Biomedical subjects

Frank M LaDuca

Publications and source records attributed to Frank M LaDuca.

5 recordsLinked to original sources

PubMed2005

Optimizing management of hirudin anticoagulation.

Accurate anticoagulation monitoring, critical during cardiac surgery (CS), is especially important for novel therapeutics such as hirudins, for which there are no known antidotes. The activated clotting time (ACT), which is standard for heparin monitoring, has been reported to be insufficiently sensitive to high levels of hirudins. A simple, accurate, and sensitive assay is needed to monitor hirudins at the levels required for CS. During the REPLACE/II clinical trials, the HEMOCHRON Jr. Signature ACT+ was used to monitor Angiomax during percutaneous cardiac intervention (PCI) procedures and was observed to lose sensitivity at bivalirudin concentrations greater than 8-10 microg/mL. A new assay, the ACTT, was developed to increase the linear sensitivity of the ACT+ over the range of 15-30 microg/mL bivalirudin to extend the clinical utility of the assay to CS levels. Both in vitro and ex vivo studies were performed using the ACTT and ACT+. In vitro ACT+ and ACTT clotting times, identical for bivalirudin levels up to approximately 5 microg/mL, diverged from each other near 10 microg/mL. The ACTT showed excellent linearity to bivalirudin at concentrations up to 30 microg/ mL. Reproducibility was also superior with coefficients of variation <15% across 13 donors at clotting times <760 seconds. The ACTT was evaluated for monitoring bivalirudin during PCI in 67 patients. The ex vivo comparison of ACTT to ACT+ <340 seconds, showed a slope near 1.0 and an average difference between the tests of 5%. At higher clotting times this slope increased to near 3.0, with an average difference between tests of 20%. These data suggest that the ACTT displays increased sensitivity to high levels of bivalirudin.

Angioplasty, Balloon, Coronary↗

PubMed2004

Racial and ethnic differences in warfarin response.

BACKGROUND AND AIM OF THE STUDY: Variability of drug response among individuals is a well-recognized problem that may result in either under- or overtreatment of patients receiving similar drug concentrations. Patients with mechanical heart valves are dependent on adequate anticoagulation to prevent thrombosis development. 'Crystalline warfarin sodium' (warfarin) is the most common antithrombotic drug prescribed to control blood hemostasis in those patients, and also in those with indications such as stroke, myocardial infarction, pulmonary embolism and atrial fibrillation. Warfarin is a narrow therapeutic index agent; a small change in systemic concentration of the drug may lead to significant changes in pharmacodynamic response. Careful clinical management is required to balance the risks of bleeding (over-anticoagulation) with those of thrombosis (under-anticoagulation). The study aim was to summarize environmental, genetic and ethnic factors that affect a patient's response to warfarin and which must be considered for optimal patient outcome. METHODS: A Medline search was carried out to summarize various factors that influence a patient's response to warfarin. RESULTS: Inter-ethnic differences may have profound implications for the efficacy and safety of warfarin. Ethnic differences can affect pharmacokinetic features such as bioavailability, protein binding and volume of distribution, as well as hepatic metabolism and renal elimination. Environmental factors and genetic variants in human enzymes that metabolize warfarin also contribute to interindividual variations and may render some patients more susceptible to serious or life-threatening adverse events. CONCLUSION: Warfarin use is complicated by an unpredictable dose response that depends on factors such as demographics, diet, interacting drugs, genetic polymorphism and ethnic differences. The impact of racial differences on the kinetics of dose response or on drug efficacy is not well defined, as few clinical trials take ethnic variation into account. The use of the point of care and frequent patient self-testing may permit standardized warfarin monitoring across diverse geographical regions and facilitate analysis of ethnic variation among subpopulations.

Anticoagulants↗

PubMed2004

The Hemochron Response RxDx heparin and protamine dosing system.

The use of dosing assays to calculate heparin and protamine dose requirements during cardiac surgery has been shown to significantly improve overall postoperative patient outcome. When patients are managed with an individualized dosing system, intraoperative and postoperative transfusion requirements and bleeding are reduced. The Hemochron RxDx system is widely used as a complement to traditional activated clotting time testing to optimize anticoagulation management. The system consists of the heparin response test, the protamine response test, and the protamine dose assay. All are modifications of the activated clotting time using either Celite (Celite Corporation, Santa Barbara, CA) or kaolin as the activator. Dosing is calculated manually using earlier version Hemochron instruments (model 801) or automatically with the Hemochron 8000 or with the early versions of the Hemochron Response and the personal digital assistant (PDA) RxDx calculator. Missing from available user options is an automated RxDx system for the Response. A study was conducted at four clinical sites to compare recently developed Response RxDx software, which eliminates the need for the PDA RxDx calculator, to the existing Hemochron 8000 RxDx and to the Response-PDA RxDx systems. Similar to the current system, the operator inputs the patient's height, weight, and gender, and the software automatically calculates the blood volume. Using the clotting times determined on the Response, bolus heparin and protamine doses and any additional heparin and protamine requirements are calculated automatically. Data were collected from 76 patients, of which, 64 patients were on pump, 11 patients were off pump, and 1 patient was converted from off to on pump. The Response estimated blood volume calculations showed a correlation coefficient of 0.989 when compared with available systems. A good correlation was also observed for the bolus heparin (r = 0.925) and protamine doses (r = 0.900) with equivalence confirmed by a paired student's t test. These data confirm that the Response RxDx system yields results that are identical (P > 0.05) to those obtained using the Hemochron 8000 RxDx or Response-PDA RxDx calculator. The Response RxDx also offers expanded user options related to blood volume limits, expanded clotting time ranges for presetting default values, and flexibility in test sequence. Case records can be printed or downloaded to a PC via the HRDM data management program. The Hemochron Response RxDx represents a complete anticoagulation management system for the cardiac surgical patient.

Adult↗

PubMed2003

Hand-held personal digital assistant program for the HEMOCHRON RxDx heparin and protamine dosing system.

The use of in vitro dosing assays for heparin and protamine during cardiac surgery has significantly improved overall postoperative patient outcome. The HEMOCHRON RxDx system (International Technidyne Corp, Edison, NJ) is widely used for anticoagulation management. Based on a series of consecutive in vitro tests, the RxDx system is used to quantify the patient's heparin requirement (heparin response test, HRT), measure the activated clotting time (ACT), calculate the blood heparin concentration and the required protamine dose (protamine response test, PRT), as well as determine the efficacy of heparin reversal (protamine dose assay, PDA-O). A hand-held personal digital assistant (PDA) program has been developed that performs the RxDx calculations used for anticoagulation management during cardiac surgery. The Palm m505 hand-held device (Palm, Inc., Santa Clara, CA) is used in concert with any standard Hemochron blood coagulation system. The Palm m505 device has been programmed to perform all the calculations required for the RxDx test system. Patient's body weight, height, and gender are entered into the program using the onscreen keypad and the template provided in the Hemochron program. The calculator automatically provides the patient's blood volume and the recommended heparin dose upon entering the baseline ACT and HRT values and a target ACT. At the end of the case, the optimal protamine dose is determined, and the total heparin level is calculated and displayed upon entry of ACT and PRT clotting times. Following protamine administration, the program calculates any additional protamine required to neutralize residual heparin using the data from a PDA-O test. The RxDx hand-held PDA is accurate, quick, simple, and easy to use, patient data are saved and can be retrieved. The inclusion of this rapid computing technology into the Hemochron RxDx system serves to expand the applications of the Hemochron RxDx system during cardiac interventions.

Alabama↗

PubMed2002

Validation of a new whole blood coagulation monitoring system.

The Hemochron Response is a third generation point-of-care (POC) whole blood coagulation analyzer that retains the clinical utility of the Hemochron standard (801/8000) while providing a data management program that assists the POC coordinator with Quality Assurance (QA) compliance. Clinical and laboratory studies were performed to ensure consistency of the target anticoagulation times with the Hemochron standard and to evaluate precision and reproducibility of the Hemochron Response. Clinical tests for prothrombin time (PT) using fresh and citrated whole blood, activated clotting time (ACT), and activated partial thromboplastin time (APTT) showed excellent correlation to the Hemochron standard where r = 0.929, r = 0.969, r = 0.947, and r = 0.992, respectively. This was confirmed by a paired Student's t-test. The standard expectation for reproducibility of ACT tests has been a coefficient of variation (CV) of 10%. Laboratory studies of reproducibility and precision for the Response instrument included analysis of the CV using ACT test tubes. For normal and abnormal control plasma (CPL), the range of CVs observed was 3.3%-4.6% and 3.0%-5.0%, respectively. For heparin dose response analysis, the range for Donor 1 and 2 was 1.0%-4.2% and 1.1%-8.0%, respectively. These data suggest that the Hemochron Response is reliable and equivalent to the Hemochron standard in clinical applications.

Autoanalysis↗