Pub Date : 2021-03-01DOI: 10.1177/26348535211028192
Baldomero Moriano, E. Barragán, Oscar Ferré, I. Casas, J. Prieto-Fernandez, C. Hernández, S. Cáceres, S. Suárez, R. Cardesa, M. J. Arcos, H. Bañas, J. Bergua
NPM1+ AML after Essential Thrombocythemia (ET) or Myeloproliferative neoplasms is extremely rare. Only 2 cases have been previously reported after Primary Myelofibrosis. Given the extremely poor prognosis of the Blastic phase of Myeloproliferative neoplasms (MPN-BP), the only curative treatment of these patients is allogeneic stem cell transplantation (allo-SCT) after achieving Complete Response (CR). De novo NPM1+/FLT3- AML is considered a good prognosis entity in which allo-SCT is not contemplated as the first option. A 41 year old diagnosed of ET JAK2 V617F+ 4 years before the diagnosis of AML with normal karyotype and NPM1+/FLT3- was treated with conventional AML induction with Cytarabine and Idarubicine and 3 cycles of high dose Cytarabine. At the diagnosis of AML other 2 mutations were noted: EZH2 and IKZ1. After treatment of AML, NPM1+ clone disappeared, and JAK2 V617F clone reappeared. We opted to treat NPM1+ AML as a de novo AML and we decided to follow up during 2 years without allo-SCT. The patient remains in complete response with NPM1 minimal residual disease negative during the follow up. This case exemplifies the nature of NPM1+ AML secondary to MPD as an extremely sensitive disease to induction therapy plus high dose cytarabine and makes that these type of patients perhaps could be managed without the use of allo-SCT.
{"title":"NPM1+ /FLT3- Acute Myeloid Leukemia after JAK2-V617F+ Essential Thrombocythemia. Management and Prognosis","authors":"Baldomero Moriano, E. Barragán, Oscar Ferré, I. Casas, J. Prieto-Fernandez, C. Hernández, S. Cáceres, S. Suárez, R. Cardesa, M. J. Arcos, H. Bañas, J. Bergua","doi":"10.1177/26348535211028192","DOIUrl":"https://doi.org/10.1177/26348535211028192","url":null,"abstract":"NPM1+ AML after Essential Thrombocythemia (ET) or Myeloproliferative neoplasms is extremely rare. Only 2 cases have been previously reported after Primary Myelofibrosis. Given the extremely poor prognosis of the Blastic phase of Myeloproliferative neoplasms (MPN-BP), the only curative treatment of these patients is allogeneic stem cell transplantation (allo-SCT) after achieving Complete Response (CR). De novo NPM1+/FLT3- AML is considered a good prognosis entity in which allo-SCT is not contemplated as the first option. A 41 year old diagnosed of ET JAK2 V617F+ 4 years before the diagnosis of AML with normal karyotype and NPM1+/FLT3- was treated with conventional AML induction with Cytarabine and Idarubicine and 3 cycles of high dose Cytarabine. At the diagnosis of AML other 2 mutations were noted: EZH2 and IKZ1. After treatment of AML, NPM1+ clone disappeared, and JAK2 V617F clone reappeared. We opted to treat NPM1+ AML as a de novo AML and we decided to follow up during 2 years without allo-SCT. The patient remains in complete response with NPM1 minimal residual disease negative during the follow up. This case exemplifies the nature of NPM1+ AML secondary to MPD as an extremely sensitive disease to induction therapy plus high dose cytarabine and makes that these type of patients perhaps could be managed without the use of allo-SCT.","PeriodicalId":29816,"journal":{"name":"Plasmatology","volume":"31 1","pages":""},"PeriodicalIF":0.3,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86521850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01DOI: 10.1177/26348535211042012
A. Turgutkaya, A. Bolaman, I. Yavaşoğlu
Purpose Daratumumab, a monoclonal anti-CD38 antibody, has been administered for relapsed refractory multiple myeloma (RRMM). The Pollux and Castor trials proved its efficacy, yet excluded patients with advanced-stage renal disease. Therefore, available experience in these patients is limited. Here, we aimed to emphasize the safety of daratumumab in 6 patients with kidney disease. Methods Six patients with RRMM diagnoses and renal impairment were included. Their mean ± standard deviation age was 63.6 ± 8.38 years. Three, two, and one patient(s) had immunoglobulin (Ig) G kappa, lambda light chain, and IgA lambda MM, respectively. All patients received 4 to 6 lines of anti-MM therapy before daratumumab treatment. Five had chronic kidney disease and 1 was admitted to the hospital with acute kidney injury due to myeloma relapse. Daratumumab was administered to all patients with close follow-up. Results Following treatment with daratumumab, kidney function was improved in 1 patient. In 1 patient, the glomerular filtration rate was slightly decreased and hemodialysis was initiated. In 2 patients already receiving hemodialysis, their dependency on hemodialysis continued. No adverse reactions were recorded. One patient achieved complete remission and 4 patients achieved very good partial remission. Conclusion Daratumumab can be administered safely, with improvements in kidney function possible in some patients. Studies involving larger patient groups are required to obtain more accurate data.
Daratumumab是一种单克隆抗cd38抗体，已被用于治疗复发性难治性多发性骨髓瘤(RRMM)。poloxx和Castor试验证明了其有效性，但排除了晚期肾病患者。因此，这些患者的可用经验是有限的。在这里，我们的目的是强调达拉单抗在6例肾脏疾病患者中的安全性。方法对6例诊断为RRMM并有肾功能损害的患者进行分析。平均±标准差年龄为63.6±8.38岁。3例、2例和1例患者分别有免疫球蛋白(Ig) G κ pa、λ轻链和IgA λ MM。所有患者在接受达拉单抗治疗前均接受4至6行抗mm治疗。5例有慢性肾病，1例因骨髓瘤复发急性肾损伤入院。所有患者均给予Daratumumab，并进行密切随访。结果经达拉单抗治疗后，1例患者肾功能得到改善。1例患者肾小球滤过率轻微下降，开始血液透析。2例已接受血液透析的患者继续依赖血液透析。无不良反应记录。1例患者获得完全缓解，4例患者获得非常好的部分缓解。结论:达拉单抗可以安全使用，部分患者的肾功能可能得到改善。需要对更大的患者群体进行研究，以获得更准确的数据。
{"title":"Experience of Daratumumab in Six Patients With Multiple Myeloma and Kidney Failure","authors":"A. Turgutkaya, A. Bolaman, I. Yavaşoğlu","doi":"10.1177/26348535211042012","DOIUrl":"https://doi.org/10.1177/26348535211042012","url":null,"abstract":"Purpose Daratumumab, a monoclonal anti-CD38 antibody, has been administered for relapsed refractory multiple myeloma (RRMM). The Pollux and Castor trials proved its efficacy, yet excluded patients with advanced-stage renal disease. Therefore, available experience in these patients is limited. Here, we aimed to emphasize the safety of daratumumab in 6 patients with kidney disease. Methods Six patients with RRMM diagnoses and renal impairment were included. Their mean ± standard deviation age was 63.6 ± 8.38 years. Three, two, and one patient(s) had immunoglobulin (Ig) G kappa, lambda light chain, and IgA lambda MM, respectively. All patients received 4 to 6 lines of anti-MM therapy before daratumumab treatment. Five had chronic kidney disease and 1 was admitted to the hospital with acute kidney injury due to myeloma relapse. Daratumumab was administered to all patients with close follow-up. Results Following treatment with daratumumab, kidney function was improved in 1 patient. In 1 patient, the glomerular filtration rate was slightly decreased and hemodialysis was initiated. In 2 patients already receiving hemodialysis, their dependency on hemodialysis continued. No adverse reactions were recorded. One patient achieved complete remission and 4 patients achieved very good partial remission. Conclusion Daratumumab can be administered safely, with improvements in kidney function possible in some patients. Studies involving larger patient groups are required to obtain more accurate data.","PeriodicalId":29816,"journal":{"name":"Plasmatology","volume":"22 1","pages":""},"PeriodicalIF":0.3,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74099160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01DOI: 10.1177/26348535211038359
J. Kloppers, J. du Plessis, W. J. Janse van Rensburg
Genetic analysis of the F8 gene can play a vital role in the diagnosis and management of people with hemophilia A (PWH). Knowing the causative mutation can assist treating clinicians in predicting the risk of inhibitor formation and a person’s response to treatment. It is also a vital tool for genetic counselors in assisting PWH with family planning. Mutational analysis has been limited in developing countries, mainly due to resource constraints; however, with the development of more cost-effective screening tools, these assays are becoming more common in developing countries. Unfortunately, the clinical utility of these assays remain unclear in some of these underresourced countries, resulting in a lack of clinician buy-in. We aimed to highlight the wide-ranging impact mutational analysis potentially has on PWH and their extended families in a developing country. We used a gel-based in-house method to determine the inversion 22 (Inv22) mutation in a family where a young boy, without a family history, was recently diagnosed with hemophilia A. Inv22 was detected in the proband and his mother, but not in any other direct family member. Therefore, we concluded that the mutation was a de novo mutation in the mother. Subsequently, this result has bearing on at least 23 direct blood-relatives. Genetic screening extends far wider than the treatment of PWH and is vital in the management of PWH and their extended families. With the availability of cost-effective genetic screening assays this should also be the case in developing countries.
{"title":"De Novo Intron 22 Inversion Carrier Detection—The Emerging Value of Genetic Analysis in a Developing Country","authors":"J. Kloppers, J. du Plessis, W. J. Janse van Rensburg","doi":"10.1177/26348535211038359","DOIUrl":"https://doi.org/10.1177/26348535211038359","url":null,"abstract":"Genetic analysis of the F8 gene can play a vital role in the diagnosis and management of people with hemophilia A (PWH). Knowing the causative mutation can assist treating clinicians in predicting the risk of inhibitor formation and a person’s response to treatment. It is also a vital tool for genetic counselors in assisting PWH with family planning. Mutational analysis has been limited in developing countries, mainly due to resource constraints; however, with the development of more cost-effective screening tools, these assays are becoming more common in developing countries. Unfortunately, the clinical utility of these assays remain unclear in some of these underresourced countries, resulting in a lack of clinician buy-in. We aimed to highlight the wide-ranging impact mutational analysis potentially has on PWH and their extended families in a developing country. We used a gel-based in-house method to determine the inversion 22 (Inv22) mutation in a family where a young boy, without a family history, was recently diagnosed with hemophilia A. Inv22 was detected in the proband and his mother, but not in any other direct family member. Therefore, we concluded that the mutation was a de novo mutation in the mother. Subsequently, this result has bearing on at least 23 direct blood-relatives. Genetic screening extends far wider than the treatment of PWH and is vital in the management of PWH and their extended families. With the availability of cost-effective genetic screening assays this should also be the case in developing countries.","PeriodicalId":29816,"journal":{"name":"Plasmatology","volume":"5 1","pages":""},"PeriodicalIF":0.3,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87011909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01DOI: 10.1177/26348535211064621
S. Dolia, S. Verma, A. Pawar, Suma Ray
BACKGROUND Fibrinogen is an important component of hemostasis and clot formation. Replacement therapy with a human Fibrinogen concentrate is the preferred therapeutic option for patients with congenital or acquired Fibrinogen insufficiency. To make the Fibrinogen available for treatment of such patients, Fibrogen-I®, a lyophilized product purified from pooled human plasma was developed and extensively characterized. The product quality attributes were assessed by different biochemical, functional and structural analytical methods. MATERIAL AND METHODS Functional activity of Fibrinogen in the Fibrogen-I® was demonstrated by determination of its clottable protein activity. Purity profiling of Fibrogen-I® was evaluated by SE-HPLC method. Activation and fibrinolysis markers like D-dimer, plasminogen was determined by automated coagulometer and fibrinopeptide A activity by ELISA. Far UV CD analysis was also performed by CD Spectrometer. RESULTS The product exhibited high purity 89.7% by SE-HPLC. Activation and Fibrinolysis marker proteins in the drug product were negligible. The high purity and integrity of Fibrogen-I® is underlined by the ratio of Fibrinogen activity by Clauss/clottable protein with mean calculated value of 0.9 which is in close proximity with theoretical value 1 indicating fully native Fibrinogen. The results of far-UV CD spectroscopy revealed that Fibrogen-I® exists mostly as a β-sheet secondary structure, which is in accordance with the three-dimensional structure of human Fibrinogen. Downscaling experiments for the two dedicated orthogonal pathogen inactivation steps, ie solvent detergent treatment and dry heat treatment, exhibited pathogen safety. DISCUSSION Fibrogen-I® exhibited specific functional activity, desirable quality attributes, pathogen safety and the ability to be made available to patients requiring fast and effective Fibrinogen replacement.
{"title":"Quality Attributes of Plasma Derived Human Fibrinogen (Fibrogen-I®)","authors":"S. Dolia, S. Verma, A. Pawar, Suma Ray","doi":"10.1177/26348535211064621","DOIUrl":"https://doi.org/10.1177/26348535211064621","url":null,"abstract":"BACKGROUND Fibrinogen is an important component of hemostasis and clot formation. Replacement therapy with a human Fibrinogen concentrate is the preferred therapeutic option for patients with congenital or acquired Fibrinogen insufficiency. To make the Fibrinogen available for treatment of such patients, Fibrogen-I®, a lyophilized product purified from pooled human plasma was developed and extensively characterized. The product quality attributes were assessed by different biochemical, functional and structural analytical methods. MATERIAL AND METHODS Functional activity of Fibrinogen in the Fibrogen-I® was demonstrated by determination of its clottable protein activity. Purity profiling of Fibrogen-I® was evaluated by SE-HPLC method. Activation and fibrinolysis markers like D-dimer, plasminogen was determined by automated coagulometer and fibrinopeptide A activity by ELISA. Far UV CD analysis was also performed by CD Spectrometer. RESULTS The product exhibited high purity 89.7% by SE-HPLC. Activation and Fibrinolysis marker proteins in the drug product were negligible. The high purity and integrity of Fibrogen-I® is underlined by the ratio of Fibrinogen activity by Clauss/clottable protein with mean calculated value of 0.9 which is in close proximity with theoretical value 1 indicating fully native Fibrinogen. The results of far-UV CD spectroscopy revealed that Fibrogen-I® exists mostly as a β-sheet secondary structure, which is in accordance with the three-dimensional structure of human Fibrinogen. Downscaling experiments for the two dedicated orthogonal pathogen inactivation steps, ie solvent detergent treatment and dry heat treatment, exhibited pathogen safety. DISCUSSION Fibrogen-I® exhibited specific functional activity, desirable quality attributes, pathogen safety and the ability to be made available to patients requiring fast and effective Fibrinogen replacement.","PeriodicalId":29816,"journal":{"name":"Plasmatology","volume":"16 1","pages":""},"PeriodicalIF":0.3,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87279584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01DOI: 10.1177/26348535211049248
R. Tavarozzi, F. Pollis, D. Inverardi, L. Depaoli, M. Massaia, F. Monaco, M. Sacchi, R. Guaschino, M. Ladetto
Hyperviscosity syndrome (HVS) is a life-threatening haematological emergency. We report a severe HSV case in which extracorporeal plasma polymerization prevented an effective plasma exchange procedure. We elaborated an unconventional successful approach consisted in the manual removal of whole patient blood followed by red blood cells (RBC) and plasma support.
{"title":"Nonconventional Management of a Hyperviscosity Syndrome Failing Plasma Exchange","authors":"R. Tavarozzi, F. Pollis, D. Inverardi, L. Depaoli, M. Massaia, F. Monaco, M. Sacchi, R. Guaschino, M. Ladetto","doi":"10.1177/26348535211049248","DOIUrl":"https://doi.org/10.1177/26348535211049248","url":null,"abstract":"Hyperviscosity syndrome (HVS) is a life-threatening haematological emergency. We report a severe HSV case in which extracorporeal plasma polymerization prevented an effective plasma exchange procedure. We elaborated an unconventional successful approach consisted in the manual removal of whole patient blood followed by red blood cells (RBC) and plasma support.","PeriodicalId":29816,"journal":{"name":"Plasmatology","volume":"6 1","pages":""},"PeriodicalIF":0.3,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91285577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01DOI: 10.1177/26348535211042015
A. Bolaman, A. Turgutkaya, I. Yavaşoğlu
Background High-dose chemotherapy with autologous stem cell rescue (HDC-ASCR) is the most effective treatment in transplant-eligible patients with multiple myeloma (MM). The complication rate of the procedure in MM is low, but its complications can be high if engraftment is delayed. In this study, we aimed to evaluate engraftment determinants in patients with MM who undergo HDC-ASCR with cryopreserved products. Methods We retrospectively reviewed MM patients who undergo HDC-ASCR from February 2015 to May 2018 at the Hematology Department of Adnan Menderes University Hospital. The induction and conditioning regimens were similar in all patients. The relationship between time to engraftment (TTE) and age, sex, infused stem cell (CD34) count, the number of transfused erythrocyte and thrombocyte units, MM type, stage, pretransplant bone marrow plasma cell ratio, pretransplant hemoglobin level, leukocyte and thrombocyte count, comorbidities such as diabetes mellitus, hypertension, and chronic kidney disease, and habits like smoking and alcoholism was investigated. Results A total of 40 patients were evaluated. The mean stem cell count was 6.23 (±3.72) × 106/kg. Spearman's analysis was used between TTE and the parameters for correlation. There were correlations found between TTE-stem cell count (CD34) and TTE-smoking. However, we did not find any correlation with the other aforementioned parameters. Conclusion Our retrospective study supported that infused stem cell count was the main engraftment determinant during the procedure of HDC-ASCR with cryopreserved products in MM.
{"title":"Factors Affecting Time to Engraftment During Autologous Stem Cell Transplantation in Patients With Multiple Myeloma","authors":"A. Bolaman, A. Turgutkaya, I. Yavaşoğlu","doi":"10.1177/26348535211042015","DOIUrl":"https://doi.org/10.1177/26348535211042015","url":null,"abstract":"Background High-dose chemotherapy with autologous stem cell rescue (HDC-ASCR) is the most effective treatment in transplant-eligible patients with multiple myeloma (MM). The complication rate of the procedure in MM is low, but its complications can be high if engraftment is delayed. In this study, we aimed to evaluate engraftment determinants in patients with MM who undergo HDC-ASCR with cryopreserved products. Methods We retrospectively reviewed MM patients who undergo HDC-ASCR from February 2015 to May 2018 at the Hematology Department of Adnan Menderes University Hospital. The induction and conditioning regimens were similar in all patients. The relationship between time to engraftment (TTE) and age, sex, infused stem cell (CD34) count, the number of transfused erythrocyte and thrombocyte units, MM type, stage, pretransplant bone marrow plasma cell ratio, pretransplant hemoglobin level, leukocyte and thrombocyte count, comorbidities such as diabetes mellitus, hypertension, and chronic kidney disease, and habits like smoking and alcoholism was investigated. Results A total of 40 patients were evaluated. The mean stem cell count was 6.23 (±3.72) × 106/kg. Spearman's analysis was used between TTE and the parameters for correlation. There were correlations found between TTE-stem cell count (CD34) and TTE-smoking. However, we did not find any correlation with the other aforementioned parameters. Conclusion Our retrospective study supported that infused stem cell count was the main engraftment determinant during the procedure of HDC-ASCR with cryopreserved products in MM.","PeriodicalId":29816,"journal":{"name":"Plasmatology","volume":"9 1","pages":""},"PeriodicalIF":0.3,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83465465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01DOI: 10.1177/26348535211051690
Olanrewaju Lauretta Ochogwu, L. Salawu, T. Owojuyigbe, Tewogbade Adeoye Adedeji
Background Vitamin D supplementation has been shown to improve hemoglobin levels in patients with sickle cell anemia (SCA). However, very little is known about the prevalence of its deficiency, its role in hemolysis, and its effects on transfusion requirements in SCA, hence this study. Patients and Methods Serum level of vitamin D was determined in 50 SCA patients in steady state, 50 SCA patients in hemolytic crises, and 50 in normal HbAA individuals. All were 18 years or older and were age- and sex-matched. In addition, PCV and hemoglobin (Hb) concentration, absolute reticulocyte count, uric acid, total and conjugated bilirubin, creatinine, lactate dehydrogenase (LDH), and estimated glomerular filtration rate (eGFR) were also assessed in all subjects and controls. Baseline sociodemographic, clinical, and anthropometric data were also recorded. Results The prevalence of vitamin D insufficiency and deficiency was found to be 18% and 79%, respectively. The mean serum levels of vitamin D were 18.84 ± 6.86 ng/mL and 17.58 ± 6.23 ng/mL in the steady-state and the hemolytic crises SCA groups, respectively. Transfusion requirements were found to be higher in SCA patients with lower vitamin D levels. Unlike those in crisis who received one or more units of blood transfusion, 42% of those in the steady state did not receive blood transfusion over the same period of 12 months. Hemoglobin levels were, however, found to predict reduced vitamin D levels. Conclusion Vitamin D deficiency (VDD) is highly prevalent among adults with SCA and those with lower vitamin D levels are more anemic and hence may require more blood transfusions.
{"title":"Vitamin D Deficiency and Its Association With Anemia and Blood Transfusion Requirements in Nigerian Adults With Sickle Cell Anemia","authors":"Olanrewaju Lauretta Ochogwu, L. Salawu, T. Owojuyigbe, Tewogbade Adeoye Adedeji","doi":"10.1177/26348535211051690","DOIUrl":"https://doi.org/10.1177/26348535211051690","url":null,"abstract":"Background Vitamin D supplementation has been shown to improve hemoglobin levels in patients with sickle cell anemia (SCA). However, very little is known about the prevalence of its deficiency, its role in hemolysis, and its effects on transfusion requirements in SCA, hence this study. Patients and Methods Serum level of vitamin D was determined in 50 SCA patients in steady state, 50 SCA patients in hemolytic crises, and 50 in normal HbAA individuals. All were 18 years or older and were age- and sex-matched. In addition, PCV and hemoglobin (Hb) concentration, absolute reticulocyte count, uric acid, total and conjugated bilirubin, creatinine, lactate dehydrogenase (LDH), and estimated glomerular filtration rate (eGFR) were also assessed in all subjects and controls. Baseline sociodemographic, clinical, and anthropometric data were also recorded. Results The prevalence of vitamin D insufficiency and deficiency was found to be 18% and 79%, respectively. The mean serum levels of vitamin D were 18.84 ± 6.86 ng/mL and 17.58 ± 6.23 ng/mL in the steady-state and the hemolytic crises SCA groups, respectively. Transfusion requirements were found to be higher in SCA patients with lower vitamin D levels. Unlike those in crisis who received one or more units of blood transfusion, 42% of those in the steady state did not receive blood transfusion over the same period of 12 months. Hemoglobin levels were, however, found to predict reduced vitamin D levels. Conclusion Vitamin D deficiency (VDD) is highly prevalent among adults with SCA and those with lower vitamin D levels are more anemic and hence may require more blood transfusions.","PeriodicalId":29816,"journal":{"name":"Plasmatology","volume":"20 1","pages":""},"PeriodicalIF":0.3,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78888898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01DOI: 10.1177/26348535211062229
D. Hajducek, Fitri Primacakti, N. Chozie, Roser Mir, Alanna McEneny-King, A. Iorio, A. Edginton
Background Population pharmacokinetics (popPK) has been reliably leveraged to generate individual PK in hemophilia patients. Specific popPK models are suited to predict individual PK under a variety of scenarios that may not be captured by clinical trials, allowing for individualized prophylactic treatment. The Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) project generates individually predicted pharmacokinetic profiles relying on concentrate-specific popPK models used for Bayesian forecasting. Objective Specification of a popPK model for the plasma-derived factor VIII (FVIII) concentrate Koate-DVI and its suitability for pharmacokinetic estimation in low-dose scenarios. Methods A popPK model was developed for Koate-DVI WAPPS-Hemo PK data in combination with the existing WAPPS-Hemo Fanhdi/Alphanate model derivation dataset using nonlinear mixed effects modelling, and was validated via cross-validation and prediction-corrected Visual Predictive Checks (pcVPC). Bootstrap and PK outcomes between the Fanhdi/Alphanate and the Fanhdi/Alphanate/Koate models were compared, and the relative error distributions from a limited sampling analysis (LSA) under the latter model for low and normal doses (10 vs 50 IU/kg) and inclusion/exclusion of pre-dose measurements. Results A Fanhdi/Alphanate/Koate model was derived (126 patients, ages 1–71 years) after deeming a Koate-brand covariate not clinically significant, resulting in similar parameter estimates than the Fanhdi/Alphanate model with satisfactory goodness of fit, cross-validation and pcVPC results. Low-dose predictions resulted in a higher accuracy and slightly lower precision of half-life ( β -phase) and time to 2% trough (TAT2%) estimates than normal dose (median absolute bias for half-life: 0.12 vs 0.5%; median interquartile range, IQR: 11.79% vs 9.95%). Precision improved under pre-dose designs by 2 to 3% and remained similar between 5- and 2-sample designs (IQR reduction<1.8%). Conclusions The Fanhdi/Alphanate/Koate model is appropriate for Bayesian forecasting in the WAPPS-Hemo platform, providing a comparable prediction capability for low and normal dosing regimens (10 vs 50 IU/Kg).
群体药代动力学(popPK)已被可靠地用于血友病患者的个体药代动力学。特定的popPK模型适用于预测临床试验可能无法捕获的各种情况下的个体PK，从而允许个体化预防性治疗。网络可访问人群药代动力学服务-血友病(wapp - hemo)项目依靠用于贝叶斯预测的浓度特异性popk模型生成单独预测的药代动力学概况。目的建立血浆源性因子VIII (FVIII)浓缩物Koate-DVI的popPK模型及其在低剂量情况下的药代动力学评估适用性。方法结合现有的WAPPS-Hemo Fanhdi/ alphaate模型衍生数据，采用非线性混合效应建模方法，对Koate-DVI WAPPS-Hemo PK数据建立popPK模型，并通过交叉验证和预测校正的视觉预测检查(pcVPC)进行验证。比较了Fanhdi/ alphaate和Fanhdi/ alphaate /Koate模型之间的Bootstrap和PK结果，以及后者模型下低剂量和正常剂量(10 vs 50 IU/kg)和纳入/排除剂量前测量的有限抽样分析(LSA)的相对误差分布。在考虑Koate-brand协变量无临床意义后，推导出Fanhdi/ alphaate /Koate模型(126例患者，年龄1-71岁)，其参数估计与Fanhdi/ alphaate模型相似，具有令人满意的拟合优度、交叉验证和pcVPC结果。与正常剂量相比，低剂量预测导致半衰期(β相)和2%谷期(TAT2%)估计的准确度更高，准确度略低(半衰期的中位数绝对偏差:0.12 vs 0.5%;中位数四分位数范围(IQR: 11.79% vs 9.95%)。在剂量前设计下，精确度提高了2%至3%，在5和2样本设计之间保持相似(IQR降低<1.8%)。结论Fanhdi/ alphaate /Koate模型适用于WAPPS-Hemo平台的贝叶斯预测，对低剂量和正常剂量方案(10 IU/Kg vs 50 IU/Kg)的预测能力相当。
{"title":"Derivation of a Pharmacokinetic Model to Include a Plasma-Derived, von Willebrand Factor-Containing Factor VIII (Koate®-DVI) Concentrate and its Low-Dose Use","authors":"D. Hajducek, Fitri Primacakti, N. Chozie, Roser Mir, Alanna McEneny-King, A. Iorio, A. Edginton","doi":"10.1177/26348535211062229","DOIUrl":"https://doi.org/10.1177/26348535211062229","url":null,"abstract":"Background Population pharmacokinetics (popPK) has been reliably leveraged to generate individual PK in hemophilia patients. Specific popPK models are suited to predict individual PK under a variety of scenarios that may not be captured by clinical trials, allowing for individualized prophylactic treatment. The Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) project generates individually predicted pharmacokinetic profiles relying on concentrate-specific popPK models used for Bayesian forecasting. Objective Specification of a popPK model for the plasma-derived factor VIII (FVIII) concentrate Koate-DVI and its suitability for pharmacokinetic estimation in low-dose scenarios. Methods A popPK model was developed for Koate-DVI WAPPS-Hemo PK data in combination with the existing WAPPS-Hemo Fanhdi/Alphanate model derivation dataset using nonlinear mixed effects modelling, and was validated via cross-validation and prediction-corrected Visual Predictive Checks (pcVPC). Bootstrap and PK outcomes between the Fanhdi/Alphanate and the Fanhdi/Alphanate/Koate models were compared, and the relative error distributions from a limited sampling analysis (LSA) under the latter model for low and normal doses (10 vs 50 IU/kg) and inclusion/exclusion of pre-dose measurements. Results A Fanhdi/Alphanate/Koate model was derived (126 patients, ages 1–71 years) after deeming a Koate-brand covariate not clinically significant, resulting in similar parameter estimates than the Fanhdi/Alphanate model with satisfactory goodness of fit, cross-validation and pcVPC results. Low-dose predictions resulted in a higher accuracy and slightly lower precision of half-life ( β -phase) and time to 2% trough (TAT2%) estimates than normal dose (median absolute bias for half-life: 0.12 vs 0.5%; median interquartile range, IQR: 11.79% vs 9.95%). Precision improved under pre-dose designs by 2 to 3% and remained similar between 5- and 2-sample designs (IQR reduction<1.8%). Conclusions The Fanhdi/Alphanate/Koate model is appropriate for Bayesian forecasting in the WAPPS-Hemo platform, providing a comparable prediction capability for low and normal dosing regimens (10 vs 50 IU/Kg).","PeriodicalId":29816,"journal":{"name":"Plasmatology","volume":"29 1","pages":""},"PeriodicalIF":0.3,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81072625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01DOI: 10.1177/26348535211002789
Khaldun Obeidat, M. Yassin
Immune Thrombocytopenic purpura (ITP) is an immune mediated thrombocytopenia caused by autoantibodies directed against platelet antigens which leads to destruction of the platelets by the spleen and inability of the bone marrow to restore normal counts. The main treatment for ITP is immunosuppressive medication and the first line treatment is glucocorticoids, intravenous immune globulin (IVIG) and Intravenous anti-D immune globulin. Here we report a 45-year old lady who was diagnosed with ITP and achieved treatment free remission after with Eltrombopag as upfront.
{"title":"Eltrombopag Can Achieve Treatment Free Remission as Upfront Therapy for Patient with Immune Thrombocytopenia","authors":"Khaldun Obeidat, M. Yassin","doi":"10.1177/26348535211002789","DOIUrl":"https://doi.org/10.1177/26348535211002789","url":null,"abstract":"Immune Thrombocytopenic purpura (ITP) is an immune mediated thrombocytopenia caused by autoantibodies directed against platelet antigens which leads to destruction of the platelets by the spleen and inability of the bone marrow to restore normal counts. The main treatment for ITP is immunosuppressive medication and the first line treatment is glucocorticoids, intravenous immune globulin (IVIG) and Intravenous anti-D immune globulin. Here we report a 45-year old lady who was diagnosed with ITP and achieved treatment free remission after with Eltrombopag as upfront.","PeriodicalId":29816,"journal":{"name":"Plasmatology","volume":"30 1","pages":""},"PeriodicalIF":0.3,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77671087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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