Abstract
Introduction: Chronic myeloproliferative neoplasms (MPNs) such as polycythaemia vera (PV) and essential thrombocytosis are associated with atherosclerosis and cardiovascular events, especially if JAK2 mutation is there. In rare cases, also spontaneous coronary artery dissection (SCAD) can be seen. Case Presentation: This case series describes two case reports of MPNs in which SCAD was found in both of them in addition to standard atherosclerosis. First one was about a 42-year-old man who was admitted for acute myocardial infarction (MI) and was later found to have PV and SCAD. The second one was about a 52-year-old man who was also admitted for acute MI and was later found to have SCAD and essential thrombocythemia. JAK2V617F missense mutation was found in both cases. Conclusion: MPNs with JAK2 mutations are associated with SCAD in addition to usual atherosclerosis. This association needs further research.
Introduction
A JAK2V617F mutation is associated with chronic myeloproliferative neoplasms (MPNs) that include polycythaemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis. Cardiovascular events represent the main cause of morbidity and mortality in PV and ET due to increased atherosclerotic/thrombotic risk, but the mutation itself may be a novel risk factor for coronary artery events [1].
Atherosclerosis can lead to weakness in vessel wall (mainly tunica media), leading to complications like spontaneous coronary artery dissection (SCAD), aortic aneurysm, etc. [2, 3]. We describe here two cases who were found to be JAK2 positive (one PV and one ET) and developed weakness in tunica media of the vessels leading to SCAD in conjunction with standard coronary atherosclerosis.
Case Series
Case 1
A 42-year-old man, with free past medical history, presented with chest tightness in January 2017 and diagnosed with inferior myocardial infarction (MI). His angiogram showed old right coronary and ramus artery SCAD and an occluded left anterior descending artery (shown in Fig. 1). He underwent coronary artery bypass surgery from which he made an uneventful recovery. He gave no prior history of chest pain, headache, or blurred vision. His haemoglobin was found 19.4 g/dL. Other laboratory results are shown in Table 1. The patient was referred to haematology team due to polycythaemia, so they did bone marrow biopsy for him and found he had PV. He was found to have the JAK2V617F mutation and he underwent multiple venesections. He was started on hydroxyurea and remained under haematological surveillance.
Coronary angiogram showing old right coronary and ramus artery type 1 dissections (arrowed) and an occluded left anterior descending artery.
Coronary angiogram showing old right coronary and ramus artery type 1 dissections (arrowed) and an occluded left anterior descending artery.
Laboratory tests of case 1
| Lab | Result | Reference range |
|---|---|---|
| White blood cells | 5.4 × 103/µL | 4.0–10.0 |
| Haemoglobin | 19.4 g/dL | 12.0–15.0 |
| Platelets | 277 × 103/µL | 150–400 |
| Prothrombin time | 10.9 s | 9.7–11.8 |
| Partial thromboplastin time | 25.1 s | 24.6–31.2 |
| International normalized ratio | 1 | NA |
| Sodium | 133 mmol/L | 133–146 |
| Potassium | 3.8 mmol/L | 3.5–5.3 |
| Adjusted calcium | 2.28 mmol/L | 2.20–2.60 |
| Phosphorus | 0.87 mmol/L | 0.80–1.50 |
| Magnesium | 0.72 mmol/L | 0.70–1.00 |
| Creatinine | 71 μmol/L | 44–80 |
| Urea | 2.4 mmol/L | 2.5–7.8 |
| Alanine transaminase (ALT) | 10 U/L | 0–33 |
| Aspartate transaminase (AST) | 11 U/L | 0–32 |
| Iron | 13.2 μmol/L | 6–35 |
| Ferritin | 45 μg/L | 18–340 |
| Total iron-binding capacity | 75 μmol/L | 45–80 |
| Transferrin | 3.1 g/L | 2.0–3.6 |
| Iron saturation | 28% | 15–45 |
| B12 | 414 pmol/L | 145–596 |
| C-reactive protein | 0.6 mg/L | 0.0–5.0 |
| Lab | Result | Reference range |
|---|---|---|
| White blood cells | 5.4 × 103/µL | 4.0–10.0 |
| Haemoglobin | 19.4 g/dL | 12.0–15.0 |
| Platelets | 277 × 103/µL | 150–400 |
| Prothrombin time | 10.9 s | 9.7–11.8 |
| Partial thromboplastin time | 25.1 s | 24.6–31.2 |
| International normalized ratio | 1 | NA |
| Sodium | 133 mmol/L | 133–146 |
| Potassium | 3.8 mmol/L | 3.5–5.3 |
| Adjusted calcium | 2.28 mmol/L | 2.20–2.60 |
| Phosphorus | 0.87 mmol/L | 0.80–1.50 |
| Magnesium | 0.72 mmol/L | 0.70–1.00 |
| Creatinine | 71 μmol/L | 44–80 |
| Urea | 2.4 mmol/L | 2.5–7.8 |
| Alanine transaminase (ALT) | 10 U/L | 0–33 |
| Aspartate transaminase (AST) | 11 U/L | 0–32 |
| Iron | 13.2 μmol/L | 6–35 |
| Ferritin | 45 μg/L | 18–340 |
| Total iron-binding capacity | 75 μmol/L | 45–80 |
| Transferrin | 3.1 g/L | 2.0–3.6 |
| Iron saturation | 28% | 15–45 |
| B12 | 414 pmol/L | 145–596 |
| C-reactive protein | 0.6 mg/L | 0.0–5.0 |
Case 2
A 52-year-old man, with free past medical history, presented with chest pain in January 2023 and was diagnosed with anterior MI. He was found to have a platelet count of 1,565 × 103 mL. Other laboratory tests are shown in Table 2. His coronary angiogram showed left main disease with an old SCAD of the right coronary artery (shown in Fig. 2). He gave no prior history of chest pain, headache, or blurred vision. He underwent CABG surgery and made an uneventful recovery. Haematology workup showed that he was positive for a JAK2V617F missense mutation. Bone marrow biopsy was done and confirmed the diagnosis of essential thrombocythemia. He was started on hydroxyurea treatment; his recent platelets are 520 × 103 mL.
Laboratory tests of case 2
| Lab | Result | Reference range |
|---|---|---|
| White blood cells | 16.4 × 103/µL | 4.0–10.0 |
| Haemoglobin | 13.4 g/dL | 12.0–15.0 |
| Platelets | 1,565 × 103/µL | 150–400 |
| Prothrombin time | 10.1 s | 9.7–11.8 |
| Partial thromboplastin time | 26.1 s | 24.6–31.2 |
| International normalized ratio | 1 | NA |
| Sodium | 137 mmol/L | 133–146 |
| Potassium | 4.2 mmol/L | 3.5–5.3 |
| Adjusted calcium | 2.3 mmol/L | 2.20–2.60 |
| Phosphorus | 0.87 mmol/L | 0.80–1.50 |
| Magnesium | 0.82 mmol/L | 0.70–1.00 |
| Creatinine | 75 μmol/L | 44–80 |
| Urea | 2.4 mmol/L | 2.5–7.8 |
| Alanine transaminase (ALT) | 11 U/L | 0–33 |
| Aspartate transaminase (AST) | 12 U/L | 0–32 |
| Iron | 13.5 μmol/L | 6–35 |
| Ferritin | 48 μg/L | 18–340 |
| Total iron-binding capacity | 70 μmol/L | 45–80 |
| Transferrin | 3 g/L | 2.0–3.6 |
| Iron saturation | 25% | 15–45 |
| B12 | 513 pmol/L | 145–596 |
| C-reactive protein | 0.8 mg/L | 0.0–5.0 |
| Lab | Result | Reference range |
|---|---|---|
| White blood cells | 16.4 × 103/µL | 4.0–10.0 |
| Haemoglobin | 13.4 g/dL | 12.0–15.0 |
| Platelets | 1,565 × 103/µL | 150–400 |
| Prothrombin time | 10.1 s | 9.7–11.8 |
| Partial thromboplastin time | 26.1 s | 24.6–31.2 |
| International normalized ratio | 1 | NA |
| Sodium | 137 mmol/L | 133–146 |
| Potassium | 4.2 mmol/L | 3.5–5.3 |
| Adjusted calcium | 2.3 mmol/L | 2.20–2.60 |
| Phosphorus | 0.87 mmol/L | 0.80–1.50 |
| Magnesium | 0.82 mmol/L | 0.70–1.00 |
| Creatinine | 75 μmol/L | 44–80 |
| Urea | 2.4 mmol/L | 2.5–7.8 |
| Alanine transaminase (ALT) | 11 U/L | 0–33 |
| Aspartate transaminase (AST) | 12 U/L | 0–32 |
| Iron | 13.5 μmol/L | 6–35 |
| Ferritin | 48 μg/L | 18–340 |
| Total iron-binding capacity | 70 μmol/L | 45–80 |
| Transferrin | 3 g/L | 2.0–3.6 |
| Iron saturation | 25% | 15–45 |
| B12 | 513 pmol/L | 145–596 |
| C-reactive protein | 0.8 mg/L | 0.0–5.0 |
Coronary angiogram showing a type 1 dissection in the right coronary artery (arrowed).
Coronary angiogram showing a type 1 dissection in the right coronary artery (arrowed).
Discussion
The risk of thrombosis is well known and established in MPNs with positive JAK2V617F mutation. The mechanism behind this is multifactorial including activation of leucocytes, platelets, and endothelium and interactions between them. Release of certain growth vascular factors and adhesion molecules is mediated through the JAK2V617F mutation [4].
Patients with MPNs have a higher risk to have severe coronary atherosclerosis defined as coronary artery calcium score >400 and aortic valve calcifications and stenosis [5]. More commonly this happens with JAK2V617F mutation because of the increased risk of thrombosis as we discussed [6]. Atherosclerosis and calcifications are also important risk factors for SCAD [7].
There are a few case reports in the literature about association between MPNs and SCAD [8]. We have found our two cases presented above are interesting and worthy to be described. Both cases underwent CABG surgery which suggests to us that atherosclerosis is the main role player in developing SCAD in MPN patients. Regarding the mechanism of SCAD, possibly the JAK2V617F mutation in conjunction with the atherosclerosis weakens the tunica media layer of coronary arteries, further leading to dissection [9].
Our reported cases highlight the importance of further research regarding this vital topic and we encourage other researchers to report any similar cases. Depending on these cases, we can ask a question: is there a need for screening or at least monitoring for high-risk group, or vice versa, should patients with unexplained SCAD be evaluated haematologically?
Conclusion
MPNs with the JAK2V617F mutation are associated with SCAD. Further research is needed to support this association. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000541036).
Statement of Ethics
This case report complies with the Declaration of Helsinki and has been approved by the Ethics Committee of Hamad Medical Corporation. This study protocol was reviewed and approved by Medical Research Centre (MRC) in Hamad Medical Corporation, MRC number is MRC-04-24-202. Written informed consent was obtained from the patients for publication of the details of their medical case and any accompanying images.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
Qatar National Library funded this case report. They had no role in preparing or writing it.
Author Contributions
Study design and conception: Ahmed K.A. Yasin. Acquisition, analysis, or interpretation of data: Girish Rao, Abdulaziz M. Alkhulaifi, Mohamed A. Yassin, Deena Mudawi, Abdulrahman F. Al-Mashdali, Samah Kohla, Feryal A. Ibrahim, and Dina Soliman. Drafting of the manuscript: Ahmed K.A. Yasin, Shehab Fareed, and Elmustafa Abdalla. Critical revision of the manuscript for important intellectual content: Shehab Fareed. Supervision: Shehab Fareed and Cornelia S. Carr.
Data Availability Statement
All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.
References
