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CORRESPONDENCE The thrombocytopenia and absent radii (TAR) syndrome is a rare
congenital defect characterized by the association of skeletal malformations with hematologic disturbances.1 Additional
manifestations are absence or hypoplasia of other bones of the
extremities, short stature, dislocation of hip, and various other
abnormalities. In an investigation on 5 unrelated children with TAR
syndrome, Ballmaier et al found that the thrombocytopenia was caused by a defective megakaryopoiesis and thrombocytopoiesis, which was due to a
lack of response to thrombopoietin, despite normal expression of the
thrombopoietin receptor on the megakaryocytes.2 Letestu et
al showed evidence of dysmegakaryopoiesis, with a blockage of cellular
differentiation at an early stage.3 In these experiments, megakaryopoiesis in cell culture was not responsive to stimulation with
mixtures of cytokines, including erythropoietin. We now report the case of a 49-year-old female with TAR syndrome who
was referred to our clinic for investigation of bleeding risk for
elective hip surgery. The patient had suffered from severe coxarthrosis
for several years. Absence of radii was confirmed by roentgenograms.
The patient is of short stature, with a body height of 148 cm. Platelet
count was in the range of 50 × 109/L to
60 × 109/L both in ethylenediaminetetraacetic acid
(EDTA) anticoagulated blood, as well as in citrated whole
blood. Red blood cells were within the normal range, whereas the
patient showed elevated leukocyte counts throughout the observation
period. Expression of platelet receptors CD41, CD61, CD42a, and CD42b
was found to be normal in flow cytometric analysis. Erythropoietin
levels were within the normal range. Erythropoietin has been shown to induce an increase in platelet
count4 and has been employed in the preparation of anaemic patients for hip surgery5 and for prevention of anaemia
and thrombocytopenia in cancer patients receiving
radiotherapy.6 Treatment with rHuEpo leads to elevated
numbers of megakaryocytes in the bone marrow of patients with renal
anemia7 and an increase in platelet counts in animal
experiments.8,9 We treated the patient with 2 courses of erythropoietin. Upon the first
instance, she received 1000 IU/d of recombinant erythropoietin (rHuEpo)
(Neo-Recormon; Roche, Mannheim, Germany) (16 IU/kg body weight) for 3 days. The second time, we administered 2000 IU/d (32 IU/kg body weight)
for 4 days. During the first series, platelet counts increased from
48 × 109/L to 84 × 109/L on day 5. In the
second series, platelet count increased from 50 × 109/L
to 80 × 109/L on day 6. Erythrocyte count, as well as
leukocyte counts, remained unchanged during rHuEpo treatment. (See
Table 1 for a summary.) The results
indicate that the thrombocytopenia of patients with TAR syndrome may be
responsive to rHuEpo treatment, resulting in a therapeutically relevant
increase in platelet count. Treatment with rHuEpo may be useful in
patients scheduled for surgical procedures, in order to reduce the
amount of heterologous platelet concentrates needed for maintaining a
sufficient hemostatic capacity. Additional experiences are needed in
order to determine the required dosage of rHuEpo. In animal
experiments, large chronic doses of rHuEpo have been shown to cause
thrombocytopenia, caused by competition between precursor cells of the
erythrocytic and megakaryocytic cell lines.10 In view of
these limitations, treatment with rHuEpo in patients with TAR syndrome
should presumably be limited to short-term applications.
Carl-Erik Dempfle, Christine Burck, Tina Grützmacher, Jan Wizenmann, and Dieter L. Heene
References 1. Hedberg VA, Lipton JM. Thrombocytopenia with absent radii. A review of 100 cases. Am J Pediatr Hematol Oncol. 1988;10:51-64[Medline] [Order article via Infotrieve].
2.
Ballmaier M, Schulze H, Strau
3.
Letestu R, Vitrat N, Massé A, et al.
Existence of a differentiantion blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome.
Blood.
2000;95:1633-1641 4. McDonald TP, Cottrell MB, Clift RE, Cullen WC, Lin FK. High doses of recombinant erythropoietin stimulate platelet production in mice. Exp Hematol. 1987;15:719-721[Medline] [Order article via Infotrieve]. 5. Hasegawa Y, Takamatsu J, Iwase T, Iwasada S, Kitamura S, Iwata H. Effects of recombinant human erythropoietin in thrombosis and fibrinolysis in autologous transfusion for hip surgery. Arch Orthop Trauma Surg. 1999;119:384-387. 6. Sweeney PJ, Nicolae D, Ignacio L, et al. Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: final report of a randomized, open-labelled, phase II trial. Br J Cancer. 1998;77:1996-2002[Medline] [Order article via Infotrieve]. 7. Horina JH, Schmid CR, Roob JM, et al. Bone marrow changes following treatment or renal anemia with erythropoietin. Kidney Int. 1991;40:917-922[Medline] [Order article via Infotrieve]. 8. Wolf RF, Peng J, Friese P, Gilmore LS, Burstein SA, Dale GL. Erythropoietin administration increases production and reactivity of platelets in dogs. Thromb Haemost. 1997;78:1505-1509[Medline] [Order article via Infotrieve]. 9. Shikama Y, Ishibashi T, Kimura H, Kawaguchi M, Uchida T, Maruyama Y. Transient effect of erythropoietin on thrombocytopoiesis in vivo in mice. Exp Hematol. 1992;20:216-222[Medline] [Order article via Infotrieve].
10.
McDonald TP, Clift RE, Cottrell MB.
Large, chronic doses of erythropoietin cause thrombocytopenia in mice.
Blood.
1992;80:352-358   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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| Copyright © 2001 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
G, et al.
Thrombopoietin in patients with congenital thrombocytopenia and absent radii: elevated serum levels, normal receptor expression, but defective reactivity to thrombopoietin.
Blood.
1997;90:612-619