Page 523 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 32 Acquired Disorders of Red Cell, White Cell, and Platelet Production 443

Diagnosing Thrombocytopenia Caused by Impaired Thrombopoiesis
Compiling a thorough patient history is the first step in a complete workup suggest platelet destruction or ineffective production. Megakaryocytes are
of a thrombocytopenic patient. Many potential causes will be revealed not evenly distributed throughout the marrow, so examination of many
by a good history, including obtaining a family history of thrombocyto- fields is required to determine if adequate numbers of cells are present.
penia, recent infection, medication or substance ingestion, radiation or Megakaryocyte morphologic characteristics are also useful to observe.
chemotherapy. The normal compensatory response to thrombocytopenia is enlargement
A careful physical examination could also contribute to making of the cells with increased ploidy. Small, microlobulated or hypolobulated
a diagnosis. For example, physical findings suggesting any of the megakaryocytes may be seen in myelodysplastic syndromes. Dysmorphic
inherited disorders described earlier might be discerned, as might megakaryocytes may also be observed in viral infections, including human
findings suggestive of malignancy such as enlarged lymph nodes. immunodeficiency virus. In the future, flow cytometry may provide a more
Splenomegaly itself is not indicative of a platelet production abnormality objective analysis of megakaryocytes.
but is often found in patients with lymphoma or other processes associ- Ultimately a diagnosis of ineffective thrombopoiesis is made by
ated with marrow infiltration and damage that might cause impaired exclusion. The marrow examination reveals quantitatively normal mega-
thrombopoiesis. karyocytes, and the apparent absence of peripheral platelet destruction
The peripheral blood smear is next examined, and this is needed together with the appropriate clinical circumstances (e.g., folate or
to rule out pseudothrombocytopenia. Moreover, the blood smear vitamin B 12 deficiency) often point to this mechanism. Platelet function
provides additional clues to both the pathophysiologic mechanism of tests may be helpful in distinguishing ineffective production from platelet
the thrombocytopenia and the diagnosis. For example, giant platelets destruction. In destructive processes such as immune thrombocytopenia,
suggest a hereditary or myelodysplastic syndrome; oval macrocytosis and function is normal, whereas in ineffective platelet production impaired
hypersegmented neutrophils suggest a folate or vitamin B 12 deficiency; function is not uncommon, as noted earlier. In complex cases, platelet
and a leukoerythroblastic smear points to an infiltrative process. survival studies may be necessary to show that consumption or splenic
Examination of the bone marrow is also required to evaluate mega- pooling are not significant contributors to the thrombocytopenia; however,
karyocyte number and morphologic features. A biopsy specimen is survival studies are rarely required for clinical purposes. In the future,
more reliable than an aspirate to determine whether megakaryocytes flow cytometric estimation of platelet production rate and measurement
are decreased in number. However, an aspirate showing abundant of thrombopoietin levels may permit a more facile approach to the dif-
megakaryocytes in the presence of thrombocytopenia is sufficient to ferential diagnosis of thrombocytopenia.

in cases of PNH, thrombocytopenia is caused by decreased or inef- low-dose contraceptives, IV gamma globulin and thrombopoietin
fective platelet production. Megakaryocyte progenitors have a mimetics have been reported (see box on Diagnosing Thrombocyto-
decreased proliferative activity and exhibit increased sensitivity to penia Caused by Impaired Thrombopoiesis). 226,227
complement. Treatment with ATG or G-CSF and cyclosporine has
ameliorated the thrombocytopenia whereas complement blockade
with Eculizumab has little impact on platelet count. SUGGESTED READINGS
Bennett CL, Christie J, Ramsdell F, et al: The immune dysregulation,
Refractory Thrombocytopenia Caused by polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused
Myelodysplasia by mutations of FOXP3. Nat Genet 27(1):20, 2001.
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diseases: 85 cases and literature review. Autoimmun Rev 15:82–92, 2016.
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nosis of MDS should be considered when there are clonal chromo- for refractory T cell large granular lymphocytic leukemia. Leukemia
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mia. Some patients with a full-blown MDS associated with marked Dellacasa CM, D’Ardia S, Allione B, et al: Efficacy of plasmapheresis for
thrombocytopenia and less than 10% blasts have been reported to the treatment of pure red blood cell aplasia after allogeneic stem cell
experience increases in platelet counts after androgen therapy. Ami- transplantation. Transfusion 55:2979, 2015.
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some of these patients have been misdiagnosed as having immune erythropoiesis-stimulating agents for the treatment of anaemia in patients
thrombocytopenia purpura. Thrombopoietin agonists like romiplos- with chronic kidney disease. Expert Opin Drug Saf 1–10, 2016.
tim have also been used in patients with MDS. In an initial study Frattini F, Crestani S, Vescovi PP, et al: Pure white cell aplasia induced by
involving 44 patients, a durable platelet response was achieved in mesalazine in a patient with ulcerative colitis. Hematology 18(3):2013.
46% of patients with less bleeding events and transfusions seen in Haapaniemi EM, Kaustio M, Rajala HL, et al: Autoimmunity, hypogamma-
patients who achieved a durable response. Other treatment strategies globulinemia, lymphoproliferation, and mycobacterial disease in patients
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