Background: Compared to their older counterparts, people under 40 are less likely to develop acute coronary syndromes (ACS) due to traditional cardiovascular (CV)-risk factors. Aim : The purpose of this study is to determine how common essential thrombocytosis (ET), a hematological condition and less common risk factor, is in young patients who report with ACS. Methodology : We created a retrospective database of all patients under 40 (n=180) who had known thrombocyte counts (n=180 ) and had undergone subsequent coronary angiography (CAG) following their initial ACS at our institution throughout the previous five years (2021-2026). This haematological condition was screened for in patients with thrombocytes greater than 450x10*9/L. Results: We found 10 individuals with thrombocytosis in our database. One was formerly referred to as ET. Of the 10 patients who remained, four were diagnosed with reactive/secondary thrombocytosis, two were lost to follow-up, four received an ET diagnosis, and one is still unknown. Conclusion : ET seems to be prevalent in patients under 40 with ACS, with an incidence of at least 2%. Additionally, 27% of patients with ACS and increased thrombocytes had a fresh diagnosis of ET after screening. In every instance, the diagnosis was originally overlooked. Cardiologists should be aware of, identify, and screen for this pathology in ACS patients, especially in those who do not have traditional CV-risk factors. An "ACS-protocol" targeted at less common risk factors could support this, since the timing of revascularization should be adjusted to thrombocyte count/initiation of ET therapy to prevent thrombotic complications.
The majority of cardiovascular (CV) events are explained by conventional risk factors [1]. As a result, there will be a relative rise in less well-known risk variables when the prevalence of traditional risk factors declines [2,3]. Traditional risk factors are generally more likely to cause acute coronary syndrome (ACS) in elderly patients [2, 3].
Therefore, the onset of ACS in patients under 40 who do not have traditional risk factors should prompt the clinician to search for other explanations of increased thrombotic risk or premature or accelerated atherosclerosis [1]. A myeloproliferative neoplasm (MPN) is one such less common risk factor [2,3].
Hematologists are well aware that patients with essential thrombocytosis (ET), polycythemia vera (PV), or primary myelofibrosis (PMF), three BCR/ABL-1-Philadelphia chromosomenegative MPNs, have a high prevalence of cardiovascular disease (CVD) [4]. Instead of dying from the condition itself (13% each), the majority of individuals with ET or PV die from CVD (26 and 25%, respectively) [5]. Furthermore, younger patients were particularly affected by this elevated relative risk of death from cardiovascular and cerebrovascular disease. Most significantly, these hematological illnesses frequently present with embolic consequences [5].
The traditional ACS caused by a plaque rupture secondary to conventional risk factors is partially being replaced by other aetiologies caused by other, frequently less common risk factors [4,6], as confirmed by pathological examinations of coronary arteries [67. This presents cardiologists with new challenges. Our initial research question was whether screening patients with thrombocytosis (i.e., a thrombocyte count >450x109/L) could help identify subjects with a less common risk factor, such as ET.
Secondly, we aimed to compare the prevalence of ET in patients who presented with ACS with the prevalence that was reported fifty years ago (i.e., less than 1% [2]).
Lastly, we looked into the awareness, recognition, and screening of ET in the ACS community. Our hypotheses were as follows: 1) screening young patients with thrombocytosis would allow us to detect multiple cases of ET; 2) the incidence of ET may be higher than previously reported, perhaps as a result of a relative decrease in other risk factors; and 3) less common risk factors for CV disease, like ET, are frequently disregarded.
We created a retrospective database of patients under 40 who had percutaneous intervention (PCI) or coronary angiography (CAG) in the context of an ACS in order to evaluate our hypotheses. We selected a cohort under 40 years old since it was anticipated that they would have the highest incidence of non-traditional risk variables and the least exposure to traditional risk factors. Elevated thrombocytes were checked for all the group. We distinguished between artifacts, reactive thrombocytosis, and essential thrombocytosis in those patients (in accordance with WHO recommendations). Lastly, we looked into the frequency of missing or noticing an underlying ET.
who had CAG/PCI in the context of their initial ACS at our referring hospital throughout the previous ten years, or from 2021 to 2026. Our local data manager developed a query to separate all patients who met the following requirements in order to get this data. 1. They had to have had a CAG before turning 41, and 2. Patients who had already had a CAG were not allowed to participate. Laboratory findings from the same admission (±one week) were tested for increased (i.e., >450x109/L) thrombocytes for every patient who met these criteria.
Additional laboratory findings in the years that followed (varying from 1 to 5 years, depending on the point of inclusion) were gathered, if available, for every patient in whom increased thrombocytes were discovered. In order to ascertain whether increased thrombocyte counts were observed or taken into consideration, peer communication was also screened. These patients' files were examined for a definitive MPN diagnosis, ranging from PCV and PMF to ET.
In order to identify additional patients who had eventually developed an MPN but had shown normal platelet counts around their CAG, the files and laboratory results of all patients in our database with platelet counts below 450x10 9/L, or those without elevated thrombocytes, during their initial visit were screened for elevated thrombocytes during subsequent visits. Terms like "thrombocytosis," "essential/primary thrombocytosis/thrombocythemia," "polycythemia vera," and "primary myelofibrosis."
According to WHO criteria, a hematologist required to diagnose essential (primary) or reactive (secondary) thrombocytosis, or another MPN, in each instance. For a definitive diagnosis of ET, a patient has to meet all four primary criteria: 1. platelets >450x109/L; 2. a distinctive bone marrow biopsy (with megakaryocyte proliferation and loose clusters); 3. not meeting WHO criteria for other myeloid neoplasms; and 4. a mutation in JAK2/CALR/MPL. If not, the patient had to meet the first three main and minor criteria, which included having another clonal marker or showing no signs of reactive thrombocytosis.
Every patient who was thought to be a suspect for an underlying MPN underwent further screening. Basic anthropometrics such as age, sex, and concurrent cardiovascular risk factors were included in this data, as were more specific details like the location of the intervention, whether the MPN was previously diagnosed, the concurrent hemoglobin level and leukocyte counts, the drugs started after the coronary intervention, the type of cytoreduction started after the diagnosis of an MPN, the delay in diagnosing the MPN, the mutations discovered after genetic screening, and the occurrence of complications during follow-up. The study was approved by the local Medical Ethical Committee.
The number of patients (and the proportion of patients in our predetermined study population) who were discovered to have an underlying MPN that could have caused the ACS for which they underwent CAG was the main outcome of our investigation.
1.the identification of every patient who has a high thrombocyte count, whether it be due to reactive or necessary artifacts, 2. to determine whether high thrombocyte counts were observed or taken into consideration; and 3. the length of time it took to diagnose an underlying MPN, if it was first overlooked.
180 people with ACS who had invasive procedures between 2021 and 2026 were screened (patients who had numerous angiographies were counted only once). 40 patients were disqualified because their thrombocyte levels were missing. Ten individuals were found to have thrombocytosis .two was formerly referred to as ET. Of the other 8 patients, four developed reactive/secondary thrombocytosis, subsequently received an ET diagnosis.
The high thrombocyte counts were copied into the discharge letter in most of our new ET instances (i.e., 3). Nevertheless, these varied values were not identified as a potential or likely cause of the ACS in the discussion or conclusion of any of these discharge letters.
Two individuals underwent routine follow-up to establish the diagnosis (ET) (average delay: six years). This study led to the identification of two new patients.
We found 10 patients with thrombocytosis in our final dataset of 180 consecutive cases. Four patients in this predetermined group were found to have either newly diagnosed or previously recognized ET. This translates to 2.2% of ACS . Patients with reactive thrombocytosis did not undergo genetic testing or bone marrow biopsies.
As a result, in these instances, the ACS was the initial obvious sign of their underlying MPN. Notably, the finding that the diagnosis (ET) was either overlooked or delayed in every instance may have had important ramifications. First, individuals with ET who have experienced a CV event are categorized as high-risk for repeated events; as a result, they need special medication, such as hydroxyurea and aspirin (sometimes twice daily) to avoid future occurrences [7]. Second, in order to avoid peri-operative thrombotic problems, it has been suggested that the scheduling of PCI/CABG in the presence of either stable angina or ACS as the initial sign of ET should be modified in accordance with thrombocyte counts or the start of cytoreductive therapy [8–10].
Even while ET is one of the uncommon illnesses linked to ACS [2] and its incidence rate is just 1.5–2.5/100,000 annually [11,12], the available data disputes that ET is incredibly uncommon when examining patients with ACS and a short exposure period to conventional CV-risk factors. To put it another way, ET is an uncommon condition in the general population, but our data indicates that much higher rates—up to 2%—can be anticipated in certain clinical settings, such as the practices of neurologists, vascular surgeons, and cardiologists who frequently treat patients with thrombi or thrombo-embolisms.
Thrombotic/thrombo-embolic events are a common (up to 84%) initial manifestation of ET in clinical practice [8,13–14]. According to several ET studies [11-12], cerebrovascular events (55–56%) are more common than either peripheral (13–22%) or coronary events (2–31%). Interestingly, the current study indicates that ET is a considerably less well-known underlying disease for ACS among cardiologists, despite thrombotic problems being a well-known complication of ET among hematologists. Although less than 20% of patients are discovered before the age of 40 [13,14] and the median age of diagnosis for ET is in the sixth decade of life [10], the current study indicates that, with proper screening, a subset of ET patients may be found before the age of 40.
Significantly, as ET is known to cause both thrombosis and arterial constriction due to persistent endothelial inflammation, ACS in ET patients has been seen both with and without underlying atherosclerosis [11,12]. Therefore, even very young individuals without risk factors can have acute, potentially fatal thrombotic events if they have underlying ET [12], as supported by these and previous investigations [14]. Therefore, we suggest that a "ACS protocol" be implemented for similar patients, i.e., those with low exposure to traditional CV-risk factors, who present with ACS, in a manner akin to the current "young stroke" protocol for stroke patients under 40 years of age and those between 40 and 50 years of age without traditional CV-risk factors.
It's interesting to note that the relevant Guidelines from the European Society of Cardiology do contain some recommendations regarding prognostic testing, such as a full blood count (CCS, 2019; CVD, 2021), renal function, lipid profile, fasting plasma glucose and HbA1c (as part of diabetes screening), and thyroid function (CCS, 2019). However, these tests are not mentioned as part of "screening for underlying disorders in ACS." Furthermore, even though a total blood count should include a leukocyte and platelet count, neither leukocytes nor platelets are listed as CV-risk factors in these guidelines, despite numerous comprehensive studies demonstrating the link between ACS/CCS and hematological malignancies with either elevated thrombocytes or leukocytes [7,11].
Ultimately, the current investigation demonstrated unequivocally that the diagnosis of ET was either overlooked or delayed in spite of the presence of both increased thrombocytes and a thrombotic event. When considered collectively, the fact that increased thrombocytes were frequently noted in the discharge letters but were infrequently linked to the ACS suggests that ET may not be well understood or acknowledged. Therefore, ACS patients should be screened for risk factors using a systematic methodology Additionally, all investigations conducted, particularly those that were abnormal, should be included in every hospital release letter. \
These letters should include recommendations for additional screening as well as a discussion or conclusion about (the differential diagnosis of the) underlying pathophysiology for the ACS.
Restrictions
Our study's limitations include the fact that it was done retrospectively, that not all of our patients had thrombocyte counts, that roughly 25% of our patients with thrombocytosis were lost to follow-up, and that we did not perform genetic testing on our entire database, so we do not have information on the presence of, for example, a JAK2-mutation in ACS patients without thrombocytosis.
At least 33% of patients under 40 having CAG/PCI in the context of ACS could have ET established if screening was limited to those with an increased platelet count (i.e., >450x10*9/L). Therefore, ET is a rather prevalent underlying illness (around 2%) in these patients. Furthermore, the ACS was typically the first sign of underlying ET and, as a result, the first chance to begin effective preventive medication.
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