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Neutropenias

The most important thing about neutropenias is defining what is a neutropenia. A normal child should really have an absolute neutrophil count that is between 2-3,000. But we donít worry about neutropenias until we fall below 1,500. Even between 1,500 and 1,000 you usually donít see many symptoms, or the symptoms are minimal. Symptoms start occurring when you drop below 1,000 and in that case what you typically see are mild skin infections, stomatitis, or gingivitis. Severe neutropenias are associated with more deep-seated infections like sepsis, abscesses and pneumonias. Most life threatening infections typically occur in children who have profound neutropenia, with ANCís of less than 100. When you think about mechanisms of neutropenia, just using the same pathophysiologic approach as we did with red cells.

We think about hereditary neutropenias. In your syllabus Iíve included a much more extensive number of these neutropenias, but Kostmannís syndrome or infantile agranulocytosis is an important one to keep in mind. These are children who often have low ANCís from early on. The most common early infection in these patients is omphalitis and they tend to have delayed separation of the umbilical cord. When you look at their bone marrows they have an ineffective granulopoiesis. They tend to have a maturation rest of their granulocytes so that they actually stop two or three stages prior to achieving a mature stage.

Pseudo-neutropenia is also an entity that I think many of us have seen. Itís secondary to increased margination of white blood cells. We have white blood cells that are circulating but a substantial number of our neutrophils, once they leave the bone marrow, are actually stuck to the internal surface of blood vessels. So for instance, when we need to have a stress response, an immediate response either in the face of infection or something else, the first response is for cells to de-marginate.

Immune-based neutropenias are important to think about, especially in certain settings. For instance, when we see newborns who have neutropenias. This can be on the basis of an antiimmune or isoimmune response, very similar to the isoimmune anemia that you see in infancy. Itís usually self limiting. Most of the children donít need to be treated at all, quite frankly. You can also can have an autoimmune neutropenia that occurs later on. They should have anti-neutrophil antibodies that are positive.

Cyclic neutropenia is an important entity in that these are patients who, at various points in time, really will have fairly normal white blood cell counts. It requires doing very frequent CBCís to detect it because the periodicity or the cycle for patients is highly variable. So doing CBCís twice weekly for six weeks really is the only way to pick up a true cycling neutropenia.

In terms of evaluation of neutropenic patients, it really depends on what else you are seeing. Again, if this is someone who is coming in who is otherwise healthy, who has no unusually high frequency of infections, things to think about are; you might really want to wait and watch that patient. So part of it is going to be getting a good history. A CBC to make sure you are not seeing any thrombocytopenia or anemia associated with this, is going to be important.

Other peripheral studies which may be useful may include things like an anti-neutrophil antibody, QIgís and T4TA to rule out immunodeficiency associated with neutropenia. B12 can be associated with neutropenia, but most of these patients should have other things going on like they should be anemic. If not you would actually be looking for a megaloblastic marrow. I also included in your syllabus a number of clues in terms of history and physical, which Iíll leave for you to go through, but I think itís sort of important to put those together with some of the things that you will be reading about or be presented later on, so that things like the age of the patients, the ethnicity of the patient, examining the nails closely, determining whether they have hepatomegaly or splenomegaly, looking at their growth, are all very important things to be able to piece together certain types of anemias and neutropenias.