RESUMEN
The relationship between asplenia and thrombophilia in ß-thalassemia disease patients is not yet completely understood. One hundred and ten adult hemoglobin (Hb) E/ß-thalassemia (E/ß-Thal) disease outpatients, dichotomized according to the presence or absence of the spleen, were prospectively studied for evidence of intravascular hemolysis (IVH) and vascular endothelial cell (EC) activation. Biomarkers of IVH (serum cell-free Hb), EC [soluble E-selectin (sE-selectin) and soluble vascular cell adhesion molecule 1 (sVCAM-1)], platelet and EC [soluble P-selectin (sP-selectin)], inflammation [high-sensitivity C-reactive protein (hs-CRP)], and coagulation [thrombin-antithrombin complexes (TAT)] activation, as well as other selected blood tests were determined. The 61 splenectomized patients had a more severe hemolytic disease and higher levels of cell-free Hb and ferritin (p = 0.003), sE-selectin, sP-selectin, hs-CRP, and TAT (p < 0.05). However, serum levels of sVCAM-1 were not different between the two groups. The findings suggested IVH and EC activation. Together with chronic iron overload and chronic low-grade inflammation activation, the findings extend our understanding of the mechanism of thrombophilia in splenectomized E/ß-Thal disease patients.
Asunto(s)
Hemoglobina E/metabolismo , Hemólisis , Esplenectomía/efectos adversos , Trombofilia/sangre , Trombofilia/etiología , Talasemia beta/sangre , Talasemia beta/cirugía , Adulto , Antitrombina III , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Selectina E/sangre , Células Endoteliales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Selectina-P/sangre , Péptido Hidrolasas/sangre , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Trombofilia/patología , Molécula 1 de Adhesión Celular Vascular/sangre , Adulto JovenRESUMEN
OBJECTIVES: To find the prevalence and risk factors of pulmonary hypertension (PHT) in adult patients with hemoglobin E/ß-thalassemia disease (E/ß-Thal). METHODS: One hundred and ten clinically stable E/ß-Thal outpatients, sixty-one of whom had undergone splenectomy, were prospectively studied using their clinical profiles, selected blood tests, chest roentgenogram, and transthoracic echocardiogram. Based on the pulmonary artery systolic pressure (PASP) values estimated by the echocardiogram of ≥36 mmHg, they were dichotomized into those with (PHT+) and without (PHT-) PHT. RESULTS: PHT was found in 41 (37.3%) patients without gender preponderance. It was not due to the left heart and was not severe (PASP = 46.3 ± 10.4 mmHg). PASP was higher in splenectomized patients (48.0 ± 11 vs. 40.3 ± 4.7 mmHg (P = 0.004)). PHT was found in 32 of 61 (52.5%) splenectomized patients, mostly (53%) in the second decade, and rarely (6.3%) during the first 5 yr after splenectomy. PHT+ patients had more hemolysis (P = 0.001-0.04 depending on the parameters), more asplenic cases (P < 0.001), and higher serum soluble vascular cell adhesion molecule-1 (sVCAM-1) and high-sensitivity C-reactive protein levels (P = 0.004 and 0.008, respectively). Strong risk factors by univariate analysis were serum sVCAM-1 levels ≥1600 ng/mL, serum cell-free Hb ≥ 3 mg/dL, asplenia, and amount of NRBCs/100 WBCs >40. CONCLUSIONS: Prevalence of PHT in E/ß-Thal patients was 37.3% without gender preponderance. Those with severe hemolysis and asplenia invariably had severer PHT. Strong risk factors were asplenia and associated markedly elevated values of sVCAM-1, cell-free Hb, and NRBCs in blood.
Asunto(s)
Hemoglobina E/genética , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/etiología , Talasemia beta/complicaciones , Talasemia beta/genética , Adulto , Biomarcadores , Femenino , Humanos , Masculino , Oportunidad Relativa , Prevalencia , Factores de Riesgo , Adulto Joven , Talasemia beta/epidemiologíaAsunto(s)
Hemoglobina E , Arteria Pulmonar/patología , Bazo , Talasemia beta , Adolescente , Adulto , Presión Sanguínea , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Arteria Pulmonar/fisiopatología , Bazo/patología , Bazo/fisiopatología , Talasemia beta/patología , Talasemia beta/fisiopatologíaRESUMEN
The hypercoagulable state is well recognized in patients with severe ß-thalassemia disease. One of the mechanisms of chronic hypercoagulable state is the abnormal expression of phosphatidylserine on red blood cells (RBC). This study aimed to determine the coagulable state in patients with severe ß-thalassemia disease following successful stem cell transplantation (SCT). Subjects were classified into three groups: normal controls (NC), ß-thalassemia disease receiving regular transfusion (Thal-RT) and ß-thalassemia disease post SCT (Thal-SCT). Sixty eight subjects, aged 3-17years, consisting of 21 NC, 28 Thal-RT and 19 Thal-SCT were enrolled. After SCT, the annexin V level in Thal-SCT was normalized. At the median follow-up time of 70.3 (50.9-84.2) months after SCT, the levels of coagulation markers (thrombin antithrombin complex, prothrombin fragment and D-dimer) and anticoagulation proteins (protein C, S and antithrombin activities) returned to the levels similar to controls.
Asunto(s)
Coagulación Sanguínea/fisiología , Trasplante de Células Madre/métodos , Talasemia beta/sangre , Biomarcadores/sangre , Pruebas de Coagulación Sanguínea , Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/metabolismo , Niño , Femenino , Humanos , Masculino , Talasemia beta/cirugíaRESUMEN
Aged or abnormal red blood cells with exposed phosphatidylserine (PSRBCs) are cleared from the circulation by splenic macrophages. In asplenic patients, other mononuclear phagocytic cells in tissues and in circulation may function in this capacity. To better understand these changes and the relationship among splenic status, PS-RBCs, blood monocytes, and serum tumor necrosis factor (TNF-α), a product of mononuclear phagocyte activation, patients with hemoglobin E/ß-thalassemia (E/ß-Thal) were studied. Whole blood of 20 nonsplenectomized, 20 splenectomized E/ß-Thal patients, and 20 healthy subjects was assayed for PS-RBCs; for monocytes, activated monocytes, and monocyte response to lipopolysaccharide stimulation; and serum was assayed for TNF-α. Asplenic E/ß-Thal patients had significantly increased (P < 0.05) amounts of PS-RBCs, monocytes, activated monocytes, and levels of serum TNF-α. The amount of PS-RBCs correlated with levels of serum TNF-α, but the amount of activated monocytes did not correlate with either the amount of PS-RBCs or levels of serum TNF-α. Monocyte response to lipopolysaccharide stimulation in asplenic patients was not as efficient as in the other patients or in normals (77 vs. 404, and 304 folds increment, respectively). The results suggest that splenectomy in E/ß-Thal patients led to an increased amount of PSRBCs and activation in the mononuclear phagocytic system.
Asunto(s)
Enfermedades Hematológicas/patología , Enfermedades Hematológicas/cirugía , Hemoglobina E/metabolismo , Fagocitos/patología , Fosfatidilserinas/sangre , Talasemia beta/patología , Adulto , Femenino , Enfermedades Hematológicas/sangre , Humanos , Masculino , Persona de Mediana Edad , Bazo/patología , Adulto Joven , Talasemia beta/sangre , Talasemia beta/cirugíaRESUMEN
Increased frequency of thrombosis has been observed in patients with hemoglobin E/beta-thalassemia (Hb E/beta-thal) disease, particularly those who have previously been splenectomized. We compared various hemostatic and thrombotic markers in blood from 15 Hb E/beta-thal patients who were not splenectomized (NS), 15 who had been splenectomized (S), and 15 normal controls (NC). Levels of plasma thrombin-antithrombin, beta2 thromboglobulin, C-reactive protein, tissue plasminogen activator antigen were significantly higher in the S group than in either the NS or the NC groups, and levels of prothrombin fragment 1.2 were significantly higher in the S than in the NC group. Levels of plasminogen activator inhibitor-1 antigen were significantly higher in the S than in the NS group. Levels of protein C, protein S, antithrombin, and fibrinogen were significantly lower in the S and NS groups than in the NC group. Plasma lipoprotein(a) levels in the S and NS groups were not statistically different from NC. Our findings indicated that there is evidence of chronic low-grade coagulation and platelet activation, chronic low-grade inflammation, endothelial cell injury, impaired fibrinolysis, and decreased naturally occurring anticoagulants in splenectomized Hb E/beta-thal patients. These changes may account for the increased risk of thrombosis in these patients.
Asunto(s)
Inhibidores de Factor de Coagulación Sanguínea/análisis , Factores de Coagulación Sanguínea/análisis , Hemoglobina E , Hemostasis/fisiología , Talasemia beta/sangre , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Esplenectomía , Talasemia beta/cirugíaRESUMEN
Antibodies to beta(2)-glycoprotein I (anti-beta(2)-GPI) have been reported to have stronger association with clinical antiphospholipid syndrome (APS) than anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). We investigated the sensitivity and specificity of ELISA for anti-beta(2)-GPI in Thai systemic lupus erythematosus (SLE) patients with clinical features of APS and compared the results with IgG/IgM aCL and LAC to find the test with the best association. The hospital records of 151 Thai SLE patients whose sera had been sent for either IgG/IgM anticardiolipin antibodies or lupus anticoagulant testing were reviewed. Sera of patients either without complete clinical records or those with APS-related manifestations other than vascular thrombosis and pregnancy morbidity (according to the international consensus statement on preliminary classification criteria for definite APS) were excluded. For the remaining subjects (112 patients), their sera were tested for anti-beta(2)-GPI antibody, IgG and IgM anticardiolipin, and lupus anticoagulant. The sensitivity and specificity of each method were compared by using the chi-square test. Among the 112 (74.2%) SLE patients in the study, 35 (31.3%) presented with preliminary clinical criteria for APS (i.e., vascular thrombosis and pregnancy morbidity) whereas 77 (68.7%) did not. The sensitivity and specificity of anti-beta(2)-GPI determination were 57.1 and 79.2%, respectively, whereas those of IgG aCL were 25.7 and 94.8%, of IgM aCL were 5.7 and 98.7%, and of LAC were 44.8 and 77.3%, respectively. The accuracy of the four tests showed similar association with clinical APS (accuracy of test = 72.3, 73.2, 69.6, and 68.3%, respectively). Concerning the sensitivity, specificity, and difficulty of the methods, the combination of anti-beta(2)-GPI and IgG aCL tests was the best for the diagnosis of APS in Thai SLE patients.
Asunto(s)
Anticuerpos Anticardiolipina/química , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Inhibidor de Coagulación del Lupus/sangre , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , beta 2 Glicoproteína I/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/etnología , Femenino , Humanos , Inmunoglobulina G/química , Inmunoglobulina M/química , Inhibidor de Coagulación del Lupus/química , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/etnología , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , TailandiaRESUMEN
Venous thromboembolism (VTE) has been reported to be less common among Thais than Caucasians. Whether this observation reflects genetic or environmental factors, or both, is uncertain. To identify genetic and acquired risk factors of Thai patients with VTE, we enrolled in the study 105 consecutive Thai patients (34 men, 71 women) who had an objectively confirmed history of VTE. A complete clinical summary was obtained from each patient, with emphasis on personal and family history of VTE, as well as circumstantial vascular risk factors (surgery, immobilization, pregnancy, postpartum condition, trauma, oral contraceptive use, and malignancy). Of the 105 patients, 19% were found to have a malignancy. The mean age at the time of the first thrombotic episode was 52.1 years (range, 29-76 years), compared with 42.6 years (range, 17-82 years) for the patients without malignancy. Of the 85 patients without malignancy, 12.3% had protein S deficiency, 8.9% had protein C deficiency, 4.7% had antithrombin deficiency, 10.4% had antiphospholipid antibody, 30.4% had an elevated factor VIII level, 26.8% had an elevated factor XI level, 5.3% had hyperhomocysteinemia, and 16.5% were on oral contraceptives before the thrombotic episode. Factor V Leiden, the G20210A prothrombin gene mutation, and homozygosity for the C677T methylenetetrahydrofolate reductase (MTHFR) gene variant were not found. The VTE in 7.1% of the patients was considered to be secondary to recent surgery, trauma, and/or immobilization. Compared with studies of Caucasian patients, there were significant differences in the risk factors for VTE, with protein S deficiency and protein C deficiency being more common in the Thai patients. In contrast, factor V Leiden, the G20210A prothrombin gene mutation, and the C677T MTHFR gene mutation are not genetic risk factors among Thai patients with VTE. Malignancy and the use of oral contraceptives were the most common acquired risk factors for VTE in the Thai patients.