Synchronous Cardiocerebral Infarction as Initial Presentation of Patient with Essential Thrombocythaemia: A Case Report

Essential thrombocythaemia (ET) is a rare chronic myeloproliferative neoplasm, with an estimated incidence of 1.5–2.5 cases per 100,000 individuals annually.¹ Along with polycythaemia vera (PV), ET is characterised by clonal proliferation of haematopoietic stem cells associated with mutations in JAK2V617F, CALR or MPL genes.² The JAK2V617F mutation occurs in about 55% of cases, CALR in 15–24% and MPL in about 4%, while about 20% of patients are triple negative.²

Elevated platelet counts in ET contribute to an increased risk of thrombotic and haemorrhagic complications. Thrombotic events may involve cerebral, coronary or peripheral arteries. From a haematological standpoint, the incidence of acute coronary syndrome (ACS) in ET ranges between 2% and 31% across studies, whereas from a cardiological perspective, ET accounts for fewer than 2.1% of ACS cases.³

Acute MI (AMI) represents an uncommon but serious manifestation of ET. The reported incidence varies across populations and time periods and AMI in ET often occurs in the absence of pre-existing atherosclerosis.^4,5 Several reports have described AMI in young people who lack traditional coronary risk factors with a median age of 30 years. Arterial thrombosis (18%) is more frequent than venous thrombosis (6%), and cerebrovascular events (13%) occur more commonly than coronary or peripheral thrombosis (2%).⁶

This case report describes synchronous cardiocerebral infarction and recurrent ST-elevation MI (STEMI) in a patient with ET, focusing on the clinical presentation, diagnostic challenges and management strategy following percutaneous coronary intervention (PCI). The report also highlights the importance of recognising ET as a potential underlying cause of recurrent ischaemic events, even in the absence of conventional atherosclerotic risk factors.

Case Presentation

The patient was a 54-year-old woman with a 2-year history of hypertension, with highest and average systolic blood pressure of 180 mmHg and 140 mmHg, respectively. She was on regular medication with candesartan 8 mg and bisoprolol 5 mg once daily. She presented to the emergency department at Dr Sardjito General Hospital with sudden-onset chest pain. Three hours prior to this, she had presented to another hospital with the chief complaint of left-sided limb weakness. A non-contrast CT scan of the head revealed an acute infarction in the right frontoparietal lobe in the territory of the right middle cerebral artery (Figure 1 ). She subsequently received IV fibrinolytic therapy for acute ischemic stroke with alteplase at 0.9 mg/kg body weight over 1 hour with clinical evidence of successful reperfusion.

During the fibrinolytic infusion, the patient developed sudden-onset severe chest pain, which she rated 8/10. An ECG demonstrated a 60 BPM junctional rhythm with acute inferior-posterior STEMI involving the right coronary artery (RCA) with symptom onset of 2 hours (Figure 2A). Her high-sensitivity troponin T (hsTnT) level was markedly elevated at 2,088 ng/l (reference range: 0–14 ng/l) and she had metabolic acidaemia (pH 7.31; HCO3 14.5 mmol/l) with an elevated lactate level (6.8 mmol/l). She was transferred to our institution. On arrival at the emergency department, the patient had persistent chest pain and was hypotensive with a blood pressure of 97/51 mmHg while receiving dobutamine 20 μg/kg/min and norepinephrine 0.3 μg/kg/min, which indicated cardiogenic shock. Upon physical examination, we found no remarkable findings, including neither splenomegaly nor hepatomegaly. A diagnosis of synchronous cardiocerebral infarction (CCI) complicated by cardiogenic shock was established. Persistent elevation of inferior-posterior ST-segment was noted. Primary percutaneous coronary intervention (PCI) was performed and a single drug-eluting stent (DES) was successfully implanted in the distal RCA (Figure 2B).

Laboratory investigations revealed relatively unremarkable lipid profile results and HbA1c level. We found significant thrombocythaemia, with platelet counts of 517,000/µl and 850,000/µl two days later, raising suspicion of ET. The patient was co-managed by the neurology and haematology departments in the intensive cardiac care unit (ICCU) for 4 days and was subsequently discharged and instructed to take the following drug regimen once daily: aspirin 80 mg, clopidogrel 75 mg, atorvastatin 40 mg, bisoprolol 5 mg, ramipril 10 mg, hydroxyurea 500 mg and folic acid 1 mg. The patient continued regular follow-up at the cardiology outpatient clinic and maintained medical therapy, including dual antiplatelet therapy (DAPT), a high-intensity statin, an angiotensin-converting enzyme inhibitor and a β-blocker for the subsequent year. However, she was lost to follow-up with the haematology department shortly afterwards. Ten months after her initial presentation, her cardiologist referred her for a haematological evaluation, including complete blood count and bone marrow aspiration or biopsy.

Further haematological evaluation with bone marrow puncture was performed (Figure 3). Morphological analysis demonstrated marked thrombocythaemia with abundant, variably sized and predominantly active megakaryocytes, including fragmented dysmegakaryocytes. Increased granulopoietic activity was observed, with 2% promyelocyte, 7% myelocytes, 3% metamyelocytes, 6% band forms, 65% segmented neutrophils, 5% monocytes and 2% eosinophils. These findings were consistent with a diagnosis of ET. However, the patient received cytoreductive therapy for only 2 months before being lost to follow-up with the haematology department shortly thereafter.

Eighteen months later, the patient was readmitted to hospital with abrupt onset of chest pain (scale 7/10) that she had been experiencing for 3 hours. On presentation, vital signs included a heart rate of 74 BPM, blood pressure of 133/86 mmHg and oxygen saturation of 95%. The results of a physical examination were unremarkable. The initial ECG revealed sinus rhythm, 90 BPM, ST segment elevation in leads II, III, aVF, with reciprocal ST depression in leads I and aVL (Figure 4A). Laboratory evaluation showed a haemoglobin level of 11.6 g/dl, a platelet count of 1,104,000/µl, hsTnT 117 ng/l (Supplementary Figure 1). Based on the clinical presentation, ECG and laboratory findings, the diagnosis of recurrent inferior STEMI secondary to ET was established. The patient’s risk was also measured to predict the risk of a thrombotic event in the future using the International Prognostic Score of Thrombosis in Essential Thrombocythemia (IPSET), which revealed a high stratification risk (annual thrombosis risk: 3.56%; median survival: 13.8 years).

Coronary arteriography demonstrated non-occlusive very late stent thrombosis in the RCA, with a thrombolysis in MI (TIMI) thrombus and flow grade 3 (Figure 4B). After the procedure, the patient was admitted to the ICCU and initiated on anticoagulation with fondaparinux for 5 days. DAPT was continued with aspirin 80 mg twice daily and clopidogrel 75 mg daily. Additional medications included atorvastatin 40 mg, candesartan 8 mg, bisoprolol 5 mg and hydroxyurea 1,500 mg, all taken daily. The patient’s clinical condition remained stable and she was discharged on the sixth day of hospitalisation with a plan for regular platelet count monitoring at the outpatient clinic. A detailed timeline can be seen in Supplementary Table 1.

Discussion

The diagnosis of ET is established according to the WHO 2016 criteria, updated in 2021, which require fulfilment of all four major criteria: (1) thrombocytosis (platelet count ≥450 × 109/L); (2) bone marrow examination showed megakaryocyte proliferation of mature forms; (3) exclusion of other myeloid neoplasms by using criteria for BCR-ABL1-positive chronic myeloid leukemia, polycthemia vera, primary myelofibrosis, or other myeloid neoplasm were not met; and (4) detection of JAK2, CALR or MPL variant; or three major plus one minor criterion: presence of clonal marker or of evidence of reactive thrombocytosis.² ET is associated with a high incidence of thrombotic and haemorrhagic complications. Thrombotic events occur in 9–84% of patients at diagnosis and 7–32% during follow-up, while haemorrhagic events are observed in 4–63% of cases at presentation.⁷ Cerebrovascular events are the most common thrombotic manifestations (56%), followed by coronary thrombosis (22–31%) and peripheral arterial embolism (13–22%).^7,8 Recurrent thrombosis is observed in about 34% of patients with prior thrombotic events, with the highest risk occurring within 2 years of the initial episode. The use of antithrombotic therapy can reduce recurrence by up to 50%.⁸

The pathogenesis of vascular complications in ET involves complex prothrombotic and haemorrhagic mechanisms. Many patients presenting with ACS have angiographically normal coronary arteries, suggesting that vascular events may arise directly from haematological abnormalities rather than atherosclerotic processes.³ The proposed mechanisms underlying ACS in ET include: platelet activation secondary to endothelial injury; coronary vasospasm leading to localised platelet aggregation; enhanced platelet procoagulant activity and aggregation tendency; structural alterations of platelet surface glycoproteins and deficiency of platelet lipoxygenase enzymes.⁹ These mechanisms collectively contribute to thrombus formation and vascular occlusion even in the absence of significant atherosclerosis.

According to the 2024 international consensus guidelines on ET, cardiovascular risk stratification divides patients into four categories: very low, low, intermediate and high risk.¹⁰ Reported overall mortality risks are 11.3% for low-risk, 22.4–46% for intermediate risk and up to 60% for high-risk groups. The median overall survival for high-risk ET patients is approximately 8 years. Other risk stratification models have also been introduced, including the Age, Absolute Neutrophil and Absolute Lymphocyte count and the IPSET models, to assist in predicting overall survival in patients with ET.^10,11

The present case describes a 54-year-old woman with a history of cardiocerebral infarction in June 2022, subsequently diagnosed with ET based on bone marrow morphology in April 2023. The patient later presented with recurrent inferior STEMI. Based on the above risk stratification, she was classified as high risk. Although exceedingly rare, multiple-site thrombosis has been reported, with an incidence of less than 1%.⁸ To the best of our knowledge, no previous case reports have described the coexistence of synchronous cardiocerebral infarction and recurrent STEMI associated with ET in one patient.

The diagnostic and therapeutic approach for ET patients presenting with ACS and acute ischaemic stroke (AIS), particularly those with recurrent inferior STEMI and suspected in-stent thrombosis, generally follows established international guidelines, including the 2023 European Society of Cardiology recommendations for ACS management, the Society for Cardiovascular Angiography and Interventions 2023 consensus on in-stent restenosis and thrombosis, and algorithms proposed for ACS in ET (Supplementary Figure 2).^3,12,13

In the present case, during the first admission in June 2022, the patient received fibrinolytic therapy for AIS with onset within 3–4.5 hours followed by primary PCI for inferior STEMI at the distal RCA. At this admission, the patient presented with cardiogenic shock characterised by hypotension and elevated serum lactate level. This situation might be caused by right ventricular infarction (RVI) as this complication affects almost 50% of cases of acute inferior STEMI.¹⁴ Although the most frequent aetiology of RVI is proximal RCA culprit lesions, Takigawa et al. found that 13.8% of RVI might also be caused by distal RCA occlusions.¹⁵ Therefore, in patients with RVI, reduced left ventricle preload is present, which later manifests as cardiogenic shock. This key management strategy for CCI was consistent with the algorithm proposed by Gao et al. and Kijpaisalratana et al., also management protocols for cardiogenic shock by the American College of Cardiology.^16–18

During the second admission, coroangiography revealed a non-occlusive intrastent thrombus in the RCA classified as TIMI thrombus grade 3 with preserved TIMI 3 flow. The patient was diagnosed with single-vessel coronary artery disease complicated by very late non-occlusive stent thrombosis. As coronary flow was preserved and chest pain resolved without additional intervention, a conservative management plan was adopted. At the second STEMI, the conservative approach was selected because TIMI 3 flow had been restored in the infarct-related artery despite the thrombotic burden and there was a concern that immediate further intervention could increase the risk of no-reflow; therefore, the operator opted not to perform an additional intracoronary intervention and instead chose to optimise anticoagulation and cytoreductive therapy.

Intravascular imaging would have been ideal to better characterise the culprit lesion in this setting; however, the decision was made based on the presence of angiographic TIMI 3 flow, acceptable residual thrombosis (non-occlusive very late stent thrombosis) and the patient’s overall clinical status. Furthermore, intravascular imaging is not routinely used in our centre in the acute or emergency setting.

At presentation, we found no remarkable findings on physical examination, including neither splenomegaly nor hepatomegaly. The diagnosis was suspected based on complete blood count, which showed a markedly elevated platelet count (1,104,000/µl). The presence of organomegaly is not prominent upon physical examination. Palpable splenomegaly is only present in 10–20% of patients with ET and hepatomegaly in up to approximately 3–20%.^3,10 Given the high thrombotic burden and absence of flow-limiting obstruction, invasive reintervention was deferred. The patient was treated with a 5-day course of fondaparinux anticoagulation, continued DAPT (aspirin 80 mg twice daily and clopidogrel 75 mg daily), and also a cytoreductive agent using hydroxyurea 1,500 mg daily. In this clinical context, fondaparinux was selected as the parenteral anticoagulant because it provides potent factor Xa inhibition with a comparatively lower rate of major bleeding than conventional unfractionated heparin or enoxaparin in people with ACS or STEMI, while maintaining efficacy in reducing death and reinfarction. Large randomised trials, including OASIS-5 and OASIS-6, have demonstrated that fondaparinux achieves similar or superior ischaemic protection with significantly fewer serious bleeding events compared with enoxaparin or standard therapy, making it an attractive option for patients with very late stent thrombosis or a high thrombotic burden.^19,20

In a study by Tanguay and Séguin, fondaparinux was considered safe and effective in patients with an underlying hypercoagulable state and in those with refractory thrombosis, supporting its use in complex prothrombotic conditions.²¹ Nevertheless, there is no clear consensus or guideline specifically addressing the optimal choice of parenteral anticoagulation in patients with ET and recurrent STEMI and also therapeutic decisions must therefore be individualised based on thrombotic and bleeding risk profiles. Initial assessment of the patient’s bleeding risk was low risk according to Academic Research Consortium for High Bleeding Risk and PRECISE-DAPT score. Bleeding risk was also monitored in the outpatient setting and a regular serial complete blood count was planned.

Another important issue concerns the selection of antiplatelet therapy, particularly the choice of P2Y₁₂ inhibitor in this patient. Currently, no specific guideline recommends one P2Y₁₂ inhibitor over another for ACS in the context of ET and evidence is limited to observational data and case-based experience. Nevertheless, several published case reports have described the successful use of ticagrelor, prasugrel and clopidogrel in patients with ET presenting with ACS, suggesting that different P2Y₁₂ inhibitors may be considered on an individualised basis, taking into account ischaemic and bleeding risks as well as local availability and clinician experience (Supplementary Table 2).^22–24

This case underscores the diagnostic and therapeutic challenges of managing CCI and recurrent ACS in patients with ET. The coexistence of extreme thrombocytosis and vascular thrombosis suggests that haematological factors play a central role in the pathogenesis. The non-occlusive in-stent thrombosis with preserved flow further emphasises the need for individualised management strategies that balance thrombotic and bleeding risks.

Antithrombotic therapy remains the mainstay of acute management but long-term control of the myeloproliferative process is essential to prevent recurrence. Cytoreductive therapy — most commonly hydroxyurea — has been shown to reduce thrombotic complications in high-risk ET patients. However, in this case, cytoreductive therapy was initially discontinued due to loss to follow-up, which may have contributed to disease progression and recurrent thrombosis. In this case, a plausible contributing factor to loss to follow-up was the substantial logistical burden placed on the patient, who was required to attend multiple specialised outpatient clinics (cardiology, neurology, physical rehabilitation and haematology), each with long waiting times and time-consuming procedures. This fragmented and intensive follow-up schedule may have led to treatment fatigue and decreased motivation to maintain regular visits.

Therefore, to improve long-term adherence in patients with ET and cardiocerebral complications, several strategies may be considered. These include streamlining care through coordinated or combined multidisciplinary clinics, optimising appointment scheduling to reduce waiting times and the frequency of visits, and enhancing patient education about the importance of sustained cytoreductive and cardiovascular therapy. In addition, implementing reminder systems, involving family support and ensuring clear communication between specialties may further support consistent follow-up and adherence in this complex patient population.

Limitations

This case report has several important limitations that should be acknowledged. First, as this is an isolated observation of a single patient, the findings cannot be generalised to broader ET or STEMI populations and any pathophysiological or therapeutic inferences should be interpreted with caution in the absence of larger, systemically collected cohorts. Second, advanced biomarker assessment, including measurement of lipoprotein(a), von Willebrand factor and factor VIII, was not performed in this patient. Several advanced biomarker tests are not routinely available or requested in our setting, so the potential contribution of these biomarkers to the patient’s thrombotic risk profile could not be evaluated. Third, intravascular imaging with intravascular ultrasound or optical coherence tomography was not undertaken during the acute coronary intervention. In our centre, intravascular imaging is not routinely performed in the primary or emergency PCI setting, which prevents the detailed characterisation of plaque morphology, thrombus burden and stent-vessel interaction. Last, molecular genetic testing for ET, including JAK2, CALR and MPL mutation analysis, was not performed in this case because these investigations were not covered by the patient’s health insurance. Consequently, precise molecular classification of the myeloproliferative neoplasm was not possible, and this constrains comparison with contemporary series in which mutational status is systematically reported.^23,24

Conclusion

ET is a rare, clinically significant, haematological disorder associated with a high risk of vascular complications, including recurrent cerebrovascular and coronary events. Early recognition, appropriate risk stratification and multidisciplinary management are critical to improving outcomes. This case highlights the importance of integrating haematological and cardiovascular care in ET patients presenting with ACS, as timely diagnosis and long-term cytoreductive therapy can mitigate the risk of recurrent thrombosis and enhance survival.

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