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Biomedical subjects

L Aledort

Publications and source records attributed to L Aledort.

At least 19 recordsLinked to original sources
PubMed1995

Transfusion requirements, risks, and costs for patients with malignancy.

BACKGROUND: Patients with cancer often develop significant anemia, which traditionally has been successfully managed by transfusion. Although substantially safer than in the past, transfusions continue to carry a variety of risks. The recent licensing of erythropoietin now provides a second treatment option, which indicates a need to reassess the use of transfusion to manage anemia in these patients. STUDY DESIGN AND METHODS: A 12-month retrospective chart review of all patients receiving outpatient transfusions at a large institution was used to identify patients with solid tumors (including lymphoma) requiring transfusions for any cause. Transfusions were considered as aberrations if they necessitated unusual laboratory monitoring or resulted in clinical evidence of a transfusion reaction. Patient charges proximately related to the transfusion were calculated. RESULTS: A total of 219 patients requiring transfusions were identified, with 483 transfusion episodes and the use of 812 units of red cells to manage anemia (mean, 3.71 units/patient). A total of 100 aberrations were recorded. Twenty-two (10%) of 219 patients had a positive antibody screen that required further work-up; transfusion reactions occurred in 19 patients (8.7%). CONCLUSION: Careful assessment by hematologists and oncologists of the risk:benefit ratio of erythropoietin and transfusion in patients with cancer is urged.

Adolescent↗
PubMed1994

Inhibitors in hemophilia patients: current status and management.

The development of inhibitor antibodies is a long-standing, well-documented complication of coagulation factor replacement therapy and is difficult to treat. Previous estimates of 5-15% of patients developing inhibitors may be low, since newer data suggest a wider range of occurrence. Factors that appear to affect inhibitor development include the severity of hemophilia, age, genetics, and, possibly, the type of replacement therapy administered. Recent studies raise the concern that recombinant factor therapies may be associated with more rapid development and higher levels of inhibitors in previously untreated patients. However, results of different studies are often difficult to compare owing to differences in methodology and populations studied. Further studies standardized in design and methods are clearly needed. Management of patients with inhibitors involves control of acute bleeding episodes and, over the long term, induction of immune tolerance for the coagulation replacement therapy. Many with low or moderate levels of inhibitors may be treated simply by administering higher doses of clotting factor. Other therapies appropriate for those with high levels of inhibitors include porcine F VIII and factor VIII "bypassing" agents, such as recombinant factor VIIa. Long-term immune tolerance has been achieved through the high-dose "Bonn" regimen and immunosuppressive regimens such as the "Malmö" method. Although management of inhibitor patients has improved, it still represents a major challenge. Further research is needed to identify which patients will develop inhibitors and tolerance, as well as to develop better methods to manage, reduce, or eliminate inhibitors from these patients.

Factor IX↗
PubMed1993

Frequency of inhibitor development in haemophiliacs treated with low-purity factor VIII.

Clinical studies evaluating highly purified monoclonal-antibody-derived and recombinant-DNA-derived clotting factor concentrates in previously untreated (PUPS) severe factor VIII (FVIII) deficient haemophilia patients, have documented an increased frequency of inhibitors compared with that seen in patients who have received less pure products. However, a valid comparison of inhibitor frequency in patients treated with pure and less pure products has not been possible because appropriate studies have not been done in PUPS treated with the less pure products. To determine the frequency of inhibitor development in PUPS treated solely with less pure plasma-derived products (specific activities < 5 FVIII U/mg protein), we reviewed the records of all haemophilia patients born between 1975 and 1985 and treated with such products at any of seven centres. 89 patients with severe FVIII deficiency (< 1%) were observed and tested for inhibitors from birth to 5 years old or until 30 bleeding episodes had been treated. 25 of the 89 patients developed inhibitors (28%), and 21 of these 25 were high-titre responders (> 5 Bethesda units). This frequency of inhibitor development is greater than that reported in patients treated with monoclonal FVIII products, but the latter patients may not have been followed as long as the patients in our report. Our data may make possible a meaningful comparison with the frequency of inhibitor development in PUPS treated solely with recombinant-DNA-derived FVIII.

Age Factors↗
PubMed1990

Efficacy and safety of vapor-heated anti-inhibitor coagulant complex in hemophilia patients. FEIBA Study Group.

The study reported here was designed to measure the efficacy and safety of a vapor-heated anti-inhibitor coagulant complex (FEIBA-VH) for the treatment of bleeding episodes in patients with hemophilia A who have inhibitors to factor VIII (FVIII). FEIBA-VH, a second-generation complex, is vapor-heated for 10 hours at a temperature of 60 degrees C and a pressure of 1190 millibar (mbar) and for 1 additional hour at 80 degrees C and 1375 mbar. The current study was performed because of concern that this vapor-heating process would reduce the efficacy of FEIBA-VH as compared with non-heat-treated FEIBA (FEIBA). Forty-one patients received FEIBA-VH for 106 evaluable bleeding episodes. Ninety-three (88%) episodes were controlled, and 13 (12%) were not. Eighty-three (79%) episodes were controlled within 36 hours of the first infusion. No significant toxicity was seen. These results were compared with those of an earlier study with FEIBA. FEIBA-VH was at least as effective as FEIBA in controlling bleeding episodes and can be compared favorably to any reported treatment of bleeding episodes in hemophiliacs with inhibitors to FVIII.

Blood Coagulation Factors↗
PubMed1989

Seroepidemiologic studies of cytomegalovirus and Epstein-Barr virus infections in relation to human immunodeficiency virus type 1 infection in selected recipient populations. Transfusion Safety Study Group.

Antibodies to human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were evaluated among 1,171 persons with and without antibodies to human immunodeficiency virus type 1 (anti-HIV-1). These included 97 blood donors, 577 persons given blood components or products, and 497 controls. A significantly higher proportion of anti-HIV-1 positive than -negative donors were anti-CMV-positive, a finding associated with homosexual contact among some of the former. Among subjects with treated clotting disorders, there was no difference in prevalence of anti-CMV or anti-EBV between anti-HIV-1-positive and -negative persons. The prevalence of antibodies to EBV early antigens showed no relationship to anti-HIV-1 status. Anti-CMV positivity in anti-HIV-1-negative donors was associated with an increase in mean CD8 counts and lower mean CD4/CD8 ratio. Anti-CMV and anti-EBV positivity in anti-HIV-1-positive subjects with treated clotting disorders was not associated with a lower CD4 or higher CD8 count than HIV-1 infection alone. Subjects who developed AIDS after enrollment had no significant difference in median time from entry to diagnosis when analyzed by serologic evidence of CMV and EBV antibody status at entry, and a few subjects had AIDS at entry without serologic evidence of prior CMV or EBV infection. The overall results are consistent with acquisition and progression of HIV-1 independently of coincident CMV or EBV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Maintenance treatment of adults with chronic refractory immune thrombocytopenic purpura using repeated intravenous infusions of gammaglobulin.

Intravenous infusion of gammaglobulin (IVGG) has been extensively used in the treatment of immune thrombocytopenic purpura (ITP) in adults to acutely raise the platelet count but not as a maintenance therapy. This report describes the maintenance treatment of adults with chronic ITP using repeated infusions of 800 to 1,000 mg/kg of IVGG. Sixteen of 40 patients were able to discontinue all therapy after receiving between one and 15 infusions. Five patients achieved remission and 11 other patients became stable without therapy (SWT) maintaining a platelet count greater than 20,000/microL without bleeding. The average quantity of gammaglobulin received for all patients was 606 g per patient. Of the 30 patients who underwent but did not respond to splenectomy, 11 (37%) were able to discontinue all therapy by either achieving remission (5) or becoming SWT (6). None of the five patients who achieved remission did so after only the initial therapy; all first received between one and 12 maintenance infusions. The ten splenectomized patients who were unresponsive to IVGG also failed to subsequently respond to conventional therapy including immunosuppressive agents and androgens. No toxicity of IVGG was seen except for postinfusion headaches. IVGG is an effective although expensive maintenance therapy for adults with ITP and is useful in patients who have not responded to splenectomy.

Adult↗
PubMed1987

Assessment for evidence of non A-non B hepatitis in patients given n-heptane-suspended heat-treated clotting factor concentrates.

Nineteen patients, (2 adults, 17 children) with inherited bleeding disorders were infused with n-heptane-suspended-heated clotting factor concentrates. Twelve of the nineteen were previously untreated. Six patients were infused with Profilnine Heat-Treated and 13 with Profilate Heat-Treated. Five separate centers participated and were given various lots of concentrates for use. Blood from the seventeen children was sampled prior to entry, at infusion, 2 weeks, 6 weeks, 12 weeks and 6 months after the first infusion. The two adults were sampled every 2 weeks. Twelve of the 19 patients were followed beyond six months. Three patients demonstrated a rise in ALT during the first six months of observation with levels above 2.5 times the upper limit of normal. One of these patients showed a parallel increment in a-CMV IgM titer and a second patient, an adult, had previously received many units of single donor blood components. During the second 6 month observation interval, two patients showed a rise in ALT. One of these patients had been exposed to only one lot of concentrate with no other viral cause being determined. Two additional patients had a moderate increase in ALT up to 98 U/L (normal less than 50). No patients were clinically ill or showed jaundice during these episodes. The hepatitis episode at 11 months in the patient using one lot of concentrate, might suggest a non-viral mechanism in this instance. This study indicates that these concentrates may be associated with episodes of ALT above 2.5 times the upper limit of normal in approximately 20% of the patients treated, but the etiology of the raised ALT may not always be Non A-Non B hepatitis.

Adult↗
PubMed1986

HTLV-III/LAV antibody and immune status of household contacts and sexual partners of persons with hemophilia.

We evaluated the human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody and immune status of 88 persons living with and/or sexual partners of 43 hemophiliacs, 12 of whom had AIDS, five of whom had AIDS-related complex (ARC), 17 of whom were clinically well but HTLV-III/LAV antibody positive, and nine of whom were well and HTLV-III/LAV antibody negative. No nonhemophilic household contacts (0/50) of healthy hemophiliacs were HTLV-III/LAV antibody positive; two of 33 nonhemophilic AIDS/ARC contacts were positive. One was a spouse and one a sexual partner of a hemophiliac. One of these antibody-positive contacts herself had AIDS, and one had ARC. Antibody-negative, nonhemophilic contacts of AIDS/ARC and of antibody-positive hemophiliacs had significantly lower numbers of lymphocytes, T helper lymphocytes, and T suppressor lymphocytes than did contacts of antibody-negative hemophiliacs. We conclude that risk of HTLV-III/LAV transmission may exist for spouses and/or sexual contacts of hemophiliacs with AIDS/ARC, but we cannot now determine the risk for contacts of asymptomatic hemophiliacs.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Immune status of blood product recipients.

Persons with hemophilia are at risk of the acquired immunodeficiency syndrome (AIDS), and clinically asymptomatic hemophiliacs have shown a high incidence of AIDS-like immune abnormalities, facts leading to speculation that many hemophiliacs have been exposed to the AIDS agent through their blood products. We therefore evaluated the immune status of three groups of blood product recipients without AIDS in New York City, including 47 persons with hemophilia A receiving factor VIII concentrate, 50 persons with homozygous beta-thalassemia, and 27 persons with sickle cell anemia receiving frozen-packed RBCs and 20 healthy persons who had not received a transfusion. Hemophiliac participants had significantly lower lymphocyte counts (median, 1,826/cu mm) than did the thalassemic (6,110/cu mm) or anemic (4,443/cu mm) participants, had lower numbers of T-helper lymphocytes (median, 533 cells/cu mm v 1,733 cells/cu mm and 1,554 cells/cu mm), and had a lower T-helper/suppressor ratio (median, 0.8 v 1.8 and 2.1). These differences remained after adjustment for age and sex. Thus, AIDS-like immune abnormalities were found in patients receiving factor concentrate, but not in those receiving RBCs. These defects could be due to both an immunosuppressive effect of the lyophilized factor itself and to contact with the AIDS agent.

Acquired Immunodeficiency Syndrome↗
PubMed1980

Hypertension and propranolol therapy: effect on blood pressure, plasma catecholamines and platelet aggregation.

The effects of propranolol on blood pressure, plasma catecholamine concentration and platelet aggregation were examined in 16 patients with uncomplicated primary hypertension. The patients were studied at rest, during isometric handrip stress and 48 hours after sudden discontinuation of propranolol therapy. Plasma catecholamine concentration and platelet aggregation studies were also carried out in 11 age-matched normotensive and healthy subjects at rest. Plasma catecholamine concentration and platelet aggregation were greater in the hypertensive than in the normotensive subjects, but the difference reached statistical significance for aggregation only. Exercise significantly increased catecholamines and platelet aggregability. The administration of propranolol (240 mg/day) produced a significant decrease in systolic and diastolic blood pressue and in aggregation (the percent of light transmission at 1 microM adenosine diphosphate, at rest) and a significant increase in catecholamine concentration. However, propranolol did not prevent the changes in all these variables with exercise. The abrupt discontinuation of propranolol was not associated with any subjective or objective untoward cardiovascular effect or abnormal changes in plasma catecholamines. However, in some patients the platelet aggregation studies demonstrated a hyperaggregable state, which may be due to a state of supersensitivity of platelets to circulating catecholamines.

Blood Pressure↗
PubMed1979

Platelet aggregation in relationship to plasma catecholamines in patients with hypertension.

Plasma catecholamine concentration and platelet aggregation were studied in 22 patients with uncomplicated primary hypertension and 13 age-matched normotensive, healthy subjects at rest and in some during isometric handgrip exercise. The effect of norepinephrine (NE) infusion upon platelet aggregation was also examined. Plasma catecholamine concentration was slightly higher in the hypertensive than the normotensive group, but the difference was not significant. However, platelet aggregation to ADP was significantly greater in the hypertensive than the normotensive subjects. Exercise increased significantly both catecholamines and aggregation in both groups. Platelet aggregation was correlated with age (r = 0.62, P less than 0.01) and plasma NE (r = -0.34, P less than 0.05 for the total group of subjects). The infusion of NE increased significantly plasma NE and platelet aggregation and there was an inverse correlation between NE increase and threshold decrease (r = -0.69, P less than 0.05). Thus, plasma catecholamines and important determinants of platelet aggregation. However, in our study, uncomplicated primary hypertension was not associated with abnormal plasma catecholamine concentration. It is likely that the observed abnormal platelet aggregability to ADP represents a secondary phenomenon, possibly related to more advanced atherosclerotic vascular changes in hypertensive than normotensive subjects.

Adult↗
PubMed1976

Amino acid metabolism of platelets in leukemia.

Platelets from patients with acute myelogenous leukemia, both before and after remission induction, were evaluated for their ability to incorporate D-[U-14C]glucose into the four amino acids, glutamine, asparagine, glutamic acid, and aspartic acid. Normal platelets incorporated about 80% of the activity into the amides, glutamine and asparagine, and only 20% into their respective amino acids, glutamic acid and aspartic acid. Platelets from patients with acute myelogenous leukemia in the acute stage showed a reversal of this pattern, which then returned to normal during remission. However, the concentration of amino acids was higher than normal, suggesting that remission platelets behaved like a young cell population. The abnormal pattern of labeling could be interpreted as a defect in the platelet citric acid cycle thereby compromising its energy source.

Amino Acids↗