The uncalibrated prothrombinase-induced clotting time test. Equally convenient but more precise than the aPTT for monitoring of unfractionated heparin.

The activated partial thromboplastin time test (aPTT) represents one of the most commonly used diagnostic tools in order to monitor patients undergoing heparin therapy. Expression of aPTT coagulation time in seconds represents common practice in order to evaluate the integrity of the coagulation cascade. The prolongation of the aPTT thus can indicate whether or not the heparin level is likely to be within therapeutic range. Unfortunately aPTT results are highly variable depending on patient properties, manufacturer, different reagents and instruments among others but most importantly aPTT's dose response curve to heparin often lacks linearity. Furthermore, aPTT assays are insensitive to drugs such as, for example, low molecular weight heparin (LMWH) and direct factor Xa (FXa) inhibitors among others. On the other hand, the protrombinase-induced clotting time assay (PiCT®) has been show to be a reliable functional assay sensitive to all heparinoids as well as direct thrombin inhibitors (DTIs). So far, the commercially available PiCT assay (Pefakit®PiCT®, DSM Nutritional Products Ltd. Branch Pentapharm, Basel, Switzerland) is designed to express results in terms of units with the help of specific calibrators, while aPTT results are most commonly expressed as coagulation time in seconds. In this report, we describe the results of a pilot study indicating that the Pefakit PiCT UC assay is superior to the aPTT for the efficient monitoring of patients undergoing UFH therapy; it is also suitable to determine and quantitate the effect of LMWH therapy. This indicates a distinct benefit when using this new approach over the use of aPPT for heparin monitoring.

Prolonged measurement improves the assessment of the barrier function of the esophago-gastric junction by high-resolution manometry.

BACKGROUND: Etiology of gastro-esophageal reflux disease (GERD) is multifactorial, but incompetence of the esophago-gastric junction (EGJ) appears to be of crucial importance. Established manometric parameters for assessment of EGJ barrier function are sub-optimal, potentially because they reflect only a very brief (up to 30 seconds), not necessarily representative period. This prospective, case-control study tested the performance of novel, high-resolution manometry (HRM) parameters of EGJ function in the assessment of GERD. METHODS: Patients with reflux symptoms and healthy controls (HC) underwent standard HRM and 24-hour pH±impedance measurements. EGJ morphology, lower esophageal sphincter pressure integral (LES-PI), EGJ contractile integral (EGJ-CI) were compared with total-EGJ-CI, a novel parameter summarizing EGJ barrier function during the entire HRM protocol. Esophageal acid exposure ≥4.2%/24 h (A-Reflux-pos) or ≥73 reflux episodes in 24 hours (V-Reflux-pos) were considered pathological. KEY RESULTS: Sixty five HC and 452 patients completed HRM, 380 (84%) patients underwent ambulatory reflux-monitoring. LES-PI, EGJ-CI and total-EGJ-CI correlated with EGJ morphology subtypes (all P<.00001). Only total-EGJ-CI was consistently lower in A-Reflux-pos and V-Reflux-pos subjects compared with HC and patients without GERD. Total-EGJ-CI was also the single best parameter for prediction of pathological reflux (optimal cut-off 47 mmHg cm, AUC 0.746, P<.0001). This cut-off value, approximately 1 SD below the mean normal value, showed modest sensitivity 54% and positive predictive value 46%, but good specificity 85% and negative predictive value 89% for GERD diagnosis. CONCLUSION & INFERENCES: Total EGJ-CI, a new metric that summarizes EGJ contractility over time, allows an improved assessment of EGJ barrier function. Pathological reflux is unlikely if this metric is within the upper two-thirds of the normal range.

Rapid Drink Challenge in high-resolution manometry: an adjunctive test for detection of esophageal motility disorders.

BACKGROUND/AIMS: The Chicago Classification for diagnosis of esophageal motility disorders by high-resolution manometry (HRM) is based on single water swallows (SWS). Emerging data suggest that a "Rapid Drink Challenge" (RDC) increases sensitivity for motility disorders. This study establishes normal values and diagnostic thresholds for RDC in clinical practice. METHODS: Two cohort studies were performed in patients with dysphagia or reflux symptoms (development and validation sets). Healthy subjects and patient controls provided reference values. Ten SWS and two 200-mL RDC were performed. Primary diagnosis for SWS was established by the Chicago Classification. Abnormal RDC was defined by impaired esophagogastric junction (EGJ) function (elevated integrated relaxation pressure during RDC [IRP-RDC]); incomplete inhibition of contractility during and ineffective contraction after RDC. Diagnostic thresholds identified in the development set were prospectively tested in the validation set. RESULTS: Normal values were determined in healthy (n=95; age 37.8 ± 12) and patient controls (n=44; age 46.4 ± 15). Development and validation sets included 178 (54 ± 17 years) and 226 (53 ± 16 years) patients, respectively. Integrated relaxation pressure during RDC was higher for SWS than RDC in all groups (overall P<.001), except achalasia. Rapid Drink Challenge suppressed contractility, except in achalasia type III, spasm, and hypercontractile motility disorders (P<.001). An effective after-contraction was present more often in health than disease (P<.001). Optimal diagnostic thresholds identified in the development set (IRP-RDC ≥12 mmHg achalasia, IRP-RDC ≥ 8mmHg "all cause" EGJ dysfunction), were confirmed in the validation set (both, sensitivity ~85%, specificity >95%). CONCLUSIONS: Rapid Drink Challenge contributes clinically relevant information to routine HRM studies, especially in patients with EGJ dysfunction.