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Biomedical subjects

B J Pennell

Publications and source records attributed to B J Pennell.

8 recordsLinked to original sources

Evaluation of a new protamine titration method to assay heparin in whole blood and plasma.

When unfractionated heparin is used for therapeutic anticoagulation, the heparin effect must be monitored to avoid thrombotic or hemorrhagic complications. The ability of a factor Xa inhibition (XaI) assay was compared with that of a low-level heparin protamine titration (LLHPT) assay to measure the concentration of heparin after heparin was added in vitro to specimens of plasma and whole blood. Heparin effect on the activated partial thromboplastin time also was assessed in the same specimens. The XaI and LLHPT assays had comparable precision and provided linear results over a wide range of heparin concentrations. Both assays slightly underestimated the total amount of heparin added to the specimens. The most rapid test was the whole blood LLHPT assay; this test therefore may be useful for bedside monitoring of heparin. A significant disadvantage of the LLHPT assay was the large sample size required to perform it. These results provide in vitro evidence that the XaI and LLHPT assays can provide equally precise monitoring of heparin concentration.

Anticoagulants↗

Errors, mistakes, blunders, outliers, or unacceptable results: how many?

We have studied 219353 individual clinical chemistry results obtained in methods comparison studies. Each result was prospectively compared with its replicate, comparative, or repeat value to identify differences from expected values. Unacceptable results were defined as differing from the expected values by < or = 7 SDs or CVs. We believe these differences represent special-cause variation and should be expressed as unacceptable rates per million results (ppm). We observed 447 ppm unacceptables: 196 ppm in control samples and 251 ppm in patients' samples. Results judged likely to alter patient care occurred at a rate of 41 ppm. To better understand the magnitude of these rates, we compared these results with reports of error rates in HIV testing and the airline industry. The measurements reported were made for the purpose of quality improvement, not judgment or discovery. The significance of these findings for laboratorians, manufacturers, and regulators is discussed.

Chemistry, Clinical↗

Analysis of changes in coagulation factors after postoperative blood loss in burn and non-burn patients.

A prospective study of the postoperative kinetics of coagulation factors was undertaken in 23 burn patients and in six non-burn patients. All procedures resulted in a large volume blood loss. Fibrinogen, platelets and factors V, VIII and IX were measured serially. Burn patients returned all parameters to preoperative levels by 48 h postoperation, while non-burn patients showed a slower rate of return of platelets and factor V. This study suggests that burn patients may safely undergo re-operation at 48 h intervals for successive wound debridements if clinically necessary.

Adolescent↗

Packed red cells in acute blood loss: dilutional coagulopathy as a cause of surgical bleeding.

The purpose of this study was: 1) to define coagulation abnormalities in patients who receive red cell concentrates rather than whole blood for large volume blood loss (greater than 0.5 blood volume); and 2) to determine when coagulation abnormalities lead to increased bleeding in the massively transfused surgical patient. We studied 32 ASA physical status I or II patients (mean age 15.6 +/- 2.3 yr) who lost more than 50% of their blood volume during elective posterior spinal stabilization. Crystalloid solutions and packed red cell concentrates were used to replace blood and fluid losses. Invasive hemodynamic measures, urinary output, and serial hematocrit determinations were used to help maintain a constant intravascular volume and confirm the estimates of blood loss. The quality of hemostasis was assessed during operation. In 15 of the 32 patients, surgical hemostasis remained effective throughout posterior spinal fusion. A coagulation profile (prothrombin time [PT] and activated partial thromboplastin time [aPTT], platelet count, and fibrinogen) was measured at the conclusion of operation in these patients. In 17 patients, increased surgical bleeding as a result of decreased clot formation and increased bleeding from the wound was present. In these 17 patients at the time increased bleeding was diagnosed, hemostatic tests (PT, aPTT, fibrinogen, platelet count, and coagulation factor assays V, VIII, and IX) were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The reliability of manufacturer-determined, instrument-specific international sensitivity index values for calculating the international normalized ratio.

Some thromboplastin manufacturers are currently supplying the instrument-specific international sensitivity index (ISI) values of their reagents, allowing clinical laboratories to calculate instrument-specific international normalized ratio (INR) values on plasma samples from patients receiving coumarin therapy. However, the assumption that systematic interinstrument variability in the INR would be eliminated if manufacturer-determined ISI values were used remains unsubstantiated. This assumption was evaluated by comparing INR values obtained on one instrument that measures a mechanical endpoint (fibrometer) with one that measures a photo-optical endpoint (MLA-700). Three thromboplastin reagents with instrument-specific ISI values supplied by the manufacturer (ISI range, 1.23-2.79) were used. For two of three reagents, the fibrometer INR values were significantly higher than the MLA-700 INR values (P < .01). Analysis of log prothrombin time ratio plots showed that this systematic variability was caused by inaccurate manufacturer ISI values. Of clinical significance is that the inaccurate ISI values produced a high number of discordant INR values between these two instruments (> 47% of plasma samples had one INR value within and one out of the recommended therapeutic range). The implication of these findings for laboratory monitoring of oral anticoagulation is discussed.

Adult↗

Isolation and characterization of an acquired antithrombin antibody.

A 68-year-old man, following mitral valve replacement, presented with a low-grade chronic consumptive coagulopathy. Laboratory analysis showed mild fibrinolysis, minimal effect of coumadin therapy, and a prolonged thrombin time (greater than 150 seconds using bovine IIa). When purified human IIa was used the thrombin time normalized to within 17 seconds of controls, suggesting a possible inhibitor of bovine IIa. An anti-IIa antibody was isolated by protein A-Sepharose (Sigma, St Louis, MO) chromatography followed by affinity chromatography using a bovine IIa-Sepharose column. The effects of this purified anti-IIa antibody on both bovine and human IIa procoagulant and anticoagulant functions were studied. The isolated immunoglobulin G (IgG) was observed to inhibit bovine IIa in all assays tested. This IgG was also able to slightly prolong fibrinogen clotting by human IIa. Using an enzyme-linked immunosorbent assay it was observed that the IgG bound to bovine IIa, bovine II, human IIa, but not to human II. Further, binding was detectable at approximately 50-fold lower concentrations to bovine IIa (1 nmol/L IgG concentration) than to human IIa (50 nmol/L IgG concentration). The effect of the antibody on the reaction between IIa and AT III/heparin was investigated. Human IIa was found to be protected from AT III/heparin neutralization in the presence of this antibody. These results suggest that this patient developed an antibody that strongly binds to and inhibits the bovine IIa in all assays tested. However, the antibody only significantly affects human IIa neutralization by AT III/heparin, and has little effect on the human IIa procoagulant activity. These data suggest that the decreased effect of AT III/heparin on this patient's IIa may have been a contributing factor in his coagulopathy. The exact cause of this antibody development is unclear, but the role of bovine topical thrombin used during cardiac valve replacement surgery is suspect.

Aged↗

Use of alpha cyclodextrin to eliminate interference by nonesterified fatty acids in calcium measurements.

This study shows that nonesterified fatty acids cause underestimation of serum calcium by some colorimetric methods. The underestimation of calcium occurs infrequently, but can be as large as 20-30 mg/l. Preincubation of the sample with alpha cyclodextrin will eliminate this interference. The procedure is simple, inexpensive, and applicable to most clinical laboratories.

Autoanalysis↗