Screening for iron deficiency in surgical patients based on noninvasive zinc protoporphyrin measurements.

BACKGROUND: Approximately every third surgical patient is anemic. The most common form, iron deficiency anemia, results from persisting iron-deficient erythropoiesis (IDE). Zinc protoporphyrin (ZnPP) is a promising parameter for diagnosing IDE, hitherto requiring blood drawing and laboratory workup. STUDY DESIGN AND METHODS: Noninvasive ZnPP (ZnPP-NI) measurements are compared to ZnPP reference determination of the ZnPP/heme ratio by high-performance liquid chromatography (ZnPP-HPLC) and the analytical performance in detecting IDE is evaluated against traditional iron status parameters (ferritin, transferrin saturation [TSAT], soluble transferrin receptor-ferritin index [sTfR-F], soluble transferrin receptor [sTfR]), likewise measured in blood. The study was conducted at the University Hospitals of Frankfurt and Zurich. RESULTS: Limits of agreement between ZnPP-NI and ZnPP-HPLC measurements for 584 cardiac and noncardiac surgical patients equaled 19.7 µmol/mol heme (95% confidence interval, 18.0-21.3; acceptance criteria, 23.2 µmol/mol heme; absolute bias, 0 µmol/mol heme). Analytical performance for detecting IDE (inferred from area under the curve receiver operating characteristics) of parameters measured in blood was: ZnPP-HPLC (0.95), sTfR (0.92), sTfR-F (0.89), TSAT (0.87), and ferritin (0.67). Noninvasively measured ZnPP-NI yielded results of 0.90. CONCLUSION: ZnPP-NI appears well suited for an initial IDE screening, informing on the state of erythropoiesis at the point of care without blood drawing and laboratory analysis. Comparison with a multiparameter IDE test revealed that ZnPP-NI values of 40 µmol/mol heme or less allows exclusion of IDE, whereas for 65 µmol/mol heme or greater, IDE is very likely if other causes of increased values are excluded. In these cases (77% of our patients) ZnPP-NI may suffice for a diagnosis, while values in between require analyses of additional iron status parameters.

Impact of rivaroxaban plasma concentration on perioperative red blood cell loss.

BACKGROUND: This study investigates the impact of preoperative calculated rivaroxaban (RXA) plasma concentration on perioperative red blood cell (RBC) loss. STUDY DESIGN AND METHODS: In this retrospective single-center study, we identified patients with RXA intake according to a preoperative determination of RXA levels within 96 hours before surgery. RXA plasma concentration at the beginning of surgery was then calculated from the last RXA intake using a single-compartment pharmacokinetic model with four categories of RXA concentration (≤20, 21-50, 51-100, and >100 µg/L). Patients were classified into surgery with high (≥500 mL) or low (<500 mL) expected blood loss. Perioperative bleeding was determined by calculating RBC loss. RESULTS: We analyzed 308 surgical interventions in 298 patients during the period from January 2012 to July 2018. Among patients undergoing surgery with low expected blood loss, RBC loss varied from 164 mL (standard deviation [SD], 189) to 302 mL (SD, 397) (p = 0.66), and no association of calculated RXA concentration with RBC loss was observed. In patients undergoing surgery with high expected blood loss, we found a significant correlation of calculated RXA concentration with RBC loss (Pearson's correlation coefficient, 0.29; p = 0.002). RBC loss increased with rising RXA concentration from 575 mL (SD, 365) at RXA concentration of 20 µg/L or less up to 1400 mL (SD, 1300) at RXA concentration greater than 100 µg/L. RXA concentration greater than 100 µg/L was associated with a significant increase of in RBC loss of 840 mL (95% confidence interval, 360-1300; p < 0.001). Transfusion of RBC and fresh frozen plasma units tended to increase in patients with RXA concentrations greater than 100 µg/L. The proportion of patients treated with prothrombin complex concentrate and coagulation factor XIII concentrate increased significantly with higher RXA concentrations. CONCLUSION: Only in surgery with high expected blood loss, a calculated RXA concentration of greater than 100 µg/L was associated with a significant increase of perioperative RBC loss.

Standard coagulation assays alone are not sufficient to exclude surgically relevant rivaroxaban plasma concentrations.

BACKGROUND: While mainly larger hospitals have introduced routine anti-Xa assays for rivaroxaban (RXA), these are not readily available to smaller hospitals often relying on routine coagulation tests such as prothrombin time (PT) and activated partial thromboplastin time (aPTT).The aim of our study was to investigate the effect of RXA plasma concentration on the standard coagulation tests PT (Quick test and INR) and aPTT in a large group of real-life patients. We further assessed whether normal results of these standard coagulation assays are sufficient to exclude surgically relevant RXA plasma concentration, defined as > 50 mcg/l. METHODS: This retrospective study included all patients between 2012 and 2016 where anti-Xa (calibrated for RXA), PT (Quick test and INR), and/or aPTT were determined from the same sample. PT is expressed as Quick value (% of normal plasma pool). In total, 1027 measurements in 622 patients were eligible for analysis: 752 measurements of 505 patients for Quick/INR and 594 measurements of 417 patients for aPTT. RESULTS: A moderate correlation of PT/Quick (Pearson's correlation coefficient - 0.59; p < 0.001), INR (Pearson's correlation coefficient 0.5; p < 0.001), and aPTT (Pearson's correlation coefficient 0.53; p < 0.001) with RXA plasma concentration was observed. However, in 50% of all samples with a normal PT/Quick, in 25% of all samples with a normal INR and in 80% of all samples with a normal aPTT residual RXA plasma concentration was surgically relevant. CONCLUSION: Although a moderate correlation of RXA plasma concentration with PT/Quick, INR, and aPTT was observed, standard coagulation assays are not sufficient to exclude surgically relevant RXA plasma concentrations.

Risk Factors for Higher-than-Expected Residual Rivaroxaban Plasma Concentrations in Real-Life Patients.

INTRODUCTION: Rivaroxaban (RXA) is a direct oral factor Xa (Xa) antagonist with a short half-life and a fast onset and offset of effect. Before elective surgery, discontinuation is recommended with an interval of at least > 24 hours. In clinical practice, this is, however, not always sufficient to achieve a residual RXA plasma concentration deemed appropriate for surgery, defined as ≤ 50 mcg/L. Our study aimed at identifying factors associated with a higher-than-expected residual RXA plasma concentration in a large group of real-life patients. MATERIALS AND METHODS: This retrospective single-centre study included all patients taking RXA between 2012 and 2016 where RXA plasma concentration was determined by pharmacodynamic anti-Xa assay (518 measurements in 368 patients). Medical records were reviewed. Residual RXA plasma concentrations were then compared with expected values according to a pharmacokinetic model. RESULTS: Residual RXA plasma concentration was significantly higher-than-expected in patients with atrial fibrillation, impaired kidney function (glomerular filtration rate [GFR] < 60 mL/min), CYP3A4-, CYP2J2- and PGP-inhibitory co-medication including amiodarone. Impaired kidney function (odds ratio [OR], 2.22, 95% confidence interval [CI], 1.30-3.78, p = 0.003) and concomitant amiodarone intake (OR, 1.97, 95% CI, 1.04-3.72, p = 0.036) were significantly associated with RXA plasma concentrations > 50 mcg/L at 24 to 48 hours after the last RXA intake. CONCLUSION: In our group of real-life patients, impaired kidney function (GFR < 60 mL/min) and co-medication with amiodarone were independently associated with higher-than-expected residual RXA plasma concentrations. In these patients, standard intervals of RXA discontinuation may not always be sufficient before elective surgery and routine pre-operative determination of the residual RXA concentration could be advisable.