Severe outcomes of allogeneic and autologous blood donation: frequency and characterization

BACKGROUND: There are few published data on severe outcomes of the donation of blood for allogeneic or autologous use. It would be helpful if blood collectors could better characterize and/or predict the likelihood of significant complications of blood donation. STUDY DESIGN AND METHODS: Very severe outcome (VSO) was defined as an event requiring hospitalization. Approximately 4.1 million American Red Cross whole-blood donation records (July 1993-March 1994) were reviewed for the incidence and type of VSO. RESULTS: A total of 33 VSOs occurred for all donations. The incidence of VSOs for allogeneic donation was 1 (0.0005%) in 198,119 and that for autologous donation was 1 (0.006%) in 16,783 (p < 0.001). First-time donors were three times as likely to have a VSO. Donors > 40 years old had 87.9 percent of the VSOs, and donors > 60 years old had 48.5 percent. Vasovagal (66.7%) and anginal (12.1%) episodes were the most frequent complications, and 66.7 percent of reactions occurred at the blood collection site. The mean hospital stay was 1.9 days. CONCLUSION: VSO is an infrequent complication of all types of blood donation, but its occurrence may be associated with significant morbidity and cost. VSO is nearly 12 times as likely in autologous blood donors.     

Stem cell factor modulates avidity of alpha 4 beta 1 and alpha 5 beta 1 integrins expressed on hematopoietic cell lines

Interactions between hematopoietic cells and bone marrow (BM) stroma, composed of extracellular matrix and stromal cells, are crucial for hematopoiesis. Integrins facilitate these interactions by mediating adherence of hematopoiesis. Integrins facilitate these interactions by mediating adherence of hematopoietic cells to both the extracellular matrix and stromal cells. Marrow stromal cells secrete a variety of growth factors, including stem cell factor (SCF). Because treatment with SCF in vivo mobilizes primitive hematopoietic cells from the BM, we investigated the effect of the growth factor SCF of hematopoietic cell adhesion. These studies show that SCF modulates adhesive function in a dose- and time-dependent manner, but does not modulate expression of the integrins alpha 4 beta 1 and alpha 5 beta 1 in the SCF- responsive cell line MO7E. Treatment of MO7E cells with SCF (200 ng/mL) produced a transient increase in adherence to cytokine-activated human umbilical vein endothelial cells (HUVECs) or to vascular cell adhesion molecule 1 (VCAM-1)-transfected Chinese hamster ovary (CHO) cells with peak adhesion at 30 minutes and return to baseline by 60 to 90 minutes. This increase in adhesion was paralleled by increased binding of the beta 1 activation-dependent monoclonal antibody (MoAb) 15/7, as determined by flow cytometry. However, prolonged incubation of MO7E with SCF induced a marked decrease in integrin-mediated adherence, with maximal inhibition by 24 hours. No change in expression of integrins, as determined by flow cytometry, was observed with short- or long-term incubation with SCF. SCF-treated cells were still able to respond to phorbol esters and to the activating beta 1 MoAb 8A2 with increased adherence, but not to the level seen in control cells. This suggests that a subpopulation of expressed alpha 4 beta 1 and alpha 5 beta 1 integrins is disengaged by prolonged incubation with SCF.     

Factors in the liquid portion of stored blood inhibit the proliferative response in mixed lymphocyte cultures

The transfusion of blood may suppress the immune responses of patients with renal transplants and with malignant disorders. To study the in vitro suppressive effects of banked blood, 4 units of blood were stored in CPDA-1 and ADSOL at 4 degrees C for 14 days. Lymphocytes and plasma or ADSOL supernatants were harvested on Days 0, 4, 7, 10, and 14. Subpopulations of lymphocytes were enumerated by flow cytometry. Recalcified and heat-treated plasma and supernatants from the units of blood were added to mixed lymphocyte cultures (MLC) composed of cells from normal individuals. No significant changes were noted in the proportions of T or B cells from blood stored under these conditions. A 60 +/− 3 percent inhibition in the proliferative response was observed when plasma from CPDA-1 units was added to MLCs (p less than 0.02). Supernatants from ADSOL units demonstrated a 29 +/− 4 percent inhibition (p less than 0.10) of the proliferative response, and this inhibition of response was observed on all 14 days of the study. When appropriate concentrations of dextrose or adenine were added to other MLCs, adenine (at the concentration found in ADSOL) caused a significant inhibition of the proliferative response. This inhibition was not, however, as marked as that observed with recalcified, heat- treated plasma from CPDA-1 units. We conclude that adenine plus some additional factor(s) found in the liquid portion of stored blood inhibits the proliferative response of normal lymphocytes. It is possible that these factors contribute to the immune suppression observed in vivo in some patients who receive blood transfusions.     

Protein A adsorption of acute myelogenous leukemia serum induces in vitro blast lysis

We studied cytotoxic activity of acute myelogenous leukemia (AML) sera for AML blasts before and after immunoadsorption with Staphylococcus aureus, Cowan I (SAC), which contains protein A. We found in vitro that incubation with treated AML sera reduced viability to 42.7% of control (p less than 0.01) for autologous and 21.0% of control (p less than 0.01) for allogeneic blasts. Normal peripheral blood cells were not killed by treated AML sera. Wood 46 strain of Staphylococcus aureus, which does not contain protein A, did not significantly reduce AML blast viability (94.8%, p greater than 0.4), while Sepharose-bound protein A reduced viability to 63.8% (p less than 0.01). Cytotoxicity does not appear to be complement-mediated, byt cytotoxic activity is trypsin-sensitive and is contained in the immunoglobulin fraction. This model for study of the tumoricidal action of protein A adsorption should be useful for predicting utility of plasma adsorption as a therapeutic adjunct in the future.     

心房扑动患者的下腔静脉-三尖瓣环峡部和房间隔缓慢传导的电生理意义

目的　用电 解剖标测方法标测右心房 ,然后比较心房扑动 (AFL)和房室结折返性心动过速(AVNRT)患者在下腔静脉 三尖瓣环峡部 (CTI)和心房间隔部 (AS)的电冲动传导速度 ,以便确定AFL患者除了解剖结构上的异常外 ,是否伴有心房电生理方面的异常变化。方法　 1 0例AFL患者 ,男性 7例 ,女性 3例 ,平均 (53± 1 0 )岁 ;1 3例AVNRT患者 ,男性 5例 ,女性 8例 ,平均 (51± 1 1 )岁。对这两组患者进行了详细的电 解剖标测、电生理检查和射频消融术。分别以周长为 60 0、40 0、和 30 0ms在冠状静脉窦 (CS)起搏的情况下测量AFL和AVNRT患者的CTI和AS的冲动传导速度 ,并将两组患者在CTI和AS的冲动传导速度进行比较。结果　与AVNRT患者相比 ,AFL患者在各个起搏周长 (PCL)时CTI和AS的冲动传导速度都明显减慢 (P <0 0 5)。另外 ,在AFL组 ,AS的冲动传导速度在起搏周长 60 0、40 0ms时低于CTI,但在 30 0ms时差异无显著性 (P >0 0 5)。因为在AFL组 ,PCL为 30 0ms时的冲动传导速度明显低于 60 0和 40 0ms时的冲动传导速度 ,致使PCL为 30 0ms时CTI和AS的冲动传导速度差异无显著性。结论　与CTI相比 ,AS的冲动传导速度在所有患者都较慢 ,而AFL患者在CTI和AS的冲动传导速度减低更明显 ,并且在CTI的冲动传导速度减慢具有频率依     

Human umbilical vein endothelial cells display high-affinity c-kit receptors and produce a soluble form of the c-kit receptor

Stem cell factor (SCF) is a hematopoietic growth factor produced by fibroblasts and endothelial cells that stimulates the growth of primitive hematopoietic cells. SCF triggers cell growth by binding to the c-kit receptor. Because endothelial cells can respond to certain hematopoietic growth factors, we tested human umbilical vein endothelial cells for display of the c-kit receptor and examined the effect of SCF on endothelial cell proliferation, adhesion molecule expression, and production of tissue factor. Quantitative binding experiments with 125I-SCF showed both high-affinity (Kd = 42 pmol/L) and low-affinity (Kd = 1.7 nmol/L) c-kit receptors. There were approximately 1,100 high-affinity c-kit receptors, and 5,400 low- affinity c-kit receptors per endothelial cell. Enzyme immunoassays showed that endothelial cells released soluble c-kit receptor and SCF. The transmembrane form of SCF was detected by indirect immunofluorescence analysis using monoclonal or polyclonal anti-SCF receptor antibodies. The addition of SCF (100 ng/mL) did not alter endothelial cell proliferation over a 7-day period. Similarly, there was no change in the release of tissue factor or expression of inducible endothelial adhesion molecules (intercellular adhesion molecule-1, endothelial-leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1) measured by enzyme-linked immunosorbant assay at 4 and 24 hours after SCF addition. The neutralizing anti-c-kit receptor monoclonal antibody SR-1 blocked binding of 125I-SCF to the c- kit receptor by 98% but did not alter endothelial cell proliferation or adhesion-molecule expression. c-kit receptors were also detected on adult endothelial cells lining small blood vessels in normal human lymph nodes. These data indicate that normal human endothelial cells produce SCF and show high-affinity c-kit receptors that have the capacity to dimerize. The lack of response to exogenous SCF may be because of intracellular activation of the c-kit receptor via autocrine production of SCF. Alternatively, SCF and c-kit may play a role other than stimulation of proliferation, adhesion-molecule display, or tissue factor production by endothelial cells. The production of soluble c-kit receptors by normal human endothelial cells may serve to regulate the bioactivity of SCF within the bone marrow microenvironment.     

Sarcoidosis: correlation of extent of disease at CT with clinical, functional, and radiographic findings

Computed tomography (CT) was compared with chest radiography in the assessment of disease severity in 27 patients with sarcoidosis. The CT scans and radiographs were each read twice by two independent observers. Disease extent was assessed on CT scans by visual scoring (0%-100% involvement of the lung parenchyma) and on radiographs by using an adaptation of the International Labour Office classification. The severity of parenchymal changes on the CT scan and on the radiograph was significantly correlated with the severity of dyspnea (r = .61 and .58, respectively; P less than .001), diffusing capacity (r = -.62 and -.52, P less than .01), and vital capacity (r = -.49 and -.51, P less than .01). Patients with predominantly irregular opacities had more severe dyspnea and lower lung volumes than patients with predominantly nodular opacities (P less than .05). The authors conclude that in patients with sarcoidosis, the radiographic and CT assessments of disease severity show similar correlation with clinical and functional impairment.