Page 521 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 32 Acquired Disorders of Red Cell, White Cell, and Platelet Production 441

A B

C D
Fig. 32.12 MARROW ASPIRATE OBTAINED FROM A CHILD WITH THROMBOCYTOPENIA
AND DYSMEGAKARYOCYTOPOIESIS. The megakaryocytes are small and hypolobular, with diminished
cytoplasm. Cells are viewed at magnifications of 250× (A), 1000× (B), 200× (C), and 1600× (D). (From van
den Oudenrijn S, Bruin M, Folman CC, et al: Three parameters: Plasma thrombopoietin levels, plasma glycocalicin levels,
and megakaryocyte culture, distinguish between different causes of congenital thrombocytopenia. Br J Haematol 117:390,
2002.)

cost-effective when compared with the relative simplicity of a bone or a thiazide diuretic, then withdrawal of the offending agent is
marrow examination. obviously indicated. If the cause is viral, IVIg or anti-HIV therapies
As is true for the congenital thrombocytopenias, acquired throm- are indicated. Despite the various causes of ineffective thrombopoi-
bocytopenia can be caused by a failure of either megakaryocytopoiesis esis, immunosuppressive therapy was found to be effective in 8 out
or thrombopoiesis. Of these two possibilities, ineffective thrombo- of 30 patients.
poiesis is the more likely cause, because pure megakaryocyte aplasia
or hypoplasia is quite rare. Indeed, thrombocytopenia secondary to
decreased marrow megakaryocytes is much more likely to be a pro- INFECTION
drome of aplastic anemia, or an early form of MDS. Clues to these
conditions can be found in the marrow, where often subtle abnor- Many infectious diseases are associated with thrombocytopenia, and
malities of other hematopoietic lineages, such as macrocytosis or it is likely that infection is the greatest noniatrogenic cause of inef-
dyserythropoiesis, can be observed. fective platelet production. Infectious agents associated with decreased
platelet counts include mycoplasma, mycobacteria, ehrlichiosis, and
malaria. In these disorders, the cause of the thrombocytopenia is
SELECTIVE MEGAKARYOCYTE APLASIA believed to be diminished platelet production although immune-
mediated thrombocytopenia has also been described in some
Acquired selective amegakaryocytic thrombocytopenia is quite rare. patients.
It is almost always because of an autoimmune mechanism, either Viral infections are by far the most common infectious agents
antibody- or cell-mediated. Autoantibodies reacting with megakaryo- associated with thrombocytopenia caused by ineffective megakaryo-
cytes or their progenitor cells, presumably leading to their destruction, cyte or platelet production. Thrombocytopenia has been reported in
have been described. Antibodies directed to cytokines that regulate cases of mumps, rubella, measles, varicella, CMV, infectious mono-
megakaryocyte development, in particular thrombopoietin, might nucleosis, chickenpox, dengue and other hemorrhagic fevers, hepati-
also play a role in the biogenesis of such disorders. Cases of cell- tis, and parvovirus infections. Live measles virus vaccination can also
mediated suppression of megakaryocytopoiesis leading to a complete induce thrombocytopenia arising from decreased production. The
selective megakaryocyte aplasia have also been described. In these mechanism responsible for viral suppression of platelet counts is not
cases, suppression was shown in one case to be caused by autoreactive completely clear. It is known that megakaryocytes are capable of being
T lymphocytes, whereas a macrophage-derived “factor” was impli- infected by a variety of viruses. Infected cells may appear dysplastic,
cated in the other. with inclusion bodies, vacuoles, or degenerating nuclei. Naked
Patients in whom an autoimmune mechanism is operative may megakaryocyte nuclei may be seen in particular after HIV infection.
respond to treatment with cyclosporine and ATG, achieving durable That such cytopathic cells might have trouble producing platelets is
remissions. Cytotoxic antibodies directed toward the CFU-Mk may not difficult to imagine. Recently it has been demonstrated that
be treated with corticosteroids, plasmapheresis, IVIg, danazol, dengue directly binds to dendritic cell-specific intracellular adhesion
cyclosporine, or cyclophosphamide. Patients with T cell–mediated molecule-3 on the surface of platelets, and could replicate its viral
inhibition of megakaryocytopoiesis may respond to ATG, cyclospo- RNA by usurping the translational machinery of platelets and raising
rine, or hematopoietic growth factors. If a particular drug or toxin the possibility that other (+)ssRNA viruses may be similarly propa-
exposure is believed to be responsible, for example ethanol gated by these anucleate cytoplasts.