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Biomedical subjects

D H Yawn

Publications and source records attributed to D H Yawn.

At least 19 recordsLinked to original sources

Transmission of retroviruses from seronegative donors by transfusion during cardiac surgery. A multicenter study of HIV-1 and HTLV-I/II infections.

OBJECTIVE: To evaluate the effectiveness of serologic testing of blood donors for human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus types I and II (HTLV-I/II) infections and to estimate the risk for transmission of HIV-1 and HTLV-I/II by transfusion of seronegative blood from screened donors. DESIGN: A prospective multicenter cohort study of cardiac surgery patients who received multiple transfusions between 1985 and 1991. SETTING: Cardiac surgery services of three large tertiary care hospitals. PATIENTS: The study included 11,532 patients in three hospitals who had cardiovascular surgery. MEASUREMENTS: Incident HIV-1 and HTLV-I or HTLV-II infection. RESULTS: We detected two new HIV-1 infections among patients transfused with 120,312 units of blood components from seronegative donors. In each case a donor was detected on follow-up who had seroconverted since the donation. The HIV-1 infection rate was 0.0017% with an upper limit of the 95% CI of 0.0053%. Before donor screening for HTLV-I, transfusion of 51,026 units resulted in two HTLV-I infections (0.0039%) and four HTLV-II infections (0.0078%). After HTLV-I screening was instituted, one recipient was infected with HTLV-II among participants exposed to 69,272 units, a rate of 0.0014%. A corresponding HTLV-I/II-infected donor was found for this patient. CONCLUSION: Serologic screening of donors for antibodies to HIV-1 and HTLV-I coupled with exclusion of donors from groups having a relatively high risk for infection has led to a low incidence of transfusion-transmitted HIV-1 and HTLV-I/II infection in the United States. A small risk remains, however, despite these measures. We estimate the residual risk for HIV-1 and HTLV-II infection from transfusion of screened blood during the time of this study to be about 1 in 60,000 units.

Aged

The declining risk of post-transfusion hepatitis C virus infection.

BACKGROUND: The most common serious complication of blood transfusion is post-transfusion hepatitis from the hepatitis C virus (HCV). Blood banks now screen blood donors for surrogate markers of non-A, non-B hepatitis and antibodies to HCV, but the current risk of post-transfusion hepatitis C is unknown. METHODS: From 1985 through 1991, blood samples and medical information were obtained prospectively from patients before and at least six months after cardiac surgery. The stored serum samples were tested for antibodies to HCV by enzyme immunoassay, and by recombinant immunoblotting if positive. RESULTS: Of the 912 patients who received transfusions before donors were screened for surrogate markers, 35 seroconverted to HCV, for a risk of 3.84 percent per patient (0.45 percent per unit transfused). For the 976 patients who received transfusions after October 1986 with blood screened for surrogate markers, the risk of seroconversion was 1.54 percent per patient (0.19 percent per unit). For the 522 patients receiving transfusions since the addition in May 1990 of screening for antibodies to HCV, the risk was 0.57 percent per patient (0.03 percent per unit). The trend toward decreasing risk with increasingly stringent screening of donors was statistically significant (P less than 0.001). After we controlled for the method of donor screening, the risk of seroconversion was strongly associated (P less than 0.001) with the volume of blood transfused, but not with the use of particular blood components. CONCLUSIONS: The incidence of post-transfusion hepatitis C has decreased markedly since the implementation of donor screening for surrogate markers and antibodies to HCV. The current risk of post-transfusion hepatitis is about 3 per 10,000 units transfused.

Alanine Transaminase

Limiting homologous blood exposure.

Successful limitation of homologous blood transfusion may necessitate multiple strategies and advance planning. Preoperative and intraoperative autologous blood collection may have to be supplemented with hemostatic pharmacologic agents. The use of cytokines is increasing. More efficient use of directed donors can have an important role in blood use. As these expensive and time-consuming techniques become available, a major challenge will be to determine which patients may benefit from or really need them.

Blood Component Removal

Impact of whole blood usage in massive transfusion.

A retrospective survey comparing blood and component usage during thoracoabdominal aortic reconstruction between patients receiving whole blood vs packed red cells was conducted. Volume of salvaged blood, usage of homologous blood components, and total homologous exposures were compared between eight patients who received only packed red blood cells and four patients who received whole blood for replacement of surgical losses, using a chi-square test for comparison. All variables demonstrated a decline among patients who received whole blood. The declines in homologous blood and plasma usage were statistically significant (P less than .05). The decline in platelet usage did not reach statistical significance. The decline in total homologous exposures approached statistical significance (P less than .1). The data suggest that use of whole blood for expected massive transfusion may reduce total blood-component requirements and total homologous exposures.

Aorta

Transfusion and coagulation: an overview and recent advances in practice modalities. Part II: Pharmacologic adjuncts, cell salvage mechanisms, alternatives in blood donation.

Increasing public awareness of the risks associated with the transfusion of blood products has encouraged the development of alternatives to the use of homologous blood. Pharmacologic agents, cell salvage, and directed donations are three such mechanisms being utilized with greater frequency for blood and component therapy. At present, only three drugs are available for clinical use: DDAVP, epsilon-aminocaproic acid, and tranexamic acid. Cell salvage is available in two system types. Salvage of whole blood in passive collection systems is simplest to use and returns more coagulation factors, but yields a larger volume with a lower hematocrit. Whole blood salvage with subsequent washing and resuspension in normal saline returns only red cells in saline with the majority of coagulation factors removed. The quality of red cells in each system remains relatively constant and the decision regarding which system to employ should be based on the nature of the surgical procedure and the anticipated blood loss. The development of directed donation programs, including autologous predonation and directed homologous donation, permits a reduction in the frequency and total number of units of homologous volunteer blood administered. Directed blood donation provides an additional source of donated blood, but is not demonstrably safer than the volunteer homologous pool, and in fact, may even be less safe. Given the increased complexity of maintaining a designated donor program, these issues of safety play an important role in the ability to maintain operation of large scale directed donation programs.

Adjuvants, Pharmaceutic

Use of pre-operatively obtained platelets and plasma in patients undergoing cardiopulmonary bypass.

Thirty-seven patients requiring cardiopulmonary bypass were prospectively studied and assigned to plateletpheresis or control groups in a non-randomized, non-blinded fashion according to apheresis exclusion criteria and our ability to perform apheresis within 24 hours of surgery. Patients were grouped by potential for hemostatic abnormalities following a risk point factor assignment established for this study. The study indicated improvement of hemostasis with autologous platelets and plasma as demonstrated by clinical and laboratory parameters and by overall blood component utilization. We conclude that pre-operative plateletpheresis in this patient population is feasible, safe, and effective.

Blood Component Removal

Transmission of retroviruses by transfusion of screened blood in patients undergoing cardiac surgery.

We determined the rates of seroconversion to human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus Type I (HTLV-I) in a cohort of patients receiving transfusions of blood components screened for antibody to HIV-1. Preoperative and postoperative serum samples were collected from 4163 adults undergoing cardiac surgery who received 36,282 transfusions of blood components. The postoperative samples from all patients were tested for serologic evidence of HIV-1 infection, and those that were positive were compared with the corresponding preoperative samples. One case of HIV-1 transmission by transfusion of screened blood components was identified; two preexisting HIV-1 infections were found. Samples from 2749 patients were tested similarly for serologic evidence of HTLV-I infection; these patients received 20,963 units of blood components. Five new cases and two preexisting cases of HTLV-I infection were detected. The observed risk of HIV-1 transmission by transfusion was 0.003 percent per unit; the risk of HTLV-I transmission was 0.024 percent per unit. We conclude that there is a very small risk of HTLV-I infection from transfused blood products that have been screened for antibodies to HIV-1, but that it is nearly 10-fold higher than the risk of HIV-1 infection.

Acquired Immunodeficiency Syndrome

Activation of the complement system by recombinant tissue plasminogen activator.

Recent trials have shown that recombinant tissue plasminogen activator (rt-PA) is an effective thrombolytic agent in patients with acute myocardial infarction. Because rt-PA converts plasminogen to plasmin, which is known to activate complement in vitro, we tested the hypothesis that rt-PA can induce in vivo activation of complement. Studies were performed in 12 patients with acute myocardial infarction. Six control patients had patent coronary arteries and did not receive rt-PA; these patients had normal values of the components of the complement system C4a (409 +/- 111 ng/ml) and C5a (8.8 +/- 1.8 ng/ml) with a slight elevation of C3a (204 +/- 6.6 ng/ml) in samples collected before coronary arteriography (253 +/- 25 minutes after onset of pain). After coronary arteriography, there was a slight decrease in the values of C4a (224 +/- 37 ng/ml), C5a (7.3 +/- 1.3 ng/ml) and C3a (164 +/- 35 ng/ml). The remaining six patients had complete coronary occlusion and received rt-PA (80 to 150 mg intravenously). In this treated group, before coronary arteriography the values of C4a (406 +/- 51.6 ng/ml) and C5a (8.1 +/- 1.9 ng/ml) were normal, and those of C3a were slightly elevated (250 +/- 76 ng/ml). All complement values obtained before rt-PA were similar to those in the untreated group. However, after administration of rt-PA (but before any angiographically detectable reperfusion), there was a striking increase in C4a (2,265 +/- 480 ng/ml; p less than 0.01), C3a (600 +/- 89 ng/ml; p less than 0.05) and C5a (30.0 +/- 4.5 ng/ml; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Posttransfusion hepatitis type A.

Hepatitis A virus (HAV) transmission through blood is a rare but potential cause of posttransfusion hepatitis. We can now document such a case supported by laboratory evidence of HAV in the donor blood. A 10-year-old girl manifested icteric hepatitis A 31 days after receiving a single unit of packed RBCs from a donor who subsequently experienced hepatitis A and died in hepatic failure. Hepatitis A virus antigen was detected in the donor's hepatocytes and in plasma obtained from the original donor unit. The density in cesium chloride of the HAV antigenic activity from the liver and plasma ranged from 1.33 to 1.37 g/cu cm, which is similar to that reported for infectious HAV particles. The implicated donor plasma had normal aminotransferase levels and was negative for antibody to HAV. Inoculation of this plasma into a chimpanzee resulted in the development of hepatitis A 23 days later based on the appearance of fecal HAV antigen, hepatitis, and IgM anti-HAV seroconversion. These data clearly document the presence of HAV in the donor sample that produced posttransfusion hepatitis A.

Antibodies, Viral

Preoperative disseminated intravascular coagulation associated with aortic aneurysms. A prospective study of 76 cases.

A prospective study of 76 preoperative patients with aortic aneurysms was undertaken to determine the true incidence of associated disseminated intravascular coagulation (DIC). Although 39% of the patients showed a notable elevation of the fibrin split products level, only three had thrombocytopenia and a clinical bleeding diathesis, as well. Thus, clinically overt DIC occurred preoperatively in only 4% of the patients. All three patients had extensive aneurysms that involved the thoracoabdominal aorta. Preoperative fibrinogen levels in this series tended to be high-normal or elevated and were not good indicators of underlying excessive fibrinolysis. Hemostatic abnormalities, such as ecchymoses and petechiae, may be the key to the clinical diagnosis of DIC in preoperative patients with aortic aneurysms.

Aged

Trimellitic anhydride Toxicity. A cause of acute multisystem failure.

A person exposed to trimellitic anhydride (TMA) an epoxy resin widely used in industry, experienced respiratory failure, anemia, and gastrointestinal bleeding. A lung biopsy specimen demonstrated intra-alveolar hemorrhage and damage to alveolar lining cells. The patient and six co-workers were examined. Results indicated the presence of hemolytic antibodies directed against TMA-haptenized erythrocytes, IgG, IgA, and IgM antibodies directed against TMA-erythrocyte complexes, and antibodies against TMA-human serum albumin. Antibody levels in the patient were greater than in the co-workers. The elevated antibody levels demonstrate the antigenic potential of TMA. However, the cause of the pulmonary and hematologic damage remains uncertain and may represent either immunologic or direct toxic effects of TMA. In patients with multisystem failure of this nature, occupational hazards should be added to the differential diagnosis.

Adult

Comparison of Brucella abortus and Brucella melitensis infections of mice and their effect on acquired cellular resistance.

By using mice infected with strains of Brucella abortus and Brucella melitensis we examined the histological responses to infection, the relationship of histology to persistence of organisms, and the relation of persistence of organisms to the acquisition of acquired cellular resistance (ACR). Infection with B. abortus resulted in well-formed granulomas in the livers, which persisted for more than 30 days. In contrast, infection with B. melitensis produced microabscesses in the livers which resolved before 30 days. The clearance of organisms from the tissues was also different. A total of 30 days after infection, large numbers of viable bacteria were recovered from the tissues of B. abortus-infected mice whereas bacteria were no longer recoverable from B. melitensis-infected animals. ACR to Listeria monocytogenes, another intracellular pathogen, persisted for more than 30 days in B. abortus-infected mice but waned rapidly in B. melitensis-infected animals. This disappearance of ACR due to B. melitensis paralleled the clearance of bacteria from the tissues.

Animals

Experimentally induced bleomycin sulfate pulmonary toxicity: histopathologic and ultrastructural study in the pheasant.

Morphological alterations in the lungs of pheasants after prolonged high-dosage administration of bleomycin sulfate were studied by light and electron microscopy. Nontreated birds acted as controls, and their lungs showed no abnormalities. Lungs of bleomycin-treated pheasants revealed collapse alternating with overexpansion, marked cuboidalization of atrial epithelium, and incipient interstitial fibrosis. There were neither lymphoplasmacytic or eosinophilic infiltrates, nor evidence of vasculitis. Ultrastructurally, type 1 alveolar epithelial cells were either reactive or conspicuously absent in the air capillaries. Type 2 alveolar epithelial cells appeared hyperplastic with numerous lamellar bodies, many of which extruded into air spaces. Immature fibroblasts were noted in the vicinity of collagen fibrils or amorphous material resembling elastin. No immune deposits were present in basement membranes. These findings are consistent with a direct toxic effect of bleomycin to the pheasant lung rather than a drug hypersensitivity reaction. Reproduction of the bleomycin lesion in a nonmammalian species corroborates even further the high propensity of the drug to affect the lung.

Animals