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Thrombosis Research Jul 2024
Topics: Humans; Polycythemia Vera; Plasma Volume
PubMed: 38788620
DOI: 10.1016/j.thromres.2024.109039 -
Biochemical Genetics May 2024Although the expression of many genes is associated with adaptation to high-altitude hypoxic environments, the role of epigenetics in the response to this harsh...
Although the expression of many genes is associated with adaptation to high-altitude hypoxic environments, the role of epigenetics in the response to this harsh environmental stress is currently unclear. We explored whether abnormal DNA promoter methylation levels of six genes, namely, ABCA1, SOD2, AKT1, VEGFR2, TGF-β, and BMPR2, affect the occurrence and development of high-altitude polycythemia (HAPC) in Tibetans. The methylation levels of HAPC and the control group of 130 Tibetans from very high altitudes (> 4500 m) were examined using quantitative methylation-specific real-time PCR (QMSP). Depending on the type of data, the Pearson chi-square test, Wilcoxon rank-sum test, and Fisher exact test were used to assess the differences between the two groups. The correlation between the methylation levels of each gene and the hemoglobin content was explored using a linear mixed model. Our experiment revealed that the methylation levels of the TGF-β and BMPR2 genes differed significantly in the two groups (p < 0.05) and linear mixed model analysis showed that the correlation between the hemoglobin and methylation of ABCA1, TGF-β, and BMPR2 was statistically significant (p < 0.05). Our study suggests that levels of TGF-β and BMPR2 methylation are associated with the occurrence of HAPC in extreme-altitude Tibetan populations among 6 selected genes. Epigenetics may be involved in the pathogenesis of HAPC, and future experiments could combine gene and protein levels to verify the diagnostic value of TGF-β and BMPR2 methylation levels in HAPC.
PubMed: 38787494
DOI: 10.1007/s10528-024-10798-2 -
Diagnostics (Basel, Switzerland) May 2024We present a case of a 59-year-old male diagnosed with polycythemia vera (PV) for many years, who presented with a relatively abrupt onset of heavy constitutional...
We present a case of a 59-year-old male diagnosed with polycythemia vera (PV) for many years, who presented with a relatively abrupt onset of heavy constitutional symptoms, including fatigue, night sweats, and a 10% weight loss over 6 weeks. Despite the known initial diagnosis of PV, the presence of profound B-symptoms prompted further investigation. A positron emission tomography/computed tomography (PET/CT) scan with F-Fluorodeoxyglucose ([F]FDG) was performed to exclude malignant diseases. The [F]FDG PET/CT revealed intense metabolic activity in the bone marrow of the proximal extremities and trunk skeleton, as well as a massively enlarged spleen with increased metabolic activity. Histopathologically, a transformation to myelofibrosis was revealed on a bone marrow biopsy. The case intends to serve as an exemplification for [F]FDG PET/CT in PV with transformation to myelofibrosis (post-PV myelofibrosis).
PubMed: 38786281
DOI: 10.3390/diagnostics14100982 -
European Journal of Haematology May 2024Rusfertide is a potent peptide mimetic of hepcidin being investigated for the treatment of polycythemia vera. This randomized, placebo-controlled, double-blind study...
Pharmacokinetics, pharmacodynamics, and tolerability of an aqueous formulation of rusfertide (PTG-300), a hepcidin mimetic, in healthy volunteers: A double-blind first-in-human study.
OBJECTIVES
Rusfertide is a potent peptide mimetic of hepcidin being investigated for the treatment of polycythemia vera. This randomized, placebo-controlled, double-blind study evaluated the safety, pharmacokinetics, and pharmacodynamics of single and repeated subcutaneous doses of an aqueous formulation of rusfertide in healthy adult males.
METHODS
Subjects received single doses of 1, 3, 10, 20, 40, or 80 mg rusfertide or placebo. A separate cohort of subjects received two doses of 40 mg rusfertide or placebo 1 week apart. Blood samples for pharmacokinetics and pharmacodynamics were collected, and adverse events, clinical laboratory tests, 12-lead electrocardiograms, and vital signs were monitored.
RESULTS
Rusfertide was well tolerated. There were no serious or severe treatment-emergent adverse events, and no patterns of clinically important adverse events, or laboratory, vital sign, or electrocardiogram abnormalities. Mean maximum rusfertide plasma concentration (C) and area under the concentration-time curve increased with dose, but less than dose proportionally. Median time to C was 2-4.5 h for 40 and 80 mg rusfertide and 8-24 h for lower doses. Apparent clearance and half-life increased with dose. Single doses of rusfertide 1-80 mg were associated with dose-dependent decreases in serum iron and transferrin-iron saturation.
CONCLUSIONS
Rusfertide was well tolerated and showed dose-dependent pharmacokinetics and pharmacodynamics.
PubMed: 38785334
DOI: 10.1111/ejh.14243 -
ACG Case Reports Journal May 2024A 59-year-old woman with polycythemia vera-related portal hypertension requiring frequent paracentesis was admitted for asymptomatic recurrent spontaneous bacterial...
A 59-year-old woman with polycythemia vera-related portal hypertension requiring frequent paracentesis was admitted for asymptomatic recurrent spontaneous bacterial peritonitis, which was diagnosed based on elevated polymorphonuclear (PMN) count. She had multiple similar admissions during which she was treated with antibiotics. The patient had chronic baseline leukocytosis due to polycythemia vera. Repeat paracentesis after intravenous antibiotics demonstrated persistent elevation of PMN count without clinical symptoms. A multidisciplinary team concluded that the increased PMN count was secondary to polycythemia. The patient was diagnosed with omental extramedullary hematopoiesis, a rare condition causing elevated PMN count in the absence of bacterial contamination.
PubMed: 38784785
DOI: 10.14309/crj.0000000000001364 -
Ethiopian Journal of Health Sciences Nov 2023Surgical treatment has transformed the course and outcome of congenital heart defects in high-income countries, but children with congenital heart diseases in...
BACKGROUND
Surgical treatment has transformed the course and outcome of congenital heart defects in high-income countries, but children with congenital heart diseases in sub-Saharan Africa, where access to cardiac surgery is limited, often experience the natural course of untreated lesions and their complications. The objective of this study was to determine the prevalence of hematologic derangements among Ethiopian children with unoperated cyanoticcongenital heart diseases, to identify factors associated with coagulopathy in this population, and to describe how these complications are managed in this setting.
METHODS
In this single-center cross-sectional study, we prospectively collected clinical and demographic data from children (<18 years) with cyanotic congenital heart diseases. Blood samples were collected to measure hematologic parameters. Polycythemia was defined as hematocrit >50% and thrombocytopenia as <150,000 per microliter.
RESULTS
Among 70 children recruited, the overall prevalence of polycythemia and thrombocytopenia was 63% (n=44) and 26% (n=18), respectively. On multivariate logistic regression analysis, hematocrit ≥65% (p-value=.024), and oxygen saturation <85% (p-value=.018) were independently associated with moderate or severe thrombocytopenia. Thirty-one (44%) patients had undergone therapeutic phlebotomy, and 84% (26/31) of these patients received iron supplementation.
CONCLUSION
We report a high prevalence of polycythemia and thrombocytopenia in Ethiopian children with untreated cyanotic congenital heart diseases. There was variable implementation of iron supplementation and therapeutic phlebotomy, highlighting the need to optimize supportive management strategies in this population to mitigate the risk of life-threatening complications.
Topics: Humans; Ethiopia; Female; Heart Defects, Congenital; Male; Cross-Sectional Studies; Polycythemia; Child, Preschool; Infant; Child; Thrombocytopenia; Prevalence; Hematocrit; Cyanosis; Adolescent; Prospective Studies; Phlebotomy
PubMed: 38784485
DOI: 10.4314/ejhs.v33i6.5 -
Innere Medizin (Heidelberg, Germany) May 2024The case of a male patient with newly diagnosed polycythemia vera showing rare and unusually rapid progression with phenotypic change towards chronic myelomonocytic...
The case of a male patient with newly diagnosed polycythemia vera showing rare and unusually rapid progression with phenotypic change towards chronic myelomonocytic leukemia is presented. The case report illustrates remarkably rapid disease progression including a structural change in usually indolent polycythemia vera and highlights the prognostic relevance of enhanced molecular genetic testing.
PubMed: 38777881
DOI: 10.1007/s00108-024-01714-2 -
Clinical and Experimental Medicine May 2024Predicting the likelihood vascular events in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN) is essential for the treatment of the disease. However,...
Predicting the likelihood vascular events in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN) is essential for the treatment of the disease. However, effective assessment methods are lacking. Thrombin-antithrombin complex (TAT), plasmin-α- plasmininhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) are the new direct indicators for coagulation and fibrinolysis. The aim of this study was to investigate the changes of these four new indicators in thrombotic and hemorrhagic events in BCR/ABL1-negative MPN. The study cohort of 74 patients with BCR/ABL negative myeloproliferative disorders included essential thrombocythemia, polycythemia vera, and primary myelofibrosis (PMF). A panel of 4 biomarkers, including TAT, PIC, TM, and t-PAIC were determined using Sysmex HISCL5000 automated analyzers, whereas fibrin/fibrinogen degradation products (FDP), D-dimer and Antithrombin III (ATIII) were analyzed using Sysmex CS5100 coagulation analyzer. A total of 24 (32.4%) patients experienced thrombotic events and hemorrhagic events occurred in 8 patients (10.8%). Compared to patients without hemorrhagic-thrombotic events, patients with thrombotic events had higher fibrinogen (FIB) level, FDP level and lower ATIII activity, while patients with hemorrhagic events had lower white blood cell count and hemoglobin level, higher FDP level (P < 0.05). Patients with a JAK2V617F mutation were more likely to experience thrombotic events (P < 0.05). In addtion, patients with thrombotic events had higher TAT, PIC, TM, and t-PAIC levels than patients without hemorrhagic-thrombotic events (P < 0.05), whereas patients with hemorrhagic events had a lower median value in TAT and TM (no statistical difference, P > 0.05). Patients with higher TAT, TM and t-PAIC were more likely to experience thrombotic events (P < 0.05), and only TAT was positively correlated with thrombotic events (Spearman r =0.287, P = 0.019). TAT, PIC, TM, and t-PAIC combined with ATIII and FDP have a certain value for predicting thrombosis in patients with BCR/ABL1-negative MPN. These 6 parameters are worth further exploration as predictive factors and prognostic markers for early thrombotic events.
Topics: Humans; Male; Female; Middle Aged; Aged; Adult; Myeloproliferative Disorders; Fusion Proteins, bcr-abl; Thrombomodulin; Fibrinolysin; Aged, 80 and over; Biomarkers; Antithrombin III; Thrombosis; Hemorrhage; Clinical Relevance; alpha-2-Antiplasmin; Peptide Hydrolases
PubMed: 38776019
DOI: 10.1007/s10238-024-01371-7 -
The Gulf Journal of Oncology May 2024Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by uncontrolled red blood cell production. Megaloblastic anemia is caused by deficiency of...
Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by uncontrolled red blood cell production. Megaloblastic anemia is caused by deficiency of cobalamin (vitamin B12) and/or folate (vitamin B9). While B12 deficiency may be caused by insufficient dietary intake or impairment of its utilization, its association with PV is described without exact knowledge of the physiopathology. We herein report the occurrence of megaloblastic anemia due to Vitamin B12 deficiency in an 85-year-old North African woman patient with PV. This case highlights this atypical presentation of PV and challenges that comes with it causing the delay of diagnosis and the complexity of its diagnosis and treatment. Keywords: megaloblastic anemia, polycythemia vera, association, case report.
Topics: Humans; Anemia, Megaloblastic; Female; Polycythemia Vera; Aged, 80 and over; Vitamin B 12 Deficiency
PubMed: 38774937
DOI: No ID Found -
CMAJ : Canadian Medical Association... May 2024
Topics: Humans; Pregnancy; Female; Hypertension, Portal; Polycythemia Vera; Adult; Pregnancy Complications, Cardiovascular
PubMed: 38772602
DOI: 10.1503/cmaj.231170