Journal of hematology最新文献

{"title":"Adverse Hematological and Non-Hematological Events in Patients With Relapsed/Refractory Multiple Myeloma That Are Responsive to Daratumumab, Pomalidomide and Dexamethasone.","authors":"Omar Alkharabsheh,&nbsp;Polina Bellman,&nbsp;Zahra Mahmoudjafari,&nbsp;Wei Cui,&nbsp;Shebli Atrash,&nbsp;Barry Paul,&nbsp;Hamza Hashmi,&nbsp;Leyla Shune,&nbsp;Nausheen Ahmed,&nbsp;Al-Ola Abdallah","doi":"10.14740/jh1085","DOIUrl":"https://doi.org/10.14740/jh1085","url":null,"abstract":"<p><strong>Background: </strong>Daratumumab, pomalidomide, and dexamethasone (DPd) is an effective option for treatment of patients with relapsed/refractory multiple myeloma (RRMM). In this study, we sought to analyze the risk of hematological and non-hematological toxicities in patients who responded to DPd treatment.</p><p><strong>Methods: </strong>We analyzed 97 patients with RRMM who were treated with DPd between January 2015 and June 2022. The patients and disease characteristics, as well as safety and efficacy outcomes were summarized as descriptive analysis.</p><p><strong>Results: </strong>The overall response rate for the entire group was 74% (n = 72). The most common grade III/IV hematological toxicities in those who responded to treatment were neutropenia (79%), leukopenia (65%), lymphopenia (56%), anemia (18%), and thrombocytopenia (8%). The most common grade III/IV non-hematological toxicities were pneumonia (17%) and peripheral neuropathy (8%). The incidence of dose reduction/interruption was 76% (55/72), which was due to hematological toxicity in 73% of the cases. The most common reason for discontinuing treatment was disease progression in 61% (44 out of 72 patients).</p><p><strong>Conclusions: </strong>Our study revealed that patients who respond to DPd are at high risk of dose reduction or treatment interruption because of hematological toxicity, typically due to neutropenia and leukopenia leading to increased risk of hospitalization and pneumonia.</p>","PeriodicalId":15964,"journal":{"name":"Journal of hematology","volume":"12 1","pages":"1-6"},"PeriodicalIF":1.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/da/f1/jh-12-001.PMC9990715.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9085831","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":"Mature Type T-Lymphoblastic Leukemia/Lymphoma Presenting With Isolated Central Nervous System Symptomatology in a Patient With Giant Cell Arteritis on Long-Term Steroid Treatment.","authors":"John Kolton Smith,&nbsp;Xinmin Zhang,&nbsp;Stephen C Machnicki,&nbsp;Salman Azhar,&nbsp;Morana Vojnic","doi":"10.14740/jh1037","DOIUrl":"https://doi.org/10.14740/jh1037","url":null,"abstract":"<p><p>T-lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) is a malignancy comprised of T-lymphoblasts that can present as one of four clinical subtypes (pro-T, pre-T, cortical T, and mature T). Clinical presentation is typically characterized by leukocytosis with diffuse lymphadenopathy and/or hepatosplenomegaly. Beyond clinical presentation, specific immunophenotypic and cytogenetic classifications are utilized to diagnose mature T-ALL. In later disease stages it can spread to the central nervous system (CNS); however, presentation of mature T-ALL by way of CNS pathology and clinical symptomatology alone is rare. Even more rare is the presence of poor prognostic factors without correlating significant clinical presentation. We present a case of mature T-ALL in an elderly female with isolated CNS symptoms in combination with poor prognostic factors including terminal deoxynucleotidyl transferase (TdT) negativity and a complex karyotype. Our patient lacked the classical symptomatology and laboratory findings of mature T-ALL but deteriorated quickly upon diagnosis due to the aggressive genetic profile of her cancer.</p>","PeriodicalId":15964,"journal":{"name":"Journal of hematology","volume":"12 1","pages":"42-48"},"PeriodicalIF":1.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c7/0a/jh-12-042.PMC9990713.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9085830","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":"The Impact of Graft CD3⁺ T-Cell Dose on the Outcome of T-Cell Replete Human Leukocyte Antigen-Mismatched Allogeneic Hematopoietic Peripheral Blood Stem Cells Transplantation.","authors":"Khalid Halahleh,&nbsp;Rawan Mustafa,&nbsp;Dania Sarhan,&nbsp;Dalia Al Rimawi,&nbsp;Hadeel Abdelkhaleq,&nbsp;Isra Muradi,&nbsp;Iyad Sultan","doi":"10.14740/jh1071","DOIUrl":"https://doi.org/10.14740/jh1071","url":null,"abstract":"<p><strong>Background: </strong>Data on whether the graft CD3-positive (CD3⁺) T-cell dose in T-cell-replete human leukocyte antigen (HLA)-mismatched allogeneic hematopoietic peripheral blood stem cells transplantation (PBSCT) influences post-transplant outcomes are controversial.</p><p><strong>Methods: </strong>Using King Hussein Cancer Center (KHCC) Blood and Marrow Transplantation (BMT) Registry database, 52 adult subjects, receiving the first T-cell-replete HLA-mismatched allogeneic hematopoietic PBSCT for acute leukemias or myelodysplastic syndrome, were identified, from January 2017 to December 2020. The cutoff value of graft CD3⁺ T-cell dose was identified using the receiver operating characteristic (ROC) formula and Youden's analysis. Subjects were divided into two cohorts: cohort 1 with low CD3⁺ T-cell dose (n = 34) and cohort 2 with high CD3⁺ T-cell dose (n = 18). Correlative analyses were performed between CD3⁺ T-cell dose and the risk of graft-versus-host disease (GvHD), relapse, relapse-free survival (RFS), and overall survival (OS). P-values were two-sided and considered significant when P < 0.05.</p><p><strong>Results: </strong>Subject covariates were displayed. Subject's characteristics were comparable, except for higher nucleated cells and more female donors in the high CD3⁺ T-cell cohort. The 100-day cumulative incidence of acute GvHD (aGvHD) was 45±7% and 3-year cumulative incidence of chronic GvHD (cGvHD) was 28±6.7%. There was no statistically significant difference between the two cohorts in aGvHD (50% vs. 39%, P = 0.4) or cGvHD (29% vs. 22%, P = 0.7). The 2-year cumulative incidence of relapse (CIR) was 67.5±16.3% for low compared with 14.3±6.8% for high CD3⁺ T-cell cohort (P = 0.018). Fifteen subjects relapsed and 24 have died, 13 due to disease relapse. There was an improvement in 2-year RFS (94% vs. 83%; P = 0.0022) and 2-year OS (91% vs. 89%; P = 0.025) in low CD3⁺ T-cell cohort compared with high CD3⁺ T-cell cohort. Graft CD3⁺ T-cell dose is the only significant risk factor for relapse (P = 002), and OS (P = 0.030) in univariate analysis which was maintained in multivariate for relapse (P = 0.003), but not for OS (P = 0.050).</p><p><strong>Conclusions: </strong>Our data suggest that high graft CD3⁺ T-cell dose is associated with lower risk of relapse, and might improve long-term survival, but has no influence on the risk of developing aGvHD or cGvHD.</p>","PeriodicalId":15964,"journal":{"name":"Journal of hematology","volume":"12 1","pages":"27-36"},"PeriodicalIF":1.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1a/29/jh-12-027.PMC9990716.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9085832","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":"Clofarabine in Pediatric Acute Relapsed or Refractory Leukemia: Where Do We Stand on the Bridge to Hematopoietic Stem Cell Transplantation?","authors":"Sarah Ramiz,&nbsp;Osama Elhaj,&nbsp;Khawar Siddiqui,&nbsp;Saadiya Khan,&nbsp;Hawazen AlSaedi,&nbsp;Awatif AlAnazi,&nbsp;Ali Al-Ahmari,&nbsp;Abdullah Al-Jefri,&nbsp;Oudai Sahvan,&nbsp;Mouhab Ayas,&nbsp;Ibrahim Ghemlas","doi":"10.14740/jh1065","DOIUrl":"https://doi.org/10.14740/jh1065","url":null,"abstract":"<p><strong>Background: </strong>Despite pronounced improvement in overall survival (OS) in pediatric leukemia, a proportion of patients continue to suffer from lack of response or relapse, and the management of such patients is exceedingly difficult. Immunotherapy and engineered chimeric antigen receptor (CAR) T-cell therapy have shown promising results in the course of relapsed or refractory acute lymphoblastic leukemia (ALL). However, conventional chemotherapy continues to be utilized for re-induction purposes whether independently or in combination with immunotherapy.</p><p><strong>Methods: </strong>Forty-three pediatric leukemia patients (age < 14 years at diagnosis) consecutively diagnosed at our institution and got treated with clofarabine based regimen at a single tertiary care hospital between January 2005 and December 2019 were enrolled in this study. ALL comprised of 30 (69.8%) patients of the cohort while the remaining 13 (30.2%) were with acute myeloid leukemia (AML).</p><p><strong>Results: </strong>Post-clofarabine bone marrow (BM) was negative in 18 (45.0%) cases. Overall clofarabine failure rate was 58.1% (n = 25) with 60.0% (n = 18) in ALL and 53.8% (n = 7) in AML (P = 0.747). Eighteen (41.9%) patients eventually underwent hematopoietic stem cell transplantation (HSCT); 11 (61.1%) were from ALL group and remaining seven (38.9%) were AML (P = 0.332). Three- and 5-year OS of our patients was 37.7±7.6% and 32.7±7.3%. There was a trend of better OS for ALL patients compared to AML (40.9±9.3% vs. 15.4±10.0%, P = 0.492). Cumulative probability of 5-year OS was significantly better in transplanted patients (48.1±12.1% vs. 21.4±8.4%, P = 0.024).</p><p><strong>Conclusions: </strong>Though almost 90% of our patients proceeded to HSCT with complete response post-clofarabine treatment, yet clofarabine-based regimens are associated with the significant burden of infectious complications and sepsis-related deaths.</p>","PeriodicalId":15964,"journal":{"name":"Journal of hematology","volume":"12 1","pages":"16-26"},"PeriodicalIF":1.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/23/jh-12-016.PMC9990710.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9078999","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":"Soft-Tissue Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma in a Child Unmasked by COVID-19.","authors":"Diego Alberto Lozano-Jaramillo,&nbsp;Esperanza Millan-Arreola,&nbsp;Oscar Omar Esquer-Cota,&nbsp;Jesus Manuel Lozano-Garcia,&nbsp;Miguel Alfonso Valenzuela-Espinoza","doi":"10.14740/jh1081","DOIUrl":"https://doi.org/10.14740/jh1081","url":null,"abstract":"<p><p>Anaplastic large cell lymphoma (ALCL) is children's most common mature T-cell neoplasm. The majority is positive for anaplastic lymphoma kinase (ALK). Initial presentation as a soft-tissue pelvic mass without nodal involvement is rare and can be easily misdiagnosed. We report a case of a 12-year-old male presenting with pain and movement restriction in the right extremity. Computed tomography (CT) scan revealed a solitary pelvic mass. Initial biopsy examination concluded rhabdomyosarcoma. After developing pediatric multisystemic inflammatory syndrome due to coronavirus disease 2019 (COVID-19), central and peripheral lymph node enlargement appeared. New cervical adenopathy and pelvic mass biopsies were performed. Immunohistochemistry concluded an ALK-positive ALCL with a small-cell pattern. The patient was treated with brentuximab-based chemotherapy and eventually improved. Differential diagnosis of pelvic masses in children and adolescents must include ALCL. An inflammatory trigger may promote the appearance of a typical nodal disease, previously absent. Attention is warranted during histopathological examination to avoid diagnostic errors.</p>","PeriodicalId":15964,"journal":{"name":"Journal of hematology","volume":"12 1","pages":"37-41"},"PeriodicalIF":1.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c6/89/jh-12-037.PMC9990711.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9085828","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":"Survival in Elderly Patients Diagnosed With Acute Myeloid Leukemia: A Hospital-Based Study.","authors":"Diana Marcela Mendoza-Urbano,&nbsp;Maria Elena Tello-Cajiao,&nbsp;Joaquin Rosales,&nbsp;Fabian Emiliano Ahumada,&nbsp;Luis Gabriel Parra-Lara,&nbsp;Elizabeth Arrieta","doi":"10.14740/jh1055","DOIUrl":"https://doi.org/10.14740/jh1055","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is a hematological neoplasm that is more frequent in elderly patients. The objective of this study was to evaluate elderly patients' survival with <i>de novo</i> AML and acute myeloid leukemia myelodysplasia-related (AML-MR), treated with intensive and less-intensive chemotherapy and supportive care.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted in Fundacion Valle del Lili (Cali, Colombia), between 2013 and 2019. We included patients ≥ 60 years old diagnosed with AML. The statistical analysis considered the leukemia type (<i>de novo</i> vs. myelodysplasia-related) and treatment (intensive chemotherapy regimen, less-intensive chemotherapy regimen, and without chemotherapy). Survival analysis was performed using Kaplan-Meier method and Cox regression models.</p><p><strong>Results: </strong>A total of 53 patients were included (31 <i>de novo</i> and 22 AML-MR). Intensive chemotherapy regimens were more frequent in patients with <i>de novo</i> leukemia (54.8%), and 77.3% of patients with AML-MR received less-intensive regimens. Survival was higher in the chemotherapy group (P = 0.006), but with no difference between chemotherapy modalities. Additionally, patients without chemotherapy were 10 times more likely to die than those who received any regimen, independent of age, sex, Eastern Cooperative Oncology performance status, and Charlson comorbidity index (adjusted hazard ratio (HR) = 11.6, 95% confidence interval (CI) 3.47 - 38.8).</p><p><strong>Conclusions: </strong>Elderly patients with AML had longer survival time when receiving chemotherapy, regardless of the type of regimen.</p>","PeriodicalId":15964,"journal":{"name":"Journal of hematology","volume":"12 1","pages":"7-15"},"PeriodicalIF":1.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e5/2a/jh-12-007.PMC9990714.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9085829","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":"Synchronous Presentation of Autoimmune Hepatitis and Multiple Myeloma.","authors":"Binoy Yohannan,&nbsp;Allen C Omo-Ogboi,&nbsp;Varaha S Tammisetti,&nbsp;Adan Rios","doi":"10.14740/jh1049","DOIUrl":"https://doi.org/10.14740/jh1049","url":null,"abstract":"<p><p>Autoimmune hepatitis (AIH) is a rare immune-mediated disease predominantly seen in women and triggered by various environmental factors. Rarely, AIH can be triggered by an underlying malignancy. We report a woman in her 60s who presented with markedly abnormal liver biochemical tests. Serology was positive for anti-smooth muscle antibodies and a liver biopsy confirmed AIH. During the hospital course, she developed sepsis and acute renal failure requiring dialysis support. Serum protein electrophoresis (SPEP) showed a monoclonal IgG kappa protein of 1.92 g/dL and a bone marrow biopsy revealed 7% clonal plasma cells. She had lytic lesions on skeletal survey confirming the diagnosis of a coexisting multiple myeloma (MM). Given her markedly abnormal liver chemistries, we decided to treat the AIH first and use the steroids (an important anti-myeloma therapy) as a bridge to the specific treatment of the MM once her clinical condition improved. She was treated with oral prednisone and azathioprine for AIH. One month later, a marked improvement in liver biochemical test results was noted and she was started on oral ixazomib, lenalidomide and dexamethasone. She received palliative radiotherapy to the lumbar spine (L2), left femur, and ischium lesions. This case highlights a rare co-occurrence of AIH and MM, the underlying mechanism of which is unknown.</p>","PeriodicalId":15964,"journal":{"name":"Journal of hematology","volume":"11 6","pages":"216-222"},"PeriodicalIF":1.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8f/e2/jh-11-216.PMC9822655.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10524885","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":"Thymoma With Triple Threat: Pure Red Cell Aplasia, Autoimmune Hemolytic Anemia, and T-Cell Large Granular Lymphocytic Leukemia.","authors":"Tara Seibert,&nbsp;Patrick J Loehrer,&nbsp;Andrew R W O'Brien","doi":"10.14740/jh1061","DOIUrl":"https://doi.org/10.14740/jh1061","url":null,"abstract":"<p><p>Thymomas are a rare neoplasm of the anterior mediastinum and often associated with paraneoplastic syndromes. Though myasthenia gravis is the most common and well-known, the list of reported paraneoplastic syndromes occurring with thymoma is extensive and ever-growing. Paraneoplastic syndromes can involve nearly every organ system, including hematologic abnormalities affecting any or all cell lines. This can present challenges to the clinician in terms of diagnosis, prognostic impact, and management. We present the case of a previously healthy 41-year-old female who was diagnosed with thymoma and three rare hematologic paraneoplastic syndromes: pure red cell aplasia (PRCA), autoimmune hemolytic anemia (AIHA), and T-cell large granular lymphocytic leukemia (T-LGLL). To the best of our knowledge, there have been only four other reported cases of PRCA and AIHA in a single patient with thymoma, all of which were treated with thymectomy. Upfront surgical resection was not possible in the present case and thus the patient was alternatively treated with corticosteroids and octreotide, which proved successful in resolving the anemia. The authors present this case to share these findings of an alternative treatment strategy for thymoma-associated PRCA and AIHA and to highlight the importance of careful monitoring with routine blood work for these complex patients.</p>","PeriodicalId":15964,"journal":{"name":"Journal of hematology","volume":"11 6","pages":"223-232"},"PeriodicalIF":1.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b5/c3/jh-11-223.PMC9822658.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9072691","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":"Acute Myeloid Leukemia Following Myeloproliferative Neoplasms: A Review of What We Know, What We Do Not Know, and Emerging Treatment Strategies.","authors":"Zoe McKinnell,&nbsp;Daniel Karel,&nbsp;Daniel Tuerff,&nbsp;Marwa Sh Abrahim,&nbsp;Samah Nassereddine","doi":"10.14740/jh1042","DOIUrl":"https://doi.org/10.14740/jh1042","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) arising from myeloproliferative neoplasms (MPNs) represents a small subtype of secondary AML (sAML). This entity is well known to be associated with poor responses to available treatment options and dismal outcomes. To date, there are no standardized treatment options and there has been very little therapeutic advancement in recent years. This is a stark contrast to other subsets of AML for which there have been significant advances in therapeutic approaches, especially for patients with targetable mutations. We aim to focus our review on the incidence, risk factors for leukemogenesis, pathogenesis, molecular landscape, and emerging therapeutic options in post-myeloproliferative neoplasm acute myeloid leukemia (post-MPN AML).</p>","PeriodicalId":15964,"journal":{"name":"Journal of hematology","volume":"11 6","pages":"197-209"},"PeriodicalIF":1.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/fb/jh-11-197.PMC9822656.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10578692","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":"Unveiling the Great Therapeutic Potential of MASPs as Hemostatic Agents.","authors":"Ashraf Abdullah Saad","doi":"10.14740/jh1060","DOIUrl":"https://doi.org/10.14740/jh1060","url":null,"abstract":"The lectin complement pathway (LP) is an important effector arm of innate immunity and exemplary pattern recognition artist that draws a fine line between friend and foe (host defense) and between innocuous and noxious (homeostasis). Intriguingly, the proteolytic activity of the LP is attributed to proteolytic enzymes, called mannan-binding lectin (MBL)-associated serine proteases (MASPs). MASPs are central components of the LP that resemble the serine proteases, C1r and C1s, of the classical complement pathway (CP). Recently, the MASPs’ important role in the coagulation cascade was unmasked by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [1-6]. MASPs (mainly MASP-1) are actually key elements that connect both complement and coagulation systems [7]. So far, research into complement-coagulation interactions focusing merely on MASP inhibition had offered promising targets for novel preventive and therapeutic strategies [8]. Conversely, here I propose that the fibrinolytic activity of MASPs can be explored in the management of bleeding disorders. In particular, traumatic and surgical bleeding are life-threating but potentially avoidable causes of death [9, 10]. Johnston et al showed that postsurgical bleeding is associated with substantial increases in postprocedural length of stay, days spent in critical care, and the risks of infection, vascular events, acute renal failure, and in-hospital mortality [11]. In addition, use of anticoagulants and antiplatelets increases the surgical bleeding risk, creates a need for multiple pharmacologic approaches and poses potential problems in managing surgical patients [1215]. On the other hand, approximately one-third of all trauma patients with bleeding present with a coagulopathy on hospital admission [16, 17]. This subset of patients has a significantly increased incidence of multiple organ failure and death compared to patients with similar injury patterns in the absence of a coagulopathy [18]. Coagulopathy frequently occurs early in the postinjury period and is an independent predictor of mortality. Compared to patients whose initial prothrombin time (PT) and activated partial thromboplastin time (aPTT) are normal, trauma patients have 35% and 326% increased risk of mortality when their initial PT and aPTT are abnormal, respectively [19]. It is important to emphasize that trauma-induced coagulopathy, also called acute traumatic coagulopathy, is distinct from massive transfusion coagulopathy that occurs in the context of loss and dilution coagulopathy [20, 21] or disseminated intravascular coagulation [22]. Hitherto, measures to reduce intraoperative blood loss have been limited to enhancement of coagulation by recombinant activated coagulation factor VII (rFVIIa), desmopressin, fibrinogen, prothrombin complex concentrates, inhibition of fibrinolysis comprising lysine analogues (tranexamic acid and epsilon aminocaproic acid) and a broad-spectrum serine protease inhibitor (aprot","PeriodicalId":15964,"journal":{"name":"Journal of hematology","volume":"11 6","pages":"240-245"},"PeriodicalIF":1.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6a/33/jh-11-240.PMC9822654.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10578687","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}