A rapid simplified prothrombin assay.
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Biomedical subjects
Publications and source records attributed to T F Zuck.
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Studies concerning the relationship between glucose level, hematocrit to which cells were packed (within three hours of initial collection) and adenosine triphosphate (ATP) concentration were undertaken in CPD supplemented with adenine (0.25 mM final concentration). It was found that apparently adequate ATP levels could be maintained in 90 per cent hematocrit packed units at 42 days only if glucose was present in amounts 1.5 times or greater than that provided by CPD. Less tight packing of the units to 70 and 80 per cent hematocrit maintained ATP at greater than 50 per cent of the initial level for a full 42 days of storage when 1.25 times the usual glucose concentration was present in the initial anticoagulant. No difference in 2,3-diphosphoglycerate or pH was found in any of the modified media under study.
In order to provide data in support of licensure applications for citrate-phosphate-dextrose (CPD) supplemented with adenine, a multi-institutional cooperative effort was organized to determine survivability of red blood cells subjected to prolonged liquid storage. Two manufacturers supplied plastic multiple bag blood storage containers prefilled with modified CPD (glucose 25% greater than the normal concentration) supplemented with adenine (17.0 to 17.3 mg per 63 ml of anticoagulant; 0.25 millimolar approximate final concentration when diluted with 450 ml of whole blood for 35 days showed a mean survival of 80.53 +/- 6.44 per cent (1 SD). Both red blood cell and supernatant plasma biochemical characteristics were comparable to those reported for whole blood stored for 21 days in either acid-citrate-dextrose (ACD) or CPD. Red blood cells from 19 units stored as concentrates for 35 days (Hct 75.03 +/- 3.74%) had a mean survival of 71.38 +/- 10.3 per cent with considerable interdonor variation in survival and interlaboratory variation in some biochemical characteristics. Red blood cells from eight units stored as concentrates (Hct 75.38 +/- 4.30%) for 28 days showed a mean survival of 83.97 +/- 6.10 per cent and biochemical characteristics comparable to those reported for red blood cell concentrates stored in CPD or ACD for 21 days. Modified CPD with adenine as formulated offers an improved anticoagulant for blood banking by extending the permissible red blood cell storage period.
Hemoglobin, prepared by crystallization, has been used as a blood substitute in total (91 to 93%) and partial (70 to 76%) blood replacement studies. Exchange transfusions have been carried out in laboratory animals to a total blood replacement of 91 to 93 per cent with hemoglobin or with albumin solutions. When albumin was used, all animals died at approximately ten minutes after transfusion was completed, whereas all animals transfused with hemoglobin survived for five hours and displayed normal activity during this time. In these studies the plasma half-disappearance time of hemoglobin was 3.5 hours and body distribution of 51Cr-labeled hemoglobin, as a percentage of initial levels, has shown six per cent in the kidney, six per cent in the liver, 10.5 per cent in the marrow and 13 to 14 per cent in the urine at three hours after transfusion. Survival was obtained with all animals transfused with hemoglobin or albumin solutions to a partial blood replacement of 70 to 76 per cent. However, the oxygen capacity of the circulating fluid in the hemoglobin transfused animals was about three times greater than that found in the corresponding albumin-transfused controls. Values of hemoglobin, hematocrit, platelets, and P50 returned to normal pretransfusion levels within five to seven days.
Because there may be inadequate dextrose in the newly licensed CPD-adenine for five or six weeks storage of high hematocrit red blood cells, this laboratory has examined some alternate sugars for their ability to maintain red blood cell metabolism during storage. In the current study, dextrose and fructose were studied as model or prototype nutrients. A third six carbon monosacharide, galactose, three dissacharides, lactose, maltose, and sucrose were studied in the same experiment. Of these, fructose best maintained ATP and 2,3-DPG during the fourth to sixth week of whole blood storage at 4 C. Dextrose was next best during this time and was nearly equivalent to fructose in the first three weeks of storage. Galactose and maltose both maintained ATP and 2,3-DPG, but not nearly so well as did fructose and dextrose. Sucrose and lactose were associated with the most rapid deterioration of ATP and DPG levels and they failed to maintain the progressive fall in pH which is usually associated with continuing, useful metabolism.
Approval of the new anticoagulant preservative, CPDA-1, was based in part on data from human clinical trials of CPDA-1 performed by six cooperating laboratories and two blood bag manufacturers. Biochemical and red blood cell survival properties of 123 units of blood stored for 28 to 35 days in CPDA-1 (as reported by cooperating laboratories) are briefly summarized.
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A workshop sponsored by the Food and Drug Administration was held recently during which available data were reviewed concerning surrogate testing of blood donated for transfusion in order to reduce the risks of posttransfusion non-A, non-B hepatitis. Clinical studies from which the efficacy of testing for alanine aminotransferase and antibody to hepatitis B core antigen (anti-HBc) could be predicted indicated such testing would be useful, although several studies using tests for anti-HBc developed recently questioned their effectiveness. Different approaches to establishing the cut-off values for the screening tests were presented and difficulties regarding test standardization were discussed. The legal, ethical, and medical implications for donors of surrogate screening programs in the United States also were considered. A meeting sponsored by the private sector that included representatives of the major blood banking organizations and was convened to discuss the workshop proceedings and nationwide screening of the blood supply also is summarized.
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