Background Heterophilic antibodies are still an important source of interference in immunoassays, but reports of interference with D‐dimers are rare. Are D‐dimer level abnormalities, found in the clinic, caused by heterophilic antibodies as well, or are other mechanisms involved? We will elaborate on this issue through two different examples in this article. Methods Serum from two patients with significantly elevated levels of D‐dimers were measured and compared by different methods, diluted, and dealt with heterophilic antibody blockers. At the same time, to retrieve the interference, we focused on the cause of D‐dimer false positives and made a systematic review of the literature. Results The D‐dimer values were normal (0.49 and 0.15 μg/mL) detected with different testing method and decreased after addition of heterophilic antibody blocking reagent. According to literature data, there were 66.7% (4/6) references showed the interference were heterophilic antibody. Conclusions The influence of heterophilic antibodies on the measurement of D‐dimers remains a big challenge. Different measuring instruments and methods may have significant differences in the measurement of D‐dimers. By using a combination of instrumental methods for measuring, incorporating heterophilic antibody blockers, and combining with clinical performance and imaging data, most of the interference can be eliminated.
Background: Hereditary elliptocytosis (HE) is a heterogeneous red blood cell membrane disorder characterized by the presence of elliptocytes on a peripheral blood smear. Clinical manifestations of HE vary widely from asymptomatic carriers to patients with severe transfusion-dependent anemia. Most patients are asymptomatic or have mild anemia, which hinders diagnosis. The proband in this case had mild anemia and jaundice over a period of 4 years, the etiology of which was unclear. Hence, he was admitted to our hospital for further diagnosis.Methods: Peripheral blood smears and routine blood tests were performed and biochemical parameters of the proband, and his family members were determined.To confirm the diagnosis, gene mutations were screened in the proband using nextgeneration sequencing (NGS) and verified by Sanger sequencing in other family members.Results: A novel mutation (c.1294delA, p.Ser432 fs) in exon 15 of the EPB41 gene was detected in the proband and his family members. This mutation results in a frameshift and a premature stop codon at position 455, encoding a truncated protein. The variant was likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. SWISS-MODEL protein structure prediction indicated partial loss of the spectrin and actin binding and C-terminal domains. Conclusion:A heterozygous mutation 1294delA in exon 15 of the EPB41 gene was identified using NGS and Sanger sequencing in members of a Chinese family. This identification expands the spectrum of EPB41 mutations and contributes to the genetic diagnosis of families with HE.
e14593 Background: CNTO 95 is a human anti-αv integrin antibody. The dose-dependent antitumor effect of CNTO 95 has been demonstrated in multiple preclinical studies. The objective of these analyses was to characterize the population pharmacokinetics (PPK) in solid tumor cancer patients treated with CNTO 95 with and without dacarbazine. Methods: Approximately 140 patients with solid tumors from two phase I and one phase II studies were included in this analysis. CNTO 95 was administered via intravenous infusion, with 11 different regimens ranging from 0.1 to 20 mg/kg every 1–4 weeks. Serum CNTO 95 concentrations were determined using a validated enzyme-linked immunosorbent assay. Serum CNTO 95 concentration data were analyzed using noncompartmental analysis (NCA) and a PPK approach. Results: The NCA results indicated that total clearance of CNTO 95 decreased as the dose of CNTO95 increased and approached saturation at 10 mg/kg. Based on the NONMEM analysis, data were best described by a 2-compartment model with dual clearance pathways (linear and nonlinear elimination). The nonlinear elimination process is likely due to the receptor-mediated clearance. Mean estimates of central volume, peripheral compartment volume, intercompartmental clearance and linear clearance, as well as an additional nonlinear clearance, were in agreement with antibodies targeting membrane-bound receptors. No differences in the PPK of CNTO 95 were found in patients treated with and without co-administered dacarbazine. Interindividual variability was moderate (<50%). Conclusions: A PPK model could adequately describe serum CNTO 95 concentration-time profiles. Extensions of this model can be used to assist in the selection of doses in diverse oncology patient populations. [Table: see text]
BackgroundLeukemoid reaction refers to reactive leukocytosis exceeding 50,000 cells/µl. Chronic neutrophilic leukemia is a rare clonal hematopoietic disorder characterized by sustained mature neutrophilia in the absence of monocytosis or basophilia. The differentiation between leukemoid reaction and chronic neutrophilic leukemia is problematic because both conditions share similar morphological features. Case presentationHere, we present an extremely rare case of a 62-year-old male patient who was initially diagnosed with chronic neutrophilic leukemia at another hospital. When the patient came to our hospital, no mutations in the CSF3R, SETBP1, ASXL1, TET2, SRSF2, SF3B1, ZRSR2 and U2AF1F genes were found by whole-exon sequencing. Further examination revealed the presence of immunoglobulin G kappa myeloma. Meanwhile, colonoscopy showed a mass in the colon, and biopsy confirmed the presence of colon adenocarcinoma. Therefore, we suggest that the increased white blood cell count in the patient was merely a neutrophilic leukemoid reaction caused by synchronous multiple myeloma and colon carcinoma.ConclusionThis is the first report of a case of coexisting multiple myeloma and colon carcinoma presenting with a neutrophilic leukemoid reaction. This case was presented to illustrate that the diagnosis of chronic neutrophilic leukemia must meet the strict WHO diagnostic criteria, especially if there is an underlying plasma cell disorder, and myeloid clonality must be demonstrated to make a distinction between chronic neutrophilic leukemia and leukemoid reaction. Meanwhile, this case provides us with a reference that further examination, especially pathological examination, should be performed on a patient diagnosed with multiple myeloma, who has extramedullary lesions, because other primary tumors may be also presenting the very similar symptoms. Pathological examination is helpful to differentiate the primary tumor from extramedullary invasion of multiple myeloma.
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