Browsing by Autor "Ariel Amaru"
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Item type: Item , Acute promyelocytic leukemia incidence in Andean highlanders with the NFKB1 haplotype (rs230511)(Elsevier BV, 2025) Ricardo Amaru; Victor R. Gordeuk; Julieta Luna; Edgar Teddy Quispe Soto; Silvia Mancilla; Javier Valencia; Luis Felipe Mamani; Daniela Patón; Ariel AmaruAbstract Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML), characterized by the oncogenic fusion protein PML-RARα, which results from the t(15;17) chromosomal translocation. APL accounts for approximately 4-10% of AML cases worldwide. The median age at diagnosis falls around the fifth decade of life, with a slight male predominance (PMID: 39682277). The PML-RARα fusion protein plays an essential role in the pathogenesis of APL by enhancing hypoxia-inducible factor (HIF)-driven transcriptional activity. PML-RARα acts as a transcriptional co-activator of HIF-α, amplifying HIF-mediated transcription independently of PML protein inhibition. This activation is unique to APL-specific fusion proteins; it is absent in other AML subtypes. The interaction of PML-RARα and HIF factors significantly influences disease progression and relapse. (PMID: 24711541). Transcriptomic analyses of APL cells reveal enrichment of NF-κB signaling pathways among differentially expressed genes, particularly those involved in cancer pathways. This suggests that NFKB1 contributes to the proliferative and survival signaling in APL cells (Villiers W, Nat. Commun, 2023). However, PML-RARα disrupts NF-κB activity by inhibiting phosphorylation and DNA binding of the NF-κB p65 subunit, suppressing NF-κB target gene expression. This disruption contributes to leukemogenesis through impaired differentiation and altered transcriptional regulation (Ahmed A, Sci.rep, March 2017). The incidence of APL varies across geographic regions and ethnic groups. Higher frequencies have been observed in Latin American populations compared to North America and Europe. These disparities suggest that genetic and environmental factors contribute to differences in disease distribution and outcomes (PMID: 12935956) and currently, there are no published data directly comparing APL incidence between populations living at sea level and those residing at high altitudes. We investigated the proportion of AML cases diagnosed as APL in Bolivian Andean highlanders residing at 4000 m, a population characterized by elevated HIF-α expression and a predominant NFKB1 haplotype rs230511 (95%) that results in a non-functional NFKB1 protein. We then compared the proportion of APL cases from Bolivian populations living at 2000m and 400 m. We analyzed 1,273 AML diagnoses from January 2000 to June 2025, grouped by altitude of residence: 406 at 4,000 m (mean age 37 years), 412 at 2,000 m (mean age 41 years), and 455 at 400 m (mean age 28 years). The overall mean age at AML diagnosis was 35 ± 25 years, with a male predominance of 54%. Among the total AML cases, 140 (11.0%) were identified as APL. We compared the proportion of AML cases classified as APL across three altitudes: at 4,000 m, 38 of 406 AML cases (9.4%) were APL; at 2,000 m, 46 of 412 cases (11.2%); and at 400 m, 56 of 455 cases (12.3%). There was a trend toward a lower proportion of APL cases at 4,000 m compared to 2,000 m and 400 m, although this difference was not statistically significant (P = 0.17). The age distribution of APL cases was as follows: 1-17 years, 44 cases (31.4%); 18-39 years, 59 cases (41.7%); 40–59 years, 30 cases (21.4%); and ≥60 years, 7 cases (5.0%). The age of AML patients was significantly lower at 400 m compared to the higher altitudes, whereas the proportion of males did not differ significantly by altitude. ConclusionsThe APL tends to decrease with increasing altitude, consistent with genetic adaptations in high-altitude Andean populations (~4000 m) involving increased HIF activity and a specific NFKB1 haplotypeThe 25-year incidence of APL was significantly lower in the La Paz population at 4000 m compared to populations at lower elevations (P &lt; 0.020).Individuals younger than 40 years are disproportionately affected, representing 73.1% of APL cases. The increased incidence in younger age groups does not vary by altitude, suggesting that genetic factors may predominantly drive this demographic pattern.Investigating genetic adaptations in high-altitude populations could offer novel insights into APL pathobiology and therapeutic strategies.Item type: Item , Allogeneic Hematopoietic Progenitor Cell from Peripheral Whole Blood in Acute Myeloid Leukemia(Elsevier BV, 2024) Ricardo Amaru; Reyna Mamani; Jeaneth Velarde; Mireya Carrasco; Edgar Teddy Quispe Soto; Silvia Mancilla; Juan Carlos Valencia; Daniela Patón; Ariel AmaruAcute Myeloid Leukemia (AML) standard treatment involves initial induction therapy administrating two cycles of the 3+7 protocol (3 days anthracycline + 7 days cytarabine), and post-remission therapy of 3 cycles of high-dose cytarabine. The 5-year overall survival is 20 % (PMID: 33734442). During prolonged aplasia, infections and hemorrhages can cause treatment failure and death (PMID: 32236160). That is why transfusions of allogeneic hematopoietic progenitor cells (Allo-HPC) from whole peripheral blood to reduce the time of aplasia and complications were of interest. We studied 6 patients (3 males, 3 females) with AML (M1, M2), average age 35 years (18-60 years), who received Allo-HPC from whole peripheral blood during aplasia after each 3+7 regimen. The transfusion was performed at day 14 (day 12-16) post-regimen, when patients had neutrophils &lt;100/ul (0-100/ul). Regarding donors, one corresponded to HLA identical sibling, and 5 to haploidentical (2 fathers, 2 mothers and 1 brother), they received G-CSF 300 μg subcutaneously every 12 hours over 3 days, then 450 ml phlebotomy was performed. Phlebotomy displayed median WBC 27,310/ul, neutrophils 21,830/ul, CD34+ cells 9/ul, hemoglobin 14.8 g/dl, and platelets 218,000/ul. Thus, whole peripheral blood obtained was transfused through patients' CVC after premedication with dexamethasone 8 mg and metamizole 1 g. FISH (Y chromosome, Vysis CEP-Y DYZ1) and RT-PCR (HUMARA gene) studies were performed for chimerism analysis. Recovery of neutrophils &gt;500/ul was observed at day 9 and platelets &gt;20,000/ul at day 6. One case of cutaneous rush was observed as an adverse event. MRD after each cycle reflected 0.01% average. Three patients remain alive with follow-up of 4 years, 5 years and 1 year respectively. Two patients relapsed and died during 1year follow-up. One patient developed optic neuritis and did not receive high-dose cytarabine therapy, relapsed and died after 6 months. None of the patients presented acute or chronic GVHD. Regarding the results of chimerism, one male patient (1year follow-up) showed mixed chimera by FISH (Y=95%) and by RT-PCR (HUMARA gene), such studies were still in progress in the other two women patients. Contrasting patients who received Allo-HPC from the ones who do not, statistically differences were found in neutrophils recovery and hospital staying, the former displayed 9 + 3 days vs 14 + 4 days (p=0.008) and 19 +5 days vs 25 + 4 days (p=0.009) respectively, infections also decreased from 83% to 25%. Transfusion of Allogeneic Hematopoietic Progenitor Cell from Peripheral whole blood reduces the duration of aplasia, infections, inpatient stays, and increases survival.Item type: Item , Atorvastan, Apsirin and Hydorxyurea for an Effective and Low-Cost Treatment in High-Risk Polycythemia Vera(European Medical Journal, 2022) Ricardo Amaru; Mireya Carrasco; Victor R. Gordeuk; Teddy Quispe; Silvia Mancilla; Daniela Patón; Ariel AmaruIntroduction: Polycythemia vera (PV) treatment focuses on preventing thrombotic events and delaying transformation to myelofibrosis or leukaemia. According to risk stratification, low-risk patients require therapeutic phlebotomy combined with acetylsalicylic acid, whilst the treatment of high-risk patients with PV relies on cytoreductive therapies, employing hydroxyurea (HU), ruxolitinib, or interferons. However, in low- and middle-income countries, the availability and cost of these drugs poses a challenge in treating high-risk patients, so optimising existing resources is required. Method: A prospective longitudinal study aimed to investigate the combination of atorvastatin (ATV), aspirin, and low-dose HU as a therapeutic strategy to treat PV in high-risk patients. The study evaluated the effect of statins on erythroid colony proliferation in vitro, as well as the applicability of ATV (20 mg/day), acetylsalicylic acid (100 mg/day), and hydroxiurea (500 mg/day) in high-risk patients with PV from La Paz, Bolivia, residing at 3,600 metres above sea level. Results: Simvastatin (3.5 μm) inhibited UKE-1 cell (JAK2V617F mutated) proliferation at 33%, and burstforming unit-erythroid colonies from patients with PV at 61%. Patients receiving ATV, aspirin, and low-dose HU displayed a good response and adequate tolerance to treatment (13-years follow-up). No patients experienced myelofibrosis or transformation to leukaemia, and no severe adverse events were observed. Conclusions: This accessible, effective, and low-cost therapeutic strategy could improve adherence to treatment and the overall survival of high-risk patients with PV in resource-limited countries.Item type: Item , Bolivian Aymara Natives with Chronic Mountain Sickness Have Autonomous BFU-E Growth(Elsevier BV, 2015) Ricardo Amaru; Ariel Amaru; Hortensia Miguez; Torres Gina; Josué Mamani; Oscar Vera; Heriberto Cuevas; Josef T. Prchal; Jaroslav F. PrchalAbstract Background Erythrocytosis / polycythemia is divided into primary and secondary. Primary polycythemia can be either acquired; i.e. polycythemia vera (PV) due to somatic JAK2 mutation, or congenital due to germ-line DNA changes (erythropoietin (EPO) receptor and VHL mutations in Chuvash polycythemia). These mutations are expressed within erythroid progenitors, drive increased erythropoiesis and are detected by hypersensitive or autonomous EPO BFU-E responses. In contrast, secondary erythrocytosis (SE), such as seen with cardiopulmonary pathologies, is driven by the circulating EPO. Chronic mountain sickness (CMS) is characterized by high altitude pathological erythrocytosis and by cognitive and neurological impairments. CMS is found in subjects living in high altitude (2500 meters and higher). In La Paz, Bolivia, (3600m) there is 7% incidence of CMS erythrocytosis. Some human populations (Tibetans, Andean Quechuas and Aymaras, and Ethiopians) are adapted to very high altitudes and their adapted phenotypes and, in some instances, evolutionarily selected haplotypes, have been reported. Whole genome was evaluated in Andeans and two genes, SENP1 and ANP32D were found to be evolutionarily selected and correlated with presence or absence of erythrocytosis. The genes down-regulation in hypoxia had survival benefit in Drosophila ortholog (1).SENP1 desumoylate GATA-1 and other regulatory proteins and is critical for definitive erythropoiesis (2,3). Here we evaluated native Aymara La Paz dwellers with three types of polycythemia: CMS, SE secondary to cardiopulmonary disease, and PV, by clinical studies and by in vitro evaluation of erythroid progenitors, and compared them to non-polycythemic subjects. Patients and Methods Complete blood count was performed by automatic hematologic counter (Micro 60, USA). Serum EPO was measured by Elisa (R&D System, USA) and JAK2V617F mutation analysis by PCR assay. Erythroid progenitors were isolated by density gradient centrifugation and cultured in methylcellulose medium with and without EPO (Stem Cell technologies, Canada) at 370 C and 5 % CO2. BFU-E colonies reading was carried out according to standardized criteria at 7 and 14 days. Results Table. Normal Control(n=10) CMS (n=15) Secondary Erythrocytosis(n=10) PolycythemiaVera (n=5) 1.Gender M/F 10/0 15/0 10/0 3/2 Age (range) 42 (40-47) 48 (29-58) 53 (34-72) 67 (42-74) Hb g/dl (SD) 16.2 (+ 0.9) 20.3 (+ 0.9) 22.8 (+ 1.4) 20.0 (+ 2.5) Ret % (SD) 1.3 (+ 0.1) 2.9 (+ 1.3) 3.6 (+ 1.2) 2.1 (+ 0.3) WBC /ul (SD) 6300 (+ 1600) 7200 (+ 1900) 6600 (+ 1700) 16600 (+ 4800) PLT 103 ul (SD) 273 (+ 80) 229 (+ 58) 193 (+ 54) 604 (+ 177) sEPO mUI/ml (SD) 10.0 (+ 3.9) 10.5 (+ 2.2) 82.9 (+ 30.4) 3.0 (+ 1.2) JAK2 V617F, No. (%) 0 (0) 0 (0) 0 (0) 100 Apoptosis Normal Delayed Normal Delayed BFU-E: EEC 0 (0-0) 10 (2-25) 0 (0-0) 45 (25-70) References: 1. Yu L et al. J Exp Med., 2010, 207:1183. 2. Sharma D et al. Cell Report, 2013, 3:1640. 3. Zhou D et al. Am J Hum Genet. 2013, 93:452. 4. Kapralova K et al. Blood. 2014,123:391 Conclusions a) Endogenous erythroid colony (EEC) are present in Aymaras with CMS, indicating primary polycythemia. b) Endogenous EECs are higher in PV than in CMS. c) CMS subjects have normal serum EPO levels. d) The role of SENP1, and hypoxia-regulated RUNX1 and NF-E2 (4) that promote erythropoiesis, is being interrogated in native erythroid cells. e) It remains to be determined if the autonomous BFU-E growth is specific for Aymara's CMS or present in CMS individuals of other ethnicities. Disclosures No relevant conflicts of interest to declare.Item type: Item , Erythroid Leukemia Is Increased at High Altitude (4000 m)(Elsevier BV, 2024) Ricardo Amaru; Maria Julieta Luna Leyza; Luis Felipe Mamani; Silvia Mancilla; Daniela Patón; Juan Carlos Valencia; Mireya Carrasco; Ariel AmaruAcute erythroid leukemia (AEL) also known as pure erythroid leukemia (PEL) from the 2016 WHO update (PMID: 35264503; Wang, Am J Hematol. 2017; 92: 292-296) is a rare and unique subtype of acute myeloid leukemia (AML). It is characterized by immature erythroid precursors predominance with a high frequency of gains and amplifications involving EPOR/JAK2 (PMID: 35839275) and phosphorylation of ERK1/2 by inhibiting Fli-1 Promoter Activity (Min Mo, Catalysts, 2022. 13.1:84). AEL accounts for 1% of AML cases and can evolve from prior myelodysplastic syndrome or develop de novo, it is typically observed in adults with a median age ranging 66-68 years, and of dismal prognosis (&lt;6 months overall median survival) (PMID: 36323674). Its distinction attributes to erythroblastic proliferation (&gt;80%), pancytopenia, and extensive bone marrow involvement by proerythroblasts (≥30%). Common immunophenotype markers include CD105, CD34, CD71, CD36, CD235 (Wang, Am J Hematol. 2017). Moreover, it has been reported that hypoxia influences the development of erythroleukemia through various mechanisms, including promoting erythroid differentiation, inducing hemoglobin production, defining cell heterogeneity, regulating erythropoiesis, and influencing the bone marrow microenvironment (PMID: 33675821; 17255519). Regardingly, an overexpression of HIFs is related with a bad prognosis in AML (PMID: 25687039), HIF-1α is involved in cancer early stages, whereas HIF-2α in the later stages (PMID: 29753878). HIF-2a expression plays an important role in regulating proliferation in erythroleukemia cells under hypoxia (PMID: 26898802). Thus, we aimed to search for the hematologic and immunophenotypic characteristics of AEL cases among all AML diagnoses at high altitude. We retrospectively analyzed cases of AML diagnosed in Bolivia from the period of May 2019 to April 2024 considering the different altitudes 4000m (n=68), 2000m (n=62), and 400m (n=71), and gathered a comprehensive account of hematologic, bone marrow morphology, and immunophenotypic features. Among AML cases (n=201), 13 cases of AEL were identified which corresponded to 6.5 %. Interestingly, AEL cases at 4000 m accounted for 13.2 % (female 2, male 7, median age 54 years), and this was significantly higher (p=0.02) when compared to cases at 2000 m representing 3.2 % (female 1, male 1, median age 75 years) or at 400 m with 2.8 % (female 2, median age 52 years). Hematologic indices displayed mean Hb 7.3 g/dl, WBC: 11515/ul and Plt: 127154/ul. Bone marrow findings reflected &gt; 80% of prominent erythroid precursors with large irregular nuclei, dispersed chromatin, 1 to 3 elongated nucleoli, deeply basophilic cytoplasm, and an intense mitotic activity. Immunophenotypic features revealed CD34, CD71, CD105, CD36 and CD235 regarding erythroid clonality. AEL incidence is increased at high altitude, reflects intriguingly morphology and hematological characteristics. This increase may be due to the increase in HIF and Epo at high altitude, since the barometric pressure (462 mmHg) and the oxygen level in the air (14%) at high altitude are low. So, further studies elucidating the genetic mechanism involved are of interest.Item type: Item , Implementation and Evaluation of the First Global Blood & Marrow Transplantation (GlobalBMT) Training Program at the University of Illinois at Chicago (UIC)(Elsevier BV, 2019) Olusola Olowoselu; Ariel Amaru; K. Filonenko; Ronald Mbiine; Sampurna Tuladhar; Damiano RondelliItem type: Item , Successful Treatment of HU-Refractory Polycythemia Vera with Atorvastatin and Low Dose Hydroxyurea. Results from a Pilot Study in Bolivia(Elsevier BV, 2015) Ricardo Amaru; Ariel Amaru; Hortensia Miguez; Gina Torres; Josué Mamani; María Aguilar; Heriberto CuevasAbstract Background Polycythemia Vera (PV) is a clonal myeloproliferative neoplasm, characterized by the JAK2V617F mutation. The main goal of current therapies for PV is to prevent thrombotic events and delay transformation to Myelofibrosis (MF) or Acute Myeloid Leukemia (AML).Treatment for PV to keep an hematocrit (Hct) level <45 %, has been associated with a reduction in cardiovascular deaths and thrombotic events (Marchioli, R et al. NEJM 2013). Currently, low-risk PV patients (<60 years and no previous thrombotic events) are treated with aspirin and phlebotomy while high-risk patients require additional cytoreductive therapy, usually with Hydroxyurea (HU). Resistance to HU is associated with an increased risk of transformation and reduced survival. This is why for HU-refractory patients, second line treatments with interferon alpha, anagrelide or even ruxolitinib are recommended. In Latin America, because of high cost and drugs availability, this last group reflects difficulties to be treated. Because statins have been reported to modulate the erythroid clonogenic activity of normal BM erythroid colonies we performed a pilot study to investigate in vitro and in vivo the biologic and clinical activity of atorvastatin in PV patients Patients and Methods Ten high risk PV patients with a median age of 64.3 years (range 58-73) entered into this study. The diagnosis of PV was done according to the 2008 World Health Organization diagnostic criteria and patients were stratified according to an algorithm proposal provided by Griesshammer et al. (Ann Hematol, 2015). The definition of HU resistance (Barosi, G et al.: BJH 2009) was applicable to five patients (median age 63.9 years) failing to achieve a satisfactory hematologic response upon treatment with more than 2 g of HU, 100 mg of Aspirin and phlebotomies. The assessment of the JAK2V617F mutation was performed as previously described (Guerini et al.: Leukemia 2009). Colony assay, proliferation and apoptosis tests were performed with or without Simvastatin (3.5 uM), as previously described (Amaru, A, Experimental Hematology 2012), on cell lines (UKE1 and K562) and bone marrow mononuclear cells obtained from PV patients and healthy donors. Patients with HU refractory PV (n=5) and high risk PV with hypercholesterolemia (n=5) were eligible to receive Atorvastatin (20 mg/day) added on the top of the ongoing treatment with phlebotomies, Aspirin (100 mg/day) and cytoreductive HU therapy (500 mg/day). All treated patients were high altitude residents (> 3.600 m.a.s.l.) of La Paz (Bolivia) where the normal Hct level of healthy subjects is 48-57% for men and 44-54% for women. This pilot study was approved by the Review Board of the Hospital and the University of San Andres, La Paz. Results In a preliminary set of in vitro proliferation cell assays, simvastatin (3.5 uM), added for 5 days, induced a 33% inhibition of cell proliferation of UKE-1 (JAK2V617F mutated) as compared to 5 % of K562 (BCR/ABL positive). A comparable result was obtained in a 7-day clonogenic cell assay where the colony inhibition was 50 % for UKE-1 and 10 % for K562. On the basis of these results similar experiments were also performed using BM mononuclear cells derived from PV patients and healthy donors. In these experiments performed with the addition of simvastatin, it induced a 41% of inhibition in BFU-E colonies of PV patients and a 25% of inhibition in healthy donors. Furthermore, BFU-E colonies inhibited by simvastatin presented a decrease in hemoglobinization and the size of colonies. HU refractory PV patients and High-risk PV patients with hypercholesterolemia treated with the addition of Atorvastatin, Aspirin, cytoreductive HU and phlebotomies; after a follow-up of 2.6 years (1-7 years), induced a decrease of WBC from 16.500 to 9.270/ul, Hct 61.1 to 52.3% and PLT 457.900,000 to 324.7000/ul. The number of required phlebotomies is reduced in comparison to the required at starting treatment. None of the patients presented thrombotic or cardiopulmonary event. One patient died within two years of starting treatment, due to complications of diabetes mellitus. Conclusions In vitro and in vivo, statins showed some evidence of inhibitory activity of the hematopoiesis of PV patients. These preliminary results might indicate the opportunity to further investigate the potential clinical value of these molecules in the treatment of PV. Disclosures Off Label Use: Atorvastatin was used for its antiproliferative activity on myeloid progenitor cells shown by in vitro experiments.Item type: Item , Transferrin and Erythropoietin Increased Levels Correlate with Thrombosis at High Altitude(Elsevier BV, 2023) Ricardo Amaru; Luis Felipe Mamani; Emma Mancilla; Daniela Patón; Juan Carlos Valencia; Ariel Amaru; Mireya CarrascoLiving at high altitude involves great interest because of the challenging multiple adaptive responses to a hypoxic environment. Native Bolivian Andeans have lived at an altitude of 4000 m in The Andes mountains for about 14,000 years exposed to a low atmospheric pressure (453 mmHg) and low oxygen concentration (12,7%). It was described Andeans adaptation to high altitude is mainly related to cardiovascular issues (PMID: 29100088), with a low significantly genetic selection in HIF pathway components responsible of erythropoiesis regulation (PMID: 36980912), so that they have adapted to exist with increased hemoglobin concentrations. Thus, Andeans can be prevalent to undergone hematological and thromboembolic disorders. Thrombotic events have been reported to be increased at high altitude, and this recently associated to increased transferrin (Tf) (PMID: 36040436), likewise to increased erythropoietin (Epo) (Amaru, RevMed 2022). Increased Tf were described to be induced by both iron deficiency and hypoxia via HIF (PMID: 9242677). In addition, iron deficiency was postulated to inhibit the function of prolyl hydroxylase 2 (PHD2) in the hydroxylation of HIF-2, necessary for recognition and degradation by VHL (PMID:22304911). Under normal conditions, Tf is bound to fibrinogen at a molar ratio of 4:1, leading to plasma Tf sequestration by fibrinogen and leaving little Tf free in the circulation. While at hypoxia conditions, abnormally upregulated Tf potentiates thrombin, factor XIIa and inhibits antithrombin, inducing hypercoagulability (PMID:36040436). Similarly, increased HIF1a at high altitude increases Tf promoting the transferrin gene expression, which contains HIF-1α binding sites in its enhancer region (PMID:36844187). HIF is a DNA-binding transcription factor for activating expression of Epo gene (PMID:32561149). Epo, in turn, is increased due to the hyperegulation of HIF as expected at low atmospheric pressure environments. Epo activates the hypoxia-inducible factor that leads to Epo synthesis to stimulate red blood cell production, which also increases the demand for iron to synthesize hemoglobin (PMID:21078592). This, added to a decreased iron and increased HIF 1a, gives rise to a hyperregulation of Tf. Epo has been described to have prothrombotic properties and be related to thrombotic events (PMID:10779449; Amaru, RevMed 2022). In this sense, to further observe a correlation of transferrin and erythropoietin increased levels with the risk of thrombotic events at high altitude, we studied patients with erythrocytosis, anemia and polycythemia vera. We analyzed clinical, lab tests and epidemiological data of 920 patients with Chronic Mountain Sickness erythrocytosis (CMS-e) (n=560), anemia (n=372), and Polycythemia Vera (PV) (n=20), all Bolivian Andeans born and residing at 4000 m. Considering at this altitude normal hemoglobin concentrations vary from 14-17 g/dl in women and 15-18 g/dl in men, erythrocytosis condition comprises Hb levels &gt;18 g/dl in women and &gt;19 g/dl in men (Amaru et al, Rev Hematol Mex, 2016); similarly, it embraces Hb &lt;12 g/dl for women and &lt;13 g/dl for men in anemias (PMID: 23317073). Positive JAK F617V tests were corroborated in PV patients. Iron deficiency correlation considered serum ferritin &lt;30 ug/L and MCV &lt;80 fL (Clark et al, Nutrition, 2008). Eco-doppler study records confirmed the occurrence of thrombotic events. Data analysis was performed through Excel 16.29.1 and SPSS program, Chi-squared, Fishers and Pearson tests were done. We observed significative increased Tf levels in erythrocytosis, anemia, and PV patients mainly on those presenting iron levels deficiency. Epo was highly increased in erythrocytosis patients with iron deficiency. These results correlated with the incidence of thrombotic events in erythrocytosis (CMS-e) and anemia patients with iron deficiency. Age was also relevant in both groups. (Table 1). The increase of Epo levels correlated with thrombosis in erythrocytosis and PV patients with iron deficiency (Table 1). Transferrin and Erythropoietin increased levels at high altitude correlated with thrombosis in Chronic Mountain Sickness erythrocytosis and iron deficiency anemia patients. However, Increased Tf did not correlate with thrombosis in PV patients at high altitude. Our data confirm that increased Tf and Epo have prothrombogenic properties in CMS-e, iron deficiency anemia patients at high altitude.Item type: Item , TRATAMIENTO DE LA ERITROCITOSIS SECUNDARIA EN LA ALTURA(2020) Ricardo Amaru; Jeaneth Velarde; Reyna Mamani; Mireya Carrasco; Daniela Patón; Ariel Amaru