Factors associated with failure to correct the international normalised ratio following fresh frozen plasma administration among patients treated for warfarin-related major bleeding. An analysis of electronic health records.

This study assessed the frequency and factors associated with failure to correct international normalised ratio (INR) in patients administered fresh frozen plasma (FFP) for warfarin-related major bleeding. This retrospective database analysis used electronic health records from an integrated health system. Patients who received FFP between 01/01/2004 and 01/31/2010, and who met the following criteria were selected: major haemorrhage diagnosis the day before to the day after initial FFP administration; INR ≥2 on the day before or the day of FFP and another INR result available; warfarin prescription within 90 days. INR correction (defined as INR ≤1.3) was evaluated at the last available test up to one day following FFP. A total of 414 patients met selection criteria (mean age 75 years, 53% male, mean Charlson score 2.5). Patients presented with gastrointestinal bleeding (58%), intracranial haemorrhage (38%) and other bleed types (4%). The INR of 67% of patients remained uncorrected at the last available test up to one day following receipt of FFP. In logistic regression analysis, the INR of patients who were older, those with a Charlson score of 4 or greater, and those with non-ICH bleeds (odds ratio vs. intracranial bleeding 0.48; 95% confidence interval 0.31-0.76) were more likely to remain uncorrected within one day following FFP administration. In an alternative definition of correction, (INR ≤1.5), 39% of patients' INRs remained uncorrected. For a substantial proportion of patients, the INRs remain inadequately or uncorrected following FFP administration, with estimates varying depending on the INR threshold used.

Failure to correct International Normalized Ratio and mortality among patients with warfarin-related major bleeding: an analysis of electronic health records.

BACKGROUND: Delayed correction of blood clotting times as measured by the International Normalized Ratio (INR) is associated with adverse outcomes among certain patients with warfarin-related major bleeding. However, there are limited data on the association between INR correction and mortality. OBJECTIVE: To assess factors associated with 30-day mortality and time to death in patients receiving fresh frozen plasma (FFP) for warfarin-associated major bleeding. METHODS: A retrospective database analysis was undertaken with electronic health record data from a large integrated health system. Patients met the following criteria: major hemorrhage diagnosis; INR ≥ 2 on the day before or day of receipt of FFP; and prescription fill for warfarin within 90 days. INR correction (defined as INR ≤ 1.3) was evaluated at the last available test 1 day following the start of FFP administration. Kaplan-Meier curves and Cox proportional hazards models were constructed to assess mortality. RESULTS: Four hundred and five patients met the selection criteria (mean age of 75 years, 54% male), and 67% remained uncorrected at 1 day following the start of FFP administration. Among all patients, 11% died within 30 days of hospital admission. An uncorrected INR was not associated with a higher risk of 30-day mortality for patients overall, but was statistically significant for the subgroup with intracranial hemorrhage (ICH) (adjusted odds ratio 2.55; 95% confidence interval 1.04-6.28). CONCLUSIONS: Among the subgroup of major bleeding patients with warfarin-associated ICH, those not correcting to either INR ≤ 1.3 or INR ≤ 1.5 with the use of FFP have an increased rate of mortality at 30 days.

Primary structure, deduced from cDNA, secondary structure analysis and conclusions concerning interaction surfaces of the delta subunit of the photosynthetic ATP-synthase (E.C. 3.6.1.34) from millet (Sorghum bicolor) and maize (Zea mays).

Lambda gt11 cDNA clones for the nuclear-encoded subunit delta of the chloroplast ATP-synthase from Zea mays and Sorghum bicolor were sequenced. The processing site for S. bicolor delta was established, and the sequence of the mature subunit delta from Z. mays was completed by N-terminal sequencing of the proteins isolated from chloroplasts. Only five amino acids are identical and not more than 16% conservatively exchanged in all sequences of delta subunits from higher plants and the corresponding proteins from alga, bacteria and mitochondria (OSCP) available. In binary comparison the comparatively high conservation of hydrophilic residues indicates the importance of the surface of delta. The degree in identities of surface residues correlates with the capacity in hybrid reconstitution of photophosphorylation. A hypothetical secondary structure model for a typical delta subunit can be deduced from prediction algorithms. Three putative amphipathic alpha helices and an antiparallel amphipathic beta sheet seem to be conserved. These common secondary structure features should be significant for the function of the delta subunit of F0F1 ATPases.

Cloning and sequencing of a cDNA for the delta-subunit of photosynthetic ATP-synthase (EC 3.6.1.34) from pea (Pisum sativum).

lambda gt10 cDNA clones for the nuclear encoded subunit delta of chloroplast ATP-synthase from Pisum sativum have been isolated. The 5' end was completed by PCR. The sequenced cDNA codes for the import precursor. N-Terminal sequencing of the mature protein isolated from chloroplasts revealed that the processing sites of the transit peptide from Pisum sativum and Spinacea oleracea are similar. The overall homology of the deduced amino acid sequences of the mature delta proteins from higher plants is about 40%. The conservation among hydrophilic residues is higher than for hydrophobic ones, indicating that the surface of delta is important for its function within the ATP-synthase.