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Table of Contents
Year : 2022  |  Volume : 11  |  Issue : 3  |  Page : 181-186

Chronic myeloid leukaemia presenting as acute pulmonary thromboembolism

Department of General Medicine, NIMS, Hyderabad, Telangana, India

Date of Submission08-Sep-2020
Date of Decision21-Mar-2022
Date of Acceptance22-Mar-2022
Date of Web Publication12-Jul-2022

Correspondence Address:
Shetty Mallikarjuna
Additional Professor, Department of General Medicine, Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad 500 082, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JCSR.JCSR_81_20

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Myeloproliferative neoplasms are associated with increased viscosity and thrombosis most commonly leading to splanchnic vein thrombosis and Budd Chiari syndrome. Pulmonary thromboembolism is a rare possibility. Chronic Myeloid Leukaemia commonly present with anaemia, splenomegaly. In cases presenting with thrombosis, leucocytosis is generally observed. Eosinophilia is also a rare presentation of CML. Here we present a case of young male presented with unprovoked Acute Pulmonary Embolism and eosinophilia. On evaluation found to be having Philadelphia Chromosome positive and improved on treatment with Tyrosine Kinase Inhibitors. This case highlights the importance of consideration of pulmonary embolism as one of cause of acute onset shortness of breath especially when there are suggestive ECG changes and emphasises the need for evaluation of cause of Acute thromboembolism.

Keywords: Chronic myeloid neoplasm, eosinophilia, myeloproliferative neoplasm, Philadelphia chromosome, pulmonary thromboembolism, tyrosine kinase inhibitors

How to cite this article:
Mallikarjuna S, Reddy Gari PR, Kumar SV, Kumar DS. Chronic myeloid leukaemia presenting as acute pulmonary thromboembolism. J Clin Sci Res 2022;11:181-6

How to cite this URL:
Mallikarjuna S, Reddy Gari PR, Kumar SV, Kumar DS. Chronic myeloid leukaemia presenting as acute pulmonary thromboembolism. J Clin Sci Res [serial online] 2022 [cited 2023 Feb 7];11:181-6. Available from: https://www.jcsr.co.in/text.asp?2022/11/3/181/350742

  Introduction Top

Chronic myeloid leukaemia (CML) is a clonal hematopoietic stem cell disorder.[1] The disease is driven by the breakpoint cluster region gene-Abelson gene (BCR-ABL1) chimeric gene product that codes for a constitutively active tyrosine kinase, resulting from a reciprocal balanced translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34.1;q11.2), known as the Philadelphia chromosome.[1],[2] Untreated, the course of CML is typically biphasic or triphasic, with an early indolent or chronic phase (blasts <10%), followed often by an accelerated phase (blasts (10%–19%) and a terminal blastic phase (>20%).[1],[2] Common symptoms, when present, are manifestations of anaemia and splenomegaly. These may include fatigue, malaise, weight loss (if high leukaemia burden) or early satiety and left upper quadrant pain or masses (from splenomegaly). Less common presenting features and complications include bleeding manifestations, recurrent infections, problems due to leucostasis and extramedullary infiltrations.[1],[3] Thrombotic and hyperviscocity related events include priapism, myocardial infarction, venous thrombosis, visual disturbances and cerebrovascular accidents.[1] Mortality and outcome drastically changed with the introduction of tyrosine kinase inhibitor therapy, with which the estimated 10-year survival is 85%.[1] We present the case of patient who presented with unprovoked pulmonary thromboembolism (PTE) with fever and shortness of breath. On evaluation found to be having lymphadenopathy, leucocytosis, eosinophilia and thrombocytopenia. Bone marrow examination revealed hypereosinophilia without blasts and cytogenetics showed BCR-ABL positivity. Eventually, the patient had a complete recovery with anticoagulation and tyrosine kinase inhibitor therapy.

  Case Report Top

A 32-year-old male resident of Siddipet district from Telangana state, toddy maker by occupation, who had no known prior co-morbidities and never had habit of smoking or alcohol intake developed generalised itching in the month of January 2 days later he started developing moderate grade of fever not associated with chills, or rigors, he used over the counter medication which partially relived fever and itching, 1 week later he started developing shortness of breath initially on exertion, within 1-day patient started developing shortness of breath even at rest which used to worsen immediately on lying down (orthopnoea), he also had pricking type of pain over the right side of chest which used to increase on deep inspiration and on lying over right side. He visited local hospital where chest imaging, electrocardiogram (ECG) and basic blood investigations were done on basis of which he was diagnosed as having sepsis secondary to right basal pneumonia. He received 1-day course of meropenem, doxycycline and vancomycin in adequate doses. The patient did not improve and he was referred to higher centre for further evaluation.

On receiving at emergency, he was afebrile having tachycardia with pulse rate of 112/min, tachypnoea with respiratory rate of 40 cycles/min, normotensive (blood pressure: 110/70 mmHg) and hypoxic with room air saturation of 86%. He was given 10 L/min of oxygen on which his saturation was 94%. General and detailed systemic examination performed. The patient had inguinal lymphadenopathy: two non-tender mobile separate (not matted) lymph nodes palpated over right inguinal region, lymph nodes were not palpable in other areas. No other significant findings were present on general examination.

On chest auscultation, air entry was decreased over right infra axillary, lower interscapular and infrascapular areas which were stony dull on percussion. Cardiovascular, gastrointestinal and nervous system examination was normal. Arterial blood analysis showed type 1 respiratory failure and high anion gap metabolic acidosis secondary to elevated lactates with compensated with respiratory alkalosis. Quick review of previous investigations done showed right pleural effusion and neutrophilic leucocytosis along with thrombocytopenia [Table 1]. Based on history, clinical examination with support from investigations done prior, provisional diagnosis of sepsis secondary to right lower lobe pneumonia was considered and the patient was started on empirical antibiotics, IV ceftriaxone and doxycycline after drawing blood for cultures and procalcitonin, along with other supportive management.
Table 1: Laboratory parameters

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Chest radiograph showed bilateral lower zone infiltrates along with right-sided moderate pleural effusion. Ultrasound-guided aspiration of pleural fluid done and analysed showing exudative effusion. Complete haemogram showed leucocytosis (15,700/mm3) with differential count of 64% neutrophils, 7% lymphocytes, 6% monocytes and 23% eosinophils. Absolute eosinophil count was 7640 cells/mm3 [Figure 1]. Curiously, ECG showed tachycardia, regular rhythm, left axis deviation and S-wave in lead I, deep Q waves and T-wave inversions in lead III [Figure 2]. Renal and liver functions were within normal limits, and serum procalcitonin was within normal limits [Table 1], and blood cultures were sterile after incubation for 2 days, making sepsis a less probable diagnosis. Taking into account of S1Q3T3 finding on ECG, PTE was considered a differential.
Figure 1: Photomicrograph of peripheral smear showing eosinophilia (Giemsa x400)

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Figure 2: Electrocardiogram showing tachycardia, regular rhythm, left axis deviation and S wave in lead I, deep Q waves and T wave inversions in lead III

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Well's score was calculated for the patient. The patient did not have any signs of deep vein thrombosis, no previous history of surgery. Well's score was calculated to be 3 (immobilised for 3 days, and heart rate of >100/min) (intermediate probability of PTE). D Dimers were elevated. Two-dimensional echocardiogram done showed normal biventricular function and no evidence of PTE. Computed tomography pulmonary angiography (CTPA) was performed, which showed evidence of PTE involving descending branch of right pulmonary artery and segmental branches to right lower lobe, ascending and descending branches of left pulmonary artery, segmental branches to left lower lobe, along with consolidations in bilateral lower lobes and lingula and bilateral pleural effusion [Figure 3]. The patient was categorised as submassive PTE (good right ventricular function and normotensive) and the patient was given therapeutic heparin infusion for 5 days monitoring augmented partial thromboplastin time.
Figure 3: CTPA coronal section (a) transverse sections (b and c) showing filling defect suggestive of embolism in bilateral pulmonary arteries and segmental branches. CTPA = computed tomography pulmonary angiography

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Meanwhile, evaluation for cause of unprovoked PTE and lymphadenopathy and eosinophilia was going on. Venous Doppler study of lower limbs showed no evidence of deep vein thrombosis. The patient did not have a family history of thrombosis. Ultrasonography of abdomen and inguinal region showed two enlarged lymph nodes in right inguinal region each of 2 cm, with maintained fatty hilum. Spleen and liver were of normal size and echotexture. There were no other enlarged lymph nodes in mediastinum, abdomen and retroperitoneum as evidenced by computed tomography (CT) of chest and abdomen. Fine-needle aspiration cytology of inguinal lymph node showed normal reactive hyperplasia. Work up for inherited and acquired thrombophilia was postponed in view of acute thrombotic events [Table 2].
Table 2: Other laboratory work-up

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Evaluation of eosinophilia done, serum immunoglobulin E levels were normal and stool examination showed no ova or cysts. The patient denied intake of drugs causing eosinophilia such as aspirin, nitrofurantoin, or cephalosporins before admission. Peripheral smear on 5th day of admission showed 55% of eosinophils. As a part of evaluation for unexplained eosinophilia and lymphadenopathy, bone marrow examination was done. Bone marrow aspiration showed particulate aspirate with increased cellularity, myeloid prominence with myeloid: Erythroid ratio of 5:1, and prominence of eosinophils and its precursors constituting 51% of cells. Blasts were not seen. Trephine biopsy report was awaited, meanwhile, genetic analysis was sent for possibility of chronic haematological malignancy which might be cause of eosinophilia, lymphadenopathy and unprovoked thrombosis.

After 4 days of heparin infusion, the patient symptomatically improved, switched over to oral dabigatran on day 5. Antibiotics were discontinued and oral diethylcarbimizine was started empirically for eosinophilia. Blood eosinophil count came down as complaint of itching resolved. Bone marrow biopsy showed hypereosinophilia but no blasts [Figure 4],[Figure 5],[Figure 6],[Figure 7]. Genetic analysis detected BCR-ABL translocation. Medical oncology consultation was taken. The patient was diagnosed to have chronic myeloid leukaemia with hypereosinophilia which presented as unprovoked PTE. Antibiotics discontinued after resolution of fever and normalisation of leucocyte count, and the patient was started on oral Imatinib for CML. The patient was discharged after 1 week in haemodynamically stable condition with advice to continue dabigatran 150 mg twice daily and imatinib 400 mg once daily. The patient was relieved completely off symptoms and kept on follow-up.
Figure 4: Photomicrograph of bone marrow aspirate showing increased myeloid precursor cells (Giemsa x40)

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Figure 5: Photomicrograph of bone marrow aspirate showing increased eosinophil precursors (Giemsa X400)

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Figure 6: Photomicrograph of bone marrow trephine biopsy imprint showing increased myeloid cells with prominence of eosinophilic precursor cells (Giemsa x400)

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Figure 7: Photomicrograph of bone marrow aspirate showing increased myeloid cells and prominence of eosinophil precursor cells (Giemsa x1000)

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  Discussion Top

The patient presented with a history of fever and shortness of breath, which was initially treated as community-acquired pneumonia and sepsis. Although the patient did not have any prior known risk factors for the occurrence of thrombosis or signs of deep vein thrombosis, the presence of sinus tachycardia and S1Q3T3 on ECG supported by elevated D-dimer shortened the time for diagnosis of acute PE. The most common and important ECG finding in a patient with PE is sinus tachycardia and the presence of S1Q3T3 pattern in the ECG.[4] CTPA confirmed the presence of bilateral PTE, luckily, the patient was hemodynamically stable and had normal right ventricular function, so treated with anticoagulation alone.

Unprovoked venous thromboembolism (VTE) in young male needs evaluation for conditions leading to hypercoagulable states like inherited thrombophilias such as factor V Leiden mutation, Prothrombin gene mutation, homocysteinemia and acquired causes such as antiphospholipid antibody syndrome, myeloproliferative disorders (MPDs).[4],[5],[6] The patient had normal homocysteine levels, and factor V Leiden mutation was not detected. Work up for antiphospholipid antibody syndrome (anticardiolipin antibodies and lupus anticoagulant) tested negative. Although the patient's age and absence of any risk factors directs against the possibility, MPD was considered one of differential considering eosinophilia, lymphadenopathy. Risk of undiagnosed cancer in a person with an unprovoked VTE (no obvious predisposing factor such as recent surgery or long-haul flight, immobility or family history of clots) is 10%.[7],[8]

MPDs, whether overt or latent, represent a main risk factor for the development of thrombosis in the portal, mesenteric, and hepatic areas.[9],[10] However, pulmonary thrombosis is a rare finding. Although leukemic thrombi are a well-known complication of acute or chronic myeloid leukaemia, they tend to occur most commonly in the setting of hyperleucocytosis when the leukemic cell burden is remarkably high (>100 × 109/L). Condition of the patients improves when put on treatment which leads to fall in total white blood cell count.[11] However, rarely patients do present with thrombotic complications in the absence of hyperleucocytosis.[12] Our patient had normal leukocyte count at presentation. Even though no blast cells were detected on peripheral smear and bone marrow. Myelopreolifetrative neoplasm (MPN) was suspected in view of hypereosinophilia on peripheral smear and marrow and cytogenetical analysis done for mutations causing MPN. Real-time polymerase chain reaction for BCR-ABL gene mutation was positive and the patient was treated with tyrosine kinase inhibitors. The patient improved symptomatically with anticoagulation and tyrosine kinase inhibitor therapy.

Acute PE should be considered as one of differential in patient presenting with recent onset shortness of breath and meticulous clinical examination and careful assessment of ECG and chest radiograph are important for coming into diagnosis. ECG findings though not much sensitive, can give clues for diagnosis of acute PE, timely reaction is key for saving patient. While evaluating cause of unprovoked PTE, rare causes like MPNs should be kept in mind especially if patient has any abnormal findings of peripheral smear, in this case eosinophilia. CML may result in hyperviscosity and thrombotic tendencies resulting commonly in splanchnic thromboembolism, rarely deep vein and pulmonary embolism.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Kantarjian H, Cortes J. Chronic myeloid leukemia. In: Jameson JL, Fauci S, Kasper DL, Hauser SL, Longo DL, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 20th ed. New York; McGraw Hill; 2019. p. 748-56.  Back to cited text no. 1
Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. Am J Hematol 2018;93:442-59.  Back to cited text no. 2
Granatowicz A, Piatek CI, Moschiano E, El-Hemaidi I, Armitage JD, Akhtari M. An overview and update of chronic myeloid leukemia for primary care physicians. Korean J Fam Med 2015;36:197-202.  Back to cited text no. 3
Tapson VF. Acute pulmonary embolism. N Engl J Med 2008;358:1037-52.  Back to cited text no. 4
Goldhaber SZ. Deep venous thrombosis and pulmonary thromboembolism. In: Jameson JL, Fauci S, Kasper DL, Hauser SL, Longo DL, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 20th ed. New York; McGraw Hill; 2019. p. 1910-6.  Back to cited text no. 5
Kekre N, Connors JM. Venous thromboembolism incidence in hematologic malignancies. Blood Rev 2019;33:24-32.  Back to cited text no. 6
Carrier M, Le Gal G, Wells PS, Fergusson D, Ramsay T, Rodger MA. Systematic review: The Trousseau syndrome revisited: Should we screen extensively for cancer in patients with venous thromboembolism? Ann Intern Med 2008;149:323-33.  Back to cited text no. 7
Prandoni P, Casiglia E, Piccioli A, Ghirarduzzi A, Pengo V, Gu C, et al. The risk of cancer in patients with venous thromboembolism does not exceed that expected in the general population after the first 6 months. J Thromb Haemost 2010;8:1126-7.  Back to cited text no. 8
Kessler CM. Propensity for hemorrhage and thrombosis in chronic myeloproliferative disorders. Semin Hematol 2004;41:10-4.  Back to cited text no. 9
Randi ML, Rossi C, Fabris F, Girolami A. Essential thrombocythemia in young adults: Major thrombotic complications and complications during pregnancy – A follow-up study in 68 patients. Clin Appl Thromb Hemost 2000;6:31-5.  Back to cited text no. 10
Muñiz AE. Myocardial infarction and stroke as the presenting symptoms of acute myeloid leukemia. J Emerg Med 2012;42:651-4.  Back to cited text no. 11
Elias HK, Mohammed N, Vanamala A, Kumar KR, Shet AS. Leucopenia in acute myeloid leukemia presenting as myocardial infarction: A case report. J Bone Marrow Res 2013;1:1.  Back to cited text no. 12


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]

  [Table 1], [Table 2]


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