Newly diagnosed essential thrombocythemia leading to cardiogenic shock: a case report

Abstract

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

Here we report a case of a 32-year-old male found to have STEMI and a markedly elevated platelet count. Angiography revealed occlusion of the left anterior descending and left circumflex arteries, requiring percutaneous intervention and Impella support. The patient was later diagnosed with essential thrombocythemia, treated with hydroxyurea and antiplatelet therapy, and discharged with a wearable cardioverter defibrillator.

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.

Background

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.

Case presentation

A 32-year-old male with a history of asthma and gastritis presented to the emergency department with chest pain for the past two days. 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. Additionally, he presented with a significantly elevated platelet count of 1,244,000 platelets/µL, although no prior symptoms of essential thrombocythemia were reported before the cardiac event. The patient’s lipid panel showed elevated triglycerides at 202 mg/dL, total cholesterol of 125 mg/dL, HDL of 35 mg/dL, and LDL of 50 mg/dL. 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.

Fig. 1.

An electrocardiogram at time of admission was notable for ST elevations in the anterolateral leads

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).

Fig. 2.

Coronary angiogram images depicting the site of the left heart catheterization prior to intervention

Percutaneous coronary intervention was performed using heparin for anticoagulation. The left main coronary artery was engaged with a guide catheter. The LCA was wired with a coronary guidewire to its distal segment, and coronary angioplasty of the ostial LCA was carried out with a 3.0 × 12 mm balloon. A flush occlusion of the ostial LAD was noted, and it was wired with a run-through wire. There was blood flow following wiring. Coronary angioplasty of the ostial LAD was then performed using 2.5 × 12 mm and 3.0 × 12 mm balloons, followed by successful stenting. Post-dilatation was done with a 3.75 × 15 mm non-compliant balloon. The final angiogram demonstrated favorable results, with TIMI-3 flow and 0% residual stenosis in both the LCA and LAD arteries (Figs. 3 and 4).

Fig. 3.

Coronary angiogram images depicting cardiac catheterization following left circumflex artery balloon angioplasty and left anterior descending artery stent placement

Fig. 4.

Left ventriculogram following the intervention

ECG following intervention was notable for serial changes of evolving anteroseptal injury (Fig. 5).

Fig. 5.

An electrocardiogram following intervention was notable for sinus tachycardia with evolutionary changes of anteroseptal injury pattern

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. 6).

Fig. 6.

Bone marrow biopsy microscopy findings under 100x magnification were notable for increased large, atypical megakaryocytes using hematoxylin and eosin stain

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. On discharge his medications included ticagrelor 90 mg twice daily, recommended to continue for at least one year, as well as aspirin 81 mg daily, recommended indefinitely. He was also discharged with rosuvastatin 20 mg daily and hydroxyurea 500 mg daily. 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.

Discussion and conclusions

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 [5–9]. 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. Although ticagrelor was recommended to be taken for one year, aspirin was advised to be continued indefinitely to prevent clinical manifestations of ET and to 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].

Notably, this patient underwent coronary angioplasty with stent placement at the ostial LAD due to 100% flush occlusion. Given that the thrombotic occlusion of the ostial LAD was thought to be secondary to essential thrombocythemia, one might question whether aspiration thrombectomy and balloon dilation alone could have been an alternative approach, rather than stent placement. Aspiration thrombectomy was not performed due to limited evidence supporting its use, for acute coronary syndrome and revascularization in STEMI. There is currently no level I recommendation preferring aspiration thrombectomy over stent placement in STEMI [17–20]. Given the lack of clear evidence for thrombectomy and the presence of underlying atherosclerotic disease in the LAD, the operator chose to proceed with stenting rather than aspiration or balloon dilation alone. Furthermore, at the time of the procedure, the diagnosis of essential thrombocythemia had not yet been established.

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.

Abbreviations

ET

Essential Thrombocythemia

LAD

Left Anterior Descending

LCA

Left Circumflex Artery

LVAD

Left Ventricular Assist Device

MI

Myocardial Infarction

STEMI

ST-Segment Elevation Myocardial Infarction

Author contributions

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.

Funding

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

Data availability

Data and materials are available upon reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Informed written consent was obtained from the patient for publication.

Competing interests

The authors declare no competing interests.