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1.
Platelets ; 33(8): 1220-1227, 2022 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-35791502

RESUMEN

The P106L mutation in the human myeloproliferative leukemia virus oncogene (MPL) was shown to be associated with hereditary thrombocythemia in Arabs. The clinical and bone marrow (BM) features of P106L mutation are unknown. Genetic databases at two tertiary hospitals in Saudi Arabia were searched to identify patients with the MPL P106L mutation. Clinical data were collected retrospectively and the BM aspirates and biopsies were independently reviewed by two hematopathologists. In total, 115 patients were included. Median age was 33 years of which 31 patients were pediatric and 65 were female. The mutation was homozygous in 87 patients. Thrombocytosis was documented in 107 patients, with a median platelet count of 667 × 109/L. The homozygous genotype was associated with a higher platelet count. Thirty-three patients had an evaluable BM and clustering of megakaryocytes was observed in 30/33 patients. At the time of last follow-up, 114 patients were alive. The median follow-up was 7.8 years from the time of thrombocytosis. No patients developed disease progression to myelofibrosis. The P106L mutation was associated with marked thrombocytosis at a younger age and with a low risk of thrombosis, splenomegaly, and marrow fibrosis. The BM demonstrated normal or hypocellular marrow with megakaryocyte clusters.


Asunto(s)
Mielofibrosis Primaria , Receptores de Trombopoyetina , Trombocitosis , Trombosis , Adulto , Médula Ósea/patología , Niño , Femenino , Humanos , Masculino , Mutación , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/patología , Receptores de Trombopoyetina/genética , Estudios Retrospectivos , Esplenomegalia/genética , Trombocitosis/genética , Trombocitosis/patología , Trombosis/complicaciones
2.
Med Princ Pract ; 29(4): 371-381, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31698356

RESUMEN

BACKGROUND: Iron deficiency (ID) and ID anemia (IDA) are common in the member states of the Gulf Cooperation Council (GCC). The unique genetic and lifestyle factors of the patient population in the region have necessitated the development of recommendations to help educate health-care professionals on appropriate diagnosis and management of ID/IDA. METHODS: A panel of regional experts, including gastroenterologists and hematologists with expertise in the treatment of IDA, was convened to develop regional practice recommendations for ID/IDA. After reviewing the regional and international literature, the expert panel developed consensus recommendations for screening, diagnosis, and treatment of patients with IDA in the GCC region. RESULTS: The recommendations proposed were customized to the patient population keeping in view the increasingly recognized burden of coeliac disease, high fertility and obesity rates, high prevalence of alpha- and beta-thalassemia traits, and poor tolerance and low treatment compliance with oral iron therapy. CONCLUSIONS: This consensus statement proposes recommendations for screening, diagnosis, and treatment of IDA in the GCC region.


Asunto(s)
Anemia Ferropénica , Guías de Práctica Clínica como Asunto , Adulto , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/etiología , Anemia Ferropénica/terapia , Preescolar , Consenso , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Medio Oriente , Embarazo , Factores de Riesgo , Adulto Joven
3.
Pak J Pharm Sci ; 33(2(Supplementary)): 861-870, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32863263

RESUMEN

The outcome of chronic myeloid leukemia has been greatly improved by the use of Imatinib (IM), a selective BCR/ABL kinase inhibitor. The aim of present study was to report long term follow-up & outcome of IM-treated CML patients along with their clinicopathological features, risk group stratification, adverse events and to compare it with CML patients reported from western countries. The mean follow-up of 123 CML patients was 5.5 years in present study, who were treated with frontline IM 400mg daily in a tertiary care hospital in Pakistan. Risk stratification scores, response to treatment (ELN guidelines) and survival outcomes estimated by Kaplan-Meier analysis. Mean age: 35 years (9-67 years) and M: F: 1.5:1, mean follow up time: 5.5 years (1-15 years). Overall survival (OS): at 5.5, 8, 10 and 12 years were 93%, 88%, 81% and 73%, respectively. Progressions free survival (PFS) was 95%, 83%, 83% and 78% at 5.5, 8, 10 and 12 years, respectively. OS estimate by Sokal score was significant (P-value: 0.0019). Additional chromosomal aberrations: 1.6%. Eighteen (14.6%) patients progressed to AP/BC. Adverse events were moderate and tolerable. We present findings from a long term follow up of CML patients treated with IM in a developing country. CML mean age at onset was considerably lower than the western populations. Furthermore, 5.5 years OS are comparable to western CML population. IM in our patients as frontline choice proved to be very effective. IM was found to be well tolerated, safe with manageable moderate side effects.


Asunto(s)
Antineoplásicos/uso terapéutico , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Países en Desarrollo , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pakistán , Resultado del Tratamiento , Adulto Joven
4.
J Pak Med Assoc ; 66(5): 528-7, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27183929

RESUMEN

OBJECTIVE: To compare direct smear technique with ethylenediaminetetraacetic acid (EDTA) preserved smear technique in terms of preparing bone marrow aspirate slides. METHODS: This prospective study was carried out between September 2009 and July 2012 at the Haematology/Oncology Department, King Khalid University Hospital, Riyadh, Saudi Arabia. With a standard gauge disposable bone marrow aspirate needle, 0.5 to 1.0 ml bone marrow was aspirated with a 10ml syringe. Half of the marrow was immediately transferred to an EDTA tube with gentle mixing, while slides were prepared directly from the rest of the sample in the syringe. The tube sample was used to prepare slides at the end of the procedure. A score of 1-4 was assigned to each slide depending on the quality and number of particles. RESULTS: A total of 245 bone marrow aspirate samples were evaluated related to 216 patients. Of the total, 238 (97%) samples were included in the study. The mean score for the direct smear group was 3.40±0.79 and for the EDTA smear group it was 3.34±0.75 (p=0.27), which was not statistically significant. An informal comparison of the morphological analysis of the samples did not reveal any differences. CONCLUSIONS: Bone marrow aspirate slides prepared at the end of the procedure from EDTA preserved samples were not inferior to slides prepared directly from the aspirated sample.


Asunto(s)
Médula Ósea/patología , Técnicas de Preparación Histocitológica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Ácido Edético , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
5.
Platelets ; 25(6): 452-4, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24102447

RESUMEN

Platelet refractoriness may lead to life-threatening gastro-intestinal, intracranial or pulmonary hemorrhage that is difficult to control despite massive platelet and red cell transfusion, antifibrinolytic agents, high dose corticosteroids, immunoglobulin and intravenous (I.V.) recombinant activated factor VII (rFVIIa). In cases with pulmonary hemorrhage, intrapulmonary administration of rFVIIa may be more effective in non-responsive cases. We report a 51-year-old man with relapsing acute lymphoblastic leukemia (ALL) and platelet refractoriness, who suffered a life-threatening pulmonary hemorrhage that was refractory to massive platelet transfusion, tranexamic acid, high dose corticosteroids, immunoglobulin and intravenous rFVIIa, but responded immediately to a single intrapulmonary dose of rFVIIa that was inhaled with a jet nebulizer assistance through the endotracheal tube.


Asunto(s)
Plaquetas , Factor VIIa/administración & dosificación , Hemorragia/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Administración por Inhalación , Hemorragia/etiología , Humanos , Enfermedades Pulmonares/etiología , Masculino , Persona de Mediana Edad , Transfusión de Plaquetas , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Proteínas Recombinantes/administración & dosificación , Recurrencia
6.
J Arthroplasty ; 28(9): 1463-72, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23528548

RESUMEN

Erythropoiesis-stimulating agents (ESAs) have been used in orthopedic patients to reduce allogeneic blood transfusion (ABT). The purpose of this systematic review of randomized clinical trials is to evaluate the efficacy of preoperative administration of ESAs on hemoglobin level at discharge and frequency of ABT in patients undergoing hip or knee surgery. Pooled results of 26 trials with 3560 participants showed that the use of preoperative ESAs reduced ABT in patients undergoing hip or knee surgery [RR: 0.48, 95% CI: 0.38 to 0.60, P<0.00001]. Hemoglobin mean difference between ESA and control groups was 7.16 (g/L) [95% CI of 4.73 to 9.59, P=0.00001]. There was no difference in the risk of developing thromboembolism between ESA and control groups [RD: 0, 95 % CI: -1%-2%, P=0.95]. ESAs offer an alternative blood conservation method to avoid ABT in patients undergoing hip or knee surgery.


Asunto(s)
Anemia/terapia , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Hematínicos/administración & dosificación , Anemia/sangre , Transfusión Sanguínea , Hemoglobinas/análisis , Humanos , Cuidados Preoperatorios , Ensayos Clínicos Controlados Aleatorios como Asunto
7.
Saudi Pharm J ; 21(2): 165-8, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23960831

RESUMEN

AIM/BACKGROUND: Treatment of DVT with LMWHs has been shown recently to be as effective as UFH with suggested lower costs. This study was conducted to determine and compare the cost of in-patient hospital treatment versus outpatient hospital treatment of patients with DVT. METHOD: All adult patients with acute proximal DVT referred to the Emergency Department of King Khalid University Hospital, Riyadh, Saudi Arabia between August 2009 and August 2010 were invited to the study. An economic analysis was performed to compare the cost impact of outpatients versus hospital treatment. RESULTS: Sixty-one patients were included in the study, 31 were followed in the outpatient setting and 30 as the control group (inpatients). There were no significant differences in the outcome between the outpatient and inpatient group; three patients (9.7%) in the outpatient group and four patients (13.3%) in the inpatient group had recurrent DVT. Mean nursing cost was $55 for the outpatient group and $215 for the inpatient group, mean laboratory monitoring cost was $638 for outpatient group and $1511 for the inpatient group. Hospital stay and doctor's fees amounted to a mean of $1000 for outpatient treatment and $2387 for inpatient treatment, p < 0.0001. The mean outpatient cost was significantly lower than the inpatient cost ($1750 vs. $4338, p < 0.0001). CONCLUSION: Outpatient treatment of patients with DVT using LMWHs is cost-effective with no significant differences in the outcome of patients. OPD treatment of DVT is feasible in Saudi Arabia provided there is enough logistic support from thrombosis clinics and those involved in DVT care.

8.
J Coll Physicians Surg Pak ; 33(5): 592-593, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37190699
9.
Int J Hematol ; 118(2): 288-291, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36892804

RESUMEN

Patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML) can develop cytopenias secondary to bone marrow hypoplasia after starting tyrosine kinase inhibitor (TKI) therapy. These adverse effects are usually transient, but cytopenias can persist in some patients. TKI-associated thrombocytopenia can develop in a significant proportion of CML patients and may require TKI dose reduction or dose interruptions. The thrombopoietin receptor agonist eltrombopag may improve thrombocytopenia in these patients, but the supporting literature for this approach is limited. Herein, we describe the case of a 56-year-old woman who developed persistent TKI-associated thrombocytopenia and intracranial hemorrhage. She could not tolerate full doses of imatinib and she failed to achieve a major molecular response (MMR). She responded to eltrombopag and platelet count improved, which allowed commencement and continuation of dasatinib as second-line TKI therapy, resulting in achievement of MMR. TKI-associated thrombocytopenia can cause serious bleeding and may also interfere with the management of CML by necessitating TKI dose interruption or reduction. Use of eltrombopag can help maintain adequate platelet counts and uninterrupted delivery of TKI therapy.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Trombocitopenia , Humanos , Trombocitopenia/inducido químicamente , Trombocitopenia/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Persona de Mediana Edad , Femenino , Hemorragias Intracraneales , Mesilato de Imatinib/uso terapéutico , Resultado del Tratamiento
10.
Cureus ; 15(4): e37201, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37159792

RESUMEN

Chronic myelogenous leukemia, or CML, is another name for chronic myeloid leukemia (CML), a cancer type that starts in certain bone marrow blood-forming cells. The primary initiator of granulocytic proliferation in CML, a myeloproliferative malignancy, is the BCR-ABL1 fusion protein or Philadelphia chromosome. CML is classified into three stages: chronic, accelerated, and blast. It has been widely recognized that the likelihood of developing CML varies by gender, geography, and age. In the chronic phase of CML (CML-CP), bleeding is a rare sign since the thrombocyte and coagulation functions are still adequate. Uncertainties exist regarding the CML bleeding mechanism. We report four cases of CML-CP in adult patients. The majority of these patients had CML and had idiopathic spontaneous bleeding in multiple locations.

11.
Saudi J Kidney Dis Transpl ; 34(6): 531-536, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-38725203

RESUMEN

Proteinuria is a manifestation of sickle cell anemia (SCA)-related renal disease and is a risk factor of renal impairment. Angiotensin-converting enzyme (ACE) inhibitors have benefits, but their role in SCA remains undefined. This study aimed to assess the role of lisinopril, an ACE inhibitor, in reducing proteinuria in SCA patients. Thirty-five patients older than 15 years with known SCA (HbSS or HbS-ß0) and a 24-h urinary protein level of 150 mg or more participated in this study. Urine was collected over 24 h to quantify proteinuria. The patients had a mean age of 28.5 ± 6.98 years. The median 24-h urinary protein before treatment was 0.3006 g and that after treatment was 0.150 g (P = 0.01). After a median follow-up of 38 months, 24-h urinary protein decreased in 27 (77%) patients and normalized in 18 (52%) patients. Urinary protein increased in 2 (6%) patients and remained stable (no change) in 6 (17%) patients. There was no significant difference in blood pressure (BP) before and after treatment. The average dose of lisinopril was 5 mg. Twenty patients were still on lisinopril at last follow-up. The reasons for stopping lisinopril included normalization of protein, noncompliance, adverse effects, and pregnancy. Lisinopril effectively reduced proteinuria in SCA patients, without significantly reducing BP. Only a few patients developed adverse effects, including coughing, dizziness, and diarrhea. It is unclear how long lisinopril should be continued and whether it can be stopped in patients with normalized urinary protein.


Asunto(s)
Anemia de Células Falciformes , Inhibidores de la Enzima Convertidora de Angiotensina , Lisinopril , Proteinuria , Humanos , Lisinopril/uso terapéutico , Proteinuria/tratamiento farmacológico , Proteinuria/orina , Femenino , Masculino , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/orina , Adulto , Adulto Joven , Resultado del Tratamiento , Factores de Tiempo , Presión Sanguínea/efectos de los fármacos , Adolescente
12.
J Pediatr Hematol Oncol ; 34(2): 79-84, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22322941

RESUMEN

Sickle cell disease (SCD) is common in the Eastern and Southwestern (SW) Provinces of Saudi Arabia. We studied 159 patients with SCD to better characterize its phenotype in the SW Province, where patients usually have a HBB haplotype of African origin. All cases had history and examination, chart review, and laboratory testing. Blood tests were obtained during steady state and included: complete blood count, reticulocytes, hemoglobin electrophoresis, lactate dehydrogenase, and G6PD level. HBB haplotype and presence of α-thalassemia were also determined. Frequency of various SCD complications was as follows: painful episodes of variable severity occurred in majority of patients (98%), osteonecrosis (14%), acute chest syndrome (22%), splenic sequestration (23%), gallstones (34%), stroke (7.5%), priapism (2.6%), serious infections (11.5%), and persistent splenomegaly (11%) beyond 5 years of age. No patient had leg ulcer. History of asthma and high steady state white blood cells count were associated with increased risk of acute chest syndrome. Coinheritance of α-thalassemia was associated with a lower frequency of gallstones. Higher fetal hemoglobin level was associated with persistent splenomegaly but not with other complications. Splenic sequestration was more common among males and was associated with lower steady state hemoglobin. SCD phenotype in the SW Province is variable and comparable with African Americans except for the rarity of priapism and the absence of leg ulcers. Fetal hemoglobin level was not associated with SCD vaso-occlusive complications. New genetic modifiers and environmental factors might modulate the phenotype of SCD in Saudi Arabia.


Asunto(s)
Anemia de Células Falciformes/complicaciones , Adolescente , Adulto , Anciano , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/fisiopatología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Fenotipo , Arabia Saudita , Adulto Joven
13.
Saudi J Med Med Sci ; 10(1): 31-35, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35283704

RESUMEN

Background: The current trends in lymphoma cases from Saudi Arabia and their long-term survival are unknown. This study was conducted to evaluate the trends of lymphoma diagnoses and survival from a major tertiary care hospital in Saudi Arabia. Methods: This retrospective study included all new cases of lymphoma diagnosed in adults (age ≥18 years) at King Saud University Medical City, Riyadh, Saudi Arabia, from 2008 to 2018, as identified from the Saudi Cancer Registry. Data on the demographics and clinical characteristics were collected, the survival outcomes were estimated, and multivariate analysis of the overall survival was calculated. Results: A total of 422 patients were included (median age: 46 years). The number new cases of lymphoma diagnosed variably increased over the study period: From 28 (7%) cases in 2009 to 48 (11%) in 2018. The most common lymphoma was diffuse large B-cell lymphoma (175; 41%): and extranodal site was GI involvement (33.5%). In terms of survival, 79% were alive at the last follow-up. On multivariable analysis, the hazard ratio (HR) for patients aged ≥60 years was 3.44 (95% CI: 2-5.9; P = 0.0000069), adjusted for lactate dehydrogenase level (LDH) and disease stage. For advanced-stage disease and high LDH, the HR was 4.2 (95% CI: 1.5-11.8, P = 0.00637) and 0.5 (95% CI: 0.28-0.97; P = 0.04106), respectively. Conclusions: The lymphoma trend in the Saudi Arabian population showed variable increase in cases over the study period, with most patients presenting with advanced-stage disease and at a younger age. The overall survival was comparable with studies from Western countries.

14.
Biomed Res Int ; 2022: 7191178, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35909467

RESUMEN

Objective: This study was aimed at evaluating the knowledge and behavior toward venous thromboembolism (VTE) prophylaxis among medical interns. Methods: This is a questionnaire-based cross-sectional observational cohort study of medical interns that used a validated questionnaire. The questionnaire comprised of items that assessed behavior, knowledge, and self-assessment of VTE risk factors, diagnosis, and prophylaxis. The study was conducted in Riyadh, Saudi Arabia, from October 2020 till September 2021. Results: The respondents were 246 medical interns. The overall rate of correct responses to behavior items was 41.82%. The overall rate of correct responses to knowledge items was 47.35%. A total of 61.8% responded negatively to the use of VTE risk assessment guidelines (p < 0.0001). For the self-assessment of knowledge of VTE, more than 70% believed they did not have appropriate knowledge, were not prepared to establish the risk of VTE, and were not prepared to provide adequate prophylaxis for VTE (p < 0.0001). A high proportion of medical interns (83.3%, p < 0.0001) believed they needed further training on this topic. Conclusion: Participants in this study showed poor knowledge and negative behavior regarding the assessment of risk factors, diagnosis, and prophylaxis of VTE. The majority of participants reported they needed training on this topic. These findings underscore the need for educational programs during undergraduate training and orientation of medical interns for VTE risk assessment, diagnosis, and prophylaxis at the beginning of their internship.


Asunto(s)
Tromboembolia Venosa , Anticoagulantes/uso terapéutico , Protocolos Clínicos , Estudios Transversales , Humanos , Estudios Observacionales como Asunto , Medición de Riesgo/métodos , Factores de Riesgo , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control
15.
Platelets ; 22(1): 1-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-20964585

RESUMEN

Splenectomy is the usual form of therapy for immune thrombocytopena (ITP) after steroid failure. We retrospectively studied the data in adult patients who underwent splenectomy for ITP from July 1996 to June 2008 to evaluate the long term responses, clinical and laboratory factors associated with long term responses and outcome of relapsed or refractory patients. Thirty eight patients, 30 (79%) females, with a median age of 23 years (range 15-69), underwent splenectomy. The procedure was laparoscopic in 28 (73.5%) and open in 10 patients. Splenectomy resulted in a response in 34/38 (89.5%) patients and failed in four (10.5%) patients. After a median follow-up of 58 months (range 7-144), 24 (63%) patients had a maintained response without treatment (platelet count of >50 × 109)/l). Most of the relapses occurred during the first year but two patients had late relapses. There were procedure-related complications in seven (18.0%) patients but no cases of overwhelming sepsis. Only four relapsed or refractory patients had a platelet count below 50 × 109/l at the last follow-up indicating response to alternative therapies. Responsiveness to steroids before the procedure (p = 0.025) along with a platelet count of ≥ 150 × 109/l at 4 weeks (p = < 0.0001) and a highest platelet count of ≥ 400 × 109/l at any time post-splenectomy (p = 0.005), were associated with a long term response in univariate analysis. In conclusion, splenectomy remains an effective treatment for ITP after steroid failure in terms of long term responses, and the majority of relapsed or refractory patients respond to alternative therapies.


Asunto(s)
Púrpura Trombocitopénica Idiopática/cirugía , Esplenectomía , Adolescente , Adulto , Anciano , Enfermedad Crónica , Femenino , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunoglobulinas Intravenosas/uso terapéutico , Laparoscopía , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Pronóstico , Púrpura Trombocitopénica Idiopática/fisiopatología , Púrpura Trombocitopénica Idiopática/terapia , Estudios Retrospectivos , Prevención Secundaria , Esteroides/administración & dosificación , Esteroides/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
16.
SAGE Open Med ; 9: 20503121211049931, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34659762

RESUMEN

INTRODUCTION: Critically ill COVID-19 patients are at increased risk of thrombosis with an enhanced risk of bleeding. We aimed to explore the role of anti-factor Xa levels in optimizing the high-intensity anticoagulation's safety and efficacy and finding possible associations between D-dimer levels, cytokine storm markers, and COVID-19-induced coagulopathy or thrombophilia. METHODS: Retrospective cohort study conducted on 69 critically ill COVID-19 patients who received three regimens of higher intensity anticoagulation. RESULTS: Seventeen patients (24.6%) received high-dose enoxaparin prophylaxis, 29 patients (42%) received therapeutic doses of enoxaparin, and 23 patients (33.3%) were on therapeutic unfractionated heparin infusion. Fewer than one-third of the whole cohort (n = 22; 31.8%) achieved the target range of anti-factor Xa. The patients were divided into three subgroups based on anti-factor Xa target status within each anticoagulation regimen; when compared, the only association observed among them was for interleukin-6 levels, which were significantly higher in both the "above the expected range" and "below the expected range" groups compared with the "within the expected range" group (p = 0.009). Major bleeding episodes occurred in 14 (20.3%) patients and were non-significantly more frequent in the "below the expected anti-factor Xa range group" (p = 0.415). Seven patients (10.1%) developed thrombosis. The majority of patients had anti-factor Xa levels below the expected ranges (four patients, 57.1%). CONCLUSION: Conventional anti-factor Xa ranges may not be appropriate as a predictive surrogate for bleeding in critically ill COVID-19. The clinical decision to initiate therapeutic anticoagulation preemptively may be individualized according to thrombosis and bleeding risks. Cytokine storm markers, namely, interleukin-6, may play a role in COVID-19-induced coagulopathy or thrombophilia.

17.
Biology (Basel) ; 10(11)2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34827175

RESUMEN

Background: Chronic myeloid leukemia (CML) is initiated in bone marrow due to chromosomal translocation t(9;22) leading to fusion oncogene BCR-ABL. Targeting BCR-ABL by tyrosine kinase inhibitors (TKIs) has changed fatal CML into an almost curable disease. Despite that, TKIs lose their effectiveness due to disease progression. Unfortunately, the mechanism of CML progression is poorly understood and common biomarkers for CML progression are unavailable. This study was conducted to find novel biomarkers of CML progression by employing whole-exome sequencing (WES). Materials and Methods: WES of accelerated phase (AP) and blast crisis (BC) CML patients was carried out, with chronic-phase CML (CP-CML) patients as control. After DNA library preparation and exome enrichment, clustering and sequencing were carried out using Illumina platforms. Statistical analysis was carried out using SAS/STAT software version 9.4, and R package was employed to find mutations shared exclusively by all AP-/BC-CML patients. Confirmation of mutations was carried out using Sanger sequencing and protein structure modeling using I-TASSER followed by mutant generation and visualization using PyMOL. Results: Three novel genes (ANKRD36, ANKRD36B and PRSS3) were mutated exclusively in all AP-/BC-CML patients. Only ANKRD36 gene mutations (c.1183_1184 delGC and c.1187_1185 dupTT) were confirmed by Sanger sequencing. Protein modeling studies showed that mutations induce structural changes in ANKRD36 protein. Conclusions: Our studies show that ANKRD36 is a potential common biomarker and drug target of early CML progression. ANKRD36 is yet uncharacterized in humans. It has the highest expression in bone marrow, specifically myeloid cells. We recommend carrying out further studies to explore the role of ANKRD36 in the biology and progression of CML.

18.
Asian Pac J Cancer Prev ; 21(12): 3517-3526, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33369447

RESUMEN

OBJECTIVE: BCR-ABL fusion oncogene is the hallmark of chronic myeloid leukemia (CML), causing genomic instability which leads to accumulation of mutations in BCR-ABL as well as other genes. BCR-ABL mutations are the cause of tyrosine kinase inhibitors (TKIs) resistance in CML. Recently, compound BCR-ABL mutations have been reported to resist all FDA approved TKIs. Therefore, finding novel compound BCR-ABL mutations can help and clinically manage CML. Therefore, our objective was to find out novel drug-resistant compound BCR-ABL mutations in CML and carry out their protein modelling studies. METHODOLOGY: Peripheral blood samples were collected from ten imatinib resistant CML patients receiving nilotinib treatment. BCR-ABL transcript mutations were investigated by employing capillary sequencing. Patient follow-up was carried out using European LeukemiaNet guidelines. Protein modeling  studies were carried out for new compound mutations using PyMol to see the effects of mutations at structural level. RESULTS: A novel compound mutation (K245N mutation along with G250W mutation) and previously known T351I utation was detected in two of the nilotinib resistance CML patients respectively while in the rest of 8 nilotinib responders, no resistant mutations were detected. Protein modelling studies indicated changes in BCR-ABL mutant protein which may have negatively impacted its binding with nilotinib leading to drug resistance. CONCLUSION: We report a novel nilotinib resistant BCR-ABL compound mutation (K245N along with G250W mutation) which impacts structural modification in BCR-ABL mutant protein leading to drug resistance. As compound mutations pose a new threat by causing resistance to all FDA approved tyrosine kinase inhibitors in BCR-ABL+ leukemias, our study opens a new direction for in vitro characterization of novel BCR-ABL compound mutations and their resistant to second  generation and third generation TKIs.


Asunto(s)
Biomarcadores de Tumor/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Proteínas de Fusión bcr-abl/química , Proteínas de Fusión bcr-abl/genética , Mesilato de Imatinib/farmacología , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Mutación , Adulto , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Modelos Moleculares , Pronóstico , Conformación Proteica , Inhibidores de Proteínas Quinasas/farmacología
19.
J Pak Med Assoc ; 59(5): 316-9, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19438139

RESUMEN

Autoimmune haemolytic anaemia (AIHA) is known to be associated with Hodgkin's disease (HD) but is uncommon. It usually presents at the time of initial diagnosis of HD or during the course of the disease but AIHA preceding the diagnosis of HD is very rare. We describe here 2 cases of AIHA who presented one year before the diagnosis of HD. There was no evidence of a coexisting disease at initial diagnosis. Both of the patients required steroids throughout this period to control AIHA. Our report illustrates that patients with AIHA should be regularly and carefully monitored, particularly in treatment resistant cases, for manifestations of a concomitant disease, such as HD, developing later.


Asunto(s)
Anemia Hemolítica Autoinmune/complicaciones , Enfermedad de Hodgkin/diagnóstico , Corticoesteroides/uso terapéutico , Adulto , Anemia Hemolítica Autoinmune/diagnóstico , Antineoplásicos/uso terapéutico , Prueba de Coombs , Hepatomegalia , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/etiología , Humanos , Ganglios Linfáticos/patología , Masculino , Esplenomegalia
20.
World J Gastroenterol ; 14(22): 3594-7, 2008 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-18567094

RESUMEN

Ascites is not an uncommon manifestation of certain solid tumors like gastrointestinal malignancies, ovarian cancer and breast cancer. However, it is unusual to encounter ascites in patients with hematological malignancies especially chronic leukemia. The patient described here presented with massive ascites and blood lymphocytosis. Further studies confirmed the diagnosis of chronic lymphocytic leukemia with ascites. The ascitic fluid was exudative, consisting of mature-looking B-lymphocytes, which were morphologically and immunophenotypically similar to peripheral blood and bone marrow cells. The patient was treated with chemotherapy and achieved a good response and diminution of ascitic fluid accumulation.


Asunto(s)
Ascitis/diagnóstico , Leucemia Linfocítica Crónica de Células B/diagnóstico , Anciano , Ascitis/complicaciones , Ascitis/patología , Líquido Ascítico/patología , Linfocitos B/patología , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/patología , Masculino
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