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Hematol. Rep., Volume 15, Issue 2 (June 2023) – 14 articles

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Review
Role of Therapeutic Anticoagulation in COVID-19: The Current Situation
Hematol. Rep. 2023, 15(2), 358-369; https://doi.org/10.3390/hematolrep15020037 - 05 Jun 2023
Viewed by 185
Abstract
Thrombotic complications from COVID-19 are now well known and contribute to significant morbidity and mortality. Different variants confer varying risks of thrombotic complications. Heparin has anti-inflammatory and antiviral effects. Due to its non-anticoagulant effects, escalated-dose anticoagulation, especially therapeutic-dose heparin, has been studied for [...] Read more.
Thrombotic complications from COVID-19 are now well known and contribute to significant morbidity and mortality. Different variants confer varying risks of thrombotic complications. Heparin has anti-inflammatory and antiviral effects. Due to its non-anticoagulant effects, escalated-dose anticoagulation, especially therapeutic-dose heparin, has been studied for thromboprophylaxis in hospitalized patients with COVID-19. Few randomized, controlled trials have examined the role of therapeutic anticoagulation in moderately to severely ill patients with COVID-19. Most of these patients had elevated D-dimers and low bleeding risks. Some trials used an innovative adaptive multiplatform with Bayesian analysis to answer this critical question promptly. All the trials were open-label and had several limitations. Most trials showed improvements in the meaningful clinical outcomes of organ-support-free days and reductions in thrombotic events, mainly in non-critically-ill COVID-19 patients. However, the mortality benefit needed to be more consistent. A recent meta-analysis confirmed the results. Multiple centers initially adopted intermediate-dose thromboprophylaxis, but the studies failed to show meaningful benefits. Given the new evidence, significant societies have suggested therapeutic anticoagulation in carefully selected patients who are moderately ill and do not require an intensive-care-unit level of care. There are multiple ongoing trials globally to further our understanding of therapeutic-dose thromboprophylaxis in hospitalized patients with COVID-19. In this review, we aim to summarize the current evidence regarding the use of anticoagulation in patients with COVID-19 infection. Full article
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Article
Etiology of Anemia and Risk Factors of Mortality among Hospitalized Patients: A Real-Life Retrospective Study in a Tertiary Center in Greece
Hematol. Rep. 2023, 15(2), 347-357; https://doi.org/10.3390/hematolrep15020036 - 02 Jun 2023
Viewed by 244
Abstract
Anemia is a prominent global health issue with a wide variety of causes and can be associated with decreased quality of life, increased hospitalization, and higher mortality, especially in older individuals. Therefore, studies further shedding light on the causes and the risk factors [...] Read more.
Anemia is a prominent global health issue with a wide variety of causes and can be associated with decreased quality of life, increased hospitalization, and higher mortality, especially in older individuals. Therefore, studies further shedding light on the causes and the risk factors of this condition should be performed. The aim of the present study was to examine the causes of anemia in hospitalized patients in a tertiary hospital in Greece and identify risk factors related to higher mortality. In total, 846 adult patients with a diagnosis of anemia were admitted during the study period. The median age was 81 years, and 44.8% were male. The majority of patients had microcytic anemia, with the median mean corpuscular volume (MCV) being 76.3 fL and the median hemoglobin being 7.1 g/dL. Antiplatelets were used by 28.6% of patients, while 28.4% were using anticoagulants at the time of diagnosis. At least one unit of packed red blood cells (PRBCs) was transfused in 84.6% of patients, and a median of two PRBCs was used per patient. A gastroscopy was performed in 55%, and a colonoscopy was performed in 39.8% of patients in the present cohort. Anemia was considered to be multifactorial in almost half the cases, while the most commonly identified cause was iron deficiency anemia, more commonly with positive endoscopic findings. Mortality was relatively low, at 4.1%. Multivariate logistic regression analysis identified higher B12 levels and longer duration of hospital stay to be independently positively associated with mortality. Full article
Review
Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment
Hematol. Rep. 2023, 15(2), 331-346; https://doi.org/10.3390/hematolrep15020035 - 24 May 2023
Viewed by 300
Abstract
Targeting kinase activity is considered to be an attractive therapeutic strategy to overcome acute myeloid leukemia (AML) since aberrant activation of the kinase pathway plays a pivotal role in leukemogenesis through abnormal cell proliferation and differentiation block. Although clinical trials for kinase modulators [...] Read more.
Targeting kinase activity is considered to be an attractive therapeutic strategy to overcome acute myeloid leukemia (AML) since aberrant activation of the kinase pathway plays a pivotal role in leukemogenesis through abnormal cell proliferation and differentiation block. Although clinical trials for kinase modulators as single agents remain scarce, combination therapies are an area of therapeutic interest. In this review, the author summarizes attractive kinase pathways for therapeutic targets and the combination strategies for these pathways. Specifically, the review focuses on combination therapies targeting the FLT3 pathways, as well as PI3K/AKT/mTOR, CDK and CHK1 pathways. From a literature review, combination therapies with the kinase inhibitors appear more promising than monotherapies with individual agents. Therefore, the development of efficient combination therapies with kinase inhibitors may result in effective therapeutic strategies for AML. Full article
(This article belongs to the Topic Leukemia-Challenges and Current Treatment Options)
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Case Report
Phenazopyridine-Induced Methemoglobinemia in a Jehovah’s Witness Treated with High-Dose Ascorbic Acid Due to Methylene Blue Contradictions: A Case Report and Review of the Literature
Hematol. Rep. 2023, 15(2), 325-330; https://doi.org/10.3390/hematolrep15020034 - 24 May 2023
Viewed by 296
Abstract
Methemoglobinemia is an acute medical emergency that requires prompt correction. Physicians should have a high degree of suspicion of methemoglobinemia in cases that present with hypoxemia that does not resolve with supplemental oxygenation, and they should confirm this suspicion with a positive methemoglobin [...] Read more.
Methemoglobinemia is an acute medical emergency that requires prompt correction. Physicians should have a high degree of suspicion of methemoglobinemia in cases that present with hypoxemia that does not resolve with supplemental oxygenation, and they should confirm this suspicion with a positive methemoglobin concentration on arterial blood gas. There are multiple medications that can induce methemoglobinemia, such as local anesthetics, antimalarials, and dapsone. Phenazopyridine is an azo dye used over-the-counter as a urinary analgesic for women with urinary tract infections, and it has also been implicated in causing methemoglobinemia. The preferred treatment of methemoglobinemia is methylene blue, but its use is contraindicated for patients with glucose-6-phosphatase deficiency or those who take serotonergic drugs. Alternative treatments include high-dose ascorbic acid, exchange transfusion therapy, and hyperbaric oxygenation. The authors report a case of a 39-year-old female who took phenazopyridine for 2 weeks to treat dysuria from a urinary tract infection and subsequently developed methemoglobinemia. The patient had contraindications for the use of methylene blue and was therefore treated with high-dose ascorbic acid. The authors hope that this interesting case promotes further research into the utilization of high-dose ascorbic acid for managing methemoglobinemia in patients who are unable to receive methylene blue. Full article
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Case Report
Additional Genetic Alterations and Clonal Evolution of MPNs with Double Mutations on the MPL Gene: Two Case Reports
Hematol. Rep. 2023, 15(2), 317-324; https://doi.org/10.3390/hematolrep15020033 - 23 May 2023
Viewed by 271
Abstract
Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are two of the main BCR-ABL1-negative chronic myeloproliferative neoplasms (MPNs) characterized by abnormal megakaryocytic proliferation. Janus kinase 2 (JAK2) mutations are detected in 50–60% of ET and PMF, while myeloproliferative leukemia (MPL [...] Read more.
Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are two of the main BCR-ABL1-negative chronic myeloproliferative neoplasms (MPNs) characterized by abnormal megakaryocytic proliferation. Janus kinase 2 (JAK2) mutations are detected in 50–60% of ET and PMF, while myeloproliferative leukemia (MPL) virus oncogene mutations are present in 3–5% of cases. While Sanger sequencing is a valuable diagnostic tool to discriminate the most common MPN mutations, next-generation sequencing (NGS) is a more sensitive technology that also identifies concurrent genetic alterations. In this report, we describe two MPN patients with simultaneous double MPL mutations: a woman with ET presenting both MPLV501A-W515R and JAK2V617F mutations and a man with PMF displaying an uncommon double MPLV501A-W515L. Using colony-forming assays and NGS analyses, we define the origin and mutational landscape of these two unusual malignancies and uncover further gene alterations that may contribute to the pathogenesis of ET and PMF. Full article
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Case Report
Acquired Factor X Deficiency without Amyloidosis Presenting with Massive Hematuria: A Case Report and Review of the Literature
Hematol. Rep. 2023, 15(2), 312-316; https://doi.org/10.3390/hematolrep15020032 - 15 May 2023
Viewed by 354
Abstract
Acquired factor X deficiency is a rare diagnosis, especially without the association of other co-existing conditions such as amyloidosis. The authors report the case of a 34-year-old male with severe frank hematuria found to have markedly prolonged prothrombin time and activated partial thromboplastin [...] Read more.
Acquired factor X deficiency is a rare diagnosis, especially without the association of other co-existing conditions such as amyloidosis. The authors report the case of a 34-year-old male with severe frank hematuria found to have markedly prolonged prothrombin time and activated partial thromboplastin time. A mixing study showed correction utilizing normal plasma and a coagulation panel testing revealed decreased factor X activity. The patient was treated with multiple blood transfusions, fresh frozen plasma, high-dose pulse steroids, and rituximab. The patient’s condition improved during his 21-day hospital stay and was followed up every 2 weeks for 3 months. The patient’s factor X level recovered after two weeks of discharge with no other hemorrhagic episodes. Full article
Case Report
A Report of a Symptomatic Progressive Myeloma during Pregnancy and Postpartum Period from Asymptomatic State
Hematol. Rep. 2023, 15(2), 305-311; https://doi.org/10.3390/hematolrep15020031 - 05 May 2023
Viewed by 422
Abstract
 Multiple myeloma is a plasma cell malignancy that is most commonly observed in males in the sixth and seventh decade of life. The clinical scenario of multiple myeloma with concurrent pregnancy is considered to be very rare. We detail here the case [...] Read more.
 Multiple myeloma is a plasma cell malignancy that is most commonly observed in males in the sixth and seventh decade of life. The clinical scenario of multiple myeloma with concurrent pregnancy is considered to be very rare. We detail here the case of a young female with known IgG kappa multiple myeloma who was found to have a steady elevation of her IgG kappa paraprotein during pregnancy and symptomatic progression in the postpartum period. She delivered a healthy baby at 40 weeks gestation. We present a review of all reported cases of known multiple myeloma progressing during pregnancy and in the postpartum period, the treatments given, and their outcomes. The report also provides suggestions for diagnosis and management of myeloma during pregnancy in order to have an outcome of successful uncomplicated pregnancy with healthy offspring.  Full article
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Article
Comparison of Two Methods of Capillary Sampling in Blood Pre-Donation Anemia Screening in Brazil
Hematol. Rep. 2023, 15(2), 298-304; https://doi.org/10.3390/hematolrep15020030 - 26 Apr 2023
Viewed by 394
Abstract
Background: The laboratory tests most used by blood banks to diagnose anemia are the hemoglobin (Hb) and microhematocrit (Hct) tests, measured from capillary samples. Objective: To analyze the two capillary screening methods for pre-donation anemia by comparing their agreement in diagnosing anemia. Method: [...] Read more.
Background: The laboratory tests most used by blood banks to diagnose anemia are the hemoglobin (Hb) and microhematocrit (Hct) tests, measured from capillary samples. Objective: To analyze the two capillary screening methods for pre-donation anemia by comparing their agreement in diagnosing anemia. Method: A cross-sectional study in a population of 15,521 blood donation candidates for whom information was available on Hb and Hct, performed from capillary blood samples. Hb was determined using the HemoCue® test and Hct by the centrifugation method. The Kappa coefficient was calculated to assess the agreement between the methods. Pearson’s correlation tests and gender-adjusted linear regression were used to assess the change in the response variable (Hb) as a function of the explanatory variable (Hct). Results: The majority of the study population were men (70.4%), aged between 18 and 44 years (72.1%), who declared themselves white or mixed skin color (85.6%), and had undergone at least 11 years of complete education (72.4%). The Kappa coefficient found was 92.7 and 99.2 for women and men, respectively. Pearson’s correlation showed a correlation coefficient of 0.98 and the linear regression graph showed an adequate relationship between the tests with R2 = 0.97. Conclusions: Comparing the Hb and Hct capillary tests, it was found that Hct can be safely used to screen for anemia in pre-blood donation. Full article
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Case Report
Testosterone Usage Leading to Pulmonary Embolisms and Deep Vein Thrombosis: A Case Report and Review of the Literature
Hematol. Rep. 2023, 15(2), 290-297; https://doi.org/10.3390/hematolrep15020029 - 26 Apr 2023
Viewed by 566
Abstract
Androgen usage has widely increased in recent times via prescribed and unprescribed means. Testosterone is a popular androgen taken by both athletes and the general population. While there is some evidence of androgens being thrombogenic, we report on a 19-year-old male who presented [...] Read more.
Androgen usage has widely increased in recent times via prescribed and unprescribed means. Testosterone is a popular androgen taken by both athletes and the general population. While there is some evidence of androgens being thrombogenic, we report on a 19-year-old male who presented to the hospital after the usage of testosterone for one month, leading to the development of multiple pulmonary emboli and deep vein thrombosis. The authors hope to elucidate the relationship between testosterone usage and thrombosis formation. Full article
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Case Report
A Case of Vancomycin-Induced Severe Immune Thrombocytopenia
Hematol. Rep. 2023, 15(2), 283-289; https://doi.org/10.3390/hematolrep15020028 - 24 Apr 2023
Viewed by 597
Abstract
A male in his 60s presented with left lower extremity fractures following a vehicle accident. Hemoglobin, initially, was 12.4 mmol/L, and platelet count was 235 k/mcl. On day 11 of admission, his platelet count initially dropped to 99 k/mcl, and after recovery it [...] Read more.
A male in his 60s presented with left lower extremity fractures following a vehicle accident. Hemoglobin, initially, was 12.4 mmol/L, and platelet count was 235 k/mcl. On day 11 of admission, his platelet count initially dropped to 99 k/mcl, and after recovery it rapidly decreased to 11 k/mcl on day 16 when the INR was 1.3 and aPTT was 32 s, and he continued to have a stable anemia throughout admission. There was no response in platelet count post-transfusion of four units of platelets. Hematology initially evaluated the patient for disseminated intravascular coagulation, heparin-induced thrombocytopenia (anti-PF4 antibody was 0.19), and thrombotic thrombocytopenic purpura (PLASMIC score of 4). Vancomycin was administered on days 1–7 for broad spectrum antimicrobial coverage and day 10, again, for concerns of sepsis. Given the temporal association of thrombocytopenia and vancomycin administration, a diagnosis of vancomycin-induced immune thrombocytopenia was established. Vancomycin was discontinued, and 2 doses of 1000 mg/kg of intravenous immunoglobulin 24 h apart were administered with the subsequent resolution of thrombocytopenia. Full article
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Article
Changes in Hematologic Lab Measures Observed in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with C5 Inhibitors, Ravulizumab and Eculizumab: Real-World Evidence from a US Based EMR Network
Hematol. Rep. 2023, 15(2), 266-282; https://doi.org/10.3390/hematolrep15020027 - 21 Apr 2023
Viewed by 957
Abstract
Paroxysmal nocturnal hemoglobinuria (PNH), a rare acquired hematologic disorder, can be treated with C5 inhibitors (C5i) such as eculizumab or ravulizumab. This retrospective study is the first to describe real-world treatment patterns and changes in hematologic PNH-monitoring laboratory tests among C5i-treated US patients. [...] Read more.
Paroxysmal nocturnal hemoglobinuria (PNH), a rare acquired hematologic disorder, can be treated with C5 inhibitors (C5i) such as eculizumab or ravulizumab. This retrospective study is the first to describe real-world treatment patterns and changes in hematologic PNH-monitoring laboratory tests among C5i-treated US patients. Data were extracted from TriNetX Dataworks Network and included patients with a PNH diagnosis between 1 January 2010, and 20 August 2021. Patients were stratified into three cohorts based on their C5i usage: eculizumab, ravulizumab (prior eculizumab), and ravulizumab (eculizumab naïve). Hematological markers (hemoglobin [Hb], lactate dehydrogenase [LDH], and absolute reticulocyte count [ARC]) and relevant clinical events (e.g., breakthrough hemolysis [BTH], complement-amplifying conditions [CAC], thrombosis, infection, and all-cause mortality) were captured any time within 12 months post-index treatment. Of the 143 (eculizumab), 43 (ravulizumab, prior eculizumab), and 33 (ravulizumab, eculizumab naïve) patients, mean age across cohorts was 42–51 years, 55–61% were female, 63–73% were White, and 33–40% had aplastic anemia. Among all cohorts 12 months post-C5i treatment, 50–82% remained anemic, 8–32% required ≥1 transfusion, and 13–59% had BTH, of which 33%-54% had CACs. Additionally, thrombosis was seen in 7–15% of patients, infection in 20–25%, and mortality in 1–7%. These findings suggest many C5i-treated patients experience suboptimal disease control. Full article
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Article
Utilization of Genomic Tumor Profiling in Pediatric Liquid Tumors: A Clinical Series
Hematol. Rep. 2023, 15(2), 256-265; https://doi.org/10.3390/hematolrep15020026 - 19 Apr 2023
Viewed by 378
Abstract
Hematologic tumors are mostly treated with chemotherapies that have poor toxicity profiles. While molecular tumor profiling can expand therapeutic options, our understanding of potential targetable drivers comes from studies of adult liquid tumors, which does not necessarily translate to efficacious treatment in pediatric [...] Read more.
Hematologic tumors are mostly treated with chemotherapies that have poor toxicity profiles. While molecular tumor profiling can expand therapeutic options, our understanding of potential targetable drivers comes from studies of adult liquid tumors, which does not necessarily translate to efficacious treatment in pediatric liquid tumors. There is also no consensus on when profiling should be performed and its use in guiding therapies. We describe a single institution’s experience in integrating profiling for liquid tumors. Pediatric patients diagnosed with leukemia or lymphoma and who underwent tumor profiling were retrospectively reviewed. Ten (83.3%) patients had relapsed disease prior to tumor profiling. Eleven (91.7%) patients had targetable alterations identified on profiling, and three (25%) received targeted therapy based on these variants. Of the three patients that received targeted therapy, two (66.7%) were living, and one (33.3%) decreased. For a portion of our relapsing and/or treatment-refractory patients, genetic profiling was feasible and useful in tailoring therapy to obtain stable or remission states. Practitioners may hesitate to deviate from the ‘standard of therapy’, resulting in the underutilization of profiling results. Prospective studies should identify actionable genetic variants found more frequently in pediatric liquid tumors and explore the benefits of proactive tumor profiling prior to the first relapse. Full article
Article
Molecular Tumor Boards: The Next Step towards Precision Therapy in Cancer Care
Hematol. Rep. 2023, 15(2), 244-255; https://doi.org/10.3390/hematolrep15020025 - 04 Apr 2023
Viewed by 810
Abstract
The application of molecular tumor profiles in clinical decision making remains a challenge. To aid in the interpretation of complex biomarkers, molecular tumor boards (MTBs) have been established worldwide. In the present study, we show that a multidisciplinary approach is essential to the [...] Read more.
The application of molecular tumor profiles in clinical decision making remains a challenge. To aid in the interpretation of complex biomarkers, molecular tumor boards (MTBs) have been established worldwide. In the present study, we show that a multidisciplinary approach is essential to the success of MTBs. Our MTB, consisting of pediatric oncologists, pathologists, and pharmacists, evaluated 115 cases diagnosed between March 2016 and September 2021. If targetable mutations were identified, pharmacists aided in the evaluation of treatment options based on drug accessibility. Treatable genetic alterations detected through molecular testing most frequently involved the cell cycle. For 85% of the cases evaluated, our MTB provided treatment recommendations based on the patient’s history and results of molecular tumor testing. Only three patients, however, received MTB-recommended targeted therapy, and only one of these patients demonstrated an improved clinical outcome. For the remaining patients, MTB-recommended treatment often was not administered because molecular tumor profiling was not performed until late in the disease course. For the three patients who did receive MTB-recommended therapy, such treatment was not administered until months after diagnosis due to physician preference. Thus, the education of healthcare providers regarding the benefits of targeted therapy may increase acceptance of these novel agents and subsequently improve patient survival. Full article
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Review
Risk of Thrombosis during and after a SARS-CoV-2 Infection: Pathogenesis, Diagnostic Approach, and Management
Hematol. Rep. 2023, 15(2), 225-243; https://doi.org/10.3390/hematolrep15020024 - 03 Apr 2023
Viewed by 927
Abstract
Coronavirus disease 2019 (COVID-19) increases the risk of thromboembolic events, especially in patients with severe infections requiring intensive care and cardiorespiratory support. COVID-19 patients with thromboembolic complications have a higher risk of death, and if they survive, these complications are expected to negatively [...] Read more.
Coronavirus disease 2019 (COVID-19) increases the risk of thromboembolic events, especially in patients with severe infections requiring intensive care and cardiorespiratory support. COVID-19 patients with thromboembolic complications have a higher risk of death, and if they survive, these complications are expected to negatively affect these patients’ quality of life. Moreover, recent data reported that the risk of thromboembolism remains high months after a COVID-19 infection. Therefore, understanding the pathogenesis of thrombosis in the setting of COVID-19 may facilitate the early prevention and treatment of COVID-19-associated thromboembolism to reduce concomitant morbidity, mortality, and disability. This review will first discuss the clinical characteristics of COVID-19 infections, particularly with regard to the underlying pathophysiology. Then, the pathogenesis of COVID-19-associated thrombosis at the molecular and cellular levels will be comprehensively reviewed. Next, the clinical manifestations of venous and arterial thromboembolism in COVID-19 as well as the potential benefits of several laboratory markers of thrombosis will be further discussed. Lastly, the preventive and therapeutic management of thromboembolism during and after COVID-19 will also be explained. Full article
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