The influence of surgical trauma in blood viscosity. A clinical study.
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Development of acylcarnitine and amino acid profiling using tandem mass spectrometry, and its application for use with dried blood specimens collected on filter-paper cards, has introduced an innovative new technology for detecting inborn errors of fatty acid, organic acid, and amino acid metabolism. From November 1, 1992 through June 30, 1999 we screened more than 700,000 newborns in Pennsylvania, Ohio, North Carolina, and Louisiana. We have prospectively detected 163 inborn errors of metabolism. Eighty-six patients have amino acid metabolism errors. Among them are phenylketonuria, hyperphenylalaninemia, maple syrup urine disease, and several urea cycle disorders. Thirty-two have organic acid metabolism errors, including glutaric aciduria type 1; 3-methylcrotonyl coenzyme A (CoA) carboxylase deficiency, propionic acidemia, methylmalonic acidemia, and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency; and 45 have fatty acid oxidation errors, including 36 with medium-chain acyl-CoA dehydrogenase deficiency. Details of the methodology are presented and the potential of this screening technology is discussed.
Approximately 12 million red blood cell units are transfused to nearly 4 million patients annually in the United States (1). The conservation of blood has historically arisen from awareness that the inventory of this resource is limited (2), as well as the knowledge that blood transfusion carries a risk (3). Estimates of current blood transfusion risks (4-12), and the costs of transfusion complications (13-17), are summarized in Table 1. In addition, emphasis on the costs of health care has raised issues related to the costs of blood transfusion (18, 19). Finally, recent guidelines have emphasized that in the elective transfusion setting, no blood transfusion is a desirable outcome (20, 21). Furthermore, these guidelines along with consensus conference recommendations (22) have emphasized that if blood is to be transfused, autologous (the patient's own) blood is preferable to allogeneic (from an anonymous, volunteer donor) blood. Thus, the costs of blood conservation, for which an increasing array of technologic procedures and products have become available (Table 2), have also become an issue (23). The purpose of this review is to provide an overview of emerging data on the cost-effectiveness of blood and blood conservation interventions in order to help identify areas important for future investigation.
We describe a novel method for detecting micrometastasis in the blood stream of cancer patients based on RT-PCR amplification of tumor-associated carcinoembryonic antigen (CEA) mRNA. To increase sensitivity and specificity of RT-PCR, CEA transcript was selectively up-regulated in cancer cells by exposure of peripheral blood to non-toxic concentrations of staurosporine (ST). Thereafter, polyA(+) RNA was extracted from tumor cells captured by means of magnetic beads coated with a monoclonal antibody against a common human epithelial antigen. Finally, RNA was subjected to RT-PCR analysis of CEA transcript. Using this approach, we demonstrated an ST-mediated increase in CEA transcript in blood specimens collected from a patient with metastatic colon cancer before receiving treatment with 5-fluorouracil/leucovorin. After a few cycles of chemotherapy, CEA-positive tumor cells were no longer detected. Clinical follow-up of this patient indicated that treatment with chemotherapy induced a dramatic reduction in liver metastasis. Therefore, it can be hypothesized that lack of CEA transcript detection might be consistent with disappearance or at least marked reduction of circulating tumor cells.
BACKGROUND: A cohort study was conducted to examine the role of genetic polymorphisms in three estrogen metabolizing enzymes (COMT, CYP1A1, CYP1B1) and the two estrogen receptors (ESR1, ESR2) in the progression of benign breast disease (BBD) to breast cancer. METHODS: Among participants in an ongoing cohort study, 1438 Caucasian women had a breast biopsy for BBD and were successfully genotyped for at least one of the polymorphisms examined in this study. Genotypes were determined using DNA extracted from blood specimens collected in 1989. Incident cases of breast cancer occurring subsequent to BBD diagnosis up to 2003 were identified through cancer registries. RESULTS: Among all participants, the ESR2 *5772G allele was associated with a significant decrease in the risk of breast cancer among women with BBD (Odds Ratio (OR) 0.38; 95% Confidence Interval (CI) 0.15, 0.96). Compared to the reference wild-type genotypes, marginally significant associations with the development of breast cancer were observed between carriers of the variant ESR1 - 104062T allele (OR 0.70, 95% CI 0.45, 1.09), the variant ESR2 *38A allele (OR 1.40; 95% CI 0.88, 2.25), and the variant CYP1B1 453Ser allele (OR 1.48, 95% CI 0.95, 2.32). CONCLUSION: The results indicate that specific polymorphisms in the CYP1B1, ESR1, and ESR2 genes may play a role in progression of BBD to breast cancer among Caucasian women. Although additional studies are needed to confirm or refute our findings, these results suggest that genetic markers may aid in the identification of women who are at risk for progression of BBD to cancer.
Anemia is a common problem in critically ill patients. It is caused, in part, by blood loss related to phlebotomy for diagnostic testing, occult gastrointestinal bleeding, renal replacement therapies, surgical intervention, and traumatic injuries. Reduced red cell life span and nutritional deficiencies (iron, folate, vitamin B12) may be other contributing factors. In addition, critically ill patients have impaired erythropoiesis because of blunted endogenous erythropoietin production and the direct inhibitory effects of inflammatory cytokines on red blood cell production by the bone marrow. Blood transfusions are commonly utilized for treatment of anemia in critical care, resulting in high use of blood transfusions in the intensive care unit (ICU). The percentage of patients transfused in the ICU is inversely related to admission hemoglobin and directly related to age and severity of illness. Patients with an increased length of stay in the ICU are also at increased risk for receiving blood transfusions. Studies are needed to improve our understanding of the pathophysiology of ICU-acquired anemia, to determine the efficacy of blood transfusions in critical care, and to investigate alternatives to blood transfusion for the treatment of anemia in the ICU.
Serum non-transferrin-bound iron (NTBI) levels assessed at arbitrary time points during transfusion cycles may not be representative if NTBI is undergoing significant changes during transfusion cycles. In 15 patients with beta-thalassemia major (age: 21 +/- 6 years, liver iron concentration: 2200 +/- 1200 microg/g-liver), NTBI and other hematologic parameters (transferrin saturation, transferrin receptor) were measured weekly. The largest variation of NTBI levels between individual patients was observed at midcycle. For long-term monitoring of NTBI levels, a particular time point relative to the last blood transfusion should be selected for blood drawing.
The rat tail vascularization is histologically re-examined especially with respect to blood sampling and vascular-injection methods. The terminal third of the tail is recommended for blood vessel puncturing. In this segment, the arteries and veins are most prominent, since the structures of the musculo-skeletal system diminish towards the tip of the tail. In addition to the commonly-known blood vessels (one ventral artery, two lateral veins), there is a dorsal vein in the rat tail that is well suited for puncture and cannulation.
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The effects of di(2-ethylhexyl) phthalate (DEHP) on hepatic function and histology were evaluated in the rhesus monkey undergoing platelet and plasma transfusion. The average cumulative amount infused in one year is comparable to that received by patients who undergo chronic transfusion. Abnormalities in hepatic scan and BSP kinetics persisted for up to 26 months after transfusion, as did histologic abnormalities. Patients undergoing maintenance hemodialysis receive a yearly dose of DEHP which is 10-20 times that which produced hepatotoxicity in the transfused rhesus.
We sought to compare coagulation test results obtained from patients using 2 plastic blood collection tubes and the traditional glass blood collection tube. Blood specimens were obtained from 241 patients in 3.2% buffered sodium citrate using standard glass tubes, in 3.2% buffered sodium citrate in plastic tubes, and in 3.2% sodium citrate "sandwich" tubes (plastic within plastic). All samples were obtained and processed contemporaneously and tested for prothrombin time (PT) and activated partial thromboplastin time (aPTT). Residual plasma was frozen at -70 degrees C for future testing, including fibrinogen, antithrombin, plasminogen, protein C and protein S (functional and antigenic), dilute Russell viper venom time (DRVVT), ristocetin cofactor, factor XIII, D dimer, anti-Xa activity, and prothrombin fragment. Although paired t test analysis revealed statistically significant differences (P < .05) between glass and plastic for PT, aPTT, fibrinogen, protein C (functional and antigenic), functional protein S, DRVVT and confirmation method, antithrombin, and factor XIII, these differences were not considered clinically significant.
Hantavirus cardiopulmonary syndrome (HCPS) is a rare but frequently lethal acute zoonotic viral infection in rural North America. The rapidity of progression from febrile prodrome to cardiogenic shock and noncardiogenic pulmonary edema requiring intensive care creates high diagnostic urgency and a need for a rapid screening tool. In this retrospective cohort study, 2 pathologists scored blinded peripheral blood smears from 52 patients with HCPS and 128 seronegative patients referred for diagnosis of suspected hantavirus infection. During the prodromal phase, thrombocytopenia was the only consistent abnormality and could be used to indicate hantavirus serologic testing. After the onset of pulmonary edema detected radiographically, the presence of 4 of 5 findings (thrombocytopenia, myelocytosis, hemoconcentration, lack of significant toxic granulation in neutrophils, and more than 10% of lymphocytes with immunoblastic morphologic features) has a sensitivity for HCPS of 96% and a specificity of 99% and missed no patients with HCPS who required intensive care. While each abnormality is commonly seen, the combination of at least 4 of these CBC count data and peripheral blood smear findings can guide early treatment and patient transport decisions until rapid, specific, serologic testing becomes widely available.
STUDY OBJECTIVE: To demonstrate the utility of a new blood-conserving arterial line system in reducing blood loss associated with blood drawing in the critical care setting. DESIGN: Prospective, randomized, crossover comparison between two arterial line systems. SETTING: Medical intensive care unit (ICU); tertiary care teaching institution. PATIENTS: Thirty-one patients who required invasive arterial blood pressure monitoring throughout their ICU course. INTERVENTIONS: For ICU days 1 to 2, patients were randomized to receive either a conventional arterial line system or a new blood-conserving arterial line system. On ICU days 3 to 7, patients with a conventional arterial line were crossed over to the blood-conserving arterial line, and vice versa. Laboratory blood volumes, mixed discard volumes, and blood discard volumes were then recorded to document how much blood loss is associated with each aspect of the blood sampling process. RESULTS: The mean total volume of blood sent to the laboratory for testing was 257.4 ml. As a result of "clearing the line" over the 7-day period, patients with the conventional arterial line system lost a mean volume of 340.2 ml of blood mixed with heparinized saline solution more than patients with the blood-conserving arterial line. In terms of the blood component of the blood-heparinized saline solution mixture, use of the conventional arterial line was associated with an average of 156.8 ml more blood discarded than with the blood-conserving arterial line. CONCLUSION: The new blood-conserving arterial line system provides a simple and effective method for reducing blood loss related to diagnostic sampling in the critical care setting.
Information on biological day-to-day variation is needed for detecting within-subject changes over time. In this study the daytime changes and the biological day-to-day variation of serum testosterone, follitropin, lutropin and oestradiol-17beta concentrations were investigated in 31 healthy males. To analyse daytime changes, blood specimens were taken at 0800 h, 1200 h, 1600 h and 2000 h during one day (n=31) and two days (n=8). The day-to-day variation was analysed from blood specimens collected at 0800 h on days 1 and 2 (n=31) and additionally on days 3, 4, 6 and 9 (n=8). The evaluation of the day-to-day variation was based on calculations of the within-subject (CVA+I) and between-subject (CV(G)) coefficients of variation. When the within-subject day-to-day variances were not too heterogeneous, they were used for the calculation of 95 % reference change limits. Serum testosterone and oestradiol-17beta concentrations showed a significant daytime variation; testosterone had higher serum concentrations at 0800 and 1200 h. A peak in the serum concentration of oestradiol-17beta occurred at 1200 h with a decrease towards the evening. There were no clear daytime changes in the serum concentrations of follitropin or lutropin. For different analytes the reference change limits were: serum testosterone +/- 32.0 %, serum follitropin +/- 24.1 % and serum oestradiol-17beta +/- 38.3 %. The reference change limit was not calculated for serum lutropin, as a high degree of heterogeneity and individuality was found. The interpretation of the results of hormone measurements requires recognition of the biological daytime and day-to-day changes of hormones. The reference change limits determine what changes are significant when monitoring the patient.
We describe a case of cord blood harvest for autologous transfusion in a neonate weighing 3,992 g with a giant sacrococcygeal teratoma. The umbilical vein was pierced with an 18-gauge needle, and placental blood was withdrawn into two 50-ml syringes filled with 4 ml of citrate-phosphate-dextrose solution. Resection of the sacrococcygeal teratoma was performed on day one. During the operation the infant lost 46 ml of whole blood, more than 15% of the estimated total blood volume, and thus underwent autologous transfusion with 27.8 ml of packed red cells obtained from autologous cord blood. Consequently, she could avoid homologous blood transfusion during the hospital stay. This case highlights the safety of this procedure, with no evidence of consumption coagulopathy, hemolysis or bacterial infection.
OBJECTIVE: Blood sampling from an umbilical artery catheter (UAC) placed in a high position (thoracal 6-9) has the potential to produce clinically significant changes in cerebral blood flow and, thereby, in cerebral oxygenation. This may contribute to cerebral impairment in preterm newborn infants. Therefore, we set up a study to determine the effects of different sampling speeds through a UAC on cerebral oxygenation in preterm infants. METHODS: Thirty pairs of measurements were conducted on 20 preterm infants (median gestational age: 30.14 weeks; median birth weight: 1170 g). For each infant, 2 blood samplings (both 2.3 mL, including flush volume) through the UAC in high position were taken at 2 different speeds (20 and 40 seconds) in alternating sequence. Cerebral oxygenation was measured noninvasively by near-infrared spectroscopy. Concentration changes in cerebral oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb), along with the tissue oxygenation index (TOI; O2Hb/[O2Hb + HHb] x 100), were recorded while blood was withdrawn and subsequently reinfused. RESULTS: A significant decrease in O2Hb and TOI occurred during blood sampling within 20 seconds (median DeltaO2Hb: -1.5 micromol/L; range: -4.1-2.3; median DeltaTOI: -0.6%; range: -6.3-2.3), whereas HHb increased (median DeltaHHb: 0.4 micromol/L, range: -1.1-3.9). No significant change was found in O2Hb, HHb, and TOI when sampling time was extended to 40 seconds. CONCLUSION: Our results show that blood withdrawal over 20 seconds from a UAC in high position significantly decreases cerebral O2Hb and TOI in preterm infants. Prolonging sampling time to 40 seconds can prevent this phenomenon.