Approach to pancytopenia: Diagnostic algorithm for clinical hematologists

Gnanaraj, Jerome; Parnes, Aric; Francis, Charles W.; Go, Ronald S.; Takemoto, Clifford M.; Hashmi, Shahrukh K.

doi:10.1016/j.blre.2018.03.001

Cited by 53 publications

(55 citation statements)

References 50 publications

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“…In recent years, targeted NGS panels have been used in oncology for early detection of tumor, risk stratification and prognosis, disease monitoring, and targeted therapy . Mutational analysis for patients with unexplained cytopenia is becoming common practice, especially in large academic medical centers . Detection of somatic mutations provides clonal evidence for MDS, but for the most part, the diagnostic utility of somatic mutations in patients with cytopenia is not well‐defined.…”

Section: Introductionmentioning

confidence: 99%

The diagnostic utility of targeted gene panel sequencing in discriminating etiologies of cytopenia

et al. 2019

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The diagnostic utility of somatic mutations in the context of cytopenias is unclear: clonal hematopoiesis can be found in healthy individuals, patients with aplastic anemia (AA), clonal cytopenia of undetermined significance (CCUS) and myelodysplastic syndrome (MDS). We examined a cohort of 207 well-characterized cytopenic patients with a 640-gene next generation sequencing (NGS) panel and compared its diagnostic utility with a "virtual" 41 gene panel. The TET2, SF3B1, ASXL1, and TP53 were the most commonly mutated genes (frequency > 10%). Mutations in the 640-gene panel show high sensitivity (98.3%) but low specificity (47.6%) for diagnosis of MDS. Notably, mutations of splicing factors and genes in the RAS pathway are relatively specific to MDS. Furthermore, high variant allele frequency (VAF) predicts MDS: when the VAF is set at 20%, the positive predictive value (PPV) for MDS is 95.9%, with a specificity of 95.3%. The presence of two or more somatic mutations with ≥10% VAF showed a PPV of 95.2%. While the "virtual" 41-gene panel showed a mild decrease in sensitivity (95.7% vs 98.3%), 100% specificity was observed when either VAF was set at ≥20% (100% vs 95.3%), or two or more somatic mutations had VAFs ≥ 10%. Our study shows targeted gene panel sequencing improves the diagnostic approach and accuracy for unexplained cytopenia, with its high sensitivity and high PPV for MDS when applying VAF cutoffs. Furthermore, a 41-gene panel was shown to have at least comparable performance characteristics to the large 640-gene panel.

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Section: Introductionmentioning

confidence: 99%

The diagnostic utility of targeted gene panel sequencing in discriminating etiologies of cytopenia

et al. 2019

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“…Bone marrow biopsies are routinely implemented in the diagnostic algorithm at some point after an appropriate clinical evaluation is made, with the aim of ruling out bone marrow failure manifestation due to other aetiologies than haematological diseases. Pancytopenia, which in itself is not a disease, but merely a symptom of an underlying disorder affecting the bone marrow and peripheral cell lines, may as well be attributable to a non‐malignant or an inherited condition as to a frank malignancy 73 . Non‐malignant causes of pancytopenia include toxicity as a consequence of drug effect or irradiation, infections, nutritional deficiencies, autoimmune diseases, splenic sequestration, PNH and haemophagocytic lymphohistiocytosis 73 .…”

Section: Other Aetiologies Of Hypoplastic Bone Marrow Failurementioning

confidence: 99%

“…Pancytopenia, which in itself is not a disease, but merely a symptom of an underlying disorder affecting the bone marrow and peripheral cell lines, may as well be attributable to a non‐malignant or an inherited condition as to a frank malignancy 73 . Non‐malignant causes of pancytopenia include toxicity as a consequence of drug effect or irradiation, infections, nutritional deficiencies, autoimmune diseases, splenic sequestration, PNH and haemophagocytic lymphohistiocytosis 73 . Furthermore, there is a significant group of patients exhibiting unexplained cytopenias without completely fulfilling diagnostic criteria for haematological diseases, termed idiopathic cytopenia of undetermined significance (ICUS) 24 .…”

Section: Other Aetiologies Of Hypoplastic Bone Marrow Failurementioning

confidence: 99%

Next‐generation sequencing in hypoplastic bone marrow failure: What difference does it make?

Skibenes

Clausen

Raaschou‐Jensen

2020

European J of Haematology

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Hypoplastic bone marrow failure is a diagnostic feature of multiple haematological disorders, which also share a substantial overlap of clinical symptoms. Hence, discrimination of underlying disorders in patients presenting with hypoplastic bone marrow failure remains a major challenge in the clinic. Recent next‐generation sequencing (NGS) studies have broadened our understanding of the varying molecular mechanisms and advanced diagnostics of disorders exhibiting hypoplastic bone marrow failure. In this article, we present a literature review of NGS studies of haematological disorders associated with hypoplastic bone marrow failure and highlight the relevance of NGS for improved clinical diagnostics and decision‐making.

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“…It's defined as a reduction in all three peripheral blood cell lineages, i.e., anemia, leucopenia, and thrombocytopenia [2]. It's not a disease entity itself but a presentation caused by diverse disease processes affecting bone marrow and/or peripheral cell lines [3][4]. Clinical presentation is related to the severity of cytopenias, leading to common presenting symptoms, including generalized weakness, shortness of breath, fever, weight loss, bleeding, etc.…”

Section: Introductionmentioning

confidence: 99%

“…Its etiology is influenced by geography, socio-economic conditions, and endemic illnesses [8]. Nutritional megaloblastic anemia, caused by folate or vitamin B12 deficiency, is one of the leading causes of pancytopenia in developing countries, as it's readily correctable and so should be suspected in patients with unexplained pancytopenia, macrocytosis, hypersegmented neutrophils, and neurological signs and symptoms [4,6]. There's a scarcity of data regarding the prevalence of pancytopenia in Pakistan.…”

Section: Introductionmentioning

confidence: 99%

Frequency and Etiology of Pancytopenia in Patients Admitted to a Tertiary Care Hospital in Karachi

Farooque

Iftikhar

Herekar

et al. 2020

Cureus

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Introduction Pancytopenia is an important hematologic problem encountered frequently in clinical practice characterized by a reduction in all three peripheral blood cell lineages, i.e., anemia, leucopenia, and thrombocytopenia, caused by myriad disease processes. Our study aimed to determine the frequency and etiology of pancytopenia in patients admitted under internal medicine services in a tertiary care hospital. Method This cross-sectional study was conducted in the in-patient internal medicine department, The Indus Hospital (TIH), Karachi, included 258 patients. To be eligible, participants had to give informed consent, be 14 years or older, and of either sex. The study involved a 20-30-minute interaction with the patient, involving an interview and physical examination, and access to electronic health record data. Results Out of 258 patients studied, 24 (9.3%) were diagnosed with pancytopenia, the male to female ratio was 1:1, no significant difference was observed in the proportion of ethnicity, religion, previous treatment, known infectious disease, and personal and occupational exposure among pancytopenic patients and other nonpancytopenic patients. Fever (n=14, 58.3%) was most common presenting complaint followed by fatigue (n=13, 54.2%) and weight loss (n=7, 29.2%) while most common signs were pallor (87.5% n=21), hepatomegaly (29.2%, n=7), and splenomegaly (25%, n=6). The most common cause of pancytopenia was megaloblastic anemia (n=10, 41.7%), followed by hypersplenism (n=4, 16.6%), acute infectious diseases (n=3, 12.5%), and autoimmune diseases (n=3, 12.5%). Conclusion Our study suggests that pancytopenia is a common finding among our patient population and a larger proportion has a treatable cause, thus carrying a favorable prognosis.

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Approach to pancytopenia: Diagnostic algorithm for clinical hematologists

Cited by 53 publications

References 50 publications

The diagnostic utility of targeted gene panel sequencing in discriminating etiologies of cytopenia

The diagnostic utility of targeted gene panel sequencing in discriminating etiologies of cytopenia

Next‐generation sequencing in hypoplastic bone marrow failure: What difference does it make?

Frequency and Etiology of Pancytopenia in Patients Admitted to a Tertiary Care Hospital in Karachi

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