Abstract
A 35-year-old male patient with acute myeloid leukemia (AML), with hyperleukocytosis, presented with acute myocardial infarction. The individual had acute onset chest pain and reached the hospital within the window period. His electrocardiogram (ECG) revealed ST elevated myocardial infarction (STEMI), ST elevated myocardial infarction, and thrombolysis was performed. Postthrombolysis, there was no resolution of ST elevation, and coronary angiography revealed normal coronaries. His blood picture showed hyperleukocytosis with 80% blasts, and bone marrow and flow cytometry confirmed the diagnosis of AML. Considering the central role of white blood cell in the remodeling of myocardial tissue, it was obvious that administration of chemotherapy with its inevitable pancytopenia could impose an increased risk for further cardiac complications. Nevertheless, cytarabine-based induction chemotherapy was initiated; on the third day, he developed bilateral diffuse alveolar hemorrhage. He was managed with mechanical ventilation, component support, empirical antibiotics, and other bundled care. The patient died 2 days later with diffuse alveolar hemorrhage and leukemia.
Keywords: Acute Leukemia, ST-elevation myocardial infarction, Hyperleucocytosis, Chemotherapy
Introduction
Hyperleukocytosis (total leukocyte count >1,00,000/μL) occurs in approximately 8.5% of patients with newly diagnosed acute leukemia.1 It is most commonly seen in patients with acute myeloid leukemia (AML), particularly monocytic variant (FAB-M5).2 The mean cell volume of myeloblasts is 350–450 cubic microns, and they are considerably less deformable.3 Therefore, with increasing blast counts, plugs of these more rigid cells can develop in the microcirculation, thereby causing leukostasis.2 It typically affects the pulmonary, renal, and cerebral vasculature because of lower caliber of these vessels. The involvement of coronary vessels and patient presenting with acute myocardial infarction due to leukostasis is extremely rare. In this case report, we present a case of AML with hyperleukocytosis, presented as acute coronary syndrome secondary to leukostasis-induced myocardial ischemia.
Case report
A 35-year-old male patient presented to emergency with complaints of severe progressive chest pain, which had started 3 h prior. He was suffering from excruciating pain radiating to the left axilla and shoulder. His past medical history was unremarkable. However, 3 days before this presentation, he had gingival bleeding while brushing his teeth. On examination, the patient was diaphoretic and in acute distress due to chest pain. Vital signs and the rest of the physical examination were normal. His electrocardiogram (ECG) revealed ST elevation in anterior and lateral leads, diagnostic of ST elevated myocardial infarction (STEMI) (Fig. 1).
Fig. 1.
Electrocardiogram showing ST elevation in anterior and lateral leads.
His creatine kinase-MB was elevated (CK-MB: 112 IU/L), and Troponin T was positive. Complete blood count revealed leukocyte count of 234,000 cells/μL. Peripheral blood smear demonstrated 80% blasts, which were myeloperoxidase positive. Lactate dehydrogenase was 1236 U/L (170–290 U/L). On further evaluation, he was diagnosed with AML based on bone marrow (Fig. 2). Flow cytometry confirmed the diagnosis as AML-M4 (Fig. 3). His subsequent ECG, after thrombolysis, did not show resolution of ST elevation, and chest pain persisted. Coronary angiogram performed was unremarkable, except for mild luminal narrowing of left anterior descending coronary artery, suggestive of atherosclerosis. Hence, the acute coronary syndrome was believed to be due to leukostasis in a patient of AML with hyperleukocytosis. He was provisionally diagnosed with two differentials of acute STEMI and acute leukemia with hyperleukocytosis. In view of STEMI, he was thrombolysed with Tenecteplase and was admitted to coronary care unit. However, repeat ECG did not show resolution of ST elevation, and coronary angiogram was normal. After the diagnosis of AML was made, the patient was started on cytoreductive agent hydroxyurea and one session of leukapheresis. Following this, the leukocyte count reduced to 142,000 cells/μL. The patient was started on induction chemotherapy with single agent cytarabine (100 mg/m2). Anthracyclines were omitted due to concerns regarding its potential cardiotoxicity. On the third day of chemotherapy, he developed acute onset dyspnea, which appeared to be yet another complication of leukostasis. Computed tomography images of the chest revealed bilateral diffuse alveolar hemorrhage (DAH). The individual was managed with steroids, mechanical ventilation, and other intensive care unit bundle care for DAH. However, his condition worsened over the next 2 days, and he succumbed to his illness. Next of kin of patients gave consent for data use for publishing.
Fig. 2.
Bone marrow aspirate smear showing clusters and sheets of myeloblasts and monoblasts.
Fig. 3.
Flowcytometry dot plots showing HLA-DR, CD13, CD14, CD11c positive; suggestive of AML-M4 type.
Discussion
The usual presenting features of AML are easy fatigue, infections, and bleeding manifestations, secondary to underlying cytopenias. However, patients with increasing leukemic blast burden may present with complications related to higher leukocyte count. Hyperleukocytosis at initial presentation is associated with poor outcomes in AML, as it results in compromised tissue perfusion because of its deleterious effect on blood rheology.4 This can predispose to leukostasis, tumor lysis syndrome, and disseminated intravascular coagulation.5 The microvasculature with lesser caliber has increased susceptibility to leukostatic insult. It usually affects the pulmonary, cerebral, and renal vessels. Involvement of major vessels and causing arterial occlusion is very uncommon. Cardiac involvement can be seen in up to 6% of patients with leukostasis.6 Moreover, cardiac microvascular occlusion causing and presenting as myocardial ischemia has seldom been reported (Table). The myocardium seems to be protected from these microvascular complications because of its unique environment and large diameters of the coronary vessels. However, when blood perfusion is previously compromised by atherosclerosis, hyperleukocytosis may lead to ischemia or even infarction.4 Management of these patients is extremely difficult, and no standardized approach has been mentioned in the literature. Anthracyclines have to be avoided due to their potential cardiotoxicity. Also, the administration of chemotherapy inevitably results in pancytopenia, further increasing the cardiac complications. Leukapheresis is typically reserved for symptomatic patients with hyperleukocytosis, and it should be continued until it is safe to administer induction chemotherapy.12 A similar case in literature has been successfully treated by leukapheresis followed by chemotherapy, achieved complete remission, and subsequently underwent allogeneic bone marrow transplant.7 Unfortunately, our patient developed yet another complication of leukostasis in the pulmonary vasculature in the form of DAH and succumbed despite of best supportive care.
Learning points
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1.
This case report is unique, with left-sided chest pain as the only presenting symptom in a patient with acute myeloid leukemia.
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2.
This highlights an extremely rare presentation of acute myeloid leukemia as ST elevation myocardial infarction in patients with hyperleukocytosis. Our patient did not have any other cardiac risk factors, which might have predisposed to myocardial infarction.
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3.
Leukostasis is a hematological emergency, causing tissue hypoperfusion secondary to hyperleukocytosis.
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4.
Timely initiation of appropriate therapy may lead to complete resolution of microvessel occlusion.
Table.
Details of reported cases of AML presenting with acute myocardial infarction.
| S.No | Authors | Age/sex | AML subtype | WBC count | Occluded vessel | Anthracy cline | Outcome |
|---|---|---|---|---|---|---|---|
| 1. | Cohen et al4 | 56/F | M1 | 316,000 | RCA | No | Death |
| 2. | Manogna et al7 | 43/M | ND | 185,200 | ND | Yes | Remission |
| 3. | Chang et al8 | 40/F | M1 | 11,000 | ND | No | Remission |
| 4. | Muñiz et al9 | 76/M | ND | 358,000 | LAD | No | Death |
| 5. | Pervez et al10 | 54/M | M4 | 9400 | RCA | ND | ND |
| 6. | Jachmann-Jahn et al11 | 42/M | M2 | 4500 | LAD | No | Remission |
| 7. | Present case | 35/M | M4 | 234,000 | LAD | No | Death |
AML, acute myeloid leukemia; LAD, left anterior descending; ND, not documented; RCA, right coronary artery; WBC, white blood cell.
Patients/ Guardians/ Participants consent
Patients informed consent was obtained.
Ethical clearance
Not Applicable.
Source of support
Nil.
Disclosure of competing interest
The authors have none to declare.
Acknowledgements
None.
References
- 1.Wang X., Lin G., Wang J. 244 patients with hyperleukocytic acute leukemia. Shanghai Leukemia Cooperation Group. Zhonghua nei ke za zhi. 1997 Aug 1;36(8):532–535. [PubMed] [Google Scholar]
- 2.Cuttner J., Conjalka M.S., Reilly M., et al. Association of monocytic leukemia in patients with extreme leukocytosis. Am J Med. 1980 Oct 1;69(4):555–558. doi: 10.1016/0002-9343(80)90467-2. [DOI] [PubMed] [Google Scholar]
- 3.Lichtman M.A., Rowe J.M. Hyperleukocytic leukemias: rheological, clinical, and therapeutic considerations. Blood. 1982 Aug;60(2):279–283. PMID: 7046844. [PubMed] [Google Scholar]
- 4.Cohen Y., Amir G., Da'as N., Gillis S., Rund D., Polliack A. Acute myocardial infarction as the presenting symptom of acute myeloblastic leukemia with extreme hyperleukocytosis. Am J Hematol. 2002 Sep;71(1):47–283. doi: 10.1002/ajh.10155. [DOI] [PubMed] [Google Scholar]
- 5.Vaughan W.P., Kimball A.W., Karp J.E., Dragon L.H., Burke P. Factors affecting survival of patients with acute myelocytic leukemia presenting with high wbc counts. Cancer Treat Rep. 1981 Nov 1;65(11-12):1007–1013. [PubMed] [Google Scholar]
- 6.Stahl M., Wei W., Montesinos P., et al. Characteristics, treatment patterns and outcomes among newly diagnosed patients (pts) with acute myeloid leukemia (AML) who present with hyperleukocytosis: findings from a large international patient cohort. Blood. 2018 Nov 29;132(Suppl 1):4040. [Google Scholar]
- 7.Manogna D., Sham R. Acute myocardial infarction as initial manifestation of acute myeloid leukemia: a rare manifestation of leukostasis. Cureus. 2020 Aug 4;12(8) doi: 10.7759/cureus.9551. PMID: 32775121; PMCID: PMC7405964. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Chang H., Lin T.L., Ho W.J., Hsu L.A. Acute myeloid leukemia associated with acute myocardial infarction and dural sinus thrombosis: the possible role of leukemia-related hyperhomocysteinemia. J Chin Med Assoc. 2008 Aug 1;71(8):416–420. doi: 10.1016/S1726-4901(08)70093-5. [DOI] [PubMed] [Google Scholar]
- 9.Muñiz A.E. Myocardial infarction and stroke as the presenting symptoms of acute myeloid leukemia. J Emerg Med. 2012 Jun 1;42(6):651–654. doi: 10.1016/j.jemermed.2009.04.061. [DOI] [PubMed] [Google Scholar]
- 10.Pervez H., Potti A., Mehdi S.A. Challenging and unusual cases: case 1. Simultaneous presentation of acute myelogenous leukemia and acute myocardial infarction. J Clin Oncol. 2003 Apr 1;21(7):1416–1417. doi: 10.1200/JCO.2003.06.168. [DOI] [PubMed] [Google Scholar]
- 11.Jachmann-Jahn U., Cornely O., Laufs U., et al. Acute anterior myocardial infarction as first manifestation of acute myeloid leukemia. Ann Hematol. 2001 Nov;80(11):677–681. doi: 10.1007/s002770100353. [DOI] [PubMed] [Google Scholar]
- 12.Villgran V., Agha M., Raptis A., et al. Leukapheresis in patients newly diagnosed with acute myeloid leukemia. Transfus Apher Sci. 2016 Oct 1;55(2):216–220. doi: 10.1016/j.transci.2016.07.001. [DOI] [PubMed] [Google Scholar]