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Infants with neonatal alloimmune thrombocytopenia are at risk of severe intracranial haemorrhage. Placental transfer of maternal immunoglobulin G (IgG) directed against fetal platelet antigens is known to be the underlying mechanism. Since breast milk contains IgG it is theoretically possible that breast feeding of these infants could cause thrombocytopenia. The following case report shows that an infant with neonatal alloimmune thrombocytopenia may be safely breast fed, even when the breast milk contains the platelet specific antibody (HPA-1a).

Based on their good activity and minimal toxicity in non-small cell lung cancer and other cancers, we initiated a phase II trial of carboplatin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with previously untreated stage IIIB and IV non-small cell lung cancer. Among 51 patients treated, the overall response rate was 27.5% (14 partial responses). Seventeen patients had stable disease, while 16 patients experienced disease progression after two cycles of treatment. Apart from myelosuppression, toxicity has been modest, with fewer than 5% of patients experiencing grade 3 or greater nonhematologic toxicity. Objective response and survival rates were modestly improved among patients given the higher of two paclitaxel doses (175 mg/m2 v 135 mg/m2). These data suggest that paclitaxel plus carboplatin warrants further study in metastatic non-small cell lung cancer.

Thrombocytopenia is a common accompaniment of disseminated histoplasmosis. The yeast form of Histoplasma capsulatum does not directly injure human platelets freed of plasma. Preincubation of H. capsulatum with plasma enabled it to induce prompt platelet aggregation and selective release of [3H]serotonin without release of lysosomal beta-glucuronidase and the cytoplasmic marker, lactate dehydrogenase. Platelet aggregation was mediated by adenosine diphosphate, as shown by the blocking of the reaction by apyrase. Indomethacin inhibited both aggregation and serotonin release, indicating their dependence on prostaglandin synthesis by platelets. Plasma IgG conferred [3H]serotonin-releasing activity after complexing with yeasts, and plasma fibrinogen was necessary for platelet aggregation; classical and alternative complement pathways were not involved. The interaction of H. capsulatum with human platelets, mediated by IgG and fibrinogen without complement, represents a new attribute of this fungal pathogen and may contribute to thrombocytopenia complicating disseminated histoplasmosis.

The interactions between platelets and dialysis membranes were studied prospectively in 10 patients undergoing long-term stable dialysis. Transient but significant thrombocytopenia and platelet activation were found during dialysis with the commonly used cuprophane membrane. Platelet counts decreased from 231 +/- 21 X 10(3)/mm3 before dialysis to 127 +/- 28 X 10(3)/mm3 at 90 minutes following initiation of dialysis (p less than or equal to 0.007). Thromboxane B2, an index of platelet activation, also increased from a baseline level of 1.06 +/- 0.2 pg/10(6) platelets to 7.3 +/- 3.0 pg/10(6) platelets at 90 minutes (p less than or equal to 0.04). Cuprophane membranes were also shown to induce complement activation with C3a desArg, the stable derivative of C3 activation, showing a threefold increase from baseline 15 minutes after initiation of dialysis. In contrast, during dialysis with a non-complement-activating dialyzer membrane, polymethylmethacrylate, thrombocytopenia and platelet activation were not observed. These data suggest that platelet activation and thrombocytopenia during hemodialysis are associated with complement activation during hemodialysis in a manner similar to dialysis-associated neutropenia.

Twenty-two patients with recurrent small-cell lung cancer (SCLC) were treated with single-agent etoposide 50 mg/m2/d by mouth for 21 consecutive days. Eleven patients had received previous chemotherapy with cyclophosphamide, doxorubicin, and vincristine (CAV) or etoposide (CAE) or both (CAVE). Four of the latter patients also received salvage treatment with cisplatin and etoposide (EP). Nine patients had been treated with EP as induction therapy, while two patients had received high-dose cyclophosphamide, etoposide and cisplatin (HDCEP). Altogether, 18 patients had received previous intravenous etoposide. The median time off chemotherapy was 4.5 months (range, 1 to 28.9 months). Ten patients (45.5%; 95% confidence interval [CI], 27% to 65%) achieved a complete or partial response. Responses were most common in patients who had responded to previous chemotherapy and who had not received any treatment in the 90 days before initiation of oral etoposide. Median response duration was 4 months (range, 1.5 to 9.5 months) and median survival was 3.5+ months (range, 1.0 to 15+ months). Leukocyte and platelet nadirs were 1,800/microL and 160,000/microL, respectively, during cycle 1 of treatment and occurred between days 21 and 28. Overall, total leukocyte count decreased to less than 1,000/microL during 10 of 56 cycles (18%). Five patients required six hospitalizations for neutropenia and fever. There were two toxic deaths due to sepsis. Platelet counts less than 50,000/microL occurred in 14 cycles (25%). Alopecia developed in all patients; gastrointestinal toxicity was uncommon. This schedule of etoposide administration warrants further study in combination with other active agents in previously untreated patients with SCLC.

PURPOSE - To determine the prevalence of lupus anticoagulant and anticardiolipin in systemic lupus erythematosus (SLE) and in non-SLE disorders, and to evaluate the clinical significance of these autoantibodies as they relate to thromboembolic events, neuropsychiatric disorders, thrombocytopenia, and fetal loss.
DATA IDENTIFICATION - A computer-assisted search of the literature (MEDLINE, 1966 to 1989) and review of the bibliographies of all identified articles.
STUDY SELECTION - Series of ten or more subjects were included if the assays used for detecting lupus anticoagulant or anticardiolipin met the specified minimal criteria for validity.
DATA EXTRACTION - Series were categorized according to antibody type and underlying disease. A systematic appraisal of patient selection methods, study design, and assay methods was done.
RESULTS OF DATA ANALYSIS - An analysis of 29 published series (comprising over 1000 patients with SLE) yielded an average frequency of 34% for the lupus anticoagulant and 44% for anticardiolipin. Antiphospholipid antibodies are also prevalent in patients with various non-SLE disorders. In patients with SLE, a statistically significant association exists between the presence of either antibody and a history of thrombosis, neurologic disorders, or thrombocytopenia. The available data suggest, but do not firmly support, an association between antiphospholipid antibodies and history of fetal loss in women with SLE. Contrary to prevailing opinion, none of these associations have been shown conclusively in patients with non-SLE disorders.
CONCLUSIONS - The results of predominantly retrospective series suggest that for certain persons (patients with SLE or closely related disorders) antiphospholipid antibodies may be important risk factors for thrombosis, neurologic disease, thrombocytopenia, and fetal loss. Standardized tests for lupus anticoagulant and anticardiolipin, as well as long-term, prospective clinical studies, are needed to determine the prognostic value of antiphospholipid antibodies.

Twenty-eight patients with unresectable, metastatic non-small cell lung cancer (NSCLC) were treated with carboplatin/oral etoposide. Carboplatin was administered intravenously on day 1 at a dose of 300 mg/m2 (12 patients) or 350 mg/m2 (16 patients); oral etoposide was administered at a dose of 50 mg/m2/d for 21 consecutive days. Treatment was repeated every 28 days. Patient characteristics included male:female ratio of 23:5, median age of 60 years, median Eastern Cooperative Oncology Group performance status of 1, weight loss of 5% or more in seven patients; stage IIIB disease in two patients and stage IV in 26. Twenty-five patients were evaluable for response and seven (28%) achieved a partial response (95% confidence interval, 14% to 48%). Median duration of response was 3+ months (range, 2+ to 6+) and median survival was 4+ months (range, 1+ to 10+). Myelosuppression was the predominate toxicity; leukocyte and platelet nadirs occurred between days 22 and 29, with median counts of 2,900/microL and 172,000/microL, respectively. The median interval between the start of cycle 1 and the start of cycle 2 was 33 days (range, 26 to 42). Carboplatin/oral etoposide is a moderately active regimen against advanced NSCLC that can be administered in an outpatient setting with manageable toxicity. Its impact on survival remains to be determined.