RESUMEN
WHAT IS KNOWN AND OBJECTIVE: Immune destruction and decreased platelet production are major components of immune thrombocytopenia (ITP) pathogenesis. The aim of this study was to critically evaluate the role of combination therapy in relapsed/refractory ITP and the concept of medication tapering/discontinuation. COMMENT: Although a number of combination regimens have been reported, little is published on combining immunosuppression with thrombopoietin receptor agonists (TPO-RAs). We report a case of refractory ITP successfully treated with combination immunosuppression added to eltrombopag. An aggressive combination approach resulted in complete remission and allowed for stepwise drug tapering. WHAT IS NEW AND CONCLUSION: Combination immunosuppression can potentiate the effect of TPO-RAs. This mechanistically reasonable strategy could result in a more rapid response than the more popular, sequential, single-agent strategy. Stepwise tapering can be successfully implemented. Comparing sequential single-agent therapy with early combination approach warrants a more extensive study.
Asunto(s)
Enfermedad Crónica/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Trombocitopenia/tratamiento farmacológico , Terapia Combinada/métodos , Humanos , Terapia de Inmunosupresión/métodos , Receptores de Trombopoyetina/agonistas , Trombocitopenia/inmunologíaRESUMEN
Kinetic parameters for the action of bovine alpha-thrombin on 24 commercially available peptide p-nitroanilides have been determined. The selectivity constant, kcat/Km, ranges from 3.3 X 10(1) to 1.1 X 10(8) M-1 X S-1 for the poorest and the best substrates, respectively. The best substrates for thrombin were identified as those with arginine in the P1 position, proline or a proline homolog in the P2 position, and an apolar amino acid in the P3 position. Quantitative distinction between lysine and arginine in the P1 position and other amino acids in the P2-P4 positions of the substrate is reported from the changes in the kinetic parameters for substrates differing in only a single amino acid in these positions. Effects of NaCl, CaCl2 and poly(ethylene glycol) concentrations, pH and temperature on the action of thrombin on selected substrates have been assessed. A source of large systematic error in thrombin concentration estimates was identified as resulting from adsorption losses. These losses were eliminated by inclusion of poly(ethylene glycol) in dilution and reaction buffers.
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Trombina/metabolismo , Compuestos de Anilina/metabolismo , Animales , Cloruro de Calcio/farmacología , Bovinos , Concentración de Iones de Hidrógeno , Cinética , Oligopéptidos/metabolismo , Concentración Osmolar , Cloruro de Sodio/farmacología , Especificidad por Sustrato , TemperaturaRESUMEN
Of 455 acute nonlymphocytic leukemia (ANL) patients who underwent marrow transplantation, 95 (21%) relapsed a median of 6.5 months posttransplantation and 62 received further treatment. Twenty achieved remission. Success of therapy was related to the length of time from marrow transplant to relapse and to the use of cytarabine (Ara-C) and daunomycin. Aggressive chemotherapy for patients relapsing within 100 days of marrow transplant was associated with a high incidence of early death (six of 14 patients) and a low probability of remission (one of 14). Of 23 patients who relapsed in excess of 1 year from marrow transplant, 15 achieved a complete remission. The median disease-free survival is 6 months (range, 0.4 to 53+ months). Acute lymphocytic leukemia (ALL) recurred in 130 of 366 patients (36%), and 94 received further therapy. Fifty-two achieved a remission. Remissions were more common in late relapse patients (greater than 1 year from transplantation): 65% v 7% for those relapsing within 100 days from transplant (P less than .05). Testicular relapse occurred in 11 patients and was the sole site of relapse in seven. Three are alive and free of disease 58 to 109+ months after relapse. The median survival for the treated patients is 10.5 months (range, 5 to 109+ months). We propose that reinduction be attempted in all patients relapsing greater than 1 year from marrow transplantation. Ara-C and daunomycin should be employed in the treatment of ANL. The decision for treatment of patients relapsing earlier than 1 year should be made on an individual basis.
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Trasplante de Médula Ósea , Leucemia Mieloide Aguda/terapia , Recurrencia Local de Neoplasia/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Terapia Combinada , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Recurrencia Local de Neoplasia/mortalidad , Recurrencia , Inducción de RemisiónRESUMEN
We report 4 acute promyelocytic leukemia cases that demonstrated karyotypic abnormalities in addition to the classic t(15;17) translocation and did not contain any Auer rods in leukemic blasts and dysplastic promyelocytes, either in the peripheral blood or in the bone marrow. Morphologically, 2 cases were characterized as the common or hypergranular type, and 2 were otherwise typical of the microgranular variant. Three patients had typical clinical and laboratory signs of disseminated intravascular coagulation. Immunophenotypic analysis of the blasts and dysplastic promyelocytes by dual-color flow cytometry revealed an immunoprofile consistent with acute promyelocytic leukemia. Cytogenetic analysis of the bone marrow revealed the following karyotypes: case 1, [47,XY,t(15;17)(q22;q12),+21]; case 2, [47,XY,t(15;17)(q22;q12),-16,+2 mar]; case 3, [47,XX,t(15;17)(q22;q12)ider(17)(q10),+8]; and case 4, [47,XY,der(5)t(5;?9)(p15;q12).t(15;17)(q22;q12]. Review of an additional 7 cases with t(15;17) as the sole cytogenetic abnormality revealed Auer rods in all cases. Our findings emphasize the importance of cytogenetics in evaluating acute myeloid leukemias. Acute promyelocytic leukemia without Auer rods, which may be morphologically confused with other types of leukemia (in particular, acute myeloblastic leukemia, type M2 or M5) or agranulocytosis with maturation arrest, appears to be associated with additional chromosomal abnormalities and possibly a poorer prognosis.
Asunto(s)
Aberraciones Cromosómicas/genética , Cuerpos de Inclusión , Leucemia Promielocítica Aguda/genética , Adulto , Anciano , Células de la Médula Ósea/patología , Cromosomas Humanos Par 15/genética , Cromosomas Humanos Par 17/genética , Resultado Fatal , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Cuerpos de Inclusión/patología , Cariotipificación , Leucemia Promielocítica Aguda/patología , Masculino , Persona de Mediana Edad , Translocación GenéticaAsunto(s)
Terapia Conyugal/métodos , Psicoterapia de Grupo/métodos , Comunicación , Mecanismos de Defensa , Miedo , Femenino , Humanos , Masculino , Percepción SocialAsunto(s)
Histeria/diagnóstico , Personalidad , Adulto , Actitud , Cultura , Mecanismos de Defensa , Femenino , Humanos , Relaciones Interpersonales , Matrimonio , Determinación de la Personalidad , Conducta SexualRESUMEN
Acquired factor VIII (FVIII) inhibitors are a rare cause of coagulopathy which are associated with a high mortality rate. Treatment of bleeding episodes is often difficult and may vary with the degree of titre elevation. Individuals with very high-titre antibodies [>100 Bethesda units mL(-1) (BU)] may have difficulty achieving a complete sustained remission and, consequently, various treatments including immunosuppression, cytotoxic chemotherapy and plasmapheresis have been reported. Rituximab is an anti-CD20 monoclonal antibody which has demonstrated efficacy in the treatment of individuals with acquired FVIII inhibitors, however there is limited data in the subgroup of patients with inhibitor titres >100 BU. In this study, we present four patients with acquired FVIII inhibitor titres >100 BU who were resistant to initial therapy with cyclophosphamide, vincristine and prednisone. The patients' inhibitor titres ranged from 249 BU mL(-1) to 725 BU mL(-1) and all received 4 weekly infusions of rituximab at 375 mg m(-2). Each patient partially responded to rituximab therapy with an improvement in inhibitor titres and FVIII activity, however, three of the four patients relapsed thereafter. The individual who did not relapse achieved a partial response for 13 months and then died of causes unrelated to her coagulopathy. We conclude that in patients with acquired FVIII inhibitors and titres >100 BU, treatment with rituximab alone is effective but not sufficient to achieve a sustained response. Rituximab in combination with other therapies may provide a better result in this high-risk population.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Inhibidores de Factor de Coagulación Sanguínea/sangre , Factor VIII/inmunología , Hemofilia A/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Isoanticuerpos/sangre , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino , Antígenos CD20/inmunología , Ciclofosfamida/uso terapéutico , Esquema de Medicación , Quimioterapia Combinada , Femenino , Hemofilia A/inmunología , Hemorragia/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Recurrencia , Rituximab , Factores de Tiempo , Insuficiencia del Tratamiento , Vincristina/uso terapéuticoRESUMEN
Inhibition of thrombin by heparin cofactor (HCII) is accelerated approximately 1000-fold by heparin or dermatan sulfate. We found recently that the mutation Arg189----His decreases the affinity of HCII for dermatan sulfate but not for heparin (Blinder, M. A., Andersson, T. R., Abildgaard, U., and Tollefsen, D. M. (1989) J. Biol. Chem. 264, 5128-5133). Other investigators have implicated Arg47 and Lys125 of anti-thrombin (homologous to Arg103 and Lys185 of HCII) in heparin binding. To investigate the corresponding residues in HCII, we have constructed amino acid substitutions (Arg103----Leu, Gln, or Trp; Lys185----Met, Asn, or Thr) by oligonucleotide-directed mutagenesis of the cDNA and expressed the products in Escherichia coli. The recombinant HCII variants were assayed for binding to heparin-Sepharose and for inhibition of thrombin in the presence of various concentrations of heparin or dermatan sulfate. All of the Arg103 variants bound to heparin with normal affinity. Furthermore, inhibition of thrombin by the Arg103----Leu variant occurred at a normal rate in the absence of a glycosaminoglycan and was accelerated by normal concentrations of heparin and dermatan sulfate. These results indicate that HCII, unlike anti-thrombin, does not require a positive charge at this position for the interaction with heparin or dermatan sulfate. The Arg103----Gln and Arg103----Trp variants inhibited thrombin at about one-third of the normal rate in the absence of a glycosaminoglycan, suggesting that these mutations exert an effect on the reactive site (Leu444-Ser445) of HCII. All of the Lys185 variants bound to heparin with decreased affinity but inhibited thrombin at approximately the normal rate in the absence of a glycosaminoglycan. These variants required greater than 10-fold higher concentrations of heparin to accelerate inhibition of thrombin and were not stimulated significantly by dermatan sulfate, suggesting that heparin and dermatan sulfate interact with Lys185 of HCII. These results provide evidence that the glycosaminoglycan-binding site in HCII includes Lys185 but not Arg103, both of which were predicted to be involved by homology to anti-thrombin.
Asunto(s)
Arginina/genética , Glicosaminoglicanos/metabolismo , Cofactor II de Heparina/metabolismo , Lisina/genética , Mutación , Secuencia de Aminoácidos , Sitios de Unión , Clonación Molecular , Codón , ADN/genética , Dermatán Sulfato/farmacología , Escherichia coli/genética , Heparina/metabolismo , Heparina/farmacología , Cofactor II de Heparina/genética , Cofactor II de Heparina/farmacología , Humanos , Datos de Secuencia Molecular , Proteínas Recombinantes/metabolismo , Relación Estructura-Actividad , Trombina/antagonistas & inhibidoresRESUMEN
Metastatic esophageal carcinoma to the brain is a rare occurrence that may account for abnormal neurological findings.
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Neoplasias Encefálicas/secundario , Carcinoma de Células Escamosas/secundario , Neoplasias Esofágicas , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico , Trastornos del Conocimiento/etiología , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Heparin cofactor II (HCII), a member of the "serpin" family of serine protease inhibitors, is a 65,600-Da plasma glycoprotein that inhibits thrombin and chymotrypsin. The rate of thrombin inhibition is stimulated approximately 1000-fold by heparin or dermatan sulfate. Thrombin and chymotrypsin cleave the Leu444-Ser445 bond (designated P1-P'1) in the reactive site of HCII, forming a stable equimolar complex in which the protease is inactive. In this study, we have determined the effects of substituting an arginine for Leu444 in recombinant HCII (rHCII). The rHCII was expressed in Escherichia coli and partially purified by heparin-Sepharose chromatography. Apparent second-order rate constants (k2) for inhibition of thrombin, coagulation factor Xa, kallikrein, plasmin, and chymotrypsin by rHCII were determined using appropriate chromogenic substrates. In the absence of a glycosaminoglycan, rHCII(Leu444----Arg) inhibited thrombin at a 98-fold higher rate (k2 = 6.2 x 10(6) M-1 min-1) than native rHCII (k2 = 6.3 x 10(4) M-1 min-1). Dermatan sulfate accelerated thrombin inhibition by both forms of rHCII, but the maximum rate constant in the presence of dermatan sulfate was only 2-fold higher for rHCII(Leu444----Arg) (k2 = 5.3 x 10(8) M-1 min-1) than for native rHCII (k2 = 2.2 x 10(8) M-1 min-1). Heparin was less effective than dermatan sulfate in stimulating both forms of rHCII. Factor Xa, kallikrein, and plasmin were inhibited more rapidly and chymotrypsin more slowly by rHCII(Leu444----Arg) than by native rHCII. These effects are qualitatively similar to those observed with the natural mutant alpha 1-antitrypsin Pittsburgh (Met358----Arg at the P1 position) and strengthen the hypothesis that the P1 residue is a major determinant of protease specificity in the serpins. Furthermore, the rapid rate of inhibition of thrombin by rHCII(Leu444----Arg) in the absence of heparin or dermatan sulfate suggests that this variant may be useful as a therapeutic agent.
Asunto(s)
Arginina , Cofactor II de Heparina/farmacología , Leucina , Trombina/antagonistas & inhibidores , Secuencia de Aminoácidos , Secuencia de Bases , Sitios de Unión , Quimotripsina/antagonistas & inhibidores , Dermatán Sulfato/farmacología , Escherichia coli/genética , Inhibidores del Factor Xa , Fibrinolisina/antagonistas & inhibidores , Expresión Génica , Vectores Genéticos , Heparina/farmacología , Cofactor II de Heparina/genética , Cofactor II de Heparina/aislamiento & purificación , Calicreínas/antagonistas & inhibidores , Cinética , Datos de Secuencia Molecular , Mutación , Proteínas Recombinantes/farmacología , Relación Estructura-Actividad , Transformación BacterianaRESUMEN
We investigated a patient with a long-standing IgGkappa monoclonal gammopathy who developed severe haemorrhagic complications. At IgG concentrations of approximately 50g/l the patient had severe bleeding associated with prolongation of the thrombin time, activated partial thromboplastin time, and reptilase time. Plasmapheresis resulted in improvement in the thrombin time and resolution of bleeding. Depletion of the IgG by absorption of plasma with protein G-Sepharose in vitro resulted in normalization of the thrombin time and reptilase time. The purified IgG bound to immobilized thrombin and immunoprecipitated human alpha-, beta- and gamma-thrombin but not prothrombin, other vitamin K-dependent coagulation factors, or fibrinogen. Purified IgG at concentrations >1 x 10(-2) g/l decreased (approximately 50%) the rate of hydrolysis of a chromogenic substrate by thrombin. Addition of purified IgG to normal pooled plasma at concentrations >1 x 10(-2) g/l prolonged the thrombin time and activated partial thromboplastin time, but the reptilase time was prolonged only at IgG concentrations >1 g/l. This finding suggests that at low concentrations the IgG produces a specific antithrombin effect, but at higher concentrations it also affects fibrin polymerization; the combination of these effects probably produced clinical bleeding. This is the first report of a monoclonal antithrombin antibody associated with bleeding in a patient with multiple myeloma.
Asunto(s)
Anticuerpos Monoclonales/análisis , Hemorragia/inmunología , Mieloma Múltiple/inmunología , Trombina/inmunología , Trastornos de la Coagulación Sanguínea/etiología , Resultado Fatal , Hematuria/etiología , Hemorragia/etiología , Humanos , Inmunoglobulina G/análisis , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Tiempo de Tromboplastina Parcial , Plasmaféresis , Tiempo de Protrombina , Trombina/antagonistas & inhibidores , Tiempo de TrombinaRESUMEN
Age has been assumed to be an independent risk factor in patients undergoing colonoscopy. However, this has never been specifically studied. We evaluated 302 patients 65 yr old or older, to determine the incidence of complications. We found that the risk is comparable to that of the heterogeneous patient population previously reported, except for a slightly increased incidence of delayed bleeding subsequent to polypectomy. In addition, the presence of cardiac, pulmonary, liver, or kidney disease was not found to be associated with an increased incidence of complications. Neither was there an increased risk of complications in patients undergoing colonoscopy, who had previously undergone abdominal or pelvic surgery. In summary, older patients experience the same risks as younger patients, except for post-polypectomy delayed bleeding, which may be related to atherosclerosis of the blood vessels, and appears to be more common in elderly patients.
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Colonoscopía/efectos adversos , Factores de Edad , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Heparin and dermatan sulfate increase the rate of inhibition of thrombin by heparin cofactor II (HCII) approximately 1000-fold by providing a catalytic template to which both the inhibitor and the proteinase bind. A variant form of HCII that binds heparin but not dermatan sulfate has been described recently in two heterozygous individuals (Andersson, T.R., Larsen, M.L., and Abildgaard, U. (1987) Thromb. Res. 47, 243-248). We have now purified the variant HCII (designated HCIIOslo) from the plasma of ne of these individuals. HCIIOslo or normal HCII (11 nM) was incubated with thrombin (9 nM) for 1 min in the presence of heparin or dermatan sulfate. Fifty percent inhibition of thrombin occurred at 26 micrograms/ml dermatan sulfate with normal HCII and greater than 1600 micrograms/ml dermatan sulfate with HCIIOslo. In contrast, inhibition of thrombin occurred at a similar concentration of heparin (1.0-1.5 micrograms/ml) with both inhibitors. To identify the mutation in HCIIOslo, DNA fragments encoding the N-terminal 220 amino acid residues of HCII were amplified from leukocyte DNA by the Taq DNA polymerase chain reaction and both alleles were cloned. A point mutation (G----A) resulting in substitution of His for Arg-189 was found in one allele. The same mutation was constructed in the cDNA of native HCII by oligonucleotide-directed mutagenesis and expressed in Escherichia coli. The recombinant HCIIHis-189 reacted with thrombin in the presence of heparin but not dermatan sulfate, confirming that this mutation is responsible for the functional abnormality in HCIIOslo.
Asunto(s)
Condroitín/análogos & derivados , Dermatán Sulfato/metabolismo , Glicoproteínas/genética , Mutación , Secuencia de Aminoácidos , Arginina/genética , Clonación Molecular , Escherichia coli/genética , Amplificación de Genes , Glicoproteínas/aislamiento & purificación , Glicoproteínas/metabolismo , Cofactor II de Heparina , Histidina/genética , Humanos , Datos de Secuencia Molecular , Proteínas Recombinantes/genéticaRESUMEN
Heparin cofactor II (HC) is a plasma serine proteinase inhibitor (serpin) that inhibits alpha-thrombin in a reaction that is dramatically enhanced by heparin and other glycosaminoglycans/polyanions. We investigated the glycosaminoglycan binding site in HC by: (i) chemical modification with pyridoxal 5'-phosphate (PLP) in the absence and presence of heparin and dermatan sulfate; (ii) molecular modeling; and (iii) site-directed oligonucleotide mutagenesis. Four lysyl residues (173, 252, 343, and 348) were protected from modification by heparin and to a lesser extent by dermatan sulfate. Heparin-protected PLPHC retained both heparin cofactor and dermatan sulfate cofactor activity while dermatan sulfate-protected PLPHC retained some dermatan sulfate cofactor activity and little heparin cofactor activity. Molecular modeling studies revealed that Lys173 and Lys252 are within a region previously shown to contain residues involved in glycosaminoglycan binding. Lys343 and Lys348 are distant from this region, but protection by heparin and dermatan sulfate might result from a conformational change following glycosaminoglycan binding to the inhibitor. Site-directed mutagenesis of Lys173 and Lys343 was performed to further dissect the role of these two regions during HC-heparin and HC-dermatan sulfate interactions. The Lys343----Asn or Thr mutants had normal or only slightly reduced heparin or dermatan sulfate cofactor activity and eluted from heparin-Sepharose at the same ionic strength as native recombinant HC. However, the Lys173----Gln or Leu mutants had greatly reduced heparin cofactor activity and eluted from heparin-Sepharose at a significantly lower ionic strength than native recombinant HC but retained normal dermatan sulfate cofactor activity. Our results demonstrate that Lys173 is involved in the interaction of HC with heparin but not with dermatan sulfate, whereas Lys343 is not critical for HC binding to either glycosaminoglycan. These data provide further evidence for the determinants required for glycosaminoglycan binding to HC.
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Cofactor II de Heparina/metabolismo , Heparina/metabolismo , Lisina/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Cromatografía en Gel , Dermatán Sulfato/farmacología , Glicosaminoglicanos/metabolismo , Modelos Moleculares , Datos de Secuencia Molecular , Alineación de Secuencia , Trombina/antagonistas & inhibidoresRESUMEN
We describe an HPLC-based method for the detection and quantification of fetal hemoglobin in stools of newborns. The new procedure is an alternative to the classic qualitative test for adult hemoglobin in meconium based on the differential stability of hemoglobin species in dilute base (Apt test). The HPLC method, based on a commercial device for hemoglobin characterization (Bio-Rad Variant), readily separates fetal and adult hemoglobin from non-hemoglobin components of meconium. To validate the method, blood and meconium were mixed in various proportions and then prepared for analysis with extraction in saline. The HPLC method accurately identified hemoglobin species even when the blood constituted only 5 mL per 100 g of the meconium specimen, and nearly quantitative recovery of hemoglobin was obtained at a blood content of 20 mL per 100 g of the meconium. Analysis time was 6.5 min, and preparation of sample was simple. HPLC detection of fetal blood in stools or other specimens markedly improves detection/characterization of blood in meconium.
Asunto(s)
Sangre Fetal , Hemoglobinas/análisis , Meconio , Cromatografía Líquida de Alta Presión , Cromatografía por Intercambio Iónico , Humanos , Recién Nacido , Sensibilidad y EspecificidadRESUMEN
Acquired inhibitors of factor V are rare causes of clinical bleeding, whose severity ranges from mild to life-threatening. Optimal treatment of patients with factor V inhibitors is uncertain. We report on our successful treatment approach in a patient with spontaneous, life-threatening intracranial bleeding caused by a factor V inhibitor. The patient deteriorated after initial treatment with fresh-frozen plasma and platelet transfusions. He was subsequently treated with a combination of plasma exchange and chemotherapy, which led to complete recovery. Our experience suggests that plasma exchange may be life-saving in cases of severe bleeding caused by factor V inhibitors. The use of plasmapheresis in conjunction with chemotherapy is an efficacious and well-tolerated treatment and should be considered in patients with factor V inhibitors.
Asunto(s)
Autoanticuerpos/inmunología , Enfermedades Autoinmunes/inmunología , Deficiencia del Factor V/inmunología , Factor V/inmunología , Hematoma Subdural/inmunología , Inmunoglobulina G/inmunología , Anciano , Autoanticuerpos/aislamiento & purificación , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/terapia , Terapia Combinada , Ciclofosfamida/uso terapéutico , Factor V/antagonistas & inhibidores , Deficiencia del Factor V/terapia , Úlcera del Pie/complicaciones , Hematoma Subdural/cirugía , Hemorragia/etiología , Hemorragia/inmunología , Humanos , Inmunoglobulina G/aislamiento & purificación , Inmunosupresores/uso terapéutico , Masculino , Paraplejía/complicaciones , Plasma , Intercambio Plasmático , Plasmaféresis , Prednisona/uso terapéutico , Úlcera por Presión/complicaciones , Infecciones Urinarias/complicaciones , Vincristina/uso terapéuticoRESUMEN
Soluble transferrin receptor (sTfR) and ferritin concentrations were measured in a variety of clinical settings to compare the ability of these two tests to identify iron deficiency. Among 62 anemic patients who either had a bone marrow aspirate performed or had a documented response to iron therapy, the diagnostic sensitivity and specificity of sTfR (at a diagnostic cutoff of > 2.8 mg/L) were 92% and 84%, respectively, with a positive predictive value of 42% in this population. Ferritin (< or = 12 microg/L) had a sensitivity of 25% and a specificity of 98%. However, the sensitivity and specificity of ferritin could be improved to 92% and 98%, respectively, by using a diagnostic cutoff value of < or = 30 microg/L, resulting in a positive predictive value of 92%. Ferritin and sTfR were also measured in 267 outpatient samples and 112 medical students. In the outpatient group, the two tests agreed in 73% of the samples; however, 25% of the samples had ferritin values > 12 microg/L and increased sTfR. Among the medical students, there was 91% agreement between the two tests, but 7% of the samples had ferritin < or = 12 microg/L and normal sTfR. Together, these data suggest that measurement of sTfR does not provide sufficient additional information to ferritin to warrant routine use. However, sTfR may be useful as an adjunct in the evaluation of anemic patients, whose ferritin values may be increased as the result of an acute-phase reaction.