| 1. |
- Bento, Celeste, et al.
(author)
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Genetic Basis of Congenital Erythrocytosis : Mutation Update and Online Databases
- 2014
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In: Human Mutation. - : Wiley-Blackwell. - 1059-7794 .- 1098-1004. ; 35:1, s. 15-26
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Journal article (peer-reviewed)abstract
- Congenital erythrocytosis (CE), or congenital polycythemia, represents a rare and heterogeneous clinical entity. It is caused by deregulated red blood cell production where erythrocyte overproduction results in elevated hemoglobin and hematocrit levels. Primary congenital familial erythrocytosis is associated with low erythropoietin (Epo) levels and results from mutations in the Epo receptor gene (EPOR). Secondary CE arises from conditions causing tissue hypoxia and results in increased Epo production. These include hemoglobin variants with increased affinity for oxygen (HBB, HBA mutations), decreased production of 2,3-bisphosphoglycerate due to BPGM mutations, or mutations in the genes involved in the hypoxia sensing pathway (VHL, EPAS1, and EGLN1). Depending on the affected gene, CE can be inherited either in an autosomal dominant or recessive mode, with sporadic cases arising de novo. Despite recent important discoveries in the molecular pathogenesis of CE, the molecular causes remain to be identified in about 70% of the patients. With the objective of collecting all the published and unpublished cases of CE the COST action MPN&MPNr-Euronet developed a comprehensive Internet-based database focusing on the registration of clinical history, hematological, biochemical, and molecular data (http://www.erythrocytosis.org/). In addition, unreported mutations are also curated in the corresponding Leiden Open Variation Database.
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| 2. |
- Enblom, Anneli, et al.
(author)
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A retrospective analysis of the impact of treatments and blood counts on survival and the risk of vascular events during the course of polycythaemia vera
- 2017
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In: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 177:5, s. 800-805
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Journal article (peer-reviewed)abstract
- Vascular and non-vascular complications are common in patients with polycythaemia vera. This retrospective study of 217 patients with polycythaemia vera aimed to determine whether blood counts with respect to different treatments influenced the complication rate and survival. We found that 78 (36%) patients suffered from at least one complication during follow-up. Older age and elevated lactate dehydrogenase at diagnosis were found to be risk factors for vascular complications. When the vascular complication occurred, 41% of the patients with a complication had elevated white blood cells (WBC) compared with 20% of patients without a complication (P = 0·042). Patients treated with hydroxycarbamide (HC; also termed hydroxyurea) experienced significantly fewer vascular complications (11%) than patients treated with phlebotomy only (27%) (P = 0·013). We also found a survival advantage for patients treated with HC, when adjusted for age, gender and time period of diagnosis (Hazard ratio for phlebotomy-treated patients compared to HC-treated patients at 5 years was 2·42, 95% confidence interval 1·03-5·72, P = 0·043). Concerning survival and vascular complications, HC-treated patients who needed at least one phlebotomy per year were not significantly different from HC-treated patients with a low phlebotomy requirement. We conclude that complementary phlebotomy in HC-treated patients in order to maintain the haematocrit, is safe.
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| 3. |
- Enblom, Anneli, et al.
(author)
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High rate of abnormal blood values and vascular complications before diagnosis of myeloproliferative neoplasms
- 2015
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In: European journal of internal medicine. - : Elsevier. - 0953-6205 .- 1879-0828. ; 26:5, s. 344-347
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Journal article (peer-reviewed)abstract
- Background: Vascular complications occurring before the diagnosis of myeloproliferative neoplasms (MPN) in 612 patients from four centers in Sweden, Denmark and France were retrospectively studied.Results: Vascular complications were observed in 151 (25%) of the 612 patients. Of these, 66% occurred during the two years preceding diagnosis. The majority of events were thromboembolic (95%), and included myocardial infarction (n = 46), ischemic stroke (n = 43), transient ischemic attack (TIA) (n = 22), deep vein thrombosis/pulmonary embolism (n = 19), splanchnic vein thrombosis (n = 7), and peripheral embolism (n = 7). Bleeding was observed in only 7 (5%) of the 151 patients with vascular events (3 with intracranial bleeding, 2 with epistaxis and 2 with gastrointestinal bleeding). Full blood counts obtained at least 3 months prior to the MPN diagnosis showed that 269 (44%) had abnormal blood values, fulfilling the diagnostic criteria for MPN. During the time from the abnormal blood test to the diagnosis of MPN, 50 patients suffered from a vascular complication.Conclusion: We therefore conclude that a large proportion of MPN patients suffer severe thromboembolic complications prior to diagnosis. If MPN were diagnosed earlier, a large proportion of these events might be prevented. An MPN should always be suspected and ruled out in patients with unexplained elevated hematocrit, leukocyte and/or platelet counts.
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| 4. |
- Sobas, Marta, et al.
(author)
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Real-world study of children and young adults with myeloproliferative neoplasms: identifying risks and unmet needs
- 2022
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In: BLOOD ADVANCES. - : ELSEVIER. - 2473-9529 .- 2473-9537. ; 6:17, s. 5171-5183
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Journal article (peer-reviewed)abstract
- Myeloproliferative neoplasms (MPNs) are uncommon in children/young adults. Here, we present data on unselected patients diagnosed before 25 years of age included from 38 centers in 15 countries. Sequential patients were included. We identified 444 patients, with median follow-up 9.7 years (0-47.8). Forty-nine (11.1%) had a history of thrombosis at diagnosis, 49 new thrombotic events were recorded (1.16% patient per year [pt/y]), perihepatic vein thromboses were most frequent (47.6% venous events), and logistic regression identified JAK2V617F mutation (P = .016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (P = .040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04% pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13% pt/y), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in essential thrombocythemia (ET) (P= .000) in logistical regression. Eight deaths (1.8%) were recorded, 3 after allogeneic stem cell transplantation. Concerning conventional risk scores: International Prognostic Score for Essential Thrombocythemia-Thrombosis and new International Prognostic Score for Essential Thrombocythemia-Thrombosis differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5 years. No contemporary scores were able to predict survival for young ET or polycythemia vera patients. Our data represents the largest real-world study of MPN patients age < 25 years at diagnosis. Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN.
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