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INTRODUCTION

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CASE HISTORY • Part 1

A 77-year-old woman is brought to the Geriatric Center by her family for evaluation of increasing frailty, forgetfulness, and decreased ability to live independently and care for herself. She has a history of at least 2 falls and has lost approximately 15 lbs in the last 3 months. As part of her evaluation, she has a blood count with the following results:

CBC: Hematocrit/hemoglobin - 33%/11 g/dL

MCV - 96 fL MCH - 34 pg MCHC - 33 g/dL

RDW-CV - 14%

Reticulocyte count/index - 1.5%/~1

White blood cell count - 5,100/μL

Platelet count - 130,000/μL

BLOOD SMEAR MORPHOLOGY

Generally normocytic, normochromic red blood cells with slight anisocytosis. No polychromasia and both white blood cell and platelet morphology are normal. Lymphocytes are decreased in number but with normal morphology.

Questions
  • Is this patient anemic or does she fall into the appropriate range of normal for her age group?

  • If a further workup is in order, what additional laboratory tests should be ordered?

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Aging is associated with subtle physiologic changes in the hematopoietic system. Unlike the renal and reproductive systems, primary hematopoietic stem cell failure is very rare. Only the immune system demonstrates a predictable decrease in competence in the elderly (see Chapters 20 and 21). At the same time, the observed incidence of anemia, myelodysplastic disorders, and thrombotic events (see Chapter 36) is progressively greater with each passing decade. This is a result of the convergence of multiple factors, many of which are environmental in origin and are, therefore, reversible.

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STEM CELLS AND THE AGING PROCESS

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Hematopoietic stem cells (HSC) emerge early in embryonic development and, after residing in the fetal liver, spleen, and thymus, populate the bone marrow and lymph glands. Fetal HSC differ from adult HSC in their rate of proliferation, differentiation, cell surface markers, and regulatory control. While the majority of adult HSC are in the G0 phase of cell division, they are capable of self-renewal and, despite a constant high level of differentiation needed to constantly repopulate the several lineages of mature blood cells, appear to gradually increase in number. In fact, based on mouse model experiments, there is a 2-fold increase in adult HSC in aging mice. Moreover, as demonstrated by serial transplant studies, these adult HSC are able to repopulate the marrow through 15–50 lifespans.

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Adult HSC do age, although the mechanisms underlying the aging process are not well defined. Telomere length, DNA methylation, reactive oxygen species exposure, and accrued DNA damage have all been advanced as playing a role in this aging process. Because of this, individual HSC function decreases with age, while total capacity is made up for by the increased number of HSC. Changes in the marrow microenvironment are also important. The ratio of marrow precursor cells to fat cells decreases in the aging marrow, although rapid expansion of the erythroid marrow secondary ...

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