ABSTRACT
Pulmonary hypertension (PH), a risk factor for mortality in sickle cell disease (SCD), has pathologic features of both pulmonary arterial hypertension (PAH) and PH related to left-sided heart disease (LHD) suggesting a link between these two entities. We hypothesized that both are characterized by endothelial dysfunction and increased adhesion molecule expression. SCD patients and normal volunteers underwent a screening questionnaire, echocardiogram, and blood donation for preparation of platelet-poor plasma. PAH was defined as a tricuspid regurgitant jet (TRJ) velocity > or =2.5 m/sec and/or the presence of isolated right ventricular hypertrophy or decreased systolic function. LHD was defined as either left-sided systolic/diastolic dysfunction or significant valvular disease. Plasma vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P- and E-selectin, nitric oxide (NO(x)), erythropoietin, and vascular endothelial growth factor (VEGF) levels were assayed by enzyme-linked immunoassay. Forty-three percent of sickle cell anemia (HbSS) and 28% of hemoglobin SC disease (HbSC) disease patients had PAH. Additionally, 10-15% of SCD patients had LHD. VCAM-1 levels were significantly increased in HbSS patients compared with HbSC patients and normal volunteers. VCAM-1 and P-selectin levels correlated positively with TRJ velocity in HbSS patients (r = 0.45, P = 0.03, r = 0.2, P = 0.05, respectively). ICAM-1, E-selectin, NO(x), erythropoietin, and VEGF levels were similar across subject groups. PH is common in SCD and, at times, due to LHD. Increased VCAM-1 and P-selectin expression was associated with TRJ elevation regardless of etiology suggesting a similar effect on endothelial gene expression and possibly providing a pathologic link between PAH and PH related to LHD in SCD.
Subject(s)
Anemia, Sickle Cell/metabolism , Heart Diseases/metabolism , Hypertension, Pulmonary/metabolism , P-Selectin/metabolism , Vascular Cell Adhesion Molecule-1/metabolism , Adult , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/epidemiology , Female , Heart Diseases/complications , Heart Diseases/epidemiology , Humans , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/epidemiology , Male , SolubilityABSTRACT
A reliable and cost-effective laboratory method for diagnosing early bacterial infection is needed. The purpose of this study is to compare the sensitivity and specificity of the mean neutrophil volume (MNV) and neutrophil volume distribution width (NDW) parameters with manual band counts, as well as absolute neutrophil count (ANC) and Creactive protein (CRP). We analyzed the clinical history and laboratory data from 242 adult patients with subsequent randomization into 3 groups: patients with no apparent clinical evidence of infection (group 1), localized infection (group 2), and severe infection (group 3). Total white blood cell counts, percentage of neutrophils, ANC, band counts, MNV, and NDW were progressively elevated from group 1 to group 3. There were good correlations between MNV and ANC (P < .05) or band counts (P < .001). Similarly, the NDW correlated well with ANC (P < .001) and band counts (P < .05). Statistical analyses further confirmed that the MNV and NDW were better parameters, with larger areas under the curve than those of CRP, band count, and ANC. The neutrophil VCS parameters, MNV and NDW, have superior sensitivity and specificity compared to manual band count, ANC, and CRP. MNV and NDW are useful indicators in diagnosing acute infectious processes.
