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INTRODUCTION

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CASE HISTORY • Part 1

A 56-year-old man presents with a complaint of rash and bleeding from the nose and mouth for the past week. His history is notable for non-Hodgkin lymphoma (NHL; follicular center cell) treated with chemotherapy and radiation therapy 10 years prior. He has been taking cholesterol-lowering medication for 3 years; no new drugs have been prescribed. Examination is notable for a petechial rash, which is prominent on the feet and shins, and multiple blood blisters in the mouth. The remainder of the examination is benign.

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CBC: Hemoglobin/hematocrit - 12 g/dL/36%

MCV - 84 fL WBC count - 7,500/μL

Platelet count - 10,000/μL

SMEAR MORPHOLOGY

Normocytic, normochromic; no abnormal red cell morphology. White blood cells are normal. There are very few platelets; giant platelets are noted.

Questions
  • What abnormality is apparent from the complete blood count (CBC)?

  • What additional workup/tests are indicated?

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Normal hemostasis requires an adequate number of well-functioning platelets in circulation. Chances of bleeding increase as the platelet count falls. The overall risk of thrombocytopenia to the patient depends, however, on the presence of other disease states. Although a normal individual can tolerate a platelet count less than 10,000/μL, an acutely ill patient is at risk for bleeding with platelet counts of 20,000–30,000/μL or even as high as 100,000/μL if surgical hemostasis is required. Thus, clinical evaluation must match the degree of thrombocytopenia to the disease state. This is also true in planning management.

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NORMAL PLATELET KINETICS

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The normal circulating platelet count is maintained within relatively narrow limits (150,000–450,000 platelets/μL in Northern Europeans and 90,000–300,000 platelets/μL in people of Mediterranean descent). This difference is related to an inherited slight variation in individual platelet volume (size). The platelet volume is inversely related to the platelet count, so the mass of circulating platelets is the same for these 2 populations. Approximately one-third of platelets are sequestered in the spleen at any one time. Splenic sequestration of platelets can increase dramatically with splenomegaly. Since a platelet has a lifespan of approximately 9–10 days, some 15,000–45,000 platelets/μL must be produced each day to maintain a steady state. New platelet production is the responsibility of the megakaryocyte, a very large multinucleated cell (10,750 fL) found in relatively small numbers in the marrow (0.1% of marrow cells) (Figure 31-1). As with other hematopoietic cells, megakaryocytes are derived from the pluripotent stem cell under the control of growth factors such as interleukin (IL)-3, IL-6, granulocyte macrophage colony-stimulating factor (GM-CSF), IL-11, and thrombopoietin (c-Mpl ligand).

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FIGURE 31-1

Megakaryocytes. Megakaryocytes (very large cells with multi-lobed nuclei) are easily identified in a marrow aspirate specimen.

Graphic Jump Location
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Thrombopoietin (TPO) is by far the most important regulatory protein in the production of platelets. The gene for TPO is located on chromosome 3 (3q26-27). TPO mRNA is expressed ...

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