A New Method for the Measurement of International Normalized Ratio in Hemodialysis Patients with Heparin-Locked Tunneled Dialysis Catheters.

BACKGROUND: To measure International Normalized Ratio (INR) in hemodialysis patients with tunneled dialysis catheters (TDCs), blood sampling is frequently obtained via the catheter at the start of the session. INR measurements via finger-prick point of care testing (POCT) and via blood sampling taken from the dialysis circuit are evaluated as alternatives. METHODS: In 14 hemodialysis patients with TDCs, treated with vitamin K antagonists (VKA), INR measurements via POCT were compared with plasma INR samples taken via the catheter at the start of dialysis and via the dialysis circuit after 30 and 60 minutes during 3 nonconsecutive dialysis sessions. RESULTS: Blood samples taken at the start of dialysis at the catheter site were frequently contaminated with heparin originating from the locking solution (unfractionated heparin concentration (UFH) >1.0 IU/ml in 13.2%). POCT INR at the start of dialysis was not different from plasma INR after 30 and 60 minutes (Wilcoxon test p=0.113, n = 37, and p=0.631, n = 36, respectively). Moreover, there was no difference between POCT INR at the start of dialysis and POCT INR after 30 and 60 minutes (Wilcoxon test p=0.797 and p = 0.801, respectively; n = 36). Passing and Bablok regression equation was used, y = 0.460 + 0.733x; n = 105. Treatment decisions based on these 2 methods showed a very good overall agreement (kappa = 0.810; 95% CI: 0.732-0.889; n = 105). CONCLUSIONS: Measuring plasma INR via the TDC at the start of dialysis should be abandoned. Measuring POCT INR via a finger prick at the start or even after 30 to 60 minutes is an alternative. The most elegant alternative is to take plasma INR samples via the dialysis circuit 30 minutes or later after the start of the dialysis.

In vitro studies, pharmacokinetic studies and clinical use of a high purity double virus inactivated FVIII/VWF concentrate (Immunate) in the treatment of von Willebrand disease.

Patients with type 2 and 3 von Willebrand disease (VWD) are treated with factor VIII/VWF concentrate in case of bleeding or surgery. Immunate (Baxter, Vienna, Austria) is a double virus inactivated FVIII/VWF concentrate and is registered in several countries for patients with VWD with reduced FVIII levels. We performed an in vitro, a pharmacokinetic and a clinical study to evaluate Immunate in VWD. In vitro studies showed a significant variation in VWF levels in 9 different batches. The median (range) values (in IU/mL) were 1.10 (0.98-1.30) for FVIII:C, 1.34 (0.95-1.61) for VWF:Ag, 0.60 (0.27-1.08) for VWF:CBA and 0.73 (0.59-0.94) for VWF:RCo. The relatively low VWF activity is mainly due to the lack of high molecular weight multimers (HMWM), as determined by electrophoresis. A pharmacokinetic study showed, based on a content of FVIII:C of 1 U/mL, in vivo recoveries (%) of 106 (56-150) (median and range) for FVIII:C, 105 (62-187) for VWF:Ag, 25 (7-41) for VWF:CBA and 43 (11-76) for VWF:RCo. Half-lives were 14.1 h (7.4-36.9) for FVIII:C, 10.8 h (7.7-26.2) for VWF:Ag, 15.3 h (7.8-44.6) for VWF:CBA and 16.4 h (4.2-26.5) for VWF:RCo. In a clinical study efficacy was determined after infusion given before surgery or dental extractions in ten patients. In two patients the hemostatic response was classified as inadequate. In conclusion, there is a wide variability in VWF concentration and activity in various batches of Immunate. In the clinical study in which the dosage was based on FVIII:C contents of the concentrate, two out of ten patients had an insufficient haemostatic response. Therefore dosing of Immunate dosing should not be based on FVIII:C levels, but should be based on VWF activity of the individual batches. Future studies using a VWF activity-guided dosage regimen have to be performed to establish the efficacy of Immunate in the treatment of von Willebrand disease.

Plasma procalcitonin and C-reactive protein in acute septic shock: clinical and biological correlates.

OBJECTIVE: To determine the relationship between plasma procalcitonin (PCT) levels, C-reactive protein (CRP), white blood cell count (WBC), ionized calcium (Ca2+), and patient outcome; and to compare the diagnostic and prognostic information provided by PCT and by CRP. DESIGN: Prospective, observational study. SETTING: Intensive care unit. PATIENTS: Fifty-three patients with septic shock, consecutively diagnosed according to consensus guidelines. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood was sampled at diagnosis and 24 and 48 hrs later and in a subgroup (n = 23) after 120 hrs. PCT was measured with LUMItest and CRP with Vitros slides. Ca2+ was calculated according to McLean-Hastings from calcium and protein levels on Vitros. In all 53 patients, PCT and CRP were elevated (>0.5 ng/mL and >10 mg/L, respectively) within 24 hrs after diagnosis. Nonsurvivors (n = 25) were older (p <.001) and had higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (p =.02) at diagnosis but did not differ in sepsis etiology, medical history, sex ratio, levels of PCT, CRP, and Ca2+, or WBC count at any time point. Using logistic regression, initial PCT levels were correlated with CRP values (p =.001) and APACHE II score (p <.05), but not with age, gender, Ca2+ levels, survival, or type of pathogen. Within 48 hrs, however, PCT levels decreased more frequently from baseline in survivors than in nonsurvivors (80% vs. 41%, p <.05). Likewise, CRP levels decreased more often in survivors (100% vs. 64%, p <.05) but only at 120 hrs. CONCLUSIONS: PCT levels were correlated with the severity of disease at onset (APACHE II) and inflammation (CRP) but not with Ca2+ levels. Inaugural PCT or CRP levels per se poorly predicted outcome but decreasing levels were associated with a higher probability of survival. In this respect, PCT was found to be an earlier marker than CRP.