Patterns of platelet response in idiopathic TTP/HUS: frequency of declining platelet counts with plasma exchange and the recognition and significance of a pseudo refractory state.

For thrombotic thrombocytopenic purpura (TTP), daily plasma exchange (TPE) is typically discontinued when the platelet count normalizes (>150 x 10(9)/L). We observed a decline in platelet count during TPE and in patients who appeared pseudo-refractory because of a platelet count plateau (100-150 10(9)/L range). In the present study, we evaluated platelet count trends in TTP patients. Retrospective review of TTP patients from 01/1999 to 12/2004 was completed. Patients were categorized based on platelet count trends: Group I, counts rose then decreased to levels <100 x 10(9)/L; Group II, counts declined following TPE initiation; Group III, counts rose continuously; Group IV, counts decreased after the count was >100 x 10(9)/L. Additionally, we identified pseudo-refractory patients caused by a platelet count plateau (>100 x 10(9)/L but <150 x 10(9)/L). We identified 60 TTP patients. Within Group I (17 patients/17 series/19.1% of total), the mean decrease in platelet count was 67.3% +/- 22.1% following initial rise. Within Group II (24 patients/25 series/28.1% of total), the mean decrease was 28% +/- 5.3% following presentation. Group III included 31 patients/39 series (43.8% of the total). Within Group IV (seven patients/eight series/9.0% of total), the mean decrease was 17.4% +/- 12.6% following a sustained rise >100 x 10(9)/L. With a declining platelet count and daily TPE, it is generally sufficient to stay the course and the decline will reverse. Our limited experience with pseudo-refractory patients supports discontinuing TPE when counts plateau between 100 and 150 x 10(9)/L when a therapy goal is a platelet count of 150 x 10(9)/L. Recognition of this pseudo-refractory state can minimize the risks of prolonged TPE and the risks of adjunct interventions.

Frequency and significance of schistocytes in TTP/HUS patients at the discontinuation of plasma exchange therapy.

INTRODUCTION: Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) is characterized by thrombocytopenia, a microangiopathic hemolytic anemia (presence of schistocytes) and elevated LDH without another likely explanation. Standard of care is daily plasma exchange, which is typically discontinued when the platelet count exceeds 100-150 x 10(9)/L for 2 days. However, residual schistocytosis, the presence of schistocytes at the time of discontinuation of plasma exchange therapy, is often disconcerting. We evaluated the frequency and significance of residual schistocytosis in TTP/HUS patients when the patients' platelet counts returned to normal levels (e.g., 100-150 x 10(9)/L). METHODS: Retrospective review in our institution from 01/1999-03/2004 of all patients treated with plasma exchange for TTP/HUS with at least 2 months of follow-up for relapse was completed. Patients were excluded if the clinical course was complicated by HIV, stem cell/bone marrow and solid organ transplant, pregnancy and auto-immune disease. Schistocytes were documented on day of presentation and on the day the platelet count reached 150 x 10(9)/L. Grading scale (using 100 x objective-a high power field, with approximately 100 red blood cells per field) for schistocytes was as follows: rare for 1 schistocyte per every other other field, 1+ for 1-5%, 2+ for 6-15%, and 3+ for >15%. The frequency of schistocytes was compared to frequency of relapse within 2 months, using Fisher's exact test. RESULTS: We identified 57 patients with TTP/HUS who received plasma exchange therapy. Of these patients, 12 did not have a follow-up microscopic examination of a peripheral blood smear at discontinuation of plasma exchange therapy and were excluded from further analysis. Of the remaining 45 patients, 16 had residual schistocytosis (35.6%). There was no statistically significant difference in relapse rate with or without residual schistocytosis (P = 1.00, Fisher's Exact test, 2 sided). CONCLUSIONS: In this study, we found that the presence of residual schistocytosis is common (35.6%). The presence of residual schistocytosis, however, was not predictive of relapse.

Differential expression of WT1 and p53 in serous and endometrioid carcinomas of the endometrium.

Wilms' tumor antibody (WT1) has recently been reported to be reactive in most ovarian and peritoneal serous carcinomas, but few studies have looked at WT1 reactivity in endometrial carcinomas. p53, like WT1, is a tumor suppressor gene and in its mutated form is frequently present in endometrial serous carcinoma. Routine immunohistochemical staining for p53 and WT1 was performed in 70 endometrial carcinomas (39 endometrioid and 31 serous) of varying differentiation using tissue microarrays. Only 2 (7.5%) serous carcinomas and none of the endometrioid carcinomas (0%) were reactive for WT1. p53 immunoreactivity was found in 26 (83.9%) serous carcinomas and in 2 (5.1%) endometrioid carcinomas. We conclude that WT1 and p53 expression are not related and that WT1 expression in endometrial serous carcinoma differs from that of its extrauterine counterparts.