Superscan-Like Pattern on 18F-Choline PET/CT in a Patient With Essential Thrombocythemia.

ABSTRACT: Few clinical and preclinical articles reported the potential usefulness of 18F-choline PET/CT in several hematological proliferative diseases. We report and incidental finding of a superscan-like pattern in a patient affected by essential thrombocythemia (ET), performing 18F-choline PET/CT for a biochemical recurrence of prostate cancer. The mild elevation of PSA values and the negativity of subsequent 68Ga-PSMA-11 PET/CT allowed to correlate the diffuse skeletal uptake detected on 18F-choline PET/CT to the underlying hematologic disease, rather than to a prostate cancer relapse.

Assessing Bone Marrow Activity with [18F]FLT PET in Patients with Essential Thrombocythemia and Prefibrotic Myelofibrosis: A Proof of Concept.

Objectives: This study aims to assess the value of FLT-PET as a non-invasive tool to differentiate between patients with ET and Pre-PMF. This study is a pilot study to have a proof of concept only. Methods: This is a prospective, interventional study where a total of 12 patients were included. Each patient underwent FLT PET imaging as well as bone marrow examination (gold standard). In addition, semi-quantitative (SUVmax and SUVmean) measurements of FLT uptake in the liver, spleen, and Lspine, SUVmean, as well as the Total Lesion Glycolysis (TLG) of the Lspine were performed. Results from the two patient cohorts were compared using = Kruskal-Wallis statistical test. A P-value of <.05 is considered to be statistically significant. Results: The differences in FLT SUVmax and SUVmean measurements in the three organs (liver, spleen, and LSpine) between the ET and Pre-PMF patients were not statistically significant (P > .05). In contrast, TLG measurements in the LSpine were statistically different (P = .013), and therefore, compared to gold standard bone marrow results, TLG can separate ET and Pre-PMF patients. Conclusion: This study is a proof of concept about the potential to discriminate between ET and pre-PMF patients in a non-invasive way. TLG of the LSpine in FLT PET images is a potential quantitative parameter to distinguish between ET and pre-PMF patients.

Volumetric splenomegaly in patients with essential thrombocythemia and prefibrotic/early primary myelofibrosis.

Non-palpable, volumetric splenomegaly at diagnosis was evaluated using computed tomography in patients with essential thrombocythemia (ET) and prefibrotic/early primary myelofibrosis (pre-PMF) based on 2016 World Health Organization guidelines. Each patient's spleen volume was adjusted for their age and body surface area. The degree of splenomegaly was classified as no, borderline volumetric, overt volumetric, or palpable splenomegaly. Seventy-six patients with ET (median age, 62.5 years) and 19 patients with pre-PMF (median age, 65 years) were followed up for a median of 2.4 years (range 0.1-17.6 years) and 4.2 years (range 0.2-19.6 years), respectively. Spleen volume was significantly greater in pre-PMF patients than in ET patients (377.9 ± 92.2 cm3 vs. 224.9 ± 115.2 cm3, P < 0.001). No, borderline volumetric, overt volumetric, and palpable splenomegaly were found in 42 (55.3%), 24 (31.6%), 10 (13.2%), and 0 (0%) patients with ET, respectively, and in 0 (0%), 8 (42.1%), 19 (52.6%), and 1 (5.2%) patient with pre-PMF, respectively (P < 0.001). Volumetric splenomegaly did not affect thrombosis-free survival in patients with ET or those with pre-PMF. This study indicates that all patients with pre-PMF present with splenomegaly, whereas half of the patients with ET have a normal-sized spleen at diagnosis.

A study of 18F-FLT positron emission tomography/computed tomography imaging in cases of prefibrotic/early primary myelofibrosis and essential thrombocythemia.

The objectives of this research project are to study in patients with primary myelofibrosis (PMF) and Essential Thrombocythemia (ET); (1) the uptake patterns of FLT-PET (FLT-PET) and its value in diagnosing, staging, and treatment response monitoring of malignant hematopoiesis, (2) compare imaging findings from FLT-PET with bone marrow biopsy (standard of care), and (3) associate FLT-PET uptake patterns with genetic makeup such as JAK2 (Janus kinase 2), CALR (Calreticulin), MPL (myeloproliferative leukemia protein), Triple negative disease, and allele burden.This trial is registered in ClinicalTrials.gov with number NCT03116542. Protocol version: Mar 2017.

Clinical characteristics and brain MRI findings in myeloproliferative neoplasms.

BACKGROUND: Myeloproliferative neoplasms (MPNs) including polycythemia vera (PV) and essential thrombocythemia (ET) have an increased risk of ischemic stroke. However, little is known about brain morphological changes and the cerebral vasculature in MPNs. The aim of the present study is to clarify the prevalence rates of brain infarcts (BIs) on magnetic resonance imaging (MRI) and to assess the detailed clinical and MRI characteristics in those patients. METHODS: We prospectively enrolled patients with MPNs who underwent brain MRI between September 2017 and June 2019. BI patterns were characterized by the numbers and locations of BIs on MRI. RESULTS: A total of 101 patients were included in the present study. BIs were observed in 23 patients (23%). Multiple logistic regression analysis showed that age > 60 years (odds ratio (OR) 7.34, 95% confidence interval (CI) 1.08-49.7, p = .041) and history of thrombosis (OR 40.6, 95% CI 7.97-207, p < .0001) were independently associated with BIs, but not the JAK2V617F mutation. Of the 23 patients with BIs, eight patients (35%) had multiple territorial infarcts, and large vessel involvement was identified in five patients (22%). Two patients had thrombus formation in large vessels. CONCLUSIONS: Among patients with MPNs who underwent MRI, BIs were observed in 23% of patients followed up in our center. Older age and thrombosis history were independently associated with BIs. Some patients with MPNs may present with distinctive MRI findings including multiple territorial infarcts and thrombus formation in large vessels.

A Rare Case of Bilateral Vertebral Artery Dissection Associated with Essential Thrombocythemia.

A young patient presented to our hospital with ischemic stroke. She underwent a routine blood test, head computed tomography (CT), brain magnetic resonance imaging, a bone marrow biopsy, and CT angiography. Her diagnosis was a bilateral vertebral artery dissection associated with essential thrombocythemia (ET). She was treated with antiplatelet therapy and a stent implantation. The association of bilateral vertebral artery dissection with ET is rare. An early diagnosis and timely management is key to the best outcome.

Specific mechanisms of subarachnoid hemorrhage accompanied by ischemic stroke in essential thrombocythemia: two case reports and a literature review.

BACKGROUND: JAK2 V617F mutation increases the risk of thrombosis, and both ischemic and hemorrhagic strokes can occur in essential thrombocythemia (ET). The mechanisms underlying ischemic stroke in ET are diverse, and hemorrhagic stroke has rarely been reported in ET. METHODS: Among 627 stroke patients, those identified as having ET were investigated retrospectively. A comprehensive systemic literature search of the PubMed database was also conducted. RESULTS: Two cases were extracted with the diagnosis of ET who developed SAH and then ischemic stroke. In Case 1, a 47-year-old woman developed SAH in the left high convexity. Eleven hours later, acute cerebellar infarction suddenly developed due to right vertebral artery dissection. In Case 2, a 70-year-old woman developed SAH in the right high convexity. Magnetic resonance angiography showed multifocal stenotic changes in intracranial arteries. Three days later, she developed acute brain infarcts in the right middle cerebral artery territory. Eight weeks later, multifocal stenotic lesions improved. The literature review revealed 5 patients with hemorrhagic stroke and 40 patients with ischemic stroke associated with ET. Age at onset varied, female gender predominated, and the frequency of JAK2 V617F mutation was high. Atherosclerotic vascular risk factors were more common in ischemic stroke, but not in hemorrhagic stroke. CONCLUSIONS: The current study describes rare cases of SAH accompanied by ischemic stroke secondary to ET along with a review of the current literature, implying specific mechanisms for cerebral artery disorders associated with JAK2 V617F mutation.

Radiological features and outcomes of essential thrombocythemia-related stroke.

BACKGROUND: Essential thrombocythemia (ET) is known to be associated with an increased vascular event, but the stroke patterns and prognosis have not been studied. METHODS: Between January 2013 and December 2017, acute ischemic stroke patients with ET who were admitted to two tertiary hospital stroke centers in Seoul, Korea were included. We retrospectively reviewed their clinical, laboratory and imaging data. Stroke mechanism was determined as ET-only when no atherosclerotic, cardioembolic, or lacunar stroke etiology was demonstrated and as ET-plus group when any specific etiology was combined. Each group was analyzed to ascertain stroke patterns and outcomes. RESULTS: A total of 26 patients were included, and their mean age was 66 ±â€¯17 years, including 12 female patients. There were 12 ET-only cases and 14 ET-plus cases per stroke mechanism. The ET-plus group included 7 large artery atherosclerosis, 5 small vessel occlusion, and 2 cardioembolic cases. Multiple scattered lesions involving multiple vascular territories were more prevalent in the ET-only group. Poor outcome (modified Rankin scale >2 at discharge) was noted in 13 cases (50.0%), and old age, female sex, prior diagnosis of ET to stroke and low hemoglobin level were associated with poor outcome. CONCLUSION: ET-related stroke displayed a characteristic infarction pattern, such as multiple embolisms.

A Case of Anagrelide-Induced Nonischemic Cardiomyopathy in a Patient With Essential Thrombocythemia.

BACKGROUND: Anagrelide is an established treatment option for essential thrombocythemia (ET). Cardiovascular adverse events can occur with its use including heart failure and cardiomyopathy. CASE REPORT: A 52-year-old African American male with ET presented with chest pain, shortness of breath, and dyspnea on exertion. His ET was managed with hydroxyurea 1500 mg by mouth twice a day and anagrelide 1 mg by mouth 3 times a day. The patient was receiving anagrelide for approximately 2 years prior to presentation. The patient's platelet count was 2.07 × 105 cells/mm3. Transthoracic echocardiography revealed decreased left systolic dysfunction. Also, cardiac magnetic resonance imaging showed an increased left ventricle cavity size with severely depressed systolic dysfunction and an ejection fraction (EF) of 18%. Anagrelide therapy was discontinued and the patient was maintained on hydroxyurea for ET. Three months later, following treatment by a heart failure clinic, the patient's EF was 55%. Five months after discontinuation, the patient improved from New York Heart Association (NYHA) class II to NYHA class I. CONCLUSION: A 52-year-old man with ET presented with an EF of 18% after 2 years of anagrelide therapy. His EF increased from 18% to 55% 3 months after discontinuation of anagrelide.

A rare vascular complication in a patient with essential thrombocythaemia: spontaneous abdominal aortic dissection.

A 27-year-old woman complained of waist and back pain. Abdominal computed tomography angiography showed abdominal aortic dissection, the blood count revealed a high platelet count of 1655 × 109 /L. Negative for JAK2V617F, CALR and MPL mutations (i.e. triple-negative), the patient was diagnosed as essential thrombocythaemia (ET) with abdominal aortic dissection and was treated with cytoreduction and antiplatelet drugs. Cases of abdominal aortic dissection in ET have not been previously reported. As such, we proposed a mechanism of abdominal aortic dissection caused by endothelial dysfunction and further emphasised appropriate management in ET with abdominal aortic dissection.

Essential thrombocythemia presenting as acute coronary syndrome: case reports and literature review.

For the patients with essential thrombocythemia (ET), systemic thrombosis presents as one of the most dangerous complications. It's been widely accepted that acute coronary syndrome (ACS) is a kind of thrombotic diseases. However, there are very few case reports about ET first presenting as ACS. For some patients diagnosed as ACS, but without markedly elevated platelet, underlying ET was missed. And there are some controversies in the principles and target of treatment in those patients. We reported three cases of ACS, in which the patients who did not have common risk factors for coronary artery diseases and presented only mild atherosclerotic stenosis during coronary angiography, one of which had recurrent coronary artery thrombosis. Noticing their elevated blood platelet level and characteristics in angiography, diagnosis of ET was made according to bone marrow morphology and genetic tests. Although they had only mild thrombocytosis, we applied intensive treatment with dual anti-platelet therapy combined with cytoreduction in addition to early coronary intervention, having satisfying outcomes. During the diagnosis and treatment of ACS, if patients present thrombocytosis, but lack common coronary disease risk factors and thrombotic coronary artery occlusion, cardiologists should search for possible ET as an underlying cause of thrombotic coronary event. All those patients were high-risk according to ET risk stratification. Treatment of cytoreduction in combination with anti-thrombosis therapy and revascularization are beneficial. Treatment aims at the target of complete response with platelet count below 400 × 109/L.

Spleen enlargement is a risk factor for thrombosis in essential thrombocythemia: Evaluation on 1,297 patients.

Spleen enlargement, present in 10-20% of Essential Thrombocythemia (ET) patients at diagnosis, is a feature clinically easy to assess, confirmable by echography with a very low chance of misinterpretation. Nonetheless, the clinical and prognostic role of splenomegaly has been seldom evaluated. From 1979 to 2013, 1297 ET patients retrospectively collected in the database of the Lazio Cooperative Group and Bologna University Hospital were evaluable for spleen enlargement at diagnosis and included in the analysis. On the whole, spleen was enlarged in 172/1297 (13.0%) patients; in most cases (94.8%) splenomegaly was mild (≤5 cm). Patients with splenomegaly were younger, predominantly male, presented higher platelet count and JAK2V617F allele burden and had a lower incidence of concomitant cardiovascular risk factors. At least one thrombotic event during follow-up occurred in 97/1,125 (8.6%) patients without spleen enlargement compared to 27/172 (15.7%) patients with spleen enlargement (P = 0.003). Despite comparable use of cytoreductive/antiplatelet therapies in the two groups, the cumulative risk of thrombosis at 5 years was significantly higher in patients with baseline splenomegaly (9.8% versus 4.4% in patients without splenomegaly, P = 0.012). In multivariate analysis exploring risk factors for thrombosis, splenomegaly retained its negative prognostic role, together with previous thrombosis, leucocyte count and male gender. Baseline splenomegaly seems to be an independent additional risk factor for thrombosis in nonstrictly WHO-defined ET patients. This data could be useful in the real-life clinical management of these patients.

Case report: radial artery occlusion post-radial angiogram in essential thrombocytosis.

Coronary angiographies that are performed via the radial artery generally have lower bleeding complications, however, patients are at risk of radial artery occlusion, with resultant digital ischaemia. This report describes a case of digital ischaemia after transradial coronary angiography in a patient with essential thrombocytosis. Risk factors for thrombo-occlusive complications, and potential prevention strategies are also explored.

Coronary microvascular dysfunction due to essential thrombocythemia and policythemia vera: the missing piece in the puzzle of their increased cardiovascular risk?

Myeloproliferative neoplasms are most commonly associated with venous thrombosis. Up to 60% of patients experience a thrombotic event in their lifetimes, including stroke or myocardial infarction. It is unclear whether pathogenetic factors linking essential thrombocythemia (ET) and polycythemia vera (PV) to thrombotic complications do play a role in the risk of coronary artery disease (CAD). We aimed to assess coronary flow reserve (CFR) as a marker of coronary microvascular function in asymptomatic patients with ET and PV. Fifty-two patients with ET (M/F 13/39, age 61 ± 7 years) and 22 patients with PV (M/F 13/9, age 60.4 ± 13 years) without clinical evidence of heart disease, and 50 controls matched for age and gender were studied. None had CAD. All control subjects were asymptomatic with no history of heart disease. CFR in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. In patients with ET and PV, CFR was lower than in controls (2.9 ± 0.94 and 2.2 ± 0.7 vs. 3.8 ± 0.7, P < 0.004 and P < 0.0001 respectively). The prevalence of CFR ≤ 2.5 was higher in patients with ET (20 cases, 38.5%) and PV (15 cases, 68.2%) compared with controls (4.1%) (P < 0.0001). Severe CFR (CFR < 2) impairment was found in eight patients with ET (15.4%), in nine patients with PV (40.9%), and in none of control subjects. The mutation of JAK2 gene was associated with abnormal CFR. Asymptomatic patients with ET and PV have coronary microvascular dysfunction in the absence of clinical conditions suggesting CAD.

Neurological disorders in essential thrombocythemia.

Patients with essential thrombocythemia often complain of various subjective neurological symptoms. This prospective study aims to assess their incidence and response to therapy. Among 37 consecutive patients with essential thrombocythemia, 11 presented with neurological symptoms. Among them 4 had thrombotic events, 7 complained of transient or fluctuating subjective symptoms, and one had both. Brain magnetic resonance imagery failed to detect any substratum in patients with subjective symptoms. JAK2V617F mutation was found in 9 of 11 patients with neurological symptoms versus 14 of 26 patients without symptoms. Ten patients received low-dose aspirin for these symptoms: complete resolution was observed in 3, improvement with persisting episodes in 2, and resistance to aspirin in 2 patients, in whom addition of cytoreductive therapy became necessary to resolve those disabling symptoms. In this prospective cohort, 30% of patients with essential thrombocythemia presented neurological symptoms. Aspirin was fully efficient in only 30% of cases. JAK2V617F mutation could be a risk factor for such symptoms.