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Antithrombin III during cardiac surgery: effect on response of activated clotting time to heparin and relationship to markers of hemostatic activation.

UNLABELLED: This study was designed to determine if, and to what extent, antithrombin III (AT) levels affect the response of the activated clotting time (ACT) to heparin in concentrations used during cardiac surgery, and to characterize the relationship between AT levels and markers of activation of coagulation during cardiopulmonary bypass (CPB). After informed consent, blood specimens obtained from eight normal volunteers (Phase I) were used to measure the response of the kaolin and celite ACT to heparin after in vitro addition of AT (200 U/dL) and after dilution with AT-deficient plasma to yield AT concentrations of 20, 40, 60, 80, and 100 U/dL. In Phase II, blood specimens collected before the administration of heparin and prior to discontinuation of CPB, were used to measure the response of the kaolin ACT to heparin (preheparin only), AT concentration, and a battery of coagulation assays in 31 patients undergoing repeat or combined cardiac surgical procedures. In Phase I, strong linear relationships were observed between kaolin (slope = 1.04 AT - 2, r2 = 0.78) and celite (slope = 1.36 AT + 6, r2 = 0.77) ACT slopes and AT concentrations below 100 U/dL. In the pre-CPB period of Phase II, only factors V (partial r = -0.49) and VIII (partial r = -0.63) were independently associated with heparin-derived slope using multivariate analysis; an inverse relationship was observed between AT and fibrinopeptide A levels (r = -0.41) at the end of CPB. Our findings indicate that the responsiveness of whole blood (ACT) to heparin at the high concentrations used with CPB is progressively reduced when the AT concentration decreases below 80 U/dL. Because AT is variably, and sometimes extensively, reduced in many patients before and during CPB, AT supplementation in these patients might be useful in reducing excessive thrombin-mediated consumption of labile hemostatic blood components, excessive microvascular bleeding, and transfusion of blood products. IMPLICATIONS: Heparin, a drug with anticoagulant properties, is routinely given to patients undergoing cardiac surgery to prevent clot formation within the cardiopulmonary bypass circuit. However, when levels are reduced, heparin is not as effective. Findings within this study indicate that administration of antithrombin III may help to preserve the hemostatic system during cardiopulmonary bypass.

Anticoagulants↗

An audit of error rates in a UK district hospital transfusion laboratory.

We have audited the error rates of our transfusion laboratory and compared these with error rates reported in the transfusion literature. Error rates were calculated using workload data from the department. The majority of errors that were detected were preanalytical and related to inadequate or incomplete data provided on the sample or request form. These errors were all corrected prior to any further action being taken on that request. The main analytical errors were transcription errors in entering patient identification information into the laboratory computer by transfusion staff together with the incorrect performance of blood group testing. For postanalytical errors the main errors were failure of nursing staff to follow procedures for the collection of blood components prior to transfusion. There were no serious consequences identified of the errors detected in this study. It was difficult to compare these results with those published in the literature in view of the different methodologies that have been reported when error rates have been determined. A standard method should be developed in the UK for calculating error rates so that laboratories can benchmark their performance against comparable organizations.

Blood Grouping and Crossmatching↗

Haematological responses of repeated large volume blood collection in the horse.

The haematological response of regular, repeated blood harvesting was investigated in 40 Thoroughbred and non-Thoroughbred horses that donate 8 litres of blood every 3 weeks for the purposes of commercial blood production. When this volume of blood was removed on five occasions over 12 weeks, no adverse effect on packed cell volume (PCV), haemoglobin (HB), and red blood cell count (RCC) was observed. Although PCV, RCC and Hb values decreased during the first week after blood collection, followed by a gradual increase in values until the next harvest time, all values remained within published reference ranges. Derived red cell indices [mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and mean corpuscular haemoglobin concentration (MCHC)] also remained within reference range. We conclude that the removal of approximately 8 litres of blood (approximately 16 ml kg(-1)or 20 per cent of blood volume for a 500 kg horse) from blood donor horses every 3 weeks allows time for adequate recovery of haematological variables and does not result in adverse haematological changes.

Animals↗

[Comparison between the blood from orbital sinus and heart in analizing plasma biochemical values--increase of plasma enzyme values in the blood from orbital sinus].

Plasma biochemical values, blood urea nitrogen (BUN), glucose, aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), were compared between the samples collected from orbital sinus, heart and tail vein in mice, rats and hamsters. The significant higher values of AST, LDH and CPK were shown in samples from orbital sinus as compared with that from other sites. The blood from orbital sinus was bleeding by two methods and compared in the plasma enzyme values. It is suggested that the leakages of these enzymes from destroyed ocular tissues result in the increase of the plasma enzyme values.

Animals↗

Effect of blood collection imitating toxicokinetic study on rat hematological parameters.

The effect of blood collection imitating a one-month toxicokinetic study on hematological parameters was studied in male rats (6 weeks of age at the beginning of the experiment). Three groups were established according to blood sampling points per day; Group I (3 points), Group II (5 points) and Group III (10 points). These repeated blood samplings were carried out on the first and last days of this study, and one-point blood sampling was also done every week during the experiment. In each sampling, 0.3 ml of blood was collected from the jugular vein. There were no changes in Group I, but in other groups, especially in Group III, red blood cell counts, hematocrit and hemoglobin concentration decreased during repeated blood sampling. On the other hand, white blood cell counts also decreased, but recovered within 24 hr. Platelet counts did not show any decrement. From the present result, less than 0.9 ml of blood per day is conceivable as the volume without causing changes in hematological parameters. The baseline of the sampling volume can become one reference for toxicokinetic and toxicological studies.

Animals↗

An evaluation of leucocyte analysis on the Coulter STKS.

The performance of leucocyte analysis on the Coulter STKS (Coulter, Hialeah, FL, USA) was evaluated for accuracy, precision and reliability. The results were compared with those obtained from visual examination of a Romanowsky stained blood film together with the automated WBC-diff. from the Technicon H*1 (Technicon, Tarrytown, NY, USA). The relationship between the number of cells counted per WBC-diff. and the WBC count of the sample was established. Precision of the STKS WBC-diff. was acceptable on blood samples with normal and low WBC counts. Correlation with an 800 cell manual WBC-diff. (n = 104) was excellent (r = 0.97, 0.97, 0.83, 0.98 and 0.53 for neutrophils, lymphocytes, monocytes, eosinophils and basophils respectively). Blood specimens, collected into dipotassium EDTA, could be stored at 20-25 degrees C for at least 8 h with no significant effect on the STKS WBC-diff. In a study of 513 patient samples, the BLASTS suspect flag gave 5.4% false positives and zero false negatives, the VARIANT LYMPHS flag gave 1.5% false positives and 0.4% false negatives, and the IMM GRANS/BANDS flag gave 30.8% false positives and 2.3% false negatives. Several instrument and sample related problems were encountered during this study. Despite these limitations, the STKS can provide efficient 5 part WBC-diffs. and effective screening for WBC abnormalities.

Blood Preservation↗

Autotransfusion following cardiac operations: a randomized, prospective study.

To evaluate the safety and effectiveness of the collection and retransfusion of postoperatively shed mediastinal blood as part of a multifaceted approach to blood conservation following cardiac operation, 113 patients were randomized into either an autotransfusion group (54 patients) or a control group (59 patients). Intraoperative and postoperative hemodilution was practiced in all patients. The clinical safety of this technique was confirmed by the lack of septic, hematological, pulmonary, renal, or hepatic complications. However, in this setting where blood conservation is already aggressively practiced, the ability of the technique to further reduce the use of banked blood following cardiac surgical procedures was not demonstrated.

Adult↗

Postoperative collection and reinfusion of autologous blood in total knee arthroplasty.

A series of 40 patients undergoing primary unilateral total knee arthroplasty were entered into a randomised controlled trial to assess the safety and efficacy of postoperative autologous blood salvage and reinfusion. The mean volume of autologous blood reinfused was 520 ml per patient (51% of the mean total drainage). Homologous blood transfusion was required in only 35% of patients in the study group compared with 95% of patients in the control group (P less than 0.001). The mean volume of homologous blood transfused was 0.9 units per patient in the study group compared with 2.5 units in the control group (P less than 0.001), a saving of 64%.

Aged↗

Cortisol and prolactin concentrations during repeated blood sample collection from freely moving, mouse-sized mammals (Phodopus spp.).

BACKGROUND AND PURPOSE: Validation of a method for obtaining blood samples that does not change cortisol or prolactin concentrations yet allows serial blood samples to be collected from animals under anesthesia, without prior handling, from freely interacting social groups of small mammals. METHODS: Results from five experiments are reported. Male dwarf hamsters (Phodopus spp.) were housed in modified home cages under continuous flow of compressed air that could be switched to isoflurane in O2 vehicle without approaching the cages. RESULTS: Dwarf hamsters respond to manual restraint with behavioral distress and increase in the concentration of the dominant glucocorticoid, cortisol, and decrease in prolactin concentration. Both effects are evident within one minute. In contrast, when this new method was used, neither cortisol nor prolactin changed in response to repeated sample collection (up to 8 successive samples at 2 hour intervals), prolonged isoflurane exposure, or substantial blood volume reduction (30%). Prolactin concentration was suppressed and cortisol concentration was increased in response to stimuli from other hamsters tested without anesthesia. Suppression of prolactin concentration was graded in response to the degree of stress and equaled the pharmacologic reduction caused by bromocryptine mesylate (50 microg of CB154 x 3 days). CONCLUSIONS: The technique is superior to alternatives for studies of behavioral endocrinology of freely interacting small mammals.

Administration, Inhalation↗

More effective suppression of hemostatic system activation in patients undergoing cardiac surgery by heparin dosing based on heparin blood concentrations rather than ACT.

This study was designed to determine whether the maintenance of higher than usual patient-specific heparin concentrations during cardiopulmonary bypass (CPB) was associated with more effective suppression of hemostasis system activation. Thirty-one patients scheduled for repeat cardiac surgery or combined procedures (i.e., coronary revascularization + valve repair/replacement) were consented and enrolled in this study. All patients received porcine heparin and protamine and were randomly assigned to monitoring of anticoagulation by either celite ACT alone (Control, n = 16) or by kaolin ACT combined with on-site measurements of whole blood heparin concentration (Intervention, n = 15). Blood specimens collected before administration of heparin, before weaning from CPB and after administration of protamine were analyzed with a battery of coagulation assays. Patients in the intervention cohort received appreciably greater heparin doses than control patients, resulting in higher anti-Xa heparin levels at the end of CPB. Fibrinopeptide A and D-dimer levels were higher in the control group before discontinuation of CPB. Percent decrease during CPB were greater in the control group for factors V and VIII, fibrinogen and antithrombin III. Percent decrease in complement 3 was greater in the control group after protamine and bleeding times measured in the Intensive Care Unit were significantly more prolonged in this group. Maintenance of higher patient-specific heparin concentrations during CPB more effectively suppresses excessive hemostatic system activation than do standard heparin doses chosen based on measurement of ACT. These findings may explain, at least in part, the significant reduction in perioperative blood loss and blood product use when higher heparin concentrations are maintained.

Aged↗

Evaluation of Cobe Trima for the collection of blood components with particular reference to the in vitro characteristics of the red cell and platelet concentrates and the clinical responses to transfusion.

This study evaluated Cobe Trima for donor and operational acceptability, the quality and storage stability of the blood components collected, and the clinical responses to transfusion. The study was carried out in 2 phases; phase 1 assessed the efficiency of red cells and platelet collection, and the characteristics of the components collected before and after storage. Phase 2 was an evaluation of operational issues and the in vitro characteristics of the red cells and platelet concentrates at the time of transfusion in respect to their cellular content, and leucocyte (interleukin IL-6 and IL-8) and platelet-derived (Rantes) cytokine levels. Cytokine levels were also measured in the donors before and after the collection procedure and in patients both before and after transfusion. The clinical responses to a small number of transfusions were assessed. The Cobe Trima was found to be straightforward to use by the operators, although additional operator training was required to manage occasional uncertainty with alarm messages. It was acceptable to the donors except for the occurrence of citrate reactions in 3/6 donors in phase 1; this problem persisted in phase 2 (6/15 donors), and needs to be addressed in the future. All blood components met UK product specifications apart from 2 platelet concentrates, 2 red cell concentrates, and one unit of FFP; the red cell and platelet concentrates had good storage characteristics. The 2 procedures, which resulted in low platelet yields, were due to occlusion of the plasma line; the method for installation of the harness has been subsequently modified to prevent this. 2 red cell concentrates showed haemolysis; the reason for this was not established. The Factor VIII level was satisfactory in plasma and the cellular content was low. The responses to 12 platelet transfusions were expected as in a group of haematology patients, and no immediate adverse effects were reported with any of the transfusions. Leucocyte-associated (IL-8 and IL-6) and platelet-associated (Rantes) cytokine levels were not elevated in donor samples taken before or after the collection procedure, or in the red cell and platelet concentrates at the time of issue. Pre- and post-transfusion IL-8 levels were raised in one patient with non-immune platelet refractoriness, and normal in 2 patients with excellent or almost satisfactory responses to platelet transfusions raising the question as whether IL-8 could be used as a laboratory marker for non-immune platelet refractoriness due to infection.

Blood Component Removal↗

Collection and transfusion of blood and blood components in the United States, 1994.

BACKGROUND: Collections and transfusions of blood in the United States in 1994 were measured and compared with those in 1992. STUDY DESIGN AND METHODS: Completed survey questionnaires were returned by all 147 regional blood centers, 1340 American Association of Blood Banks (AABB) member hospitals, and 523 non-AABB hospitals. Statistical tests verified the representativeness of the sample. RESULTS: The United States domestic blood supply in 1994 (13,340,000 units) was 3.3 percent less than in 1992. It included allogeneic blood (11,773,000 units), autologous blood (1,013,000 units), and directed donations (334,000 units). Of these, 432,000 units were rejected on testing, 11,107,000 units were transfused to 3,398,000 patients, and 1,801,000 units were discarded or unaccounted for. Platelet transfusions amounted to 7,866,000 units. Compared with the totals for 1992, transfusions of single-donor platelets (714,000 packs or 4,284,000 units) increased by 17.6 percent, while transfusions of platelet concentrates (3,582,000 units) fell by 23.6 percent. Fresh-frozen plasma transfusions (2,621,000 units) increased by 16.2 percent over the number for 1992. CONCLUSIONS: The US blood collection rate in 1994 was 74.6 units per 1000 population of donor age, the lowest recorded level since 1971. The US RBC transfusion rate in 1994 was 42.8 units per 1000 population, about the same as 1979. Transfusions of single-donor platelets, 16.5 units per 1000 population, exceeded transfusions of platelet concentrate (13.8/1000) for the first time. Plasma transfusions were 10.1 units per 1000 population. The US blood supply in 1994 was adequate to meet patient demands.

Blood Banks↗

Leukapheresis and granulocyte transfusion.

Newer cell separators can collect more PMN, especially using macromolecular agents and steroid stimulation of donors. Proper indications for PMN transfusion are severe neutropenia and sepsis, or certain localized infections, when prolonged marrow aplasia is expected. Optimal dosage is at least 2 x 10(10) PMN per day, probably more. There is a need for more accurate definition of clinical indications for PMN support, for still greater PMN yields from leukapheresis, and for better PMN storage capability.

Adrenal Cortex Hormones↗

[Studies on serotyping of sporadic acute viral hepatitis].

Two hundred and forty-eight blood specimens collected from patients of sporadic acute viral hepatitis were serotyped with enzyme immunoassay (EIA), to study its pathogenic components during non-epidemic seasons of hepatitis A (HA). Results showed that HA accounted for 61.3% of the total sporadic acute hepatitis cases during its non-epidemic seasons, occurred mainly in youngsters and decreased with increase of their age. Hepatitis B (HB) ranked the second and accounted for 26.2%, occurred mainly in the middle-aged and the elderly and its prevalence increased with age. Hepatitis C (HC) accounted for 9.9% and hepatitis E (HE) 22.2% of the total cases, without obvious age difference. Prevalence of hepatitis D (HD) was 12.7%, with a positive rate of hepatitis D antigen (HDAg) of 12%. Superinfection accounted for 18.9%, and the viral hepatitis markers were all negative in 0.8% of the total cases. There was very significant difference in prevalence of HCV-IgG and HEV-IgG between sporadic acute hepatitis patients and blood donors during the same periods. Icterus occurred in 68% of the total cases, 86.8% in HA. Patients of HB complicated with HD were liable to chronicity.

Acute Disease↗

[Autologous blood transfusion using preoperative collection and intraoperative recovery in orthopedic elective surgery].

Between the period of January 1994 and June 1995, the results of Autotransfusion Program of the Hospital do Aparelho Motor SARAH-BSB were evaluated. The goals of the program are: 1. Minimise and, if possible, eliminate the risks of homologous transfusion; 2. Increase the security, efficiency and cost to benefits relation of the hemotherapic procedures; 3. Minimise the demand of blood products for those patients with difficult compatible blood to be found. The program has received 194 patients, among these, 100 have been selected for this study because they had had blood collection and surgery concluded. The average age of the patients was 34.3 years (11/72 years) median was 30 years and mode 15 years. The patients have undergone elective orthopaedic operations. Autologous transfusions have been made by predeposit and intraoperative salvage (Cell Saver). Six patients (6%) presented mild reactions associated to blood drawn. Additional homologous blood was needed to 20 (20%) patients. Our experience demonstrates the security and efficiency of transfusion in patients from childhood until elderly. It recommends the creation and expansion of existing programs using autologous transfusion in services with elective surgery. We also consider that nursing care stimulates patients participation in the program.

Adolescent↗

Autologous deposit of blood by oncology patients: an evaluation of actual use and wastage.

BACKGROUND: Transfusions of autologous deposited blood have continued to grow since the 1980s. Together with the growth in the deposit of autologous blood, issues such as appropriateness of indications, reimbursement, cost effectiveness, etc., have emerged and require addressing. Also, the patient's concerns about safety of the blood supply must be taken into account. METHODS: We conducted a 20-week study to determine the collection and transfusion/wastage of autologous blood and the need to transfuse additional allogeneic units of packed red blood cells. The disposition of every autologous unit was followed until its disposal. RESULTS: One hundred fifty-seven patients deposited 260 units of autologous blood. Of these, 144 units (55.4%) were transfused whereas 44.6% were discarded. In addition, 25 or 157 patients (15.9%) received an additional 58 units of allogeneic blood. CONCLUSION: These data demonstrate that there are surgical procedures where autologous blood is drawn unnecessarily whereas others could afford a higher number of autologous blood deposits. Physicians may be pressured by patients into ordering autologous blood deposits, to allay fear of patients about safety of the blood supply. It is important that health care professionals undergo periodic education to be able to address patient's apprehension about safety of the blood supply.

Adolescent↗

Automatic measurement of hemoglobin F in blood obtained from patients with hemoglobin E/E and beta-thalassemia/hemoglobin/E.

This paper presents an automated determination of hemoglobin (Hb) F in Hb E/E disease using Hi-Auto A1c. Blood specimens collected in Bangkok were frozen, and sent to Japan by air mail for the determination. The automatically determined values showed a high correlation with the values obtained by the classical alkali denaturation method. Hb E/E cases showed 4.24 +/- 1.75% of Hb F. On the other hand, Hb, Hct, MCV and MCH in the disease samples were lower than in the controls, but higher than those of beta-thalassemia/HbE disease. From the results it was concluded that Hb E/E could be differentiated from beta-thalassemia/HbE by combination of Hb F value and MCH or Hb in CBC.

Adult↗

Platelet collection and transfusion using the fenwal CS-3000 cell separator.

A prototype model of the Fenwal CS-3000 Blood Cell Separator (Deerfield, IL) was studied for plateletpheresis in 63 donors and 5 transfusions in patients. Donor effects were consistent with platelet removal and mild hemodilution. The incidence of reactions (9 of 63) was low and all were mild "citrate" type. A two-hour collection yielded 4.0 +/- 0.72 x 10(11) platelets at an efficiency of 45 +/- 6.9 per cent. The product had little contamination with leukocytes (0.26 +/- 1.2 x 10(9) and red blood cells (hematocrit less than 1%). Morphology and pH were well preserved during 24 hours of storage. Four patients with uncomplicated aregenerative thrombocytopenia were transfused on five occasions, with a mean of 4.5 +/- 0.87 x 10(11) platelets resulting in a mean platelet count increment of 55,000/microliter and dramatic reduction in template bleeding times.

Blood Platelets↗