Newly Diagnosed Essential Thrombocythemia Leading to Cardiogenic Shock: A Case Report

doi:10.21203/rs.3.rs-4854785/v1

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Case Report

Newly Diagnosed Essential Thrombocythemia Leading to Cardiogenic Shock: A Case Report

https://doi.org/10.21203/rs.3.rs-4854785/v1

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published 21 Oct, 2024

Read the published version in BMC Cardiovascular Disorders →

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Background

Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by uninhibited platelet production. It can present with vasomotor symptoms, and less commonly, severe thrombotic events such as myocardial infarction. ST-segment elevation myocardial infarction (STEMI) secondary to the hypercoagulable state in ET is a diagnostic challenge as the complication is rare, especially outside the typical demographics affected by ET such as the female and elderly populations.

Case Presentation:

A 32-year-old male presented to the emergency department with chest pain. On admission, the patient’s platelet count was 1,244,000 platelets/µL. A clinical diagnosis of STEMI was made by electrocardiogram, and the patient underwent emergent cardiac catheterization with placement of an Impella. Angiographic findings revealed a 100% flush occlusion of the ostial left anterior descending (LAD) artery and 80% occlusion of the ostial left circumflex artery (LCA) with thrombus. Successful percutaneous coronary intervention of the ostial LAD with a drug-eluting stent and balloon angioplasty of the ostial LCA was performed with full restoration of blood flow. He was initiated on aspirin and ticagrelor. The patient’s condition was complicated by cardiogenic shock for which the Impella remained in place. Subsequent transthoracic echocardiogram showed a left ventricular ejection fraction of 20–25%. Due to the patient’s markedly elevated platelet count, there was concern for possible underlying ET. A PCR assay on peripheral blood isolated from the patient was positive for a JAK2 V617F mutation. The patient was slowly weaned off the Impella over five days, and once he was hemodynamically and clinically stable, he was initiated on hydroxyurea and discharged with a wearable cardioverter defibrillator. Cardiac rehabilitation was planned.

Conclusions

This case illustrates the potential for severe thrombotic complications such as STEMI due to ET. Severe thrombotic complications are less common manifestations of ET in general, particularly in young males. Recognition and diagnosis of ET are critical for the institution of appropriate therapy and prevention of STEMI and cardiogenic shock among other complications.

Essential thrombocythemia

ST-segment elevation myocardial infarction

cardiogenic shock

hypercoagulability

case report

Essential thrombocythemia (ET) is a rare myeloproliferative neoplasm characterized by unregulated and excessive production of platelets. This condition can lead to a variety of clinical presentations, including vasomotor symptoms such as headaches, dizziness, and erythromelalgia, as well as more severe thrombotic events like myocardial infarction (MI). Patients with ET have an increased risk for both thrombosis (e.g., cerebrovascular event, MI, superficial thrombophlebitis, deep vein thrombosis, and pulmonary embolus) and hemorrhage, which is believed to be attributable to both qualitative and quantitative alterations in their platelets [1–3]. The relative infrequency with which ET is encountered, especially in younger male patients, can make the diagnosis of ST-segment elevation MI (STEMI) secondary to the hypercoagulable state of ET a significant clinical challenge. This is particularly true outside the more typical demographic profile of ET, which tends to affect elderly and female individuals more frequently.

A 32-year-old male with a history of asthma and gastritis presented to the emergency department with chest pain. He had no known history of heart disease, smoking, alcohol use, recreational drug use, prior surgical interventions, or family history of cardiovascular disease. On admission, he had no reproducible chest wall tenderness and his remaining physical exam was unremarkable. His troponin level was initially mildly elevated at 0.048 ng/mL and peaked at > 80 ng/mL with a notably elevated platelet count at 1,244,000 platelets/µL. A clinical diagnosis of STEMI was made by electrocardiogram which showed ST elevations in his anterolateral leads (Fig. 1), and the patient underwent emergent cardiac catheterization with placement of a mechanical circulatory assist device i.e. Impella CP.

Angiographic findings revealed a 100% flush occlusion of the ostial left anterior descending (LAD) artery and 80% occlusion of the ostial left circumflex artery (LCA) with thrombus (Fig. 2).

Successful percutaneous coronary intervention of the ostial LAD with a drug-eluting stent and balloon angioplasty of the ostial LCA was performed with full restoration of blood flow (Figs. 3 and 4).

The patient was initiated on aspirin 81 mg daily and ticagrelor 90 mg twice daily. The patient’s condition was complicated by cardiogenic shock for which the Impella remained in place. Subsequent transthoracic echocardiogram showed a left ventricular ejection fraction of 20–25%. Due to the patient’s markedly elevated platelet count, there was concern for possible underlying ET. A PCR assay on peripheral blood isolated from the patient was positive for a JAK2 V617F mutation, and his presentation did not meet the criteria for other myeloid neoplasms. The patient was slowly weaned off the Impella over five days, and once he was hemodynamically and clinically stable, he underwent a bone marrow biopsy. The patient's biopsy showed a proliferation of atypical megakaryocytes with areas of clustering as well as megakaryocytes exhibiting variable morphology with numerous segmented and hyperchromatic forms (Fig. 5).

The patient was formally diagnosed with ET and initiated on cytoreductive therapy with hydroxyurea. He was later discharged with a wearable cardioverter defibrillator, and cardiac rehabilitation and hematology/oncology follow-up were planned. There were no unexpected or adverse events during his hospital stay, and he has tolerated his medications well without any reported adverse effects or complications during follow-up appointments. The patient has reported adhering to his antiplatelet regimen and hydroxyurea, which correlates with the improved platelet count observed in his subsequent complete blood count tests performed at his follow-up visits.

The current case report demonstrates an atypical profile of a patient who developed thrombotic complications due to ET. This report suggests the possibility that early detection of ET with the initiation of appropriate therapy could prevent or reduce the risk of thrombotic sequelae.

Established risk factors for arterial thrombosis in ET include advanced age, prior history of thrombosis, presence of cardiovascular risk factors, elevated white blood cell count, and the JAK2 V617F mutation [4]. Of these, only the JAK2 V617F mutation was applicable to the patient in this case. Interestingly, a platelet count > 1,000,000 platelets/µL has been associated with a notably decreased risk of arterial thrombosis, potentially due to the development of acquired von Willebrand disease in this patient population [4]. Despite the patient's platelet count exceeding 1,000,000 platelets/µL, he unfortunately developed thrombosis; evaluation for concurrent von Willebrand disease was not performed.

While the incidence of ET varies by race/ethnicity, sex, and age, it is generally more common in Black Americans compared to other racial/ethnic groups in the United States [5]. Additionally, ET is more prevalent in women, with an approximate female-to-male ratio of 2:1 [5, 6–9]. ET incidence also increases with advancing age, with a median age at diagnosis of 60 years [9]. There is a wide range of reported thrombosis rates at the time of ET diagnosis (9–22%), and thrombosis is more commonly observed in women [6–12]. Although the patient was Black, the patient in this case did not fit the typical profile of ET, as he was a young male, which further highlights the uniqueness of his presentation.

According to the World Health Organization and the International Consensus Classification, a diagnosis of ET requires the fulfillment of all four major diagnostic criteria: platelet count ≥ 450,000 platelets/µL; bone marrow biopsy showing proliferation mainly of the megakaryocyte lineage with increased numbers of enlarged, mature megakaryocytes with hyper lobulated nuclei; criteria of other myeloid neoplasm not met; and demonstration of a JAK2, CALR, or MPL mutation [13]. Alternatively, a diagnosis requires the first three major criteria plus a minor criterion (i.e., demonstration of another clonal marker, such as ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, or SRF3B1 mutation). In this case, the patient met all four of the major criteria and was subsequently diagnosed with ET.

Multiple treatment options are available for ET. Low-dose aspirin can mitigate vasomotor symptoms and thrombohemorrhagic complications in most ET patients. In the present case, the patient was started on low-dose aspirin after experiencing a STEMI, aiming to reduce future thrombotic complications of the disease and prevent stent thrombosis following percutaneous coronary intervention. Cytoreductive therapy is recommended for high-risk ET patients, defined as those with a history of thrombosis or age > 60 years with the JAK2 V617F mutation. This therapy may also be considered for intermediate-risk ET patients, characterized by age > 60 years, absence of the JAK2 mutation, and no prior thrombotic events [14].

For most high-risk ET patients, hydroxyurea is recommended as the preferred cytoreductive agent. PEGylated interferon alfa can serve as a reasonable alternative based on patient preference and drug tolerance. However, hydroxyurea is generally preferred over other cytoreductive options such as interferon alfa and anagrelide, which have increased toxicity and reduced efficacy in preventing thrombotic complications, respectively [15, 16].

Our case highlights the importance of early diagnosis of ET and prompt initiation of aspirin and cytoreductive agents to prevent thrombotic complications. Although ET was diagnosed after the patient had developed a STEMI, he did not have any prior established medical care or baseline laboratory workup. Regular medical follow-up may have prompted further evaluation of his elevated platelet levels, leading to an earlier diagnosis and the implementation of appropriate therapy to prevent thrombotic events. This case illustrates the critical need for recognition and diagnosis of ET to institute proper treatment and prevent serious complications, such as STEMI and cardiogenic shock.

essential thrombocythemia

LAD

left anterior descending

LCA

left circumflex artery

LVAD

left ventricular assist device

myocardial infarction

STEMI

ST-segment elevation myocardial infarction

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Consent for publication:

Consent for publication was obtained from the patient.

Competing interests:

The authors declare that they have no competing interests.

Funding:

No funding was received to assist with the preparation of this manuscript.

Author Contribution

RP and ND collaborated closely on this work. RP conducted the analysis and interpretation of the patient data and hospital records, and was a key contributor to drafting the manuscript. ND managed the care of the patient, verified the critical findings, and revised the manuscript. Both authors reviewed and approved the final version of the manuscript.

Acknowledgements:

Not applicable

Availability of data and materials:

Not applicable.

Schafer AI. Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia. Blood. 2006;107:4214–22.
Elliott M, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol. 2005;128:275–90.
Hobbs CM, Manning H, Bennett C, Vasquez L, Severin S, Brain L, et al. JAK2V617F leads to intrinsic changes in platelet formation and reactivity in a knock-in mouse model of essential thrombocythemia. Blood. 2013;122:3787–97.
Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, et al. Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood. 2011;117:5857–9.
Srour SA, Devesa SS, Morton LM, Check DP, Curtis RE, Linet MS, et al. Incidence and patient survival of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms in the United States, 2001-12. Br J Haematol. 2016;174:382–96.
Cortelazzo S, Viero P, Finazzi G, D'Emilio A, Rodeghiero F, Barbui T. Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. J Clin Oncol. 1990;8:556–62.
Fenaux P, Simon M, Caulier MT, Lai JL, Goudemand J, Bauters F. Clinical course of essential thrombocythemia in 147 cases. Cancer. 1990;66:549–56.
Bellucci S, Janvier M, Tobelem G, Flandrin G, Charpak Y, Berger R, et al. Essential thrombocythemias. Clinical evolutionary and biological data. Cancer. 1986;58:2440–7.
Gugliotta L, Marchioli R, Fiacchini M, Vianelli N, Baravelli S, Valdr L et al. Epidemiological, diagnostic, therapeutic and prognostic aspects of essential thrombocythemia in retrospective study of the GIMMC group in two thousand patients. 1997.
Wolanskyj AP, Lasho TL, Schwager SM, McClure RF, Wadleigh M, Lee SJ, et al. JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol. 2005;131:208–13.
Chistolini A, Mazzucconi MG, Ferrari A, la Verde G, Ferrazza G, Dragoni F, et al. Essential thrombocythemia: a retrospective study on the clinical course of 100 patients. Haematologica. 1990;75:537–40.
Colombi M, Radaelli F, Zocchi L, Maiolo AT. Thrombotic and hemorrhagic complications in essential thrombocythemia. A retrospective study of 103 patients. Cancer. 1991;67:2926–30.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.
Barbui T, Vannucchi AM, Buxhofer-Ausch V, De Stefano V, Betti S, Rambaldi A, et al. Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia. Blood Cancer J. 2015;5:e369.
Mascarenhas J, Kosiorek HE, Prchal JT, Rambaldi A, Berenzon D, Yacoub A, et al. A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia. Blood. 2022;139:2931–41.
Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005;353:33–45.

No competing interests reported.

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Journal Publication

published 21 Oct, 2024

Read the published version in BMC Cardiovascular Disorders →

Editorial decision: Revision requested
12 Aug, 2024
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Submission checks completed at journal
09 Aug, 2024
First submitted to journal
03 Aug, 2024

You are reading this latest preprint version

Newly Diagnosed Essential Thrombocythemia Leading to Cardiogenic Shock: A Case Report

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Journal Publication

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Abstract

Background

Case Presentation:

Conclusions

Figures

Background

Case presentation

Discussion and Conclusions

Abbreviations

Declarations

Competing interests:

Funding:

Author Contribution

Acknowledgements:

Availability of data and materials:

References

Additional Declarations

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