Platelet corrected count increments by apheresis platform.

BACKGROUND: Automated blood collection platforms use different technological systems to isolate and collect individual blood components. These unique systems could potentially result in differences in platelet in vivo viability, as measured by the corrected count increment (CCI). STUDY DESIGN AND METHODS: This retrospective study evaluated CCI data of platelet transfusions among oncology patients who received multiple unmanipulated apheresis platelets between January 1, 2006 and December 31, 2009. Apheresis platelets were collected from our community blood center by standard procedures using two different collection systems and were transfused to patients in a blinded manner. RESULTS: The CCI of the platelet recipient was significantly higher at 0-2 hours post-transfusion among the individuals who received platelets collected on Trima Accel (Terumo BCT) (mean = 6281, standard deviation = 3650) compared to the platelets collected by the Amicus system (Fresenius Kabi) (mean = 5251, standard deviation = 3311, p = 0.004). CONCLUSIONS: These hypothesis-generating data suggesting improved recovery and survival of Trima Accel platelets demonstrate the need for the investigation and implementation of the best collection methods to provide better platelet transfusion support.

The impact of platelet additive solution apheresis platelets on allergic transfusion reactions and corrected count increment (CME).

BACKGROUND: Allergic transfusion reaction (ATR) incidence ranges from 1% to 3% of all transfusions. We evaluated the impact of InterSol platelet additive solution (PAS) apheresis platelets (APs) on the incidence of ATRs and the posttransfusion platelet (PLT) increment. STUDY DESIGN AND METHODS: This retrospective study evaluated all ATRs among patients at a university hospital that maintained a mixed inventory of PAS APs and non-PAS APs (standard plasma-suspended PLTs). Corrected count increments (CCIs) were calculated for AP transfusions of individuals who received both a PAS and a non-PAS AP transfusion within a 7-day period. Hypothesis testing was performed with chi-square test for dichotomous variables and t tests for continuous variables. RESULTS: The incidence of ATRs among the non-PAS APs was 1.85% (72 ATRs/3884 transfusions) and 1.01% (12 ATRs/1194 transfusions) for PAS APs (risk ratio [RR], 0.54; 95% confidence interval [CI]=0.30-0.99; p=0.04). However, there was no difference in the incidence of febrile nonhemolytic transfusion reactions between non-PAS APs (incidence, 0.70%; 27/3884) compared to PAS APs (incidence, 0.59%; 7/1194; p=0.69). Among 223 individuals with paired non-PAS and PAS AP transfusions, the mean CCI at 1 to 4 hours after transfusion was 4932 (95% CI, 4452-5412) for non-PAS APs and was lower for PAS APs (CCI, 3766; 95% CI, 3375-4158; p ≤ 0.001). However, there was no significant difference in mean CCI at 12 to 24 hours between non-PAS (CCI, 2135; 95% CI, 1696-2573) and PAS APs (CCI, 1745; 95% CI, 1272-2217; p=0.14). CONCLUSIONS: PAS APs substantially reduce the number of ATRs. CCIs for PAS APs were lower immediately after transfusion, but not significantly different at 12 to 24 hours.

Insulin receptor substrate 1 regulation of sarco-endoplasmic reticulum calcium ATPase 3 in insulin-secreting beta-cells.

We have previously characterized an insulin receptor substrate 1 (IRS-1)-overexpressing beta-cell line. These beta-cells demonstrated elevated fractional insulin secretion and elevated cytosolic Ca(2+) levels compared with wild-type and vector controls. This effect of IRS-1 may be mediated via an interaction with the sarco-endoplasmic reticulum calcium ATPase (SERCA). Here we demonstrate that IRS-1 and IRS-2 localize to an endoplasmic reticulum (ER)-enriched fraction in beta-cells using subcellular fractionation. We also observe co-localization of both IRS-1 and IRS-2 with ER marker proteins using immunofluorescent confocal microscopy. Furthermore, immuno-electron microscopy studies confirm that IRS-1 and SERCA3b localize to vesicles derived from the ER. In Chinese hamster ovary-T (CHO-T) cells transiently transfected with SERCA3b alone or together with IRS-1, SERCA3b co-immunoprecipitates with IRS-1. This interaction is enhanced with insulin treatment. SERCA3b also co-immunoprecipitates with IRS-1 in wild-type and IRS-1-overexpressing beta-cell lines. Ca(2+) uptake in ER-enriched fractions prepared from wild-type and IRS-1-overexpressing cell lines shows no significant difference, indicating that the previously observed decrease in Ca(2+) uptake by IRS-1-overexpressing cells is not the result of a defect in SERCA. Treatment of wild-type beta-cells with thapsigargin, an inhibitor of SERCA, resulted in an increase in glucose-stimulated fractional insulin secretion similar to that observed in IRS-1-overexpressing cells. The colocalization of IRS proteins and SERCA in the ER of beta-cells increases the likelihood that these proteins can interact with one another. Co-immunoprecipitation of IRS-1 and SERCA in CHO-T cells and beta-cells confirms that these proteins do indeed interact directly. Pharmacological inhibition of SERCA in beta-cells results in enhanced secretion of insulin. Taken together, our data suggest that interaction between IRS proteins and SERCA is an important regulatory step in insulin secretion.