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Biomedical subjects

E L Gottfried

Publications and source records attributed to E L Gottfried.

At least 19 recordsLinked to original sources
PubMed1998

Highly sensitive thromboplastins do not improve INR precision.

For determination of the international normalized ratio (INR), it has been suggested that "highly sensitive" thromboplastin reagents (International Sensitivity Index [ISI] < or = 1.2) provide the most consistent performance and minimize interlaboratory variability. We compared the INR values obtained from 69 specimens drawn from patients receiving long-term oral anticoagulant therapy, using four thromboplastin preparations (manufacturer-assigned ISI range of 0.96-1.10) and two automated photo-optical analyzers. Multivariate analysis of the INR response matrix (552 INR values) indicated that the eight reagent-coagulometer combinations did not produce equivalent INR values. Similar analysis indicated that INR values were not normalized when uncorrected prothrombin ratios or INR values, calculated after assignment of "local ISI values" to each thromboplastin reagent, were compared. The INR differences also seemed to be clinically significant because 17% to 29% of paired thromboplastin values were discordant when all INR values were assigned to one of four therapeutic categories used in oral anticoagulant therapy (< 2.0; 2.0-3.0; 3.0-4.5; or > 4.5). These differences in INR values obtained with two photo-optical coagulometers and four highly sensitive thromboplastin reagents suggest that the existing INR system has not achieved the goal of standardized prothrombin time values and does not support the recommendation to use only highly sensitive reagents for the regulation of oral anticoagulant therapy.

Anticoagulants↗
PubMed1998

Prolonged prothrombin time and activated partial thromboplastin time due to underfilled specimen tubes with 109 mmol/L (3.2%) citrate anticoagulant.

Underfilling of specimen tubes containing 129 mmol/L (3.8%) buffered citrate prolongs prothrombin time (PT) and activated partial thromboplastin time (APTT) values. We studied this phenomenon by using 109 mmol/L (3.2%) buffered citrate as the anticoagulant, anticipating some increase in tolerance to underfilling. Venous blood drawn from 12 healthy subjects and 30 patients receiving long-term oral warfarin therapy was mixed with 109 mmol/L buffered citrate solution in proportions equivalent to filling the collection tubes from 52% to 100% of capacity. Accurate PT values were obtained from normal specimens if the tubes were filled to 65% or more of capacity. Accurate PT results in the therapeutic range were obtained only with filling to 80% or more of capacity (using a "moderately sensitive" thromboplastin reagent, International Sensitivity Index [ISI] = 2.06) or 90% or more of capacity (using a "highly sensitive" thromboplastin reagent, ISI = 1.01). In contrast, APTT was much less tolerant to underfilling, with prolonged values observed in most specimens filled to less than 90% of capacity. No false low values were observed. Specimen tubes should be filled to at least 90% of capacity to avoid falsely elevated PT or APTT results, but values within the reference range may be acceptable even from underfilled tubes.

Adult↗
PubMed1997

Prothrombin time and activated partial thromboplastin time can be performed on the first tube.

The current practice standard for coagulation studies on venous blood specifies the use of the second (or subsequent) tube for testing. Unless other tests are ordered, the first tube is discarded. This practice, derived from early experience using nondisposable materials, gained support from a report based on modern phlebotomy methods but inexperienced phlebotomists. For our study, paired blood specimens were collected by experienced phlebotomists from 175 outpatients whose physicians had ordered coagulation tests. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were performed on the first and second tubes. Similar values were obtained for PT and APTT. (PT: n = 174; mean = 15.36 seconds; mean difference = 0.10 seconds; y = 1.02x - 0.28; t = 0.24; P>.81; r = 0.995; APTT: n = 160; mean = 38.25 seconds; mean difference = 0.48 seconds; y = 1.03x - 0.71; t = 0.25; P=.80; r = 0.993.) For coagulation tests on specimens collected by experienced phlebotomists, the first tube yields accurate results and need not be discarded.

Blood Coagulation Tests↗
PubMed1993

Hereditary hemolytic disease with increased red blood cell phosphatidylcholine and dehydration: one, two, or many disorders?

We have compared characteristics of red cells from patients who were originally diagnosed as having two different disorders, high phosphatidyl choline hemolytic anemia (HPCHA) and hereditary xerocytosis (HX). Both types of cells had reduced intracellular potassium, with attendant cell dehydration and an increase in the relative amount of membrane phosphatidyl choline. Neither these observations nor a review of previous studies of HX and HPCHA revealed any means of distinguishing between the two disorders. Measurements of chloride-dependent potassium transport revealed flux characteristics in both HX and HPCHA red cells that were different from those in simultaneously run control samples. HX and HPCHA red cells did not show the same kinds of deviations from the normal pattern. However, extensive characterization of transport behavior under a variety of controlled conditions will be required to determine whether these differences represent intrinsic differences in chloride-dependent transport properties. It appears likely that HX and HPCHA both represent a spectrum of disorders resulting from a variety of defects that produce the same general pattern of abnormalities in cation content and membrane phospholipid composition.

Adult↗
PubMed1993

Laboratory medicine education in United States medical schools.

The Academy of Clinical Laboratory Physicians and Scientists conducted a survey of US medical schools to examine the current status of laboratory medicine education, estimate the amount of teaching time available in the curriculum, and identify the most effective teaching practices. Questionnaires were sent to department heads and course directors at 126 US medical schools. Replies were received from 120 schools (95%), 83 of which offered a total of 132 courses in laboratory medicine. Only 68 schools (57%) had required courses. Most of the elective courses (35 of 50; 70%) were in general clinical pathology. Lectures remained the most common teaching format, with or without laboratory sessions and workshops. Computer-assisted instruction was used in only 10 schools. Laboratory medicine courses were offered in all 4 years of medical school, with the majority (70 of 132; 53%) in the second year, often integrated with general pathology. Opinion was divided over the relative importance of laboratory medicine instruction in the preclinical versus clinical years.

Computer-Assisted Instruction↗
PubMed1993

Failure of the International Normalized Ratio to generate consistent results within a local medical community.

Use of the International Normalized Ratio (INR) has been recommended as a means of standardizing prothrombin time (PT) results for management of oral anticoagulant therapy. During the evaluation of a new lot of thromboplastin reagent, however, INR values were obtained that were inconsistent with results obtained with the prior lot of reagent from the same manufacturer. A local normalized ratio (LNR) was substituted for the INR for the new reagent, based on a calculated local sensitivity index (LSI). Validation of the LSI was performed at the three hospitals in the medical community by testing an identical panel of aliquots from 64 plasmas obtained from patients who were chronically receiving oral anticoagulants. Each test result was classified according to the INR value as low, low therapeutic, high therapeutic, or high. Local normalized ratio values obtained at one hospital in the community were in reasonable agreement with INR determinations in the other two hospital laboratories. Classification mismatches occurred using the INR, however, in 84 of 280 (30%) of the paired samples. Thus, the inability to generate consistent INR values within a local medical community raises serious concern about the reliability of the INR concept in its current form.

Anticoagulants↗
PubMed1987

Utility of the three-part leukocyte differential count.

The utility of the automated three-part leukocyte differential count was evaluated in an acute care hospital setting. The manual method was specified in 92 of 223 (41%) requests for differentials on one day. For the others, 79 three-part differentials (60%) were completed; 19 (15%) were rejected for histogram abnormalities ("R-flags") or could not be computed; and 33 (25%) were rejected for out-of-range values that were later verified by slide review. The automated method missed 4 of 39 (10%) band elevations and 2 of 2 (100%) cases of eosinophilia reported on manual differentials, but those results had no apparent influence on patient management. In 98 cases of septicemia, automated and manual methods showed similar overall sensitivity (87% and 83%, respectively). Selectively combined with a qualitative slide review, the three-part differential was applicable to 84% of all specimens submitted for a differential count, with acceptable sensitivity and accuracy and substantial savings in personnel time.

Evaluation Studies as Topic↗
PubMed1982

Increased erythrocyte osmotic fragility in pregnancy.

An unexpected increase in erythrocyte osmotic fragility during pregnancy in two healthy women prompted a study of the effects of pregnancy on osmotic fragility. The incubated glycerol lysis time, a rapid, sensitive measure of osmotic fragility, was determined in 100 pregnant women and 50 nonpregnant control subjects. Twenty-two of the pregnant women (22%) showed abnormal results when compared to normal nonpregnant women (p less than 0.0005). Increased erythrocyte fragility was observed primarily in the last trimester of pregnancy. Twenty-one of 65 women in the last trimester (32.3%) had abnormal incubated glycerol lysis time values, but only one of 34 (2.9%) showed increased fragility during early pregnancy. Physiologic shifts in erythrocyte osmotic fragility may create a problem in the diagnosis of hereditary spherocytosis during the last trimester of pregnancy.

Adult↗
PubMed1982

The effects of inaccurate blood sample volume on prothrombin time (PT) and activated partial thromboplastin time (aPTT).

The results of determinations of the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are frequently used to assess hemostatic function. Accurate results for these laboratory tests depend on many variables, one of which is the ratio of plasma to anticoagulant. We studied 12 patients and 4 normal subjects to determine the effects of sample volume on PT and aPTT. We conclude that underfilling may produce profound effects, particularly on the aPTT. In contrast, overfilling rarely affects the results. The greatest effects of sample volume were observed in specimens in which the true PT or aPTT was elevated. A normal PT or aPTT result on any specimen, regardless of sample volume, strongly suggests that the true value is normal.

Adult↗
PubMed1980

Unusual intracytoplasmic inclusions in acute myeloblastic leukemia.

Unusual intracytoplasmic inclusions within early granulocyte precursor cells from a patient with acute myeloblastic leukemia (AML) are described. Based upon their staining characteristics and electron- and light-microscopic appearance, the inclusions are distinctly different from any previously described. The inclusions display a variety of shapes, including rectangles, squares, circles, ovals, and irregular, globular forms. Most of the inclusions are refractile and crystal-like. The possible composition of these inclusions is discussed. They are compared with inclusions previously described within leukemic and granulocytic cells.

Aged↗
PubMed1979

Reliable estimation of hemoglobin A2 concentration by electrophoresis with densitometry.

Elevated hemoglobin A2 (Hb A2) levels can be identified conveniently by densitometry after electrophoresis on cellulose acetate strips. Because a recent report questioned the accuracy of this technic, the method was re-evaluated by paired comparison with microcolumn chromatography. Analysis of 100 patient specimens showed high correlation (r = +0.84), but an average Hb A2 concentration 0.7% higher by densitometry than by chromatography (P less than 0.001). With upper limits set at 4.5%, and 3.8%, respectively, results were divided into "normal" and "high" for each method. Concordant results were obtained in 97 of the 100 cases (82 normal, 15 high). Another densitometer of improved design was used for paired analysis of 50 additional specimens, 25 normal and 25 with beta-thalassemia trait. The two groups were well separated by both procedures, and Hb A2 levels were similar (r = +0.92, P greater than 0.6). This study demonstrates that it is possible, with carefully controlled technics and properly calibrated instruments, to use electrophoresis with densitometry as a reliable means of identifying abnormal Hb A2 levels.

Child↗