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NORMAL HEMATOLOGIC VALUES
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The normal ranges for peripheral blood counts vary with age. Neonates have a hematocrit of 45%–65% accompanied by an increased reticulocyte count of 2%–8% in the first 24 hours. Within the first few days of life, erythrocyte production decreases as serum erythropoietin levels fall in response to increased tissue oxygenation, and the hemoglobin and hematocrit fall to a physiologic nadir around 10 g/dL and 30%, respectively, at 6–8 weeks of life. Thereafter, the normal values for hemoglobin and hematocrit gradually increase until adult values are reached after puberty with post-pubertal males having an average hemoglobin concentration about 1 g/dL higher than postpubertal females. Premature infants may have a more exaggerated and delayed hemoglobin nadir of 7–8 g/dL at 8–10 weeks. Anemia is defined as a hemoglobin concentration less than the 2.5th percentile for a normal population of the same gender and age.
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Newborns have larger red cells than children and adults, with a mean corpuscular volume (MCV) at birth of more than 94 fL. The MCV subsequently falls to a nadir of 70–84 fL at about age 6 months. Thereafter, the normal MCV increases gradually until it reaches adult values after puberty.
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The total white blood cell count (WBC) typically decreases with age. Lymphocytes are the predominant type of WBC in children between the ages of 1 and 6 years whereas neutrophils predominate at other ages. Previously referred to as benign ethnic neutropenia, patients with the Duffy null red cell phenotype (Fya-/Fyb-) have lower baseline absolute neutrophil counts (ANCs) with almost a quarter of patients having ANCs less than 2000/mcL. The Duffy null phenotype has a higher incidence (> 50%) in self-identified patients of African descent.
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Normal values for the platelet count are 150,000–400,000/μL and vary little with age.
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Merz
L: Absolute neutrophil count by Duffy status among healthy black and African American adults. Blood Adv 2023;7:317–320
[PubMed: 35994632]
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Failure of the marrow to produce adequate numbers of circulating blood cells may be congenital or acquired (eg, immune, medication, or toxin-associated) and may result in pancytopenia or single lineage cytopenias. Poor growth, comorbid congenital anomalies, and red cell macrocytosis should increase suspicion for an inherited bone marrow failure syndrome (IBMFS). Bone marrow failure caused by malignancy or other infiltrative disease is discussed in Chapter 31.
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ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Progressive pancytopenia.
Macrocytosis.
Multiple congenital anomalies in two-thirds.
Increased chromosome breakage in peripheral blood lymphocytes.
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General Considerations
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Fanconi anemia is the most common IBMFS. It is a DNA repair disorder and cancer predisposition syndrome resulting from defects in the FA/BRCA pathway. Most commonly, inheritance is autosomal recessive, but X-linked and autosomal dominant forms do exist. Approximately 75%–90% of affected individuals develop bone marrow failure in ...