I am posting the highlights:
Autoimmune thrombocytopenia is a relatively common disorder. Best estimates are 66 million cases a year in the United States. We are seeing more of it because everyone who gets a blood count today also gets a platelet count -- which was not the case 25 years ago. This is primarily a disease of younger women: 70 percent of patients are women, and 72 percent of these women are under age 40. Also, it's seen in association with other diseases, such as the autoimmune disorders of systemic lupus erythematosus or rheumatoid arthritis. We frequently see it as concomitant in patients with leukoproliferative disorders, and not uncommonly in patients with HIV infection. The acute form of this disease is a childhood disorder. Onset is abrupt, it usually follows an infectious illness, and it spontaneously remits in six months. The chronic form of autoimmune thrombocytopenia has duration greater than six months, and is an organ-specific autoimmune disease.
Antibodies actually are directed to important platelet glycoprotein receptors, which not only leads to a decrease in platelet count but also to functional abnormalities.
There are problems with this, though, in terms of consumptive process as much as phagocytosis. In fact, the removal of spleen is ineffective in about 30% to 40% of patients with autoimmune thrombocytopenia. That does not necessarily mean that it is not consumptive, but when you do a bone marrow, many patients do not have increased megakaryocytes. When we looked at labeled platelets with indium, they showed improved platelet survival after splenectomy, but the patient was still thrombocytopenic. Moreover, we know that the hallmark of the diagnosis of autoimmune hemolytic anemia is the reticulocyte -- very important to measuring and sorting out immune destruction of red cells vs. underproduction. Reticulated platelets are not increased; there is something else going on. In fact, early studies (Ingram and Coopersmith. Br J Haematol. 1969;17(3):225-9) showed that platelets contain ribonucleic acid (RNA) after acute blood loss, and subsequent studies showed that increased RNA present in patients with consumptive thrombocytopenia can be measured by fluorocytometry (Ault et al. Am J Clin Pathol. 1992;98(6):637-46). This is not something we have been able to do very easily in the clinic, though, because we do not have a fluorocytometer.
In 37 patients with autoimmune thrombocytopenia, about 10 of them did not have elevated reticulated platelets. We went back and looked in medical records, and these, in fact, were patients who were not responding to steroids. Post-splenectomy, they still had thrombocytopenia. In other consumptive thrombocytpoenias disseminated intravascular coagulation (DIC), we also see patients in the normal range. This is going to be a useful, readily available tool to help us monitor patients’ response.
Until about 10 years ago, we did bone marrow on patients with suspected autoimmune thrombocytopenia. Now, the dogma is careful physical exam, history, a look at the blood smear, ensuring there is nothing to suggest lymphoma or monodysplasia, or hypergranular lymphocytes, or whatever -- and there is no need to do a bone marrow. When we did bone marrows, and many parts of the world still do, we actually could see increased megakaryocytes or absence of decrease of megakaryocytes.
When should antibody testing of the platelets be done?
We do it when we are not quite sure of the disease, not quite sure what is going on. Patients with chronic lymphatic leukemia could have decreased production, or they might have an antibody. Therefore, there are complicated disorders or major antibodies. These antibodies do lead to functional abnormalities; they impair fibrinogen binding, Von Willebrand adhesion.
The bottom line clinically from these observations is that we might see some patients with a platelet count of 50,000 who have a normal bleeding time and not much problem. However, we see other patients who have platelet counts of 50,000 who really have a lot of bleeding. Part of the difference in the disease presentation is due to these qualitative abnormalities, these antibodies.
In general, the long-term results of splenectomy -- long-term being defined as at least three to five years -- show a platelet count of about 50,000 in about 50% of patients. We see an awful lot of patients referred for refractory autoimmune thrombocytopenia. They have been splenectomized already. Sometimes these cases are frustrating because most of the drugs already have been tried at other institutions. With these patients, we are using a fair amount of Rituximab®. There are no large controlled studies, though. Frequently, we just go back to prednisone and IV-IgG.
I have defined autoimmune thrombocytopenia, and discussed some of the diagnostic issues, emphasizing the use of cognitive skills. I emphasized that antibodies do lead to platelet destruction, they can lead to platelet function abnormalities, and we have to deal with impaired thrombopoiesis. I also gave you an approach to treatment emphasizing that we do not bring platelet counts up to 200,000, but we are happy with 50,000.
www.hopkins-arthritis.org/physician-corner/cme/rheumatology-rounds/thrombocytopenia_rheumrounds8.html
Topic Author