Thrombocytopenias Due to Reduced Cell Production

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In this condition, blood contains few, usually small, pyknotic ("old") thrombocytes. Only a very few megakaryocytes are found in the bone marrow, and these have a normal appearance.

Causes

Chronic alcoholism. There may be some overlap with increased turnover and folic acid deficiency.

Chemical and radiological noxae. Cytostatics naturally lead directly to a dose-dependent reduction in megakaryocyte counts. A large therapeutic radiation burden in the area of blood-producing bone marrow has the same result, which may persist for many months.

Virus infections. Measles, mononucleosis (Epstein-Barr virus, cytomegalovirus), rubella, and influenza may (usually in children) trigger thrombocytopenias of various types. In these cases, the virus affects the megakaryocytes directly. However, antibodies to thrombocytes may also arise in the course of these infections (p. 166), so that the pathomechanism of the parainfectious thrombocytopenias described by Werlhof in children may lie in impaired production and/or increased degradation of thrombo-cytes.

Neoplastic and aplastic bone marrow diseases. All neoplasms of the bone marrow cell series (e.g., leukemia, lymphoma, and plasmacytoma), together with their precursor forms (e.g., myelodysplasia), lead to progressive thrombocytopenia, as do panmyelophthisis and bone marrow infiltration by metastases from solid tumors.

Vitamin deficiency. Folic acid and vitamin B12 deficiencies from various causes (p. 152) also affect the rapidly proliferating megakaryocytes. In these cases, thrombocytopenia is often present before anemia and leukocytopenia in circulating blood, while the bone marrow shows copious megakaryocytes that have been blocked from maturation.

Constitutional diseases. An amegakaryocytic thrombocytopenia without any of the above causes is rare. It is seen in children with congenital radial aplasia; in adults it tends usually to be an early sign of leukemia, myelodysplastic syndrome, or aplastic anemia.

Wiscott-Aldrich syndrome (thrombocytopenia, immune deficiency, and eczema) is an X-chromosomal recessive disease in boys and presents with thrombocytopenia with ineffective megakaryopoiesis.

The May-Hegglin anomaly (dominant hereditary transmission) is characterized by thrombocytopenia with giant thrombocytes and granulocyte inclusions, which resemble Döhle bodies (endoplasmatic reticulum aggregates).

Variant forms of thrombocyte and megakaryocyte morphology in the bone marrow are diagnostic aids in thrombocytopenia a c e

Causes Thrombocytopenia Adults

Fig. 60 Morphology of thrombocytes and megakaryocytes. a Bone marrow in thrombocytopenia due to increased turnover (e.g., immunothrombocytopenia). Mononuclear "young" megakaryocytes clearly budding a thrombocyte (irregular, cloudy cytoplasm structure). b In thrombocytopenia against a background of myelodysplasia, the bone marrow shows various megakaryocyte anomalies: here, too small a nucleus surrounded by too wide cytoplasm. c-f In myelodysplasia (c and d) and acute myeloid leukemia (e and f), bizarre anomalous thrombocyte shapes (arrows) may occasionally be found.

Fig. 60 Morphology of thrombocytes and megakaryocytes. a Bone marrow in thrombocytopenia due to increased turnover (e.g., immunothrombocytopenia). Mononuclear "young" megakaryocytes clearly budding a thrombocyte (irregular, cloudy cytoplasm structure). b In thrombocytopenia against a background of myelodysplasia, the bone marrow shows various megakaryocyte anomalies: here, too small a nucleus surrounded by too wide cytoplasm. c-f In myelodysplasia (c and d) and acute myeloid leukemia (e and f), bizarre anomalous thrombocyte shapes (arrows) may occasionally be found.

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