IntroductionHeparin-induced thrombocytopenia (HIT) results from antibodies to PF4/heparin complexes and clinical diagnosis is difficult. We evaluated the particle immunofiltration anti-platelet factor 4 (PIFA) rapid assay, in conjunction with a clinical risk score, in the diagnosis of HIT.MethodsWe performed a prospective observational study in all patients admitted to the medical intensive care unit (MICU) in a large academic medical center. Patients were screened daily for thrombocytopenia defined as either a platelet count that decreased by at least 33% or an absolute platelet count less than 150,000/μL. Patients with suspected HIT underwent PIFA and ELISA testing for anti-PF4/heparin antibodies. Available residual frozen sera were sent to a reference laboratory for serotonin release assay (SRA) testing.ResultsDuring the study period, 340 patients were admitted to the MICU, of which 143 patients met criteria for thrombocytopenia. Forty-three patients had no evidence of recent heparin exposure. PIFA and ELISA testing were performed on 100 patients, of which 92 had samples available for SRA analysis. PIFA results were negative in 62, positive in 28 and inconclusive in 2 patients. The 4Ts score showed low to intermediate risk in 57 of the PIFA negative patients. The ELISA results were negative in 86 and positive in 6 patients. SRA testing identified 3 patients with a positive SRA test and 89 patients with a negative result. All patients with a negative PIFA result also had a negative SRA result. In the one patient deemed to have clinical HIT, the pretest probability was high (4Ts score of 6) and the anti-PF4/heparin antibody testing revealed a positive SRA, inconclusive PIFA and a negative ELISA result.ConclusionsWhile thrombocytopenia in our population is common, the prevalence of HIT is low. The combination of a low to intermediate pretest probability with a negative PIFA test can rapidly exclude the presence of platelet activating anti-PF4/heparin antibodies and, therefore, HIT as the cause of the thrombocytopenia. Since a positive PIFA result has a low positive predictive value, a positive PIFA is not diagnostic of HIT and additional evaluation is warranted.

No abstract

Cell line R9 generated by continuous exposure of MOLT-4 cells to adriamycin was cross-resistant to a variety of unrelated drugs. The following data indicate that diminished apoptotic response was the mechanism of acquired pleiotropic drug resistance: (i) apoptosis was a common mechanism of cell death for agents expressing cross-resistance; (ii) induction of apoptosis by drugs, medium depletion and serum deprivation was decreased in R9 cells; (iii) DNA degradation in apoptotic cells was lower in resistant lines, probably reflecting a modification of apoptotic pathway in resistant cells; (iv) inhibition of cell division and DNA synthesis by drugs was similar in sensitive and resistant cells. These data indicated a similar level of initial damage, as typical for resistance based on modified apoptotic response. There was no difference in bcl-2 protein level between sensitive and resistant cells. Thus acquired pleiotropic resistance and diminished apoptotic response in R9 cells were induced by a bcl-2-independent mechanism. Surface T-cell antigen CD4 was expressed in MOLT-4 and lost in R9 cells. The role of CD4 down-regulation in apoptosis-related drug resistance remains to be explored. The association between acquired pleiotropic drug resistance and increased survival capacity in unfavorable growth conditions indicated that drug-induced selection of cells with diminished apoptotic response may stimulate neoplastic progression. Alkylating agents induced similar cytotoxicity and only slightly lower apoptosis in R9 cells in comparison with MOLT-4 cells. Our data show that some drugs may overcome acquired pleiotropic drug resistance based on the modified apoptotic pathway.

The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.

No abstract

No abstract

No abstract

No abstract