RESUMO
Seven patients with venous thrombosis and contraindications to traditional thrombolytic therapy, consisting of recent intracranial surgery, recent pineal or retroperitoneal hemorrhage, active genitourinary or gastrointestinal bleeding, epidural procedures, and impending surgery, were successfully treated with a modified thrombolytic regimen. To improve safety, prolonged continuous infusions of tissue plasminogen activator (tPA) was eliminated in favor of once-daily low-dose intraclot injections of tPA to minimize the amount and duration of tPA in the systemic circulation, and low-therapeutic or regional anticoagulation was used to reduce anticoagulant risks. These modifications may allow thrombolytic treatment for selected patients with severe venous thrombosis who are deemed to be at high risk.
Assuntos
Anticoagulantes/administração & dosagem , Ativador de Plasminogênio Tecidual/administração & dosagem , Trombose Venosa/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Ativador de Plasminogênio Tecidual/genética , Resultado do TratamentoRESUMO
Gray platelet syndrome (GPS) is an inherited bleeding disorder characterized by macrothrombocytopenia and absence of platelet α-granules resulting in typical gray platelets on peripheral smears. GPS is associated with a bleeding tendency, myelofibrosis, and splenomegaly. Reports on GPS are limited to case presentations. The causative gene and underlying pathophysiology are largely unknown. We present the results of molecular genetic analysis of 116 individuals including 25 GPS patients from 14 independent families as well as novel clinical data on the natural history of the disease. The mode of inheritance was autosomal recessive (AR) in 11 and indeterminate in 3 families. Using genome-wide linkage analysis, we mapped the AR-GPS gene to a 9.4-Mb interval on 3p21.1-3p22.1, containing 197 protein-coding genes. Sequencing of 1423 (69%) of the 2075 exons in the interval did not identify the GPS gene. Long-term follow-up data demonstrated the progressive nature of the thrombocytopenia and myelofibrosis of GPS resulting in fatal hemorrhages in some patients. We identified high serum vitamin B(12) as a consistent, novel finding in GPS. Chromosome 3p21.1-3p22.1 has not been previously linked to a platelet disorder; identification of the GPS gene will likely lead to the discovery of novel components of platelet organelle biogenesis. This study is registered at www.clinicaltrials.gov as NCT00069680 and NCT00369421.
Assuntos
Cromossomos Humanos Par 3/genética , Síndrome da Plaqueta Cinza/genética , Síndrome da Plaqueta Cinza/fisiopatologia , Adolescente , Adulto , Plaquetas/ultraestrutura , Separação Celular , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Citometria de Fluxo , Ligação Genética , Estudo de Associação Genômica Ampla , Síndrome da Plaqueta Cinza/sangue , Humanos , Masculino , Repetições de Microssatélites , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Neutrófilos/ultraestrutura , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Vitamina B 12/sangue , Adulto JovemRESUMO
Iron deficiency is one of the most common disorders affecting humans, and iron-deficiency anemia continues to represent a major public health problem worldwide. It is especially common among women of childbearing age because of pregnancy and menstrual blood loss. Additional patient groups include those with other sources of blood loss, malnutrition, or gut malabsorption. Iron-deficiency anemia remains prevalent despite the widespread ability to diagnose the disease and availability of medicinal iron preparations. Therefore, new approaches are needed to effectively manage these patient populations. In this review, the diagnosis and treatment of iron-deficiency anemia are discussed with emphasis placed on consideration of patient-specific features. It is proposed that all patients participate in their own care by helping their physician to identify a tolerable daily iron dose, formulation, and schedule. Dosing cycles are recommended for iron replacement based on the tolerated daily dose and the total iron deficit. Each cycle consists of 5000 mg of oral elemental iron ingested over at least 1 month with appropriate follow-up. This approach should assist physicians and their patients with the implementation of individualized treatment strategies for patients with iron-deficiency anemia.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Ferro/administração & dosagem , Oligoelementos/administração & dosagem , Adulto , Anemia Ferropriva/etiologia , Suplementos Nutricionais , Humanos , Individualidade , Ferro/farmacocinética , Oligoelementos/farmacocinética , Falha de TratamentoRESUMO
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic disorder of the bone marrow that produces intravascular hemolysis, proclivity to venous thrombosis, and hematopoietic failure. Mutation in the PIG-A gene of a hematopoietic stem cell abrogates synthesis of glycosylphosphoinositol (GPI) anchors and expression of all GPI-anchored proteins on the surface of progeny erythrocytes, leukocytes, and platelets. Urokinase plasminogen activator receptor (uPAR), a GPI-linked protein expressed on neutrophils, mediates endogenous thrombolysis through a urokinase-dependent mechanism. Here we show that membrane GPI-anchored uPAR is decreased or absent on granulocytes and platelets of patients with PNH, while soluble uPAR (suPAR) levels are increased in patients' plasma. Serum suPAR concentrations correlated with the number of GPI-negative neutrophils and were highest in patients who later develop thrombosis. In vitro, suPAR is released from PNH hematopoietic cells and from platelets upon activation, suggesting that these cells are the probable source of plasma suPAR in the absence of GPI anchor synthesis and trafficking of uPAR to the cell membrane. In vitro, the addition of recombinant suPAR results in a dose-dependent decrease in the activity of single-chain urokinase. We hypothesized that suPAR, prevents the interaction of urokinase with membrane-anchored uPAR on residual normal cells.
Assuntos
Fibrinolisina/análise , Células-Tronco Hematopoéticas/metabolismo , Hemoglobinúria Paroxística/sangue , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Trombose/sangue , Ativador de Plasminogênio Tipo Uroquinase/sangue , Células Sanguíneas/metabolismo , Feminino , Regulação da Expressão Gênica/genética , Hematopoese/genética , Hemoglobinúria Paroxística/complicações , Hemoglobinúria Paroxística/genética , Hemólise/genética , Humanos , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mutação , Transporte Proteico/genética , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , Solubilidade , Trombose/etiologia , Trombose/genética , Ativador de Plasminogênio Tipo Uroquinase/genéticaRESUMO
OBJECTIVE: To characterize a monoclonal IgG(kappa) (MAb) from a patient with planar xanthoma that precipitated with serum lipids at reduced temperature. METHODS: The molecular weight (Mr), sensitivity to proteases, and glycosylation of the purified MAb were analyzed. The specificity of the MAb was tested by measuring cryoprecipitation with pure high- (HDL) and low-density (LDL) lipoproteins. The effect of choline, phosphocholine, and glycerol 3-phosphate on the precipitation temperature of LDL by the MAb was studied. RESULTS: The MAb was larger than normal IgG due to hyperglycosylation of the MAb light chain. It formed cryoprecipitates with pure HDL and LDL as well as the lipids extracted from these lipoproteins. Fab fragments of the MAb lowered the temperature of its precipitation with LDL. Choline, phosphocholine, and glycerol 3-phosphate also lower the precipitation temperature. CONCLUSION: This is the first human IgG reported with apparent specificity for phosphocholine antigens. Its precipitation with lipids at reduced temperature suggests that it recognizes conformations of phospholipid head groups that develop below core body temperature.
Assuntos
Imunoglobulina G/imunologia , Xantomatose/imunologia , Anticorpos Monoclonais/imunologia , HDL-Colesterol/isolamento & purificação , LDL-Colesterol/isolamento & purificação , Cromatografia em Gel , Eletroforese em Gel de Poliacrilamida , Humanos , Técnicas In VitroRESUMO
The hypereosinophilic syndromes (HESs) are characterized by persistent marked eosinophilia (>1500 eosinophils/mm(3)), the absence of a primary cause of eosinophilia (such as parasitic or allergic disease), and evidence of eosinophil-mediated end organ damage. Cardiovascular complications of HES are a major source of morbidity and mortality in these disorders. The most characteristic cardiovascular abnormality in HES is endomyocardial fibrosis. Patients who have an HES also may develop thrombosis, particularly in the cardiac ventricles, but also occasionally in deep veins. Because of the rarity of these disorders, specific guidelines for the management of the cardiac and thrombotic complications of HES are lacking. This article reviews the diagnosis and management of the cardiovascular manifestations of HES.
Assuntos
Cardiopatias , Síndrome Hipereosinofílica , Trombose Coronária/diagnóstico , Trombose Coronária/etiologia , Trombose Coronária/fisiopatologia , Trombose Coronária/terapia , Citocinas/metabolismo , Diagnóstico Diferencial , Cardiopatias/diagnóstico , Cardiopatias/fisiopatologia , Cardiopatias/terapia , Humanos , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/fisiopatologia , Síndrome Hipereosinofílica/terapiaRESUMO
We studied the blood coagulation system of 14 patients with metastatic malignancies before and after they had undergone major surgery. In addition to measuring a battery of coagulation factors, we assessed the function of the system with assays of whole blood thrombin generation. With the exceptions of factor VIII (fVIII), which increased, and fibrinogen and fIX, which did not change, the activities of all the pro- and anticoagulant proteins were significantly lower postoperatively. However, the thrombin generating capacity of the system was relatively preserved. Although the integral of thrombin activity over time was lower after surgery, the mean peak thrombin concentration was unchanged and the time to clot formation was shortened. Similar changes could be reproduced by lowering the concentrations of pro- and anticoagulant factors together in control blood samples. Therefore, simultaneous reductions in pro- and anticoagulant proteins postoperatively worked to maintain the functional integrity of the blood coagulation system.
Assuntos
Fatores de Coagulação Sanguínea/análise , Hemostasia Cirúrgica , Trombina/biossíntese , Adulto , Fatores de Coagulação Sanguínea/metabolismo , Testes de Coagulação Sanguínea , Carcinoma/complicações , Carcinoma/cirurgia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Fatores de TempoRESUMO
BACKGROUND: High serum vitamin B12 concentrations have been reported in patients with hepatic disease, disseminated neoplasia, myeloproliferative disorders, and hypereosinophilic syndromes. We recently discovered an extraordinarily increased vitamin B12 concentration in a patient without these underlying conditions. METHODS: Affinity and size-exclusion chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and ELISA methods were used to determine the cause of the increased vitamin B12 concentrations in this patient's serum. RESULTS: The protein G column eluates from 2 apparently healthy volunteers and 2 patients with recent vitamin B12 treatment for anemia had vitamin B12 concentrations of <74 pmol/L, whereas the vitamin B12 concentration in the protein G column eluate from the patient was 7380 pmol/L. The elution profile from size-exclusion chromatography of vitamin B12-binding proteins in the patient's serum revealed an abnormal vitamin-B12-binding protein. SDS-PAGE analysis of the concentrated eluates from the protein G column, under reducing conditions, revealed an additional band with an apparent molecular mass of 76 kDa, which was not present in control column eluates. MALDI-TOF MS identified this band as an IgM heavy chain. By use of a modified ELISA, we determined that the IgM present in the patient's eluates was associated with the IgG to form IgG-IgM immune complexes. CONCLUSIONS: This case demonstrates the unusual circumstance of a patient with markedly increased vitamin B12 concentrations attributed to immune complexes composed of IgG, IgM, and vitamin B12 and illustrates techniques that can be used to identify this occurrence.
Assuntos
Esclerose Lateral Amiotrófica/sangue , Complexo Antígeno-Anticorpo/sangue , Demência/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Vitamina B 12/sangue , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/diagnóstico , Anticorpos Bloqueadores/sangue , Anticorpos Heterófilos/sangue , Cromatografia , Técnicas de Laboratório Clínico/métodos , Demência/complicações , Reações Falso-Positivas , Humanos , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Vitamina B 12/imunologia , Vitamina B 12/metabolismoRESUMO
OBJECTIVE: To describe a case of venlafaxine-induced ecchymoses. METHODS: A patient with a history of ecchymoses coincident with venlafaxine therapy was rechallenged with the drug. Her platelet function was assessed with aggregation and ATP release studies before the rechallenge and after she developed ecchymoses. In addition, the effect of venlafaxine on platelet aggregation and ATP release was studied in vitro by adding the drug to platelet-rich plasma from normal donors. RESULTS: After 4 wk of treatment with venlafaxine our patient developed extensive ecchymoses. At that time her platelet aggregation and release responses to epinephrine, ADP, collagen, and arachidonic acid were markedly suppressed. Adding venlafaxine to normal platelet-rich plasma also dramatically reduced the aggregation and release responses to the same agonists as well as to serotonin, but the concentrations of venlafaxine required were 1000-fold greater than those normally achieved clinically. CONCLUSIONS: Our patient demonstrated an idiosyncratic hypersensitivity to the platelet inhibitory effects of venlafaxine. Because venlafaxine is an inhibitor of serotonin uptake by platelets and neurons, this mechanism may contribute to the impact of this drug on platelet function. However, our in vitro studies suggest that this hypothesis is inadequate to explain the observations completely.
Assuntos
Cicloexanóis/efeitos adversos , Cicloexanóis/farmacologia , Equimose/induzido quimicamente , Agregação Plaquetária/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Trifosfato de Adenosina/metabolismo , Adulto , Ácido Araquidônico/farmacologia , Colágeno/metabolismo , Colágeno/farmacologia , Epinefrina/farmacologia , Feminino , Humanos , Serotonina/metabolismo , Fatores de Tempo , Cloridrato de VenlafaxinaRESUMO
STUDY OBJECTIVE: To determine whether lepirudin flushes are more effective than heparinized saline in preventing withdrawal occlusion of central venous access devices. DESIGN: Randomized, double-blind clinical trial. SETTING: Research institution-tertiary referral center. PATIENTS: Forty-nine adults undergoing bone marrow transplantation for hematologic malignancies or metastatic solid tumors. INTERVENTION: Twenty-four patients received heparin and 25 received lepirudin flushes. The heparin dose was 3 ml of porcine heparin 100 U/ml (300 U) per catheter lumen at least once/day; the lepirudin dose was 3 ml of lepirudin 100 microg/ml (300 microg) per catheter lumen at least once/day. After 3-4 weeks, all 49 patients received the heparin flushes. MEASUREMENTS AND MAIN RESULTS: Efficacy was assessed by the frequency with which the patients were treated with alteplase instillations for withdrawal occlusion of their central venous access devices during the first 4 months of catheterization. Three (12.5%) patients treated with heparin alone and five (20%) treated initially with lepirudin required alteplase instillations for an estimated relative risk with lepirudin versus heparin of 1.6 (95% confidence interval [CI] 0.40-13.86, p=0.70). CONCLUSION: Lepirudin was not more effective than heparin, which may have been related to the conservative dose of lepirudin administered. However, higher lepirudin doses are likely to incur an unacceptable risk of systemic anticoagulation.
Assuntos
Anticoagulantes/uso terapêutico , Cateterismo Venoso Central/efeitos adversos , Heparina/uso terapêutico , Trombose/prevenção & controle , Anticoagulantes/efeitos adversos , Transplante de Medula Óssea , Método Duplo-Cego , Feminino , Fibrinolíticos/uso terapêutico , Heparina/efeitos adversos , Hirudinas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Trombose/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêuticoRESUMO
PURPOSE: To increase nurses' knowledge of the Factor V Leiden (FVL) genetic trait for venous thromboembolism. ORGANIZING FRAMEWORK: An overview of the history, prevalence, and predisposition of the FVL genetic mutation, including who should be tested and how and in what circumstances people with FVL should be treated. FINDINGS: FVL is the most commonly recognized genetic trait associated with venous thrombosis. It is found predominantly in Caucasian populations. Biochemically it causes "activated protein C resistance (APCR)." The decision to test for FVL depends on whether the information gained will potentially improve the health care of the person or family. For people who have had deep venous thrombosis, testing for FVL will likely not alter treatment approaches. Currently the advantage for testing is primarily limited to asymptomatic family members who carry FVL and who have had deep vein thrombosis. Close relatives who also carry the mutated gene might benefit from prophylactic anticoagulation when their risk of thrombosis is increased by temporary factors such as surgery. CONCLUSIONS: Nurses are in a unique position to provide accurate information and counseling when patients and their family members are presented with the results of thrombophilia testing.
Assuntos
Resistência à Proteína C Ativada/genética , Fator V/genética , Predisposição Genética para Doença/genética , Tromboembolia/genética , Trombose Venosa/genética , Resistência à Proteína C Ativada/diagnóstico , Resistência à Proteína C Ativada/epidemiologia , Adulto , Distribuição por Idade , Idoso , Anticoagulantes/uso terapêutico , Terapia de Reposição de Estrogênios/efeitos adversos , Triagem de Portadores Genéticos , Aconselhamento Genético , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/prevenção & controle , Testes Genéticos , Saúde Global , Humanos , Incidência , Pessoa de Meia-Idade , Papel do Profissional de Enfermagem , Educação de Pacientes como Assunto , Seleção de Pacientes , Linhagem , Prevalência , Fatores de Risco , Tromboembolia/epidemiologia , Tromboembolia/prevenção & controle , Trombose Venosa/epidemiologia , Trombose Venosa/prevenção & controle , População Branca/genética , População Branca/estatística & dados numéricosRESUMO
PURPOSE: To evaluate the use of pulsed high-intensity focused ultrasound exposures to improve tissue plasminogen activator (tPA)-mediated thrombolysis in an in vitro model. MATERIALS AND METHODS: All experimental work was compliant with institutional guidelines and HIPAA. Clots were formed by placing 1 mL of human blood in closed-off sections of pediatric Penrose tubes. Four experimental groups were evaluated: control (nontreated) clots, clots treated with pulsed high-intensity focused ultrasound only, clots treated with tPA only, and clots treated with pulsed high-intensity focused ultrasound plus tPA. The focused ultrasound exposures (real or sham) were followed by incubations of the clots in tPA with saline or in saline only. Thrombolysis was measured as the relative reduction in the mass of the clot. D-Dimer assays also were performed. Two additional experiments were performed and yielded dose-response curves for two exposure parameters: number of pulses per raster point and total acoustic power. Radiation force-induced displacements caused by focused ultrasound exposures were simulated in the clots. A Tukey-Kramer honestly significant difference test was performed for comparisons between all pairs of experimental groups. RESULTS: The clots treated with focused ultrasound alone did not show significant increases in thrombolysis compared with the control clots. The clots treated with focused ultrasound plus tPA showed a 50% ([30.2/20.1]/20.1) increase in the degree of thrombolysis compared with the clots treated with tPA only (P < .001), further corroborating the d-dimer assay results (P < .001). Additional experiments revealed how increasing both the number of pulses per raster point and the total acoustic power yielded corresponding increases in the thrombolysis rate. In the latter experiment, simulations performed at a range of power settings revealed a direct correlation between increased displacement and observed thrombolysis rate. CONCLUSION: The rate of tPA-mediated thrombolysis can be enhanced by using pulsed high-intensity focused ultrasound exposure in vitro.
Assuntos
Trombose/terapia , Terapia por Ultrassom , Humanos , Terapia por Ultrassom/métodosRESUMO
OBJECTIVES: Cytokine mobilization of progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia. BACKGROUND: Patients with coronary artery disease (CAD) have low numbers of endothelial progenitor cells compared with healthy subjects. METHODS: Granulocyte colony-stimulating factor (G-CSF), 10 microg/kg/day for five days, was administered to 16 CAD patients. Progenitor cells were measured by flow cytometry; ischemia was assessed by exercise stress testing and by dobutamine stress cardiac magnetic resonance imaging. RESULTS: Granulocyte colony-stimulating factor increased CD34+/CD133+ cells in the circulation from 1.5 +/- 0.2 microl to 52.4 +/- 10.4 microl (p < 0.001), similar to the response observed in 15 healthy subjects (75.1 +/- 12.6 microl, p = 0.173). Indices of platelet and coagulation activation were not changed by treatment, but C-reactive protein increased from 4.5 +/- 1.3 mg/l to 8.6 +/- 1.3 mg/l (p = 0.017). Two patients experienced serious adverse events: 1) non-ST-segment elevation myocardial infarction (MI) 8 h after the fifth G-CSF dose, and 2) MI and death 17 days after treatment. At 1 month after treatment, there was no improvement from baseline values (i.e., reduction) in wall motion score (from 25.7 +/- 2.1 to 28.3 +/- 1.9, p = 0.196) or segments with abnormal perfusion (7.6 +/- 1.1 to 7.7 +/- 1.1, p = 0.916) and a trend towards a greater number of ischemic segments (from 4.5 +/- 0.6 to 6.1 +/- 1.0, p = 0.068). There was no improvement in exercise duration at 1 month (p = 0.37) or at 3 months (p = 0.98) versus baseline. CONCLUSIONS: Granulocyte colony-stimulating factor administration to CAD patients mobilizes cells with endothelial progenitor potential from bone marrow, but without objective evidence of cardiac benefit and with the potential for adverse outcomes in some patients.
Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Idoso , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
The purpose of this study was to determine whether chronic thyroid hormone suppression therapy (THST) is prothrombotic. We obtained blood samples from 14 thyroid cancer patients while on THST and after they had become hypothyroid for radioiodine whole-body scanning and therapy. Prothrombin fragment 1 + 2, fibrinogen, factor VIII, antithrombin, tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor 1 (PAI-1), PAI-1/tPA, and C-reactive protein were significantly (P < 0.05) higher in the hyper- than in the hypothyroid state, whereas protein C and plasmin-antiplasmin complexes were significantly lower during the hyperthyroid period. When the 10 female patients were hyperthyroid, their levels of prothrombin fragment 1 + 2, fibrinogen, protein S, antithrombin, tPA, PAI-1, and PAI-1/tPA were significantly higher (P = 0.05) than in healthy female controls, whereas when the female patients were hypothyroid, their antithrombin and plasmin-antiplasmin were lower and their protein S was higher than in controls. Factor II, plasminogen, and D-dimer were not significantly affected by the thyroid status in either assessment. In conclusion, we found evidence that the majority of patients treated with THST have a prothrombotic profile.
Assuntos
Trombose/etiologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Adulto , Idoso , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Proteína S/análise , Tireotropina/sangue , Ativador de Plasminogênio Tecidual/sangueRESUMO
Because central venous catheters often become blocked by clot at their tip despite heparin flushes, a more effective anticoagulant is needed. We hypothesize that lepirudin, a recently introduced protein anticoagulant, might be more effective than heparin because of its tendency to adsorb to silicone, a commonly used catheter material. We preliminarily tested this hypothesis in vitro by measuring residual lepirudin and heparin activity at the tip of a catheter that had been submerged in a flowing stream of water for various periods of time. We observed that lepirudin is less readily removed than heparin from the catheter by fluid washing over it. This "slow-release" property of lepirudin might provide prolonged protection against clot formation at the catheter tip. A clinical trial will be necessary, however, to determine whether this property translates into significant improvement in catheter function.
Assuntos
Anticoagulantes/química , Cateterismo Venoso Central/instrumentação , Hirudinas/química , Proteínas Recombinantes/química , Silicones/química , Adsorção , Análise de Variância , Preparações de Ação Retardada , Heparina/química , Hirudinas/análogos & derivados , Humanos , Modelos Anatômicos , Reologia , Irrigação Terapêutica , Veia Cava Superior , Água/químicaRESUMO
STUDY OBJECTIVE: To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. DESIGN: Retrospective analysis of a randomized phase II trial. SETTING: National Institutes of Health clinical research center. PATIENTS: Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer. INTERVENTION: Each patient received either intravenous docetaxel 30 mg/m2/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression. MEASUREMENTS AND MAIN RESULTS: None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025). CONCLUSION: The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Paclitaxel/análogos & derivados , Paclitaxel/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Taxoides , Talidomida/efeitos adversos , Trombose Venosa/induzido quimicamente , Idoso , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Talidomida/uso terapêuticoRESUMO
BACKGROUND: Leukapheresis procedures are generally performed at citrate anticoagulation rates extrapolated from shorter plateletpheresis procedures. However, neither the metabolic effects nor the management of associated symptoms have been critically evaluated during leukapheresis in healthy donors. STUDY DESIGN AND METHODS: Symptom assessments (n = 315) and laboratory analyses (n = 49) were performed during 244 procedures performed with and 71 without prophylactic calcium (Ca) chloride or Ca gluconate given at a dose linked to the citrate infusion rate (1.0-2.2 mg/kg/min). RESULTS: During leukapheresis of 12 to 25 L processed, ionized Ca and ionized magnesium (Mg) decreased as much as 35 and 56 percent, respectively, each exhibiting a tight negative correlation with marked increases in serum citrate levels. Significant increases in urinary Ca and Mg excretion accompanied the renal excretion of a large citrate load. Serum divalent cation levels remained depressed 24 hours after leukapheresis. Symptoms were more frequent in donors who were women, had low initial total Mg levels, and underwent procedures in which larger volumes were processed at higher citrate infusion rates. Ca infusions reduced clinically significant paresthesias by 96 percent and also attenuated decreases in serum potassium. Ca chloride maintained higher Ca levels than Ca gluconate. CONCLUSIONS: Prophylactic Ca infusions safely attenuate the marked metabolic effects of citrate administration and promote faster, more comfortable, leukapheresis procedures.