AA is not the most common cause of pancytopenia (see Table 1). A rational diagnostic algorithm can be very helpful in establishing a correct diagnosis (see box on Diagnostic Algorithm in Aplastic Anemia). Pancytopenia is unlikely to be the presenting feature of hypersplenism in cirrhosis or of Evans syndrome (autoimmune hemolytic anemia and thrombocytopenia) in systemic lupus erythematosus. Findings on physical examination can point strongly toward another diagnosis. For example, the patient with myelofibrosis usually has splenomegaly, which is very unusual in AA. Although vitamin B12 and folate deficiencies have been reported to be associated with erythroid hypoplasia, this must be an exceedingly rare event. For the practicing hematologist, the most important and difficult task is distinguishing the primary BM disorder in patients with pancytopenia.

Table1. Differential Diagnosis of Pancytopenia

In moderate AA, the modest depression of BM cellularity can muddle the single most reliable diagnostic criterion. BM cellularity is imprecisely quantitated at best, and further uncertainty is introduced by sampling errors. “Hot spots” of hematopoietic activity in an otherwise acellular specimen may reflect biologic heterogeneity in the pattern of cell loss. In patients with a syndrome of transient pancytopenia, spontaneous recovery occurs within a few months; although the blood cell counts can be severely depressed, the BM is much more commonly normo/hypercellular than hypoplastic. In patients with chronic BM failure, serial BM specimens may not be identical because of sampling error or because the original disease was misdiagnosed or has changed its character. Some patients with AA are not pancytopenic; they do not have uniform depressions of RBCs, neutrophils, and platelets, despite an empty BM, and their clinical course is dominated by failure in two cell lines or a single hematopoietic lineage. Related conditions such as pure red cell aplasia, amegakaryocytic thrombocytopenia, and agranulocytosis, although usually distinctive in their clinical presentation, can evolve into more generalized BM failure. A hypocellular BM often precludes the proper morphologic diagnosis, especially in hypoplastic BM (see Table 2).

Table2. Bone Marrow Morphologic and Molecular Findings That Discriminate Myelodysplasia From Aplastic Anemia

BM cytogenetics, if positive for chromosome abnormalities, usually leads to a diagnosis of MDS or leukemia. However, some random chromosomal abnormalities may be transient, and some experts believe that typical AA is not incompatible with an abnormal karyotype. Often, an acellular specimen precludes successful culture and generation of metaphase smears. In such cases, single nucleotide polymorphisms arrays–based karyotyping can disclose chromosome abnormalities. Screening for monosomy 7 and trisomy 8 can be also performed using interphase FISH.

Molecular diagnostics has entered the BM failure clinic. To establish the diagnosis of constitutional AA, commercial panels are now available to screen germline DNA for genes responsible for FA, telomeropathy, and Schwachman-Bodian-Diamond syndrome, and many other genes implicated in inherited BM failure syndromes.

The presence of multiple somatic mutations typical for myeloid neoplasia at high clonal burden, especially in spliceosome genes, supports the diagnosis of MDS. Acquired mutations of recurrently mutated genes in MDS/AML can be detected in circulating white blood cells in about one-third of otherwise typical AA patients. Some mutated clones occur transiently and disappear upon recovery (see Table 2). Clones may reflect coexisting clonal hematopoiesis of indeterminate potential, be a result of oligoclonality or correspond to potential founder hits for clonal evolution. In contrast to MDS and AML, somatic mutations in AA occur in a limited subset of genes, and the clone size, as estimated by variant allele frequency, is also small. Somatic hits in RUNX1, DNMT3A, ASXL, CBL and SETBP1 correlate with patient age but independently predict for a poorer long-term outcome. Some of these mutations can be also found to expand during progression of MDS. Mutations in PIGA and BCOR/ BCORL correlate with responsiveness to immunosuppressive therapy (see Table 2). Detection of unfavorable mutations in a patient who has failed treatment may influence the decision to undertake hematopoietic stem cell transplantation.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم صناعة الشبابيك يباشر أعمال إدامة شباك مقام الإمام المهدي (عجّل الله فرجه)

المجمَع العلمي ينظم ندوته القرآنية الأسبوعية في جامعة الكوفة

جامعة العميد تقيم الملتقى العلمي الثاني لخريجي كلية طب الأسنان

ضمن دورتها العلمية (في رحاب العقيدة) الهيأة العليا لإحياء التراث تقدم محاضرة عن مفهوم الأسبقية في الإسلام

المزيد

الآخبار الصحية

اللحظات الأخيرة قبل الموت.. هذا هو تسلسل "فقدان الحواس"

وخز الأطراف وضعف الذاكرة.. علامات على نقص فيتامين هام

عادة صباحية بسيطة.. تأثيرها قد يحسن ضغط الدم

عادات يومية تدمر قلبك بصمت.. خبراء يطلقون التحذير

المزيد

الآخبار التكنلوجية

الذكاء الاصطناعي يفك لغز آثار أقدام الديناصورات

القمر أولا.."سبيس إكس" تؤجل خططها الخاصة بالرحلات إلى المريخ

الذكور أم الإناث؟ دراسة "تنسف الشائع" بشأن التوحد

خبير يكشف عن اقتراب العلماء من فك شفرات "لغات الحيوانات" !

المزيد

مواضيع ذات صلة

Diagnosis of Aplastic anemia

Diagnosis of Upper Respiratory Tract Infections

tuberculosis testing (TB testing, Interferon gamma release assay [IGRA, T-Spot.TB], QuantiFERON-TB Gold [QFT, QFT-G, TB Gold test, TB blood test], Nucleic acid amplification for TB [NAAT], TB antibody)

thyrotropin-releasing hormone stimulation test (TRH stimulation test, Thyrotropin-releasing factor stimulation test [TRF stimulation test])

Laboratory Diagnosis of Lower Respiratory Tract Infections: Specimen Processing

Laboratory Diagnosis of Lower Respiratory Tract Infections: Specimen Collection and Transport

thyroid scanning (Thyroid scintiscan)

thyroid fine needle aspiration biopsy (FNAB, Skinny needle thyroid biopsy, Fine-needle aspiration [FNA])

thoracentesis and pleural fluid analysis (Pleural tap)

The Role of Laboratory in Urgency: Altered State of Consciousness

Preoperative Laboratory Test

sputum culture and sensitivity (C&S, Culture and Gram stain)