Thrombocytopenia with a sex-linked pattern of inheritance has been reported in a number of families. The presence of a normal number of megakaryocytes in the bone marrow suggests that the thrombocytopenia is a result of shortened platelet survival due to an intrinsic platelet defect. The response to steroids is poor. A complete response to splenectomy has occurred in some patients.
X-linked anemia with severe thrombocytopenia, due to defects in the GATA-1 gene, has been reported. Bone marrow shows many large megakaryocytes with nuclei pushed to the side and unorganized granular content.
The Wiskott-Aldrich is an X-linked syndrome consisting of eczema, recurrent infections, and thrombocytopenia. The gene involved is on the short arm of the X chromosome. It has been cloned and designated WASp.
Infants are ill from the first few months of life and die in early childhood. Bleeding is frequently ushered in by melena during the neonatal period, later followed by purpura. Thrombocytopenia is associated with a shortened platelet survival time caused by an intrinsic platelet defect, as well as impaired platelet production. The clinical course is punctuated by recurrent pyogenic infections, including otitis media, pneumonia, and skin infections. There is also lowered resistance to nonbacterial infections, including herpes simplex and Pneumocystis carinii pneumonia.
1. Thrombocytopenia (platelet count, about 30,000/mm3); micro thrombocytes; low mean platelet volume (MPV)
2. Anemia (due to blood loss)
3. Leukocytosis (due to infection)
4. Normal or increased megakaryocytes
5. Absent isohemagglutinins, reduced IgM, and normal or elevated IgG and IgA
6. Defective cell-mediated immunity in some cases. Treatment
1. Platelet transfusion: for hemorrhagic episodes
2. Corticosteroids: for eczema; no effect on the thrombocytopenia
3. Splenectomy: reserved only for very severe cases because of high risk of overwhelming infection following splenectomy
4. Hematopoietic stem cell transplantation.
This heterogeneous group of rare disorders includes both dominant and recessive forms of pure thrombocytopenia and the autosomal dominant May Hegglin anomaly.
In the pure form, families with both dominant and recessive modes of inheritance occur. Bone marrow examination usually demonstrates normal numbers of megakaryocytes. Autologous platelet survival studies indicate a shortened life span, pointing to an intrinsic platelet defect.
The May Hegglin anomaly consists of:
1. Autosomal dominant inheritance
2. Thrombocytopenia, variable degree
3. Giant platelets; normal platelet function and platelet survival
4. Döhle bodies in the cytoplasm of the granulocytes
5. Normal megakaryocytes
6. Most patients asymptomatic, with only a few showing hemorrhagic manifestations; no sign of bleeding in newborns
7. May Hegglin, Fetchner, Sebastian, and Epstein syndromes all map to the same region on the long arm of chromosome 22 (see Table 10-14 later in the chapter).
Familial platelet deficiency/AML is dominantly inherited. Thrombocytopenia is mild (100,000/mm3). Some families have a severe storage pool defect. There is a 30% risk of developing AML and other cancers.
Patients with Paris-Trousseau syndrome exhibit mild thrombocytopenia with a subpopulation of platelets containing giant a-granules. Bone marrow examination shows expansion of immature megakaryocytic progenitors with normal erythroid and granulocytic series. Some patients have trigonocephaly, facial dysmorphism, cardiac defects, syndactyly, and psychomotor retardation in addition to platelet defects. This constellation of findings is called Jacobsen syndrome.
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