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Biomedical subjects

Richard A Marlar

Publications and source records attributed to Richard A Marlar.

6 recordsLinked to original sources
PubMed2006

Effect on routine and special coagulation testing values of citrate anticoagulant adjustment in patients with high hematocrit values.

Recommendations to adjust citrate concentration for blood coagulation specimens with high hematocrit values are based on indirect experimental studies and not direct studies of patient samples with high hematocrit values. We compared the effect of adjusted and non-adjusted citrate concentrations on coagulation test results in samples from 28 patients with high hematocrit values (55%-72% [0.55-0.72]). Prothrombin time (PT) and activated partial thromboplastin time (aPTT) results from nonadjusted and adjusted samples were statistically different and exponentially increased with increasing hematocrit values. Results for fibrinogen, factor VIII, and protein C activity were statistically different and increased linearly with increasing hematocrit values; however, the difference was not as clinically significant. The protein C antigen value increased with increasing hematocrit values but was not significant. The effects on PT and aPTT are due to a dilutional effect of plasma and an interference effect of the higher final citrate concentration on the clotting test result. For patients with high hematocrit values, citrate concentrations must be adjusted for accurate results.

Anticoagulants↗
PubMed2003

Single-nucleotide polymorphism genotyping on optical thin-film biosensor chips.

Single-nucleotide polymorphisms (SNPs) constitute the bulk of human genetic variation and provide excellent markers to identify genetic factors contributing to complex disease susceptibility. A rapid, sensitive, and inexpensive assay is important for large-scale SNP scoring. Here we report the development of a multiplex SNP detection system using silicon chips coated to create a thin-film optical biosensor. Allele-discriminating, aldehyde-labeled oligonucleotides are arrayed and covalently attached to a hydrazinederivatized chip surface. Target sequences (e.g., PCR amplicons) then are hybridized in the presence of a mixture of biotinylated detector probes, one for each SNP, and a thermostable DNA ligase. After a stringent wash (0.01 M NaOH), ligation of biotinylated detector probes to perfectly matched capture oligomers is visualized as a color change on the chip surface (gold to blue/purple) after brief incubations with an anti-biotin IgG-horseradish peroxidase conjugate and a precipitable horseradish peroxidase substrate. Testing of PCR fragments is completed in 30-40 min. Up to several hundred SNPs can be assayed on a 36-mm2 chip, and SNP scoring can be done by eye or with a simple digital-camera system. This assay is extremely robust, exhibits high sensitivity and specificity, and is format-flexible and economical. In studies of mutations associated with risk for venous thrombosis and genotyping/haplotyping of African-American samples, we document high-fidelity analysis with 0 misassignments in 500 assays performed in duplicate.

Biosensing Techniques↗
PubMed2003

Activated protein C resistance assay detects thrombotic risk factors other than factor V Leiden.

Activated protein C (APC) resistance is a common risk factor for venous thromboembolism (VTE) attributed to various mechanisms, including factor V Leiden (FVL) polymorphism. FVL is considered responsible for up to 95% of APC resistance; however, other factor V polymorphisms and elevated factor VIII levels also have been implicated. We assessed whether additional mechanisms contribute to APC resistance in a blinded case-control study of 65 subjects by measuring APC resistance using 3 methods: 2 activated partial thromboplastin time-based methods with and without dilution in factor V-deficient plasma and 1 Russell viper venom-based assay (RVV). Without factor V-deficient plasma, 24 subjects were APC resistant; with factor V-deficient plasma, the assay identified fewer APC-resistant subjects, as did RVV. All assays detected the 7 heterozygous FVL subjects. Thirteen subjects had factor VIII levels above 150% (1.50). After excluding subjects with FVL or elevated factor VIII levels, 4 subjects still had APC resistance. VTE risk trended higher for subjects with APC resistance in the absence of FVL. Measurement of APC resistance without dilution in factor V-deficient plasma is needed to assess for potentially important thrombotic risk factors other than FVL.

Activated Protein C Resistance↗
PubMed2002

D-dimer: establishing a laboratory assay for ruling out venous thrombosis.

Patients with venous thrombosis (DVT or PE) have elevated D-dimer, a break-down product of cross-linked fibrin. The determination of D-dimer levels is both a diagnostic and a cost savings tool to rule out VTE. The assay can be used to eliminate those individuals without VTE, but with low or moderate clinical suspicion. The D-dimer assay is inexpensive, automated, has a rapid turnaround time, and uses standard blue-top tubes. After appropriate validation, the assay can be 100 percent sensitive in ruling out DVT or PE, but it will not confirm the presence of VTE as numerous other diseases and procedures can increase levels. The assay should not be used routinely on inpatients or surgery patients. Caution should be used when interpreting results from patients on anticoagulation therapy, since lower D-dimer levels may be found. If properly used, the D-dimer assay can save a healthcare facility significant money by eliminating imaging studies on patients with low or moderate suspicion of DVT or PE.

Antifibrinolytic Agents↗