just as your own platelets are removed. Standard therapy for this is either prednisone to stop the production of the antibody or splenectomy to remove the site which takes the coated but still functional platelets out of the blood stream.

TERRY HAMBLIN

Platelets are tiny cells present in the blood whose job it is to plug up holes in the circulation to stop bleeding. They derive from large cells in the bone marrow called megakaryocytes. Normally you have between 150, 000 and 400,00 / cu mm in the blood. (depending on units used sometimes this is written as 150-400 x 10 (superscript 9) /L but I can't do superscripts on AOL). (If anyone knows how let me know)

In CLL the usual cause of a low platelet count is that the bone marrow isn't making enough of them. Of course, this can be caused by chemotherapy, but in the absence of chemotherapy it is usually because the marrow is full of CLL cells. Traditionally we tend to think that the CLL cells are occupying the space that should be occupied by megakaryocytes, but I suspect that it is because the CLL cells are making something that suppresses the megakaryocytes. When the platelet count falls below 100,000 from this cause most doctors think that it is time for treatment.

But there are other causes for a low platelet count that do not necessarily mean that treatment should start. they be being destroyed too quickly.

Platelets normally last for 9 days in the circulation. They either get used up by plugging a hole, or they get old and die in the spleen. If the spleen is very large platelets get pooled in the spleen and there are fewer in the blood. So some people with CLL have platelet counts of about 80,000 and a big spleen and don't need treatment. Another reason that platelets disappear too quickly is that the body may make antibodies against them. This condition is known as immune thrombocytopenia or ITP for short. ITP occurs in about 2% of patients with CLL.

ITP is difficult to diagnose. A very low platelet count in the absence of anemia or neutropenia, in a patient without a big spleen who has not had recent chemotherapy, who is otherwise well is likely to be ITP, but that scenario is rare. At last one third of patients with ITP also have autoimmune hemolytic anemia (this is called Evans' syndrome). Just like hemolytic anemia, ITP can be triggered by chemotherapy - fludarabine, CAMPATH and chlorambucil have all been reported to do it.

Unlike hemolytic anemia there is no simple test like an anti-globulin test (Coombs test) to diagnose ITP. There are some tests like platelet associated IgG, but doctors don't feel that they are reliable. What you do find in ITP is that the megakaryocytes are increased in the bone marrow biopsy, but when the marrow is almost totally replaced by CLL cells this may be difficult to be sure about. So the doctor has to take the picture as a whole to fathom out the problem and sometimes in retrospect they have got it wrong, but it is not easy.

Some drugs cause ITP - one of them is quinine - so it is important to ask about these.

Platelet transfusions are usually only indicated if a low platelet count is associated with bleeding. The problem with them is that they only last a couple of days (less in ITP). There are guidelines on how low the platelet count should get before you start transfusions. Generally, it has to be lower than 10,000, though some have recommended lower than 5000. If the patient has septicemia then a higher figure is recommended. Very few patients with CLL require platelet transfusions.

SUSAN LECLAIR

Platelets are highly interactive. They adhere to lots of difference substances and aggregate to each other when stimulated by specific stimulants called "agonists". Different drugs can work at any of these sites. Some very common examples include: Aspirin causes a decrease in both specific agonists (prostanoids) and a lessening of an inflammatory protein (hs-CRP). Clopidogrel (Plavix) prevents platelets from responding to ADP, a major agonist.

As it turns out, approximately 1/4 of people are resistant to aspirin's action and there is an approximately equal number of people who are resistant to clopidogrel. You would probably want to know if one or both of these will actually work you rather than take them (with their potential side effects) for no real improvement. There are tests available to determine if one is resistant.

There are also folks who cannot be exposed to any amount of heparin because their platelets aggregate in the small blood vessels when heparin is present - an odd reaction since heparin should be exactly the opposite. There are tests to determine "heparin induced thrombocytopenia" .

So - there are lots of these tests and the average physician would probably not be all that cognizant of the different variations to them which is the reason I suggested that they need to communicate with an expert in this testing.

SUSAN LECLAIR

Platelets are made in the bone marrow. Once in the peripheral blood, approximately 30% of them are sequestered in the spleen. When the spleen is removed (for any reason), that sequestration obviously ends and the platelet count will increase sharply and then fall to a new "normal" for that person. Typically it is higher than the platelet counts from before the surgery which leads some folk to be at a higher risk for unusual clotting.

If the spleen starts to enlarge, then the possibility that more platelets will be sequestered happens. This can be purely a physical trapping of the platelets. Another possible mechanism is that the platelets are damaged in some way (for example - coated with antibody or made incorrectly in the marrow) and that damage is sufficient for the spleen's macrophage to recognize the platelets as "foreign" and remove them from the circulation. As a result of this situation, the spleen becomes enlarged due to the stress of the additional "work". It is important to know which mechanism is involved and one relatively mild way is to use prednisone. Prednisone is a medication which stops the production of antibodies. If, after a course of prednisone, the platelet count increases, then you have reasonably good proof that the problem is with an immune process which is causes both the lowered platelet count and the enlarged spleen. If no increase or a continued decrease of platelets occur, then you have the sense that antidobides were not the cause. Additional platelet function tests might be used now.

SUSAN LECLAIR

Giant platelets are platelets that have been released from the marrow prematurely. They do function normal so neither bleeding nor clotting improperly are a problem. But they and the low reds are signs that the marrow is stressed.

TERRY HAMBLIN

It all depends why his platelet count is low. Sometimes platelets sit at around 70 after rituximab and there is no great problem about this. That level is safe for most things. If it is due to platelets being trapped in the spleen
then a splenectomy is a possibility, but most people would not do a splenectomy with platelets at this level.

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