Journal of Blood Medicine最新文献

{"title":"Prevalence of Inherited Thrombophilia in Women with Recurrent Pregnancy Loss During the First Trimester of Pregnancy.","authors":"Tagwa Yousif Elsayed Yousif","doi":"10.2147/JBM.S401469","DOIUrl":"https://doi.org/10.2147/JBM.S401469","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to investigate the prevalence of inherited thrombophilia in women with recurrent pregnancy loss during the first trimester of pregnancy. The study was assessed the potential role of inherited thrombophilia in recurrent miscarriages and evaluate the consequences of this condition on the reproductive outcomes of affected women.</p><p><strong>Material and methods: </strong>This study was an analytical descriptive carried out in Khartoum, Sudan. The research comprised 98 controls who had given birth twice or more without experiencing a miscarriage and 120 patients. Each patient had done more than two miscarriages especially when the pregnancy is at its beginning trimester. (APCR), and (PS) were investigated using the clotting approach. There was an assessment of biological activities of (ATIII), (PC), and (PS) for both groups using the chromogenic method.</p><p><strong>Results: </strong>The average age of the patients was 34, which was higher than the average age of the controls (33.5). The patient group had a much higher rate of multiple miscarriages among the women.: 35 (29.17%), 45 (37.50%), and 40 (33.33%). The incidence of PC deficiencies was determined to be 1.02% (1/98), whereas neither ATIII nor PS deficiencies were seen in the control group (0/98). APCR was more prevalent in the control group (4.10% or 4/98).</p><p><strong>Conclusion: </strong>Despite contradicting evidence to the contrary in the literature, our findings imply that most miscarriages occur when pregnancy is at the first trimester when a woman is pregnant and they are all caused by thrombophilia.</p>","PeriodicalId":15166,"journal":{"name":"Journal of Blood Medicine","volume":"14 ","pages":"253-259"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/98/10/jbm-14-253.PMC10083015.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9294980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Myeloid Leukemia, from Pathophysiology to Treatment-Free Remission: A Narrative Literature Review.","authors":"Ikhwan Rinaldi,&nbsp;Kevin Winston","doi":"10.2147/JBM.S382090","DOIUrl":"https://doi.org/10.2147/JBM.S382090","url":null,"abstract":"<p><p>Chronic myeloid leukemia (CML) is one of the most common leukemias occurring in the adult population. The course of CML is divided into three phases: the chronic phase, the acceleration phase, and the blast phase. Pathophysiology of CML revolves around Philadelphia chromosome that constitutively activate tyrosine kinase through BCR-ABL1 oncoprotein. In the era of tyrosine kinase inhibitors (TKIs), CML patients now have a similar life expectancy to people without CML, and it is now very rare for CML patients to progress to the blast phase. Only a small proportion of CML patients have resistance to TKI, caused by BCR-ABL1 point mutations. CML patients with TKI resistance should be treated with second or third generation TKI, depending on the BCR-ABL1 mutation. Recently, many studies have shown that it is possible for CML patients who achieve a long-term deep molecular response to stop TKIs treatment and maintain remission. This review aimed to provide an overview of CML, including its pathophysiology, clinical manifestations, the role of stem cells, CML treatments, and treatment-free remission.</p>","PeriodicalId":15166,"journal":{"name":"Journal of Blood Medicine","volume":"14 ","pages":"261-277"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/da/88/jbm-14-261.PMC10084831.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9303846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Laboratory Biomarkers for Early Detection and Clinical Management of Post-Acute Syndrome Among Survivors of the 2013-2016 West Africa Ebola Outbreak in Sierra Leone.","authors":"Raoul Emeric Guetiya Wadoum,&nbsp;Stephen Sevalie,&nbsp;Maurice Baimba Kargbo,&nbsp;Andrew Clarke,&nbsp;Sherry Bangura,&nbsp;Mariatu Kargbo,&nbsp;Hawa Mariama Sesay,&nbsp;Abdul H Kamara,&nbsp;Jamil Bangura,&nbsp;Alie F Kamara,&nbsp;Sophie Allieu,&nbsp;Hassan Rogers,&nbsp;Maurizio Mattei,&nbsp;Vittorio Colizzi,&nbsp;Carla Montesano,&nbsp;Edwin J J Momoh","doi":"10.2147/JBM.S371239","DOIUrl":"https://doi.org/10.2147/JBM.S371239","url":null,"abstract":"<p><strong>Background: </strong>The clinical management of persistent medical conditions affecting Ebola survivors, generally described as a post-Ebola syndrome, remains a public health concern. We aimed to analyze Ebola survivors' laboratory biomarkers as compared to their non-infected household relatives to identify biomarkers that could guide the identification of survivors at increased risk of developing severe at odds with the non-severe post-Ebola syndrome.</p><p><strong>Materials and methods: </strong>Data were extracted from medical records of the Ebola survivors clinic, and we included only Ebola survivor's parameters recorded during the first baseline follow-up visit 2 weeks interval after their second negative PCR result. Moreover, household non-infected family contacts of survivors visiting the clinic during the same period were recruited as community control.</p><p><strong>Results: </strong>The mean age of survivors was 32.65 (IQR: 15.5, 38.25) years, and Ebola IgG immunoglobulin was detected in all, thus confirming their status. The statistical significance (all p < 0.05) observed in monocyte percentage (MONO%), cluster of differentiation 4 percentage (CD4%), alanine aminotransferase (ALT), creatinine (CREA), and creatinine kinase (C-kinase) proved to be clinically significant as compared to the household relatives' group. Interestingly, the linear regression analysis indicated that the duration at ETU was negatively associated with lymphocyte percentage with a 5% lymphocyte decrease per day spent at ETU. Finally, there was a significant (p < 0.05) association between hematological (Hb, PCV, MCV, MCH), biochemical (ALT, CREA, C-kinase, T-cholesterol, triglycerides) parameters and the risk of developing severe complications.</p><p><strong>Conclusion: </strong>We recommend clinicians closely monitor Hb, PCV, MCV, MCH, ALT, CREA, C-kinase, T-cholesterol, triglycerides and lymphocytes as clinically relevant laboratory biomarkers to identify survivors at higher risk of developing severe post-acute syndrome upon discharge from Ebola treatment unit including headache, abdominal pain, chest pain, ocular complication, arthralgia, hearing difficulty and erectile dysfunction which can impact health-related quality of life among Ebola survivors.</p>","PeriodicalId":15166,"journal":{"name":"Journal of Blood Medicine","volume":"14 ","pages":"119-132"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/08/65/jbm-14-119.PMC9930681.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9315414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of ABO and Rh Blood Group Among Volunteer Blood Donors at the Blood and Tissue Bank Service in Addis Ababa, Ethiopia.","authors":"Getu Jenbere Debele,&nbsp;Fekadu Urgessa Fita,&nbsp;Melatwork Tibebu","doi":"10.2147/JBM.S392211","DOIUrl":"https://doi.org/10.2147/JBM.S392211","url":null,"abstract":"<p><strong>Background: </strong>The discovery of the ABO blood group system and testing of blood donors highly reduced the fatalities associated with blood transfusion reactions and improved the safety of blood transfusion. Blood group antigens are found on the surface of red blood cells that are inherited biological characteristics that do not change throughout life in healthy individuals.</p><p><strong>Objective: </strong>To determine the prevalence ABO and Rh blood groups Among Volunteer Blood Donors at Ethiopian blood and tissue bank service (EBTBS), Addis Ababa.</p><p><strong>Methods: </strong>A cross-sectional study was carried out from January 2022 to May 2022, on 1700 volunteer blood donors to assess prevalence of ABO and Rh blood groups among volunteer blood donors at the Ethiopian blood and tissue bank service. All tests were performed using fully automated immunohematology analyzer (Galileo Neo Immucor). Data processing and analysis were undertaken by using Statistical Package for the Social Sciences (SPSS) version 26. An ethical clearance letter was obtained from Addis Ababa University and informed consent was also obtained from the participants of the study.</p><p><strong>Results: </strong>A total of 1700 donors were included, of which 57% of donors were males. The majority of the donors belonged to the age group between 18 and 25 years old (53%). The antigen frequencies of ABO and Rh(D) blood group system showed that O was the most prevalent blood group 44.65% followed by A (28.41%), B (21.24%), and AB (5.71%). The Rh-positive donors were more prevalent (94.82%) as oppose to the Rh-negative (5.18%).</p><p><strong>Conclusion: </strong>The knowledge of the distribution of blood groups is very important for blood banks and transfusion services which play an important role in the patient's health care. The findings of the ABO blood group in this study were comparable to other studies conducted in Ethiopia.</p>","PeriodicalId":15166,"journal":{"name":"Journal of Blood Medicine","volume":"14 ","pages":"19-24"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/51/09/jbm-14-19.PMC9868278.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10614312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Thrombocytopenia Relapse in Patients Who Received mRNA COVID-19 Vaccines [Letter].","authors":"Anumta Ali,&nbsp;Syeda Adeena Zafar,&nbsp;Syeda Sakina Zehra","doi":"10.2147/JBM.S419849","DOIUrl":"https://doi.org/10.2147/JBM.S419849","url":null,"abstract":"","PeriodicalId":15166,"journal":{"name":"Journal of Blood Medicine","volume":"14 ","pages":"377-378"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/69/4c/jbm-14-377.PMC10243605.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9653471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiply Relapsed Secondary CNS Non-Germinal Center Diffuse Large B-Cell Lymphoma Successfully Treated with CNS-Centric Therapy.","authors":"Lyndsey L Fournier,&nbsp;ErinMarie O Kimbrough,&nbsp;Muhamad Alhaj Moustafa,&nbsp;Ke Li,&nbsp;Madiha Iqbal,&nbsp;Vivek Gupta,&nbsp;Han W Tun","doi":"10.2147/JBM.S405521","DOIUrl":"https://doi.org/10.2147/JBM.S405521","url":null,"abstract":"<p><p>Secondary central nervous system involvement by systemic diffuse large B-cell lymphoma (DLBCL) carries a very poor prognosis. We present a female patient who had two episodes of intracerebral central nervous system (CNS)-only relapse of systemic non-germinal center diffuse large B-cell lymphoma (NGC-DLBCL). Her treatment at initial diagnosis consisted of induction with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and intrathecal (IT) - methotrexate (MTX) followed by consolidation with autologous stem cell transplant (ASCT) after high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy. She had the first CNS-only relapse 1.5 years post-ASCT and received whole brain radiation therapy (WBRT). She developed the second intracerebral CNS-only relapse 2 years post-WBRT. A CNS-centric therapeutic approach with salvage chemoimmunotherapy incorporating rituximab, high-dose methotrexate (HD-MTX), high-dose cytarabine (HiDAC), and ibrutinib was utilized for her second CNS-only relapse. She underwent consolidation with a second ASCT following high-dose carmustine (BCNU) and thiotepa chemotherapy. Given her high risk of CNS recurrence, she was started on maintenance ibrutinib. To date, she has remained in complete remission for 3 years. In our experience, multiply relapsed secondary CNS lymphoma (SCNSL) with this response is very rare. We suggest one CNS-centric therapeutic approach that can potentially salvage patients with SCNSL who have not had prior exposure to adequate CNS-directed therapies but acknowledge that additional research is necessary to validate our findings.</p>","PeriodicalId":15166,"journal":{"name":"Journal of Blood Medicine","volume":"14 ","pages":"455-461"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/14/3b/jbm-14-455.PMC10440079.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10053234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of rFIXFc versus N9-GP Prophylaxis in Patients with Hemophilia B: Matching-Adjusted Indirect Comparison of B-LONG and PARADIGM 2 Trials.","authors":"Maria Elisa Mancuso,&nbsp;Daniel Eriksson,&nbsp;Aletta Falk,&nbsp;Zalmai Hakimi,&nbsp;Piotr Wojciechowski,&nbsp;Marlena Wdowiak,&nbsp;Robert Klamroth","doi":"10.2147/JBM.S389094","DOIUrl":"https://doi.org/10.2147/JBM.S389094","url":null,"abstract":"<p><strong>Purpose: </strong>For patients with hemophilia B, extended half-life factor IX (FIX) products are available for prophylaxis and for treating bleeds. Different methods are used to extend the half-lives of recombinant FIX Fc fusion protein (rFIXFc) and nonacog beta pegol (N9-GP). This affects their biodistribution and plasma FIX levels, although differences do not always correlate with clinical outcomes. A matching-adjusted indirect comparison (MAIC) of prophylaxis with rFIXFc and N9-GP was performed, based on licensed dosing in the European Union.</p><p><strong>Patients and methods: </strong>Combined rFIXFc data from the weekly and individualized interval prophylaxis arms of the B-LONG clinical trial, and N9-GP data from the 40 IU/kg once-weekly prophylaxis arm of PARADIGM 2 were used in a MAIC. Individual patient data for rFIXFc (n=87) were matched to aggregated data for N9-GP (n=29). Estimated annualized bleeding rates (ABRs) for rFIXFc were recalculated using a Poisson regression model with adjustment for over-dispersion, and compared with ABRs reported for N9-GP, using incidence rate ratios (IRRs) with 95% confidence interval (CI).</p><p><strong>Results: </strong>There was no evidence of significant differences in estimated ABRs between prophylaxis with rFIXFc and N9-GP. Analysis of pooled rFIXFc weekly and interval-adjusted dosing compared with N9-GP 40 IU/kg once weekly produced estimated ABRs of 2.59 versus 2.51 (IRR 1.03; 95% CI 0.56-1.89), as well as 1.34 versus 1.22 (IRR 1.10; 95% CI 0.42-2.91) and 1.13 versus 1.29 (IRR 0.88; 95% CI 0.47-1.63) for overall, spontaneous, and traumatic bleeding events, respectively.</p><p><strong>Conclusion: </strong>The study did not reveal any significant differences in the efficacy of rFIXFc and N9-GP prophylaxis. Given differences in trough levels (rFIXFc dosing was targeted to achieve a trough 1-3 IU/dL above baseline versus a reported estimated N9-GP mean trough of 27.3 IU/dL), interpreting plasma FIX levels as potential surrogate efficacy markers requires consideration of compound-specific pharmacokinetic profiles.</p>","PeriodicalId":15166,"journal":{"name":"Journal of Blood Medicine","volume":"14 ","pages":"427-434"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a8/d4/jbm-14-427.PMC10390690.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9930383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacologically Treated Anxiety and Depression in People Diagnosed with von Willebrand Disease: Matched Cohort Study.","authors":"Katrina Wilcox Hagberg,&nbsp;Susan Jick,&nbsp;Gülden Özen,&nbsp;Ping Du","doi":"10.2147/JBM.S407993","DOIUrl":"https://doi.org/10.2147/JBM.S407993","url":null,"abstract":"<p><strong>Background: </strong>People diagnosed with von Willebrand disease (VWD) have reduced quality of life versus the general population, and there is limited evidence of increased rates of anxiety and/or depression among people diagnosed with VWD.</p><p><strong>Aim: </strong>To understand the association between VWD and mental health outcomes.</p><p><strong>Design and setting: </strong>A retrospective cohort study was conducted using the UK Clinical Practice Research Datalink (CPRD) GOLD database (1988-2016).</p><p><strong>Methods: </strong>People diagnosed with VWD were matched 1:10 to randomly selected people in the database without VWD based on sex, birth year ±2 years, CPRD record start year ±2 years, and general practice attended. Individuals were followed from VWD diagnosis or match date to censoring (first event date, CPRD end date, or death). Treated anxiety and treated depression were identified by a diagnostic Read Code and a prescription for anxiety/depression medication recorded within 90 days of each other, after VWD diagnosis/match date.</p><p><strong>Results: </strong>Treated anxiety was recorded in 89 of 1119 (8.0%) people diagnosed with VWD and 624 of 10,423 (6.0%) without VWD (age- and sex-adjusted incidence rate ratio [IRR], 1.37; 95% confidence interval [CI], 1.10-1.71). Treated depression was recorded in 119 of 1083 (11.0%) people diagnosed with VWD and 846 of 9845 (8.6%) without VWD (adjusted IRR, 1.35; 95% CI, 1.11-1.63). Females aged 20-39 and 0-19 years were at greatest risk for treated anxiety and treated depression, respectively.</p><p><strong>Conclusion: </strong>Higher rates of treated anxiety and depression were observed among people diagnosed with versus without VWD, predominantly in young females.</p>","PeriodicalId":15166,"journal":{"name":"Journal of Blood Medicine","volume":"14 ","pages":"413-425"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4b/c5/jbm-14-413.PMC10349568.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10201661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Howell-Jolly Body-Like Inclusions in Coronavirus Disease 2019 (COVID-19): Possible Novel Findings.","authors":"Amaylia Oehadian,&nbsp;Ian Huang,&nbsp;Andini Kartikasari,&nbsp;Bachti Alisjahbana,&nbsp;Delita Prihatni","doi":"10.2147/JBM.S399596","DOIUrl":"https://doi.org/10.2147/JBM.S399596","url":null,"abstract":"<p><strong>Background: </strong>During COVID-19 pandemic, it is difficult to distinguish febrile patient infected by SARS-CoV-2 or bacterial causes. Howell-Jolly bodies are a well-known entity found in red blood cells. They are nuclear fragments, composed of deoxyribonucleic acid, commonly observed in the peripheral blood smears of hyposplenic or asplenic patients. Recently, similar inclusions often referred to as Howell-Jolly body-like inclusions (HJBLIs) have been reported in the neutrophils of patients with acquired immune deficiency syndrome (AIDS) and COVID-19 patient.</p><p><strong>Aim: </strong>To explore whether HJBLIs in peripheral blood smear could differentiate between patients with confirmed SARS-CoV-2 and bacterial pneumonia.</p><p><strong>Methods: </strong>We performed cross-sectional study using secondary data from COVID-19 database and re-evaluated peripheral blood smears to identify HJBLIs. We included confirmed COVID-19 adults age >18 years who were hospitalized in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia from March 1st 2020-May 31st 2020. We also examined peripheral blood smears in patients with confirmed bacterial pneumonia as a control group. Clinical characteristics including disease severity, CURB-65 score, comorbidity, and the present of HJBLIs in peripheral blood smears were evaluated.</p><p><strong>Results: </strong>Overall, 33 patients were included: 22 were confirmed COVID-19 and 11 were confirmed bacterial pneumonia. The median (interquartile range) age in COVID-19 and patients with bacterial pneumonia were 53 years (40-64) vs 57 years (53-71), respectively. Compared with patients with bacterial pneumonia, HJBLIs were significantly higher in COVID-19 patients [21/22 (80.8%) vs 5/11 (45.5%), p 0.001].</p><p><strong>Conclusion: </strong>Howell-Jolly body-like inclusions could be a potential feature to help differentiate between COVID-19 and bacterial pneumonia.</p>","PeriodicalId":15166,"journal":{"name":"Journal of Blood Medicine","volume":"14 ","pages":"233-238"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/57/d3/jbm-14-233.PMC10066893.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9253206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic-Pharmacodynamic Comparison of Recombinant and Plasma-Derived von Willebrand Factor in Patients with von Willebrand Disease Type 3.","authors":"Alexander Bauer,&nbsp;Sofia Friberg-Hietala,&nbsp;Giovanni Smania,&nbsp;Martin Wolfsegger","doi":"10.2147/JBM.S395845","DOIUrl":"https://doi.org/10.2147/JBM.S395845","url":null,"abstract":"<p><strong>Background: </strong>Recombinant von Willebrand factor (rVWF, vonicog alfa, Vonvendi/Veyvondi, Takeda Pharmaceuticals USA, Lexington, MA) and several plasma-derived VWF/factor VIII (pdVWF/FVIII) concentrates are available for treating bleeding episodes in patients with von Willebrand disease (VWD).</p><p><strong>Purpose: </strong>To develop population pharmacokinetic (PK)/pharmacodynamic (PD) models that describe VWF:ristocetin cofactor (VWF:RCo) activity and its relationship with FVIII activity (FVIII:C) over time following intravenous administration of either rVWF or a pdVWF/FVIII concentrate (VWF:RCo/FVIII:C 2.4:1) in patients with VWD; to use the final PK/PD models for an in silico comparison of rVWF and pdVWF/FVIII.</p><p><strong>Methods: </strong>The population PK model for rVWF was based on data from four clinical studies in which rVWF was administered to adult patients with VWD type 1, 2 or 3 (phase 1: NCT00816660; phase 3: NCT01410227 and NCT02283268) or severe hemophilia A (phase 1: EudraCT 2011-004314-42). The PK and PK/PD models for pdVWF/FVIII were based on data from the phase 1 study (NCT00816660) in patients with type 3 VWD who received either rVWF plus recombinant FVIII (rFVIII, octocog alfa, ADVATE^®, Takeda Pharmaceuticals USA, Lexington, MA, USA) or pdVWF/FVIII.</p><p><strong>Results: </strong>There was a marked difference in clearance following rVWF administration compared with pdVWF/FVIII in type 3 VWD, leading to a ~1.75 longer mean residence time (ie, persistence of VWF:RCo activity in the body) and half-life for rVWF versus pdVWF/FVIII. Simulations showed that following repeated administration of rVWF (50 IU/kg), a FVIII:C activity of >40 IU/dL can be maintained for the full 72 h dosing interval.</p><p><strong>Conclusion: </strong>The slower elimination of VWF:RCo following rVWF administration results in a prolonged effect on FVIII turnover compared with pdVWF/FVIII administration.</p>","PeriodicalId":15166,"journal":{"name":"Journal of Blood Medicine","volume":"14 ","pages":"399-411"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b4/a8/jbm-14-399.PMC10276593.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}