Toby L. Simon

Controlled Trial of Routine Administration of Platelet Concentrates in Cardiopulmonary Bypass Surgery

Prophylactic administration of platelet concentrates to patients undergoing their first cardiopulmonary bypass operation (coronary artery bypass grafting or uncomplicated valve replacement) was evaluated in a controlled randomized study of 28 patients. Four units of platelet concentrates administered at the end of bypass prevented prolongation of the bleeding time seen in patients not receiving platelets. However, chest tube blood loss, transfusion requirements, and clinical outcome were not improved. Moreover, thrombocytopenia and prolongation of bleeding time did not correlate with blood loss or transfusion needs. Mild thrombocytopenia (to 58,000 platelets per microliter) and transient platelet dysfunction after bypass do not require administration of platelet concentrates, and prophylactic use of this blood component in the surgical setting of bypass is not indicated.

Iron supplementation for menstruating female blood donors

Depletion of body iron stores is a major factor limiting regular blood donations by menstruating females. To determine if regular iron supplementation would solve this problem, we conducted a double‐blind study in which menstruating female donors were randomly placed into one of three groups: one taking 39 mg elemental iron, a second taking 39 mg of iron plus 75 mg vitamin C, and a third taking 100 mg vitamin C daily. The women were requested to donate every 8 weeks for at least 1 year. Blood samples were taken on each donation for measurements of hemoglobin, total iron binding capacity (TIBC), and ferritin. In the two groups taking iron supplements hemoglobin and ferritin increased from baseline values and the TIBC decreased. The vitamin C control group showed decreases from baseline for hemoglobin and ferritin and increases in TIBC. Differences between groups taking iron supplements and the group not taking supplements were highly significant. Drop‐out from the study was due to various causes; however, iron intolerance was uncommon. Minimal daily iron supplementation was beneficial in maintaining body iron stores and hemoglobin levels in menstruating females on a schedule of blood donation as often as every 8 weeks.

Collection of platelets with a new cell separator and their storage in a citrate‐plasticized container

A new apheresis device using microprocessor control for the collection of a high‐purity single‐donor platelet concentrate was evaluated, as was the storage of platelets for up to 5 days in a citrate‐plasticized polyvinylchloride blood bag. The study was conducted in three phases: collection of platelets for in vitro studies and determination of donor safety; autologous transfusion of platelets in healthy volunteers; and transfusion of platelets in patients requiring platelet transfusion therapy. Donors had mild hypocalcemia and minimal changes in blood counts except for a platelet count reduction from 288 +/− 50 × 10(3) (288 +/− 50 × 10(9)/L) to 217 +/− 43 × 10(3) per microL (217 +/− 43 × 10(9)/L). A mean of 3.36 +/− 1.24 × 10(11) platelets was collected in the mean volume of 214 mL with red cell and white cell contamination in the range of 10(7). Morphology and aggregation were as described previously in stored platelets. Platelet survival data in eight subjects showed a mean recovery of 61 +/− 11 percent and mean survival of 5.03 +/− 1.07 days by a weighted‐mean model. Patients transfused with platelets had mean increments of 23,000 immediately and of 8000 at 24 hours; corrected count increments were 6000 at 1 hour and 4000 at 24 hours. The platelets were successful in providing hemostasis to these patients. Clinically useful 5‐day‐stored platelets are obtained by using this apheresis technology with a functionally closed system and a citrate‐plasticized blood bag.

Concentration of platelet units into small volumes

To determine the best procedure for concentrating platelets in a smaller volume after storage, we studied platelet loss after concentration at various centrifugation g forces for various times. In vitro studies demonstrated the need to let platelets sit for 1 hour prior to resuspension by gentle kneading. 500 × g gave unacceptable results. Losses were minimal at 1500 × g for 7 minutes, 2000 × g for 10 minutes and 5000 × g for 6 minutes. Reinfusion of 51 Cr‐labeled platelets into normal volunteers after concentration at both 2000 × g for 10 minutes and 5000 × g for 6 minutes showed normal viability. Numbers and viability of platelets stored up to 5 days in 50 ml plasma and then concentrated in 10 ml plasma after centrifugation at 1500 × g for 7 minutes, 2000 × g for 10 minutes or 5000 × g for 6 minutes should be clinically acceptable.

The Urokinase-Streptokinase Pulmonary Embolism Trial (Phase II) Results

IN 1967 the National Heart and Lung Institute organized a multi-institutional controlled clinical trial to evaluate thrombolytic agents in the treatment of pulmonary embolism. The results of the first phase of that study (The Urokinase Pulmonary Embolism Trial) showed that 12 hours of urokinase compared to heparin and oral anticoagulants alone increased the resolution rate of pulmonary thromboemboli, especially massive emboli, as judged by arteriography, hemodynamics, and lung scanning, assessed within 24 hours of therapy.2 3 4 Serial lung scanning revealed that these differences in embolus resolution rates decreased when assessed at 14 days.4 A second phase (The Urokinase-Streptokinase Pulmonary Embolism Trial), recently completed and reported in more detail in the Journal of the American Medical Association,5 compares 12 hours of urokinase to 24 hours of urokinase and to 24 hours of streptokinase. One hundred sixty-seven patients who satisfied the clinical criteria for embolism within five days of treatment and the specific angiographic criteria applied by

Impact of previously frozen deglycerolized red blood cells on cytomegalovirus transmission to newborn infants

The incidence of cytomegalovirus (CMV) infection in low birth weight newborn infants was compared in infants transfused with liquid red blood cells (RBC) and previously frozen deglycerolized red blood cells (FRBC). Three of 21 transfused infants with seropositive mothers who had positive CMV titers developed positive cultures; two became clinically ill. Two of the 16 infants born to seronegative mothers developed positive cultures, one became clinically ill. There were no deaths. With FRBC, one culture was positive in the 23 babies born to seropositive mothers and one in the 26 born to seronegative mothers. This infant received a single transfusion of 28 mL FRBC from a donor with a positive titer, but his mothers serology converted while she was breast-feeding him. Neither of these two infants who received FRBC developed clinical disease. Substitution of FRBC for transfusion of the low birth weight newborns was associated with a significantly lower incidence of transfusion-associated CMV infection and clinical illness.

How we manage requests for recombinant factor VIIa (NovoSeven)

From the Departments of Pathology and Pediatrics, University of New Mexico, United Blood Services of New Mexico, and TriCore Reference Laboratories, Albuquerque, New Mexico. Address reprint requests to: Toby L. Simon, MD, 5201 Congress Avenue, Suite 220, Boca Raton, FL 33487; e-mail: toby.simon@zlbplasma.com. Received for publication March 31, 2006; revision received August 17, 2006, and accepted August 30, 2006. doi: 10.1111/j.1537-2995.2007.01058.x TRANSFUSION 2007;47:8-14. H O W D O I . . . ?

Plasma proteins and lymphocyte phenotypes in long-term plasma donors

BACKGROUND: The possible effects of long‐term plasma donation remain unknown, but it is important to investigate them so that donor safety is ensured. The purpose of this study was to determine if long‐term plasma donation alters plasma proteins or lymphocyte phenotypes.

Changes in plasma coagulation factors during blood storage

Abstract Changes in plasma coagulation factors during blood storage primarily consist of a gradual reduction in biologic activity. The major exception is the more rapid loss of coagulation factor V and VIII activity due to their lability. By 35 days of storage of whole blood in CPD-Adenine, factor V falls to 15–21% activity and factor VIII 16–20%. Only slight declines are seen in factor II and X during the same time, while other factors, except for factor VII, are virtually unchanged. Factor VII may be activated in the cold, but otherwise declines slightly. In fresh frozen plasma stored for a year only factor VIII declines, and this is reduced by more rapid freezing to lower temperatures. In platelet concentrates, coagulation factors are well maintained, with the exception of the labile factors. Paradoxically, factor V falls more rapidly with room temperature storage and agitation while factor VIII decline is lessened.

Investigation of the effect of long‐term whole blood donation on immunologic parameters

Few studies addressing possible immune sequelae of long‐term whole blood donation have been published. The purpose of this study was to determine if there were any differences in lymphocyte subsets, monocyte and neutrophil receptors, and antigens important to host defense in committed whole blood donors and in nondonor controls. Blood samples were obtained from 27 whole blood donors who had been donating on a regular basis for at least 4 years and from 21 nondonor controls. A panel of single‐ and dual‐labeled monoclonal antibodies was used to characterize peripheral white cells, and then the cells were analyzed by flow cytometry. Lymphocyte subsets included T (CD3) cells, helper T (CD4) cells, suppressor T (CD8) cells, B (CD19) cells, natural killer (NK) (CD56) cells, and subpopulations of T cells defined by the coexpression of markers for CD3/HLA‐DR, CD3/CD56, and CD8/CD11b. Monocyte and neutrophil analysis included quantitation of receptors for C5a, formyl‐met‐leu‐phe, and C3bi (CR3). Monocytes were also analyzed for expression of HLA‐DR and CD14 antigens. No significant differences were observed in the whole blood donors and nondonor controls for any of these factors used to assess immunologic status, except for an increase in C3bi receptors on both neutrophils and monocytes from whole blood donors. These findings indicate that the lymphocyte parameters analyzed in this study are unaltered by long‐term whole blood donation. Further research is necessary to determine the significance of complement receptor upregulation in whole blood donors and to identify any changes in the functional characteristics of peripheral white cells from whole blood donors.