Browsing by Author "Pantic, Nikola (57221630977)"

Patients with acute leukemia (AL) have a high mortality rate from coronavirus disease 2019 (COVID-19). However, studies including patients with AL and COVID-19 are few. Fifty-one patients with AL and COVID-19 were included in our study. The mortality rate was 17/51 (29.4%). In all cases, death was associated with COVID-19 pneumonia. The major driver of outcome was the disease status (worse outcome was observed in newly diagnosed (OR, 6.00; 95% CI, 1.133–15.188) and patients with bone marrow aplasia (OR 4.148 [95% CI 1.133–15.188])). Higher mortality rate was associated with lower platelet count, prolonged PT, higher ISTH DIC score, CRP and LDH. Moreover, careful risk-benefit assessment regarding the continuation of anticancer therapy is required in patients receiving nonintensive and supportive therapy. Considering the high frequency of intrahospital viral transmission (50.98%), isolation of AL patients in single rooms, and permanent symptom monitoring and testing should be prioritized. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

Patients with acute leukemia (AL) have a high mortality rate from coronavirus disease 2019 (COVID-19). However, studies including patients with AL and COVID-19 are few. Fifty-one patients with AL and COVID-19 were included in our study. The mortality rate was 17/51 (29.4%). In all cases, death was associated with COVID-19 pneumonia. The major driver of outcome was the disease status (worse outcome was observed in newly diagnosed (OR, 6.00; 95% CI, 1.133–15.188) and patients with bone marrow aplasia (OR 4.148 [95% CI 1.133–15.188])). Higher mortality rate was associated with lower platelet count, prolonged PT, higher ISTH DIC score, CRP and LDH. Moreover, careful risk-benefit assessment regarding the continuation of anticancer therapy is required in patients receiving nonintensive and supportive therapy. Considering the high frequency of intrahospital viral transmission (50.98%), isolation of AL patients in single rooms, and permanent symptom monitoring and testing should be prioritized. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

Introduction: Hemorrhagic early death (HED) remains a major cause of treatment failure among patients with acute promyelocytic leukemia (APL). We aimed to investigate the prognostic potential of rotational thromboelastometry (ROTEM) for bleeding in patients with APL. Materials and Methods: 31 newly-diagnosed APL patients (median age of 40 years; 14 female/17 male) that underwent treatment at the Clinic of Hematology UCCS from 2016-2020 with all-trans retinoic acid and anthracyclines were recruited. CBCs (complete blood count), conventional coagulation tests (CCTs), and ROTEM parameters obtained before treatment initiation were evaluated. Results: All patients demonstrated at least one ROTEM parameter out of the reference range. ROTEM parameters associated with significant hemorrhage were EXTEM clotting time (CT) (P = 0.041) and INTEM amplitude 10 (A10) (P = 0.039), however, only EXTEM CT (P = 0.036) was associated with HED. Among CBCs and CCTs, only platelets were associated with significant bleeding (P = 0.015), while D-dimer was associated with both bleeding and HED (P = 0.001 and P = 0.002, respectively). Conclusion: Our results indicate that ROTEM parameters may reveal hypocoagulability in APL patients and have the potential to improve current hemorrhage prognostic methods. Additionally, these results suggest the combination of ROTEM and CCTs might be useful in identifying patients at risk for HED. © The Author(s) 2022.

Background: Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. Aim: The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. Methods: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. Results: Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23–6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581–63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329–13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212–23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948–21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092–5.007). Conclusions: Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30. © 2023 by the authors.

Background: Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. Aim: The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. Methods: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. Results: Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23–6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581–63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329–13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212–23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948–21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092–5.007). Conclusions: Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30. © 2023 by the authors.

Background: Cytarabine-anthracycline-based induction chemotherapy remains the standard of care for remission induction among patients with newly diagnosed acute myeloid leukaemia (AML). There are remarkable differences in therapy response among AML patients. This fact could be partly explained by the patients’ genetic variability related to the metabolic paths of cytarabine and anthracyclines. This study aims to evaluate the effect of variants in pharmacogenes SLC29A1, DCK, ABCB1, GSTM1, and GSTT1, as well as laboratory and AML-related parameters on clinical outcomes in adult AML patients. Methods: A total of 100 AML patients were included in the study. Pharmacogenetic variants SLC29A1 rs9394992, DCK rs12648166, ABCB1 rs2032582, and GSTM1 and GSTT1 gene deletions were detected by methodology based on PCR, fragment analysis and direct sequencing. The methods of descriptive and analytic statistics were used. Survival analysis was done using the Kaplan-Meier method using the Log-Rank test. Results: This is the first study of adult AML pharmacogenetics in the Serbian population. Clinical outcomes in our cohort of AML patients were not impacted by analysed variants in SLC29A1, DCK, ABCB1 and GSTT1, and GSTM1 genes, independently or in combinations. Achievement of complete remission was identified as an independent prognostic indicator of clinical outcome. Conclusions: The population-specific genomic profile has to be considered in pharmacogenetics. Since the data on AML pharmacogenetics in European populations is limited, our results contribute to knowledge in this field and strongly indicate that a high-throughput approach must be applied to find particular pharmacogenetic markers of AML in the European population. © 2024 Society of Medical Biochemists of Serbia. All rights reserved.

Background: Cytarabine-anthracycline-based induction chemotherapy remains the standard of care for remission induction among patients with newly diagnosed acute myeloid leukaemia (AML). There are remarkable differences in therapy response among AML patients. This fact could be partly explained by the patients’ genetic variability related to the metabolic paths of cytarabine and anthracyclines. This study aims to evaluate the effect of variants in pharmacogenes SLC29A1, DCK, ABCB1, GSTM1, and GSTT1, as well as laboratory and AML-related parameters on clinical outcomes in adult AML patients. Methods: A total of 100 AML patients were included in the study. Pharmacogenetic variants SLC29A1 rs9394992, DCK rs12648166, ABCB1 rs2032582, and GSTM1 and GSTT1 gene deletions were detected by methodology based on PCR, fragment analysis and direct sequencing. The methods of descriptive and analytic statistics were used. Survival analysis was done using the Kaplan-Meier method using the Log-Rank test. Results: This is the first study of adult AML pharmacogenetics in the Serbian population. Clinical outcomes in our cohort of AML patients were not impacted by analysed variants in SLC29A1, DCK, ABCB1 and GSTT1, and GSTM1 genes, independently or in combinations. Achievement of complete remission was identified as an independent prognostic indicator of clinical outcome. Conclusions: The population-specific genomic profile has to be considered in pharmacogenetics. Since the data on AML pharmacogenetics in European populations is limited, our results contribute to knowledge in this field and strongly indicate that a high-throughput approach must be applied to find particular pharmacogenetic markers of AML in the European population. © 2024 Society of Medical Biochemists of Serbia. All rights reserved.

There are limited data on the impact of severe acute respiratory syndrome corona virus 2 infection in patients previously diagnosed with primary immune thrombocytopenia (ITP) on thrombopoietin receptor agonist therapy (TPO-RA). Seven chronic ITP patients who had contracted COVID-19 and had been treated with TPO-RA are included in the study. Demographic, ITP treatment and comorbidities data were collected retrospectively from patients' medical records. Data regarding clinical course of COVID-19 were collected prospectively. During the infection, all patients had platelet count higher than average, and platelet count peak was mainly observed on day 7. For that reason, therapy modification was required. However, platelet count increment was transient in most ITP patients. One patient developed pulmonary embolism despite the use of therapeutic dose of anticoagulants. One patient died of respiratory failure whereas another developed rebound thrombocytopenia after the infection and consequential intracerebral hemorrhage. Careful platelet count monitoring and therapy management are needed in chronic ITP patients on TPO-RAs with COVID-19. © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired clonal haematological disease characterized by complement-mediated haemolysis, bone marrow failure and venous thrombosis. Anticomplement therapy eculizumab improves survival and reduces complications. Severe acute respiratory distress syndrome corona virus 2 (SARS-CoV-2) disease 2019 (COVID-19) is associated with high incidence of both venous and arterial thrombosis in hospitalized patients with pneumonia. Deep venous thrombosis (DVT) as the presenting symptom of COVID-19 is a rare event. We describe a well-controlled PNH patient on eculizumab for more than 5 years who presented with DVT, while on warfarin, as the first sign of COVID-19. To our knowledge, this is the first described case of DVT in a PNH patient with COVID-19. © 2021 Georg Thieme Verlag. All rights reserved.

Patients with coronavirus disease 19 (COVID-19) have increased susceptibility to secondary respiratory infections including invasive pulmonary aspergillosis (IPA). COVID-19-associated pulmonary aspergillosis (CAPA) is difficult to diagnose and can be associated with increased mortality especially in severe immunodeficiency such as hematological malignancies. Our study evaluates IPA in COVID-19 patients defined as COVID-19-CAPA among patients with acute leukemia (AL). A retrospective single-center study analyzed 46 patients with COVID-19 infection and acute leukemia, admitted to the Clinic for Haematology, Clinical Center of Serbia, Belgrade between the 2 April 2020 and 15 May 2021. During hospitalization, all participants were diagnosed with probable IPA according to the previous consensus definitions. Positive serology and galactomannan (GM) detection values in bronchoalveolar lavage (BAL) and serum were used as microbiological criteria. COVID-19 associated probable IPA was found in 22% (9/41) tested patients, where serum GM and IgM anti-Aspergillus antibodies were positive in 12% (5/41) and 10% (4/41) had positive serology for aspergillosis. One patient died while eight recovered during follow-up. Our study showed that COVID-19 might be a risk factor for IPA development in patients with AL. Early diagnosis and prompt treatment are required as reported mortality rates are high. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Patients with coronavirus disease 19 (COVID-19) have increased susceptibility to secondary respiratory infections including invasive pulmonary aspergillosis (IPA). COVID-19-associated pulmonary aspergillosis (CAPA) is difficult to diagnose and can be associated with increased mortality especially in severe immunodeficiency such as hematological malignancies. Our study evaluates IPA in COVID-19 patients defined as COVID-19-CAPA among patients with acute leukemia (AL). A retrospective single-center study analyzed 46 patients with COVID-19 infection and acute leukemia, admitted to the Clinic for Haematology, Clinical Center of Serbia, Belgrade between the 2 April 2020 and 15 May 2021. During hospitalization, all participants were diagnosed with probable IPA according to the previous consensus definitions. Positive serology and galactomannan (GM) detection values in bronchoalveolar lavage (BAL) and serum were used as microbiological criteria. COVID-19 associated probable IPA was found in 22% (9/41) tested patients, where serum GM and IgM anti-Aspergillus antibodies were positive in 12% (5/41) and 10% (4/41) had positive serology for aspergillosis. One patient died while eight recovered during follow-up. Our study showed that COVID-19 might be a risk factor for IPA development in patients with AL. Early diagnosis and prompt treatment are required as reported mortality rates are high. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Inferior vena cava (IVC) anomalies are uncommon congenital causes of deep vein thrombosis (DVT). KILT syndrome (kidney and IVC abnormalities with leg thrombosis) has only been described as case reports in the literature. Therefore, the characteristics, evaluation, and management of patients with KILT syndrome have not yet been standardized. This study aimed to systematically review and analyze the clinical and radiographic data and treatment of previously reported cases of KILT syndrome. In this systematic review, we performed a literature search of the PubMed, Scopus, and Web of Science databases in December 2023, with no restrictions on the publication date. After duplicate extractions, 4195 articles were screened. Case reports and case series reporting on KILT syndrome were included. In addition to previously published cases, we included a new case of a previously healthy 25-year-old man with KILT syndrome in the analysis. A total of 34 cases were therefore included in this study. The majority (76.5%) were male patients with a median age of 24 years. In most patients, unprovoked bilateral iliofemoral thrombosis was diagnosed, and 64.7% had left kidney abnormalities. Our study suggests that anomalies of the IVC should be suspected in all young patients, especially male patients, with proximal, recurrent, or idiopathic DVT. If an IVC anomaly is confirmed, the kidneys should be examined to monitor and preserve healthy kidneys in cases of KILT syndrome. The data collected from all patients emphasize the requirement of long-term anticoagulation and risk factor control. Surgical measures may be effective for treating symptomatic refractory cases. © The Author(s) 2024.

Hemophagocytic lymphohistiocytosis (HLH) secondary to tick-borne infections is a rare but potentially life-threatening syndrome. We performed a scoping review according to PRISMA guidelines to systematically analyze the existing literature on the topic. A total of 98 patients were included, with a mean age of 43.7 years, of which 64% were men. Most cases, 31%, were reported from the USA. Immunosuppression was present in 21.4%, with the most common cause being previous solid organ transplantation. Constitutional symptoms were the most common, observed in 83.7% of the patients, while fever was reported in 70.4% of cases. Sepsis was present in 27.6%. The most common laboratory abnormalities in this cohort were thrombocytopenia in 81.6% of patients, while anemia, leukopenia, and leukocytosis were observed in 75.5%, 55.1%, and 10.2%, respectively. Liver enzyme elevation was noted in 63.3% of cases. The H-score was analyzed in 64 patients, with the mean value being 209, and bone marrow analysis was performed in 61.2% of patients. Ehrlichia spp. was the main isolated agent associated with HLH in 45.9%, followed by Rickettsia spp. in 14.3% and Anaplasma phagocytophilum in 12.2%. Notably, no patient with Powassan virus infection or Lyme borreliosis developed HLH. The most common complications were acute kidney injury (AKI) in 35.7% of patients, shock with multiple organ dysfunction in 22.5%, encephalopathy/seizure in 20.4%, respiratory failure in 16.3%, and cardiac complications in 7.1% of patients. Treatment included antibiotic therapy alone in 43.9%, while 5.1% of patients were treated with immunosuppressants alone. Treatment with both antibiotics and immunosuppressants was used in 51% of patients. Appropriate empiric antibiotics were used in 62.2%. In 43.9% of cases of HLH due to tick-borne disease, patients received only antimicrobial therapy, and 88.4% of those recovered completely without the need for immunosuppressive therapy. The mortality rate in our review was 16.3%, and patients who received inappropriate or delayed empiric therapy had a worse outcome. Hence, we suggest empiric antibiotic treatment in patients who are suspected of having HLH due to tick-borne disease or in whom diagnostic uncertainty persists due to diagnostic delay in order to minimize mortality. © 2024 by the authors.

Coagulopathy continues to be a major challenge in the management of patients with acute promyelocytic leukemia (APL). Novel differentiating agents have led to improved survival in these patients, but perturbations in coagulation continue to have an impact on their prognosis. The most worrisome of coagulation disturbances is bleeding, which is not an uncommon cause of early death in APL. Despite this, there are no consistent predictors of this high risk of fatal hemorrhage in APL. In this context, the fibrinolytic system has been identified as a crucial role player in APL coagulopathy. However, the current guidelines for the management of APL give little regard to tests that measure the fibrinolytic system while giving more importance to close monitoring of conventional coagulation tests and platelet counts to identify the coagulopathy. More recently, viscoelastic tests have come to usefulness in determining global hemostasis and have been widely used for “diagnosing” hyperfibrinolysis in selected clinical settings. In this review, we attempt to describe risk assessment models for diagnosing APL coagulopathy, describe the possible application of viscoelastic tests in this setting, and persuade clinicians to reconsider the use of antifibrinolytics to improve survival of APL patients. © 2024 The Authors

Examination of central nervous system (CNS) involvement is not routine diagnostic practice in adult patients with acute myeloid leukemia (AML). Therefore, many asymptomatic patients with CNS involvement might go undetected. The effect of CNS involvement on the AML disease course is not well defined, with conflicting results regarding clinical outcome. This study aimed to determine the incidence of asymptomatic CNS involvement in AML estimated by multiparametric flow cytometry of cerebrospinal fluid (MFC-CSF) at diagnosis, the related potential risk factors, and prognosis. In total, 645 patients with de novo AML were screened; 183 (28.4%) of them fulfilled institutional practice for MFC-CSF analysis based on presence of CNS symptoms and/or clinical features. CNS symptoms and signs were observed in 8/183 (4.4%) patients, but most patients (175/183, 95.6%) were asymptomatic. In the asymptomatic group, 73/175 (41.7%) patients had positive or suspicious cerebrospinal fluid (CSF) findings categorized as CNS positive (CNSpos) and 102/175 (58.3%) had normal CNS findings categorized as CNS negative (CNSneg). The presence of leukemic blasts was confirmed in 81/183 (44.3%) patients; the total incidence of CNS involvement in the whole AML group was 12.6% (81/645). Compared with asymptomatic patients with CNSneg, those with CNSpos had a significantly higher frequency of lymphadenopathy, white blood cell count ≥30 × 109/L, presence of the monocytic phenotype, and a high percentage of bone marrow (BM) blasts. The multivariate logistic regression model identified monocytic phenotype (p = 0.047) and high percentage of BM blasts (p = 0.042) as predictors for CNSpos. CNSpos did not affect overall survival in patients with AML. There was a higher incidence of CNS involvement in asymptomatic adult patients with de novo AML, emphasizing possible undervalued rates of CNS disease at diagnosis. Prospective studies should determine whether diagnostic lumbar puncture for MFC-CSF analysis and CNS prophylaxis could contribute to better selection and prognosis in this patient population. © 2024 John Wiley & Sons Ltd.

Examination of central nervous system (CNS) involvement is not routine diagnostic practice in adult patients with acute myeloid leukemia (AML). Therefore, many asymptomatic patients with CNS involvement might go undetected. The effect of CNS involvement on the AML disease course is not well defined, with conflicting results regarding clinical outcome. This study aimed to determine the incidence of asymptomatic CNS involvement in AML estimated by multiparametric flow cytometry of cerebrospinal fluid (MFC-CSF) at diagnosis, the related potential risk factors, and prognosis. In total, 645 patients with de novo AML were screened; 183 (28.4%) of them fulfilled institutional practice for MFC-CSF analysis based on presence of CNS symptoms and/or clinical features. CNS symptoms and signs were observed in 8/183 (4.4%) patients, but most patients (175/183, 95.6%) were asymptomatic. In the asymptomatic group, 73/175 (41.7%) patients had positive or suspicious cerebrospinal fluid (CSF) findings categorized as CNS positive (CNSpos) and 102/175 (58.3%) had normal CNS findings categorized as CNS negative (CNSneg). The presence of leukemic blasts was confirmed in 81/183 (44.3%) patients; the total incidence of CNS involvement in the whole AML group was 12.6% (81/645). Compared with asymptomatic patients with CNSneg, those with CNSpos had a significantly higher frequency of lymphadenopathy, white blood cell count ≥30 × 109/L, presence of the monocytic phenotype, and a high percentage of bone marrow (BM) blasts. The multivariate logistic regression model identified monocytic phenotype (p = 0.047) and high percentage of BM blasts (p = 0.042) as predictors for CNSpos. CNSpos did not affect overall survival in patients with AML. There was a higher incidence of CNS involvement in asymptomatic adult patients with de novo AML, emphasizing possible undervalued rates of CNS disease at diagnosis. Prospective studies should determine whether diagnostic lumbar puncture for MFC-CSF analysis and CNS prophylaxis could contribute to better selection and prognosis in this patient population. © 2024 John Wiley & Sons Ltd.

Introduction: Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections and decrease hospitalisation and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, whereas molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir because it is associated with fewer drug-drug interactions and contraindications. A caveat for molnupiravir is the mode of action induces viral mutations. Mortality rate reduction with molnupiravir was less pronounced than that with nirmatrelvir/ritonavir in patients without haematological malignancy. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, molnupiravir and nirmatrelvir/ritonavir were compared in a cohort of patients with haematological malignancies. Methods: Clinical data from patients treated with molnupiravir or nirmatrelvir/ritonavir monotherapy for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched by sex, age (±10 years), and severity of baseline haematological malignancy to controls treated with nirmatrelvir/ritonavir. Results: A total of 116 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. In each of the groups, 68 (59%) patients were male; with a median age of 64 years (interquartile range [IQR] 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 56.9% (n=66) of the patients had controlled baseline haematological malignancy, 12.9% (n=15) had stable disease, and 30.2% (n=35) had active disease at COVID-19 onset in each group. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of patients in the two groups were vaccinated (molnupiravir n=77, 66% vs. nirmatrelvir/ritonavir n=87, 75%), more of those treated with nirmatrelvir/ritonavir had received four vaccine doses (n=27, 23%) compared with those treated with molnupiravir (n=5, 4%) (P<0.001). No differences were detected in COVID-19 severity (P=0.39) or hospitalisation (P=1.0). No statistically significant differences were identified in overall mortality rate (P=0.78) or survival probability (d30 P=0.19, d60 P=0.67, d90 P=0.68, last day of follow up P=0.68). Deaths were either attributed to COVID-19, or the infection was judged by the treating physician to have contributed to death. Conclusions: Hospitalisation and mortality rates with molnupiravir were comparable to those with nirmatrelvir/ritonavir in high-risk patients with haematological malignancies and COVID-19. Molnupiravir is a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy. © 2023 The Author(s)

Introduction: Thrombopoietin receptor agonists (TPO-RAs) increase platelet counts (PC) in the majority of patients with chronic immune thrombocytopaenia (ITP). Platelet kinetics study (PKS) might contribute to the understanding of mechanisms that lead to durable response. Objectives: To evaluate the effects of TPO-RAs on PKS parameters in chronic ITP patients. Methods: Fifteen chronic ITP patients, aged 59 years [range: 22–84], female/male: 10/5, splenectomised 7/15, were treated with TPO-RAs (eltrombopag/romiplostim: 11/4). Durable response was defined as PC ≥30 × 109/L at 6 months. Autologous 111Indium-oxinate PKS was performed before and 5 months after TPO-RAs initiation. Accordingly, platelet survival (PS), platelet turnover, production ratio and sequestration site were assessed. Results: Durable response was achieved in 13/15 of patients (eltrombopag/romiplostim: 10/3). Pre-treatment parameters were: PC 10 × 109/L [range: 1–110], PS 0.5 days [range: 0.1–1.7 (normal values: 7–10)], platelet turnover 30 857 Plt/μL/day [range: 944–103 500] and platelet production ratio 0.64 [range: 0.01–3.2 (normal values: 1 ± 0.2)]. Post-treatment assessment showed significantly higher: PC 92.5 × 109/L [range: 28–260, p =.001], PS 2.2 days [range: 0.1–3.6, p =.008], platelet turnover 70 213 Plt/μL/day [range: 2800–462 236, p =.02] and platelet production ratio 1.8 [range: 0.5–37.9, p =.011] compared to the pre-treatment values. Platelet sequestration site altered in 3/15 treated with TPO-RAs. Conclusions: TPO-RAs could increase PC by simultaneous increasing of platelet production and decreasing of platelet destruction. © 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Background: Acute promyelocytic leukemia (APL) is frequently associated with disseminated intravascular coagulation (DIC), leading to potentially life-threatening bleeding. Compared to bleeding, thromboses are a less commonly encountered problem. Objective: The objective of our study was to identify the incidence and predictive value of demographic data, clinical–laboratory parameters, and thrombosis risk assessment models (RAMs) for venous thromboembolism (VTE) in patients with APL. Methods: This study was a retrospective study conducted on adult patients with APL who were treated between 2006 and 2024 at the Clinic of Hematology UCCS with all-trans retinoic acid (ATRA) and anthracycline. The demographic and clinical–laboratory data related to VTE were collected and analyzed alongside the predictive value of two RAMs proposed by Al-Ani and Paterno and colleagues. Results: Among the one-hundred-fifty-five adult patients with APL, VTE was diagnosed in twenty-eight cases (18.1%). The most common location for thrombosis was in the central venous catheter (CVC), which affected twelve (42.8%) patients. A total of six (21.4%) patients had deep vein thrombosis (DVT), one patient (3.6%) showed a pulmonary embolism (PE), and thrombosis at unusual sites was present in nine (32.1%) patients. Our analyses showed that neither Al-Ani’s RAM nor the RAM proposed by Paterno and colleagues were predictive for VTE in patients with APL. The C statistics value for the Al-Ani model was ROC = 0.514, and, for Paterno’s RAM, it was ROC = 0.521. The independent risk factors for VTE, identified via multivariate analysis, were CD114 expression (p = 0.005, OR = 6.4 IC 95%: [1.8–23.2]) and the absence of bleeding at presentation (p = 0.013, OR = 0.086 IC 95%: [0.01–0.59]). Conclusions: To the best of our knowledge, this is the first study showing that a higher expression of CD114 increases the risk of VTE. The absence of bleeding at presentation in patients with APL correlates with thrombosis. Further analyses are needed to confirm these findings and help to develop therapeutic strategies to prevent VTE complications. So far, no risk assessment model has been sufficient to stratify patients with APL according to their risk of VTE. © 2024 by the authors.

Background: Acute promyelocytic leukemia (APL) is frequently associated with disseminated intravascular coagulation (DIC), leading to potentially life-threatening bleeding. Compared to bleeding, thromboses are a less commonly encountered problem. Objective: The objective of our study was to identify the incidence and predictive value of demographic data, clinical–laboratory parameters, and thrombosis risk assessment models (RAMs) for venous thromboembolism (VTE) in patients with APL. Methods: This study was a retrospective study conducted on adult patients with APL who were treated between 2006 and 2024 at the Clinic of Hematology UCCS with all-trans retinoic acid (ATRA) and anthracycline. The demographic and clinical–laboratory data related to VTE were collected and analyzed alongside the predictive value of two RAMs proposed by Al-Ani and Paterno and colleagues. Results: Among the one-hundred-fifty-five adult patients with APL, VTE was diagnosed in twenty-eight cases (18.1%). The most common location for thrombosis was in the central venous catheter (CVC), which affected twelve (42.8%) patients. A total of six (21.4%) patients had deep vein thrombosis (DVT), one patient (3.6%) showed a pulmonary embolism (PE), and thrombosis at unusual sites was present in nine (32.1%) patients. Our analyses showed that neither Al-Ani’s RAM nor the RAM proposed by Paterno and colleagues were predictive for VTE in patients with APL. The C statistics value for the Al-Ani model was ROC = 0.514, and, for Paterno’s RAM, it was ROC = 0.521. The independent risk factors for VTE, identified via multivariate analysis, were CD114 expression (p = 0.005, OR = 6.4 IC 95%: [1.8–23.2]) and the absence of bleeding at presentation (p = 0.013, OR = 0.086 IC 95%: [0.01–0.59]). Conclusions: To the best of our knowledge, this is the first study showing that a higher expression of CD114 increases the risk of VTE. The absence of bleeding at presentation in patients with APL correlates with thrombosis. Further analyses are needed to confirm these findings and help to develop therapeutic strategies to prevent VTE complications. So far, no risk assessment model has been sufficient to stratify patients with APL according to their risk of VTE. © 2024 by the authors.