Marcia L. Zucker

The use of a HEMOCHRON® JR. HEMONOX™ point of care test in monitoring the anticoagulant effects of enoxaparin during interventional coronary procedures

AbstractBackground: Enoxaparin is increasingly used for the anticoagulation of patients undergoing percutaneous coronary intervention (PCI). Several reports have suggested the utility of using point of care tests in monitoring the anticoagulation levels of enoxaparin in patients undergoing PCI. The objective of this study was to evaluate a new point-of-care test (POCT) HEMONOX™ in monitoring the anticoagulant effect of enoxaparin in non citrated fresh whole blood samples from patients undergoing elective PCI procedure. Methods: Following IRB approval, blood samples were obtained from fifty-four patients who received two sequential intravenous doses of enoxaparin; 0.1 mg/kg followed 5 min later by 0.4 mg/kg for a total of 0.5 mg/kg. Blood was drawn at baseline and at 5, 10, 30 and 60 min post first bolus for evaluation in the clot-based POCT HEMONOX, ACT and aPTT and the chromogenic anti-Xa activity assay. Results: HEMONOX clotting time (CT) at baseline was 62.6 ± 6.2 secs, (n = 32) in healthy donors and statistically higher in PCI patients (71.6 ± 9.1 secs, p = 0.0001). The peak HEMONOX response that was always achieved at 10 min post bolus was >100 secs in all 54 patients, of these 83% yielded CT >150 secs (range: 150–466). There was no detectable anti-Xa activity level at baseline while peak HEMONOX CT corresponded to therapeutic levels (0.85 ± 0.14 U/ml; range: 0.61–1.34). Both HEMONOX CT and anti-Xa level significantly decreased at the time of sheath removal. HEMONOX CT at peak response suggested 3 patient subgroups with different levels of sensitivity to enoxaparin: low, intermediate and high responders. The correlation between anti-Xa activity level and HEMONOX CT was ≥0.85 in each patient subgroup when data from the 3 critical time points; baseline (absence of drug), peak response (10 min post bolus) and sheath removal (60 min post bolus) were analyzed. The correlation diminished to ≥0.83 when the analyses included data from all 5 time points [baseline, 5, 10, 30, and 60 min post bolus]. The HEMONOX test was the most sensitive POCT to measure the anticoagulant effects of enoxaparin. All patients completed PCI successfully. Conclusion: The HEMONOX test may be able to guide anticoagulation with enoxaparin during PCI.Abbreviated abstractThe HEMONOX assay is a one step whole blood coagulation test performed on the HEMOCHRON® Jr. Signature + POC system. The method was evaluated to monitor the anticoagulant level of enoxaparin in blood samples from patients undergoing PCI after receiving an intravenous dose of 0.5 mg/kg. The results suggest a clear distinction of HEMONOX CT between the baseline value of untreated patients and patients achieving therapeutic enoxaparin levels.

Comment: Prothrombin Time Monitoring Devices

TO THE EDITO R : Baclofen is indicated as a muscle relaxant and an antispasmodic for the alleviation of spasticity in patients with multiple sclerosis or spinal cord disease. The manufacturer1 reports that doses of baclofen approximately 13 times the recommended human dose could increase the incidence of omphaloceles (ventral hernias), substantial reductions in food intake and weight gain, and incomplete sternebral ossification in rat fetuses. At seven times the recommended human dose, baclofen was associated with an increased incidence in unossified phalangeal nuclei of forelimbs and hindlimbs in rabbit fetuses; reduction in mean fetal weight occurred in offspring of mice receiving 17 or 34 times the human daily dosage of baclofen.2 There are no adequate controlled studies of baclofen use in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus (Category C).1 , 2 We present the results of treatment with intrathecal baclofen in a pregnant woman. Case Report. In June 1992, a 34y e a r-old woman was in a traffic accident and experienced a complete fifth cervical vertebra (C5)–level medular injury, resulting in severe spasticity according to the Ashworth scale for rigidity evaluation and the Penn scale for spasticity. Because the spasticity was resistant to treatment with oral drugs (baclofen 30 mg q8h, diazepam 5 mg q8h), the patient met the criteria for treatment with intrathecal baclofen. A Medtronic pump (Syncromed, Minneapolis, MN) with intrathecal baclofen was implanted in April 1993. Oral baclofen and diazepam were discontinued after intrathecal baclofen was initiated. In September 1 9 9 6 , the patient became pregnant and was given intrathecal baclofen 140 μg/d throughout the pregnancy; her spasticity remained under control. Delivery was by Caesarean section performed at 36 weeks’ gestation. The newb o rn was a boy with APGAR scores of 9 at one minute and 10 at five minutes; his weight (2155 g), length (47 cm), and head circumference (33 cm) were within the n o rmal range for gestational age. He did not display any major or minor extern a l m a l f o rmations, and ultrasonographic examinations of head, heart, and abdominal o rgans were normal. Karyotyping did not disclose chromosomal anomalies. Xrays of bones at 20 months of age did not show osseous malformations. Neurologic examination and psychomotor development up to the age of 24 months were within the normal range. Three months after the previous delivery, the patient became pregnant again. During this pregnancy, it was not necessary to modify the dosage of intrathecal baclofen. The pregnancy was uncomplicated, and delivery was by Caesarean section at 34 weeks’ gestation. The infant was a boy with APGAR scores of 8 at one minute and 10 at five minutes; weight (2240 g), length (46 cm), and head circumference (32 cm) were within the normal range for gestational age. Physical examination as well as laboratory studies (identical to those of the previous infant) were n o rmal. At 12 months of age, he showed normal psychomotor development. The patient is currently receiving intrathecal baclofen 154 μg/d. Discussion. In the first pregnancy, the risk/benefit ratio of stopping the intrathecal baclofen infusion was ethically valued, and maintaining the treatment was considered the best option since spasticity was controlled and discontinuing the treatment might be dangerous for the patient and even more dangerous for the fetus. The patient was informed of the risks and benefits of treatment with intrathecal baclofen and her autonomy was respected. The administration of intrathecal baclofen seemed more eff e ctive and safer than oral treatment in this patient because she did not respond adequately to oral treatment; baclofen crosses the blood–brain barrier in only small amounts following oral administration,2 and intrathecal baclofen produces effective cerebrospinal fluid concentrations while plasma concentrations are 100 times less than those occurring with oral adm i n i s t r a t i o n .3 In addition, one case4 of treatment with intrathecal baclofen 1000 μg/d was described in a woman who gave birth to a healthy girl.4 Given the positive results of our patient’s first pregnancy, the treatment was continued during the second pregnancy. The treatment with intrathecal baclofen during pregnancy was successful in controlling severe s p a st i c i t y, and there was no display of teratogenicity in these two children.

Assessing heparin neutralization following cardiac surgery: sensitivity of thrombin time-based assays versus protamine titration methods

Adequate assessment of heparin neutralization following cardiac surgery is critical in reducing the patient’s exposure to protamine. Both excessive protamine and residual heparin have been associated with postoperative bleeding and poor patient recovery. The activated clotting time (ACT) is the preferred intraoperative heparin monitor, while both protamine titration (i.e. a protamine-containing ACT) and thrombin time methods have been used to detect circulating residual heparin after protamine administration. Following initial protamine dosing using the protamine response test (PRT), postoperative monitoring was employed in the operating room prior to transport of the patient to intensive care. Two point-of-care assays, the thrombin time (TT) and the protamine dose assay (PDA), were evaluated to determine their relative heparin sensitivity and their usefulness to quantitate protamine dose. The PDA, which is based on the ACT, was shown in laboratory and clinical studies to detect residual heparin above 0.25 units/ml and to quantify additional minidoses of protamine (as low as 25 mg) required to obtain complete heparin neutralization. Differential evaluation of the TT and heparin neutralized thrombin time (HNTT) was shown in laboratory studies to be more sensitive to small amounts of residual heparin than the ACT. Clinical evaluations confirmed that additional protamine is required in approximately 12% of cardiac surgical cases managed using the PRT system. Both the PDA and TT/HNTT provided useful postoperative assessment of the adequacy of heparin neutralization. The TT/HNTT had slightly improved heparin sensitivity even in the presence of significant fibrinogen loss. These point-of-care assays provide the opportunity to optimize heparin and protamine management in the cardiac surgery patient.

Clinical correlation between a point-of-care testing system and laboratory automation for lipid profile.

BACKGROUND We evaluated the clinical correlation between the CardioChek PA analyzer and a clinical laboratory reference method to use for screening program purposes. METHODS Fasting blood samples were collected on 516 patients (age 20-85 y). One venous sample was collected using a serum tube for the evaluation on a COBAS reference analyzer. A second venous sample was collected in a lithium heparin tube and was evaluated on the CardioChek PA analyzer (CCPA venous). A fingerstick sample (CCPA fingerstick) was evaluated only on the CardioChek PA analyzer. Linear regression analyses were performed for each measured analyte, total cholesterol, HDL-cholesterol and triglycerides. RESULTS The correlation between the CCPA fingerstick and CCPA venous was extremely high for HDL-C and triglycerides, and good for total cholesterol. Our results demonstrated a good clinical agreement for total cholesterol, HDL-C and triglycerides between 97.7% and 94.6% in the comparison of the CCPA to the reference analyzer. CONCLUSIONS We identified the pre-analytic phase as an important step to guarantee the quality of results and indicate that the CardioChek PA is a reliable lipid point-of-care testing system that can be used for the application of clinical screening anywhere.

ProTime self-management yielding improvement of fluency and quality of life

Patient self-management (PSM), as the standard of care for vitamin K-antagonist therapy management in Germany requires a detailed, point-of-care (POC) device-specific training program to ensure quality patient care. In a multi-center trial using the ProTime System (Training program plus POC device), 105 patients were enrolled to evaluate efficacy of training, knowledge retention, patient satisfaction and quality of life (QoL). Patients returned to the centers 1, 3 and 6 months after training to complete questionnaires and demonstrate INR test proficiency. Training assessment employed self-evaluation and comparison of POC results between PSM and professional operators. Patient satisfaction and QoL were assessed using a modification of the questionnaire described by Sawicki and the SF12v2 QoL Survey, respectively. Patients demonstrated statistically significant improvements in knowledge post training (p < 0.001) and retained the acquired information (p = NS vs. post-training; N = 45) after 6 months. Trained patients yielded equivalent INR results to professional operators (r = 0.92) with little or no bias across all clinic visits. Compliance with weekly testing improved from 1 to 3 months (p = 0.03), remaining at the required weekly frequency through 6 months. Average patient satisfaction improved significantly during the first month and remained constant thereafter. There was a statistically significant improvement in the Physical Component Summary of SF12 between baseline and 3/6 month assessments in all centers. In conclusion, PSM requires a comprehensive system including appropriate disease and POC device training. Such a system fosters compliance, improved knowledge about underlying disease, patient satisfaction and QoL.

Bedside measurement of factor VIII:C activity in individuals with hemophilia A

Factor VIII replacement therapy for patients with hemophilia A is conventionally monitored using a plasma‐based factor VIII:C assay (a modified activated partial thromboplastin time [APTT] test). The plasma factor VIII assay requires the preparation of plasma from citrated whole blood and measurement of the clotting times of mixtures of patient plasma, factor VIII‐deficient substrate, and APTT reagent. Results are not routinely available in less than 1.5 hr, reducing the clinical value of the laboratory data regarding the ability to immediately adjust patient therapy. Results from the whole blood factor VIII assay, performed on a portable coagulation analyzer and using test tubes prefilled with the necessary APTT and factor VIII‐deficient reagents, are available within 5–7 min. This immediate determination of the factor VIII:C level from citrated whole blood provides the opportunity to greatly reduce turnaround time and improve the efficacy of factor VIII replacement therapy. Based on clotting time, factor VIII:C activity is read from a standard curve. A clinical evaluation of this whole blood test was performed in two hemophilia centers. A high degree of correlation was seen (r = 0.813, n = 220) between the whole blood values obtained and conventional laboratory results. This level of correlation was superior to that obtained when comparing two different plasma‐based systems (r = 0.753, n = 23). Factor VIII:C activity levels measured using the whole blood assay system were similar, irrespective of the test operator (laboratory technologist, nurse clinician, or patient). This study indicates that the whole blood factor VIII assay provides results comparable to those of conventional plasma‐based assays, but in a more rapid and efficient manner. It provides an opportunity to reduce unnecessary patient consumption of replacement preparations, hence reducing the cost of hemophilia A maintenance and prophylaxis regimens, and to reduce overall patient exposure to human blood products.