Search Results (25)

Elevated levels of neutrophil extracellular traps (NETs) are associated with thrombotic risks, in particular, for patients with elevated platelet counts, such as those with essential thrombocythemia (ET). Here, the tendency for NETosis and neutrophil activity in such patients was assessed. A total of forty-one pediatric patients with elevated platelet counts diagnosed with ET (nine with CALR driver mutation, eleven with JAK2, thirteen triple-negative, and one dual-negative (TN)) or secondary thrombocytosis (five) were recruited. The tendency for NETosis was determined in a leucocyte-rich blood plasma smear using immunofluorescence staining with antibodies against myeloperoxidase and elastase. Activity of neutrophils was assessed ex vivo in parallel-plate flow chambers. The mean level of NETosis in healthy volunteers was 2.7–6.7% (95% CI). Among the ET patients, there was no statistically significant difference in NETosis level between those with mutations in CALR (19–43%), JAK2 (22–58%), and TN ones (6–27%). Patients with secondary thrombocytosis also had an elevated level of NETosis (8–66%). The velocity of neutrophil chemotaxis was significantly increased in all patients, in particular for those with mutations in CALR. These data reveal a major shift in the neutrophil activity in ET and suggest that the immunomorphological techniques presented here may allow reproducible and widely available characterization of neutrophil status. Full article

Background and Clinical Significance: Fever of undetermined origin (FUO is a diagnostic challenge. It is essential to exclude infections, paraneoplastic syndromes, and large-vessel vasculitis (LVV). Case presentation: We describe a 59-year-old female with FUO and no apparent signs of infection. Laboratory results were consistent with inflammation (ESR 83, CRP 203 (ref. value (RV) < 5 mg/dl), ferritin 311 (RV < 120 µg/L), microcytic anemia, thrombocytosis. With administration of both ceftriaxone and levofloxacin, a decrease in CRP was monitored (51 mg/L). HRCT of the chest, abdomen, and pelvis revealed a saccular aneurysm of the descending thoracic aorta and an ectatic right common iliac artery. Due to suspicion of LVV, CT angiography was performed to exclude inflammatory changes in the blood vessels. Diffuse atherosclerosis with a 30 mm penetrating thoracic aortic ulcer (PAU) was found. PET-CT and leukocyte scintigraphy were used to rule out vasculitis and infection. The patient was successfully treated with Thoracic Endovascular Aortic Repair (TEVAR). Conclusions: As sophisticated imaging techniques become more widely used, more PAUs are being detected as incidental abnormalities in individuals without acute aortic syndrome. With adequate management, many people with PAU can live a stable and healthy life without experiencing significant consequences. Full article

Background and Objectives: Philadelphia (Ph)-negative myeloproliferative neoplasms can exhibit defects in Janus kinase 2 (JAK2), Calreticulin (CalR), and MPL genes. It is possible that the presence of other driver mutations may influence diagnosis and prognosis in patients who do not have a JAK2 gene mutation. The purpose of this study was to assess the frequency of CalR and MPL gene mutations and the clinical effects of these mutations in JAK2 gene-unmutated MPN patients from a single center. Materials and Methods: We examined 46 patients (ET/PMF: 34/12) diagnosed with MPNs regarding their genetic conditions, diagnoses, and complications. Results: CalR Type 1 gene mutation was detected in 26.1% of cases, CalR Type 2 gene mutation in 13.0%, MPL-L gene mutation in 2.2%, and MPL-K gene mutation in 6.5%. In total, 56.5% of patients were triple-negative. The presence of CalR Type 1 and Type 2 mutations was significantly more prevalent in patients with essential thrombocytosis (ET), although the difference did not reach statistical significance (p = 0.51, p = 0.57). In contrast, MPL mutations were only observed in patients with primary myelofibrosis (PMF). Conclusions: We found no correlation between thrombosis, leukemic transformation, and driver mutations. MPL gene mutation was present in only myelofibrosis patients, and CALR gene mutation was present in one of the three cases of leukemic transformation. The triple-negative group had a lower survival rate, but this difference was not statistically significant (110.3 months vs. 121.4 months, respectively, p = 0.53). However, the sample size was quite small. Our limited observations suggest a possible trend that requires confirmation. Full article

Background: Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by the uncontrolled proliferation of megakaryocytes and sustained thrombocytosis. Although its impact on renal function is not well established, a few case reports have described glomerular involvement and associated kidney impairment. Case Report: We present the case of a 79-year-old man with ET and stage 3b/A2 chronic kidney disease (CKD), who was admitted with severe acute kidney injury (AKI). This episode was associated with a progressive rise in platelet count, reaching 1,350,000/μL after discontinuation of anagrelide and loop diuretics. Renal biopsy (RB) revealed structural lesions compatible with a myeloproliferative neoplasm, including acute tubular necrosis (ATN), glomerulomegaly, and thrombotic microangiopathy (TMA). Cytoreductive therapy with hydroxyurea and corticosteroids was initiated, resulting in improvement of renal function and achievement of complete hematologic remission. Discussion: During follow-up, a linear correlation was observed between increasing platelet counts and declining renal function, underscoring the need for dynamic therapeutic adjustment and close monitoring to prevent progression to end-stage renal disease (ESRD). Conclusions: This case highlights the importance of nephrological evaluation in patients with ET and supports the role of cytoreductive therapy in managing ET-associated renal complications. Full article

Background/Objectives: Overt primary myelofibrosis (PMF), secondary post-polycythemia vera (post-PV), and post-essential thrombocythemia (post-ET) myelofibrosis (SMF) are chronic myeloproliferative neoplasms (MPN) that sometimes present with extreme thrombocytosis (ExTh, platelet count > 1000 × 10⁹/L), a phenomenon of uncertain clinical significance since there are no published data available. Methods: We retrospectively investigated the clinical correlations and associated outcomes of ExTh in a cohort of 172 patients with overt myelofibrosis diagnosed in six Croatian hematology centers. Results: ExTh was present in 5.8% of patients and was associated with post-ET etiology of myelofibrosis, older age, smaller spleen size, and the presence of arterial hypertension (p < 0.05 for all analyses). No significant associations were observed with sex, degree of bone marrow fibrosis, or driver mutation status. Over the follow-up period, patients with ExTh experienced a favorable course regarding survival (p < 0.001) and bleeding risk (p = 0.034), whereas no significant association with thrombotic risk was observed (p = 0.682). Conclusions: In contrast to its context in ET, ExTh in overt fibrotic MPN does not appear to confer higher bleeding or thrombotic risk. Instead, it is associated with more favorable survival outcomes and reduced bleeding risk. Full article

Essential thrombocythemia (ET) is a rare myeloproliferative neoplasm characterized by excessive platelet production and a predisposition to thrombotic or hemorrhagic complications. We report a case of a 62-year-old male with no conventional cardiovascular risk factors who presented with a non-ST-segment elevation myocardial infarction (NSTEMI). Initial coronary angiography showed isolated proximal LAD stenosis. Laboratory tests revealed marked thrombocytosis (>1,000,000/μL) and a CALR mutation, confirming a diagnosis of ET. The patient was treated with percutaneous coronary intervention (PCI), dual antiplatelet therapy, and cytoreductive therapy with hydroxyurea, leading to a favorable outcome. This case illustrates how ET, particularly CALR-mutated subtypes, can manifest as acute coronary syndrome in the absence of atherosclerosis and underscores the need to consider hematologic malignancies in atypical presentations of myocardial infarction. Full article

Background and objective: Iliopsoas abscess (IPA) is a rare condition with varied symptomology and etiology. Less than one-third of patients with IPA present in the emergency department (ED) with the traditional triad of fever, back pain, and restricted hip motion (or limp), leading to delays in diagnosis and management. Acute liver failure is also a rare clinical presentation in the ED, being associated with high morbidity and mortality. It occurs most often in young patients without pre-existing liver disease, presenting unique challenges in clinical management. Most cases currently happen because of drug-induced liver injury (DILI), mainly from acetaminophen or idiosyncratic drug reactions. This case report aims to raise awareness among healthcare professionals regarding the two atypical presentations in ED and introduce a potential differential diagnosis when evaluating patients with fever and back pain or liver enzyme elevations with or without nonspecific symptoms associated with the development of jaundice. The intention is to provide insights into the signs and symptoms that may indicate the presence of an iliopsoas abscess and prompt additional investigations. Case report: Here, we describe a case of primary iliopsoas abscess associated with drug-induced liver injury in our ED. The patient complained of pain in the left lumbar region and fatigue that started two weeks before this presentation, claiming that, during the previous night, the pain suddenly worsened. At the first clinical examination in the ED, the patient presented pain at palpation in the right hypochondriac and left lumbar regions, accompanied by fever, vomiting, and jaundice. On abdominal ultrasonography, the diagnosis of acute cholangitis was suspected. The laboratory test shows leukocytosis with neutrophilia, thrombocytosis, elevated liver enzymes, and hyperbilirubinemia with the predominance of indirect bilirubin. After analyzing the laboratory test results, we repeated and performed a more detailed anamnesis and medical history of the patient. Because of her increasing pain and persistent fever, she recognized excessive consumption in the last five days of drug-induced hepatotoxicity. We performed abdominal and pelvic computed tomography, which confirmed the diagnosis of cholelithiasis observed with the diameter of the bile duct within normal limits but also showed an abscess collection fused to the interfibrillar level of the left iliopsoas muscle, a diagnosis we most likely would have missed. The patient was hospitalized in the General Surgery Department, and surgical abscess drainage was performed. The patient’s evolution was excellent; she was discharged after 11 days. Conclusions: The case presented here exemplifies how iliopsoas abscess, a rare cause of back pain, can quickly go unrecognized, especially in the emergency department. Our experiences will raise awareness among doctors in emergency departments about this uncommon but essential diagnosis. With advancements in diagnostic tools and techniques, we hope that more cases of iliopsoas abscess will be accurately diagnosed. Moreover, no case report from the literature has presented IPA associated with DILI. This case is unique because our patient did not exhibit classic features of either pathology. This case also emphasizes the importance of a medical history that includes thorough evaluations of potential high utilization of drug-induced hepatotoxicity. Full article

Myeloproliferative neoplasms, polycythemia vera, essential thrombocytosis, and primary myelofibrosis are a unique group of clonal hematopoietic stem cell neoplasms that share somatic, gain-in-function driver mutations in JAK2, CALR, and MPL. As a consequence, these disorders exhibit similar phenotypic features, the most common of which are the ceaseless production of normal erythrocytes, myeloid cells, platelets alone or in combination, extramedullary hematopoiesis, myelofibrosis, and a potential for leukemic transformation. In the case of polycythemia vera and essential thrombocytosis, however, prolonged survival is possible. With an incidence value in the range of 0.5–2.0/100,000, myeloproliferative neoplasms are rare disorders, but they are not new disorders, and after a century of scrutiny, their clinical features and natural histories are well-defined, though their individual management continues to be controversial. With respect to polycythemia vera, there has been a long-standing dispute between those who believe that the suppression of red blood cell production by chemotherapy is superior to phlebotomy to prevent thrombosis, and those who do not. With respect to essential thrombocytosis, there is a similar dispute about the role of platelets in veinous thrombosis, and the role of chemotherapy in preventing thrombosis by suppressing platelet production. Linked to these disputes is another: whether therapy with hydroxyurea promotes acute leukemia in disorders with a substantial possibility of longevity. The 21st century revealed new insights into myeloproliferative neoplasms with the discovery of their three somatic, gain-of-function driver mutations. Almost immediately, this triggered changes in the diagnostic criteria for myeloproliferative neoplasms and their therapy. Most of these changes, however, conflicted with prior well-validated, phenotypically driven diagnostic criteria and the management of these disorders. The aim of this review is to examine these conflicts and demonstrate how genomic discoveries in myeloproliferative neoplasms can be used to effectively complement the known phenotypic features of these disorders for their diagnosis and management. Full article

Despite advances in diagnosis of erythrocytosis and thrombocytosis due to driver mutation testing, many cases remain classified as “idiopathic”. This can be explained by the absence of an evident secondary cause, inconclusive bone marrow biopsy or neglection of family history. Analysis of a broad panel of genes through next-generation sequencing (NGS) could improve diagnostic work-up identifying underlying genetic causes. We reviewed the results of NGS performed in our laboratory and its diagnostic impact on 117 patients with unexplained erythrocytosis and 58 with unexplained thrombocytosis; six patients (5.1%) were diagnosed with polycythaemia vera (PV) and 8 (6.8%) with familial erythrocytosis after NGS testing. Low EPO and a family history seemed to predict a positive result, respectively. However, a greater percentage of patients were ultimately diagnosed with secondary erythrocytosis (36%), remained as idiopathic (28.2%) or were self-limited (15%). The yield of NGS was shown to be slightly higher in patients with thrombocytosis, as 15 (25.9%) were diagnosed with essential thrombocythemia (ET) or familial thrombocytosis after variant detection; previous research has shown similar results, but most of them carried out NGS retrospectively, while the present study exhibits the performance of this test in a real-world setting. Overall, the low rate of variant detection and its poor impact on diagnostic work-up highlights the need for a thorough screening prior to NGS, in order to improve its yield. Full article

Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) characterized by clonal erythrocytosis and thrombocytosis, respectively. The main goal of therapy in PV and ET is to prevent thrombohemorrhagic complications. Despite a debated notion that red blood cells (RBCs) play a passive and minor role in thrombosis, there has been increasing evidence over the past decades that RBCs may play a biological and clinical role in PV and ET pathophysiology. This review summarizes the main mechanisms that suggest the involvement of PV and ET RBCs in thrombosis, including quantitative and qualitative RBC abnormalities reported in these pathologies. Among these abnormalities, we discuss increased RBC counts and hematocrit, that modulate blood rheology by increasing viscosity, as well as qualitative changes, such as deformability, aggregation, expression of adhesion proteins and phosphatidylserine and release of extracellular microvesicles. While the direct relationship between a high red cell count and thrombosis is well-known, the intrinsic defects of RBCs from PV and ET patients are new contributors that need to be investigated in depth in order to elucidate their role and pave the way for new therapeutical strategies. Full article

Essential thrombocythemia (ET) is a myeloproliferative neoplasm variant characterized by excessive production of platelets. Since the most common cause of mortality and morbidity in ET patients is thrombosis, the excessive production of platelets may cause thrombotic events. However, little is known about the function of platelets in ET. We report a female patient who presented as asymptomatic, without a remarkable medical history, and ET was diagnosed after an incidental finding of moderate thrombocytosis. Notably, together with thrombocytosis, an abnormal platelet phenotype was found for the presence of a massive, rapid and spontaneous formation of aggregates and platelet hypersensitivity to subthreshold concentrations of aggregating agonists. Bone marrow histopathological examination and genetic analysis with the JAK2 (V617F) gene mutation findings confirmed the initial suspicion of ET. Although the ET patient was placed on aspirin, the persistence of the platelet hyperactivation and hyperaggregability prompted a switch in antiplatelet medication from entero-coated (EC) to plain aspirin. As result, platelet hypersensitivity to agonists and spontaneous aggregation were no longer found. Collectively, our study demonstrates that platelet function analysis could be a reliable predictor of ET and that plain aspirin should be preferred over EC aspirin to attenuate platelet hyperreactivity. Full article

Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (prePMF) initially have a similar phenotypic presentation with thrombocytosis. The aim of our study was to determine significant clinical-laboratory parameters at presentation to differentiate prePMF from ET as well as to develop and validate a predictive diagnostic prePMF model. This retrospective study included 464 patients divided into ET (289 pts) and prePMF (175 pts) groups. The model was built using data from a development cohort (229 pts; 143 ET, 86 prePMF), which was then tested in an internal validation cohort (235 pts; 146 ET, 89 prePMF). The most important prePMF predictors in the multivariate logistic model were age ≥ 60 years (RR = 2.2), splenomegaly (RR = 13.2), and increased lactat-dehidrogenase (RR = 2.8). Risk scores were assigned according to derived relative risk (RR) for age ≥ 60 years (1 point), splenomegaly (2 points), and increased lactat-dehidrogenase (1 point). Positive predictive value (PPV) for pre-PMF diagnosis with a score of ≥points was 69.8%, while for a score of ≥3 it was 88.2%. Diagnostic performance had similar values in the validation cohort. In MPN patients with thrombocytosis at presentation, the application of the new model enables differentiation of pre-PMF from ET, which is clinically relevant considering that these diseases have different prognoses and treatments. Full article

Myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell-derived disorders characterized by uncontrolled proliferation of differentiated myeloid cells. Two main groups of MPN, BCR::ABL1-positive (Chronic Myeloid Leukemia) and BCR::ABL1-negative (Polycythemia Vera, Essential Thrombocytosis, Primary Myelofibrosis) are distinguished. For many years, cytomorphologic and histologic features were the only proof of MPN and attempted to distinguish the different entities of the subgroup BCR::ABL1-negative MPN. World Health Organization (WHO) classification of myeloid neoplasms evolves over the years and increasingly considers molecular abnormalities to prove the clonal hematopoiesis. In addition to morphological clues, the detection of JAK2, MPL and CALR mutations are considered driver events belonging to the major diagnostic criteria of BCR::ABL1-negative MPN. This highlights the preponderant place of molecular features in the MPN diagnosis. Moreover, the advent of next-generation sequencing (NGS) allowed the identification of additional somatic mutations involved in clonal hematopoiesis and playing a role in the prognosis of MPN. Nowadays, careful cytomorphology and molecular biology are inseparable and complementary to provide a specific diagnosis and to permit the best follow-up of these diseases. Full article

Classical BCR-ABL-negative myeloproliferative neoplasms (MPN) include polycythaemia vera, essential thrombocythaemia, and primary myelofibrosis. Unlike monogenic disorders, a more complicated series of genetic mutations are believed to be responsible for MPN with various degrees of thromboembolic and bleeding complications. Thrombosis is one of the early manifestations in patients with MPN. To date, the driver genes responsible for MPN include JAK2, CALR, MPL, TET2, ASXL1, and MTHFR. Affords have been done to elucidate these mutations and the incidence of thromboembolic events. Several lines of evidence indicate that mutations in JAK2, MPL, TET2 and ASXL1 gene and polymorphisms in several clotting factors (GPIa, GPIIa, and GPIIIa) are associated with the occurrence and prevalence of thrombosis in MPN patients. Some polymorphisms within XRCC1, FBG, F2, F5, F7, F12, MMP9, HPA5, MTHFR, SDF-1, FAS, FASL, TERT, ACE, and TLR4 genes may also play a role in MPN manifestation. This review aims to provide an insightful overview on the genetic perspective of thrombotic complications in patients with MPN. Full article

Introduction: Chronic mesenteric ischemia is a rare entity with non-specific symptomatology; combined with rare etiologies, it could lead to unwarranted surgical indication. Case report: We report the case of an 85-year-old woman, with a history of hypertension, persistent thrombocytosis, atherosclerosis, and recent minor COVID-19 infection, presenting to the hospital with postprandial abdominal pain and nonspecific clinical examination findings; upon abdominal CT, superior mesenteric artery circumferential thrombosis was revealed. A bone marrow biopsy was performed due to suspected essential thrombocythemia, confirming the diagnosis. An endovascular approach was chosen as therapy option and a stent was placed in the occluded area. Dual antiplatelet and cytoreductive therapies were initiated after the intervention. Clinical course was excellent, with no residual stenosis 1 month after stenting. Conclusions: The therapeutic strategy in elderly patients with exacerbated chronic mesenteric ischemia requires an interdisciplinary approach in solving both the exacerbation and the underlying conditions in order to prevent further thrombotic events. Although the patient presented a thrombotic state, other specific risk factors such as COVID-19 related-coagulopathy and essential thrombocythemia should be considered. Full article