Transient thrombocytosis with megathrombocytes in a case of acute myeloblastic leukemia

Mrinalini Kotru; Madhu Batra; Sunil Gomber; Usha Rusia

doi:10.4103/0377-4929.44992

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CASE REPORT

Year : 2009 | Volume : 52 | Issue : 1 | Page : 113-114

Transient thrombocytosis with megathrombocytes in a case of acute myeloblastic leukemia

Mrinalini Kotru¹, Madhu Batra¹, Sunil Gomber², Usha Rusia¹
¹ Department of Pathology, University College of Medical Sciences and Associated Guru Teg Bahadur Hospital, New Delhi - 110 095, India
² Department of Pediatrics, University College of Medical Sciences and Associated Guru Teg Bahadur Hospital, New Delhi - 110 095, India

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Abstract

Thrombocytosis is commonly seen in reactive conditions and certain neoplastic states, such as chronic myeloproliferative disorders. It is rarely seen in acute leukemia. A 12-year-old girl with acute myeloblastic leukemia (FAB M2) in remission presented with pyoderma. Her hemogram revealed anemia (Hb-6.4g/dl), leucopenia (TLC - 1.2 x 109/L) and thrombocytosis (platelet count- 580 x 109/L). A peripheral blood film showed numerous abnormally large platelets with few atypical cells. The thrombocytosis subsided with the clearance of infection but atypical cells persisted. One month later, she relapsed. Cytogenetic analysis revealed variable results (trisomy 9 and deletion 3). This case has been presented because thrombocytosis is rare in AML and its appearance calls for a close follow-up.

Keywords: Acute myeloblastic leukemia, cytogenetics, megathrombocytes, thrombocytosis

How to cite this article:
Kotru M, Batra M, Gomber S, Rusia U. Transient thrombocytosis with megathrombocytes in a case of acute myeloblastic leukemia. Indian J Pathol Microbiol 2009;52:113-4

How to cite this URL:
Kotru M, Batra M, Gomber S, Rusia U. Transient thrombocytosis with megathrombocytes in a case of acute myeloblastic leukemia. Indian J Pathol Microbiol [serial online] 2009 [cited 2023 Dec 1];52:113-4. Available from: https://www.ijpmonline.org/text.asp?2009/52/1/113/44992

Introduction

Thrombocytosis is commonly seen in reactive conditions, chronic myeloproliferative disorders,^[1] myelodysplastic syndrome with 5q- syndrome,^[2] and very rarely in acute leukemia. Patients with acute leukemia usually have thrombocytopenia at the time of presentation.^[3] Upon use of chemotherapy, the platelet count may return to normal or may require thrombopoietin (TPO) therapy. High platelet counts are seldomly seen in acute myeloblastic leukemia (AML). Extensive literature survey revealed only a few case reports of thrombocytosis in AML seen in association with thrombopoietin administration^[4] or chromosomal abnormalities such as t(2;14)(p13;q32)^[5] and 3q21q26 syndrome.^[3] We present an unusual case of transient thrombocytosis preceding a relapse in AML.

Case Report

Clinical findings

A 12-year-old girl was diagnosed with AML FAB M2 in October 2005. She received combination chemotherapy with daunorubicin and cytarabine arabinoside C and achieved complete remission. In December 2005, a cerebrospinal fluid (CSF) examination revealed immature myeloid cells and an occasional blast, following which she was given a second cycle of chemotherapy (cyclophosphamide, methotrexate and 6-mercaptopurine) and cranial irradiation (1800 rads). After the second cycle, she remained in remission for 7 months. In July 2006, she presented with pyoderma. She was referred to our laboratory for a routine hematological work-up.

Hematological findings

Her hemoglobin was 6.4 g/dl, total leucocyte count was -1.2 x 10⁹ /L and platelet count was -580 x 10⁹ /L. A peripheral blood film showed normocytic normochromic red cells and moderate leucopenia with a few atypical cells (suspicious of blasts). There was thrombocytosis with numerous abnormally large platelets [Figure 1], some as large as Red blood cells (RBC) (7-10 µm). The platelets were present singly and in clumps and showed normal granularity. An occasional megakaryocytic fragment was also seen. As marked thrombocytosis with the presence of megathrombocytes is an unusual finding in AML, a cytogenetic analysis was performed, which revealed variable results (trisomy 9 and deletion 3). None of these chromosomal abnormalities have been reported in literature. She was started on a course of antibiotics for the pyoderma and her complete blood count was repeated after 2 days. At this time, her platelet count was 220 x 10⁹ /L and was of normal morphology. A peripheral blood film showed leucopenia with few atypical cells (4%) with similar morphology as seen before. Due to the persistance of atypical cells, there was a suspicion of a relapse and a bone marrow aspirate was performed. The bone marrow showed chemotherapy induced changes with marked myelosuppression and an occasional blast. Megakaryocytes were adequate and functional. Though the bone marrow was in remission, the patient was kept on a weekly follow-up. One month later, the patient relapsed. There were 85% blasts in the peripheral blood and the marrow was packed with blasts with an occasional erythroid cell and megakaryocyte. However, the patient refused to have any further chemotherapy and was thus further managed with supportive therapy. She expired 3 months later.

Discussion

Thrombocytosis is often discovered as an incidental laboratory finding. It can be a reactive (secondary thrombocytosis) or a clonal bone marrow (myeloproliferative) process. Reactive thrombocytosis, which is more common, is caused by increased levels of thrombopoietin (TPO), other cytokines, or catecholamines that may be produced in inflammatory, infectious, stressful or neoplastic conditions. Clonal thrombocytosis is commonly seen in chronic myeloproliferative disorders such as chronic myeloid leukemia, essential thrombocythemia, polycythemia vera,^[1] and myelodysplastic syndrome with 5q- syndrome.^[2] It is largely a diagnosis of exclusion but important to identify because of therapeutic implications.

Thrombocytosis is rarely seen in AML. The majority of AML cases have thrombocytopenia at presentation. Those AML cases that have a normal or increased platelet count may have abnormalities of the long arm of chromosome 3 such as inv(3)(q21;q26) and t(3;3)(q21;q26). Clinically, these patients have a young median age and a poor prognosis.^[3] In 1993, Bouscary, et al. [6] demonstrated that Thrombopoietin (TPO) was not responsible for the thrombocytosis seen in AML with 3q21q26 syndrome, as was believed earlier. They studied 4 patients with 3q21:q26 syndrome: 3 patients with inv(3)(q21q26) and 1 patient with t(3;3)(q21q26). Increased mRNA levels of EVI 1, located on 3q26 locus and expressed by leukemia cells, were detectable while the TPO transcript gene, also located at 3q26 locus, was undetectable, thus demonstrating that the TPO gene transcription is not activated in patients with 3q26 chromosomal abnormality and that abnormal TPO production is not responsible for the observed thrombocytosis in these patients. Besides 3q21q26 syndrome, thrombocytosis in AML has been reported in association with leukemic (AML) transformation in a case of cutaneous T cell lymphoma^[7] and following relapse in a case of AML in which it was attributed to t(2;14)(p13;q32).^[5]

In this case, there was no history of TPO administration, which is one of the major causes of thrombocytosis in AML. Among the reactive causes of thrombocytosis, infection is an important one. Our patient also had a skin infection at the time of sampling. The thrombocytosis then subsided 2 days later as the infection was treated. This could possibly explain the presence of thrombocytosis in this case. However, there were atypical cells in the peripheral blood at the time of thrombocytosis and their persistence despite resolution of thrombocytosis, followed by the development of relapse within a month suggested that the preceding thrombocytosis might not have been a mere simple reactive change but possibly a harbinger of a more ominous event. Fujita, et al. had observed thrombocytosis in association with leukemic transformation in a case of cutaneous T cell lymphoma. ^{[ 6]} A similar observation was made by Tasaka who observed thrombocytosis in a case of AML following relapse and attributed it to a chromosomal alteration t(2;14)(p13;q32).^{[ 5]} In the present case, none of the chromosomal changes, seen in association with thrombocytosis in AML as mentioned in literature, were observed. Rather, new chromosomal abnormalities were observed to a variable degree, which needs to be further validated. In this case, whether the thrombocytosis was purely reactive or a harbinger of an impending relapse is a matter of contention, as the patient has died. Nevertheless, the appearance of thrombocytosis in a case of AML should be considered seriously and warrants a close follow-up.

References

1.	Schafer AI. Thrombocytosis. N Engl J Med 2004;350:1211-9. [PUBMED] [FULLTEXT]
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3.	Greer P, Baer MR, Kinney MC. Acute myeloid leukemia in adults. In: Greer JP, Foerster J, Lukens JN, Rodgers GM, Paraskevas F, Glader B, editors. Wintrobe's clinical haematology. 11th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2004. p. 2097-142.
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6.	Bouscary D, Fontenay-Roupie M, Chretien S, Hardy AC, Viguie F, Picard F, et al . Thrombopoietin is not responsible for the thrombocytosis observed in patients with acute myeloid leukemias and the 3q21q26 syndrome. Br J Haematol 1995;91:425-7.
7.	Fujita A, Matsuoka M, Shimonaka Y, Imai N, Asano S. Acute myeloid leukemia possibly producing thrombopoietic factor(s). Jpn J Clin Oncol 1993;23:366-72. [PUBMED] [FULLTEXT]