Μελέτη του ινωδολυτικού μηχανισμού ασθενών με ιδιοπαθή θρομβοκυττάρωση με τη μέθοδο της θρομβοελαστογραφίας

Η Ιδιοπαθής θρομβοκυττάρωση ανήκει στα Ph αρνητικά Μυελοΰπερπλαστικά νοσήματα. Οι ασθενείς με ΙΘ κινδυνεύουν από θρομβωτικές επιπλοκές, που αποτελούν την κύρια αιτία νοσηρότητας και θνητότητας. Τα θρομβωτικά επεισόδια αφορούν το αρτηριακό και φλεβικό δίκτυο, αλλά και την μικροκυκλοφορία. Διάφοροι παράγοντες κινδύνου για θρόμβωση έχουν αναγνωριστεί, με κυριότερους την ηλικία άνω των 60 ετών, το προηγούμενο ιστορικό θρόμβωσης και την παρουσία της μετάλλαξης JAK2V617F.Επίσης, διάφορα μοντέλα διαστρωμάτωσης κινδύνου έχουν προταθεί για την ανάδειξη των ασθενών υψηλού κινδύνου, όπως το IPSET-t score. Η παθοφυσιολογία της θρόμβωσης στην Ιδιοπαθή θρομβοκυττάρωση είναι σύνθετη και πολυπαραγοντική. Η αλληλεπίδραση και η ενεργοποίηση λευκών αιμοσφαιρίων και αιμοπεταλίων-με τη δημιουργία συσσωρεύσεων μεταξύ αυτών των κυττάρων-, ο ρόλος της χρόνιας φλεγμονής, της νέτωσης, η ενεργοποίηση του καταρράκτη της πήξης από τα μικροκυστίδια και η δυσλειτουργία του ενδοθηλίου παίζουν πρωτεύοντα ρόλο στην παθογένεση της θρόμβωσης. Τα παραπάνω βρίσκονται υπό την επίδραση μεταλλάξεων, όπως η JAK2V617F, η CALR και η MPL.Και ενώ η προπηκτική διάθεση των ασθενών αυτών έχει σε μεγάλο βαθμό διαλευκανθεί, ασαφής παραμένει η συμπεριφορά τους μετά τη δημιουργία του θρόμβου, καθότι το ινωδολυτικό σύστημα σε αυτή την ομάδα ασθενών είναι λιγότερο μελετημένο. Σε αυτή την εργασία μελετήσαμε το ινωδολυτικό σύστημα 15 ασθενών με ΙΘ, χρησιμοποιώντας μια νέα μέθοδο Σφαιρικής θρομβοελαστογραφίας, το TPA test, δηλαδή γρήγορη ενεργοποίηση της ινωδόλυσης με την προσθήκη σε ολικό αίμα Ιστικού ενεργοποιητή του πλασμινογόνου. Ασθενείς κατά τη διάγνωση του νοσήματος ή με αντίσταση στην ασπιρίνη εμφανίζουν αντίσταση στην ινωδόλυση. Η χορήγηση Υδροξυουρίας φαίνεται να μειώνει αυτήν την αντίσταση και να βελτιώνει το πηκτικό προφίλ των ασθενών.Essential Thrombocythemia (ET) belongs to Philadelphia negative Myeloproliferative disorders, according to the 2016 WHO classification of Hemopeitic neoplasms. Patients with ET suffer from vascular complications, thrombotic and hemorrhagic, which consist the main cause of morbidity and mortality. Thrombotic events affect both arterial and vein vessels. Several risk factors for thrombosis have been identified, such as age>60 years, history of thrombosis and the presence of JAK2V617F mutation. Furthemore, many models for stratification of thrombotic risk have been proposed, such as IPSET score. The underlying mechanism of thrombosis in Essential Thrombocythemia is complex and multifactorial. The activation and interaction of white blood cells and platelets, the role of chronic inflammation, NETs, the endothelium disfunction, the role of microparticles and the subsequent activation of the coagulation cascade play a crucial role in the pathogenesis of thrombosis. Certain driver mutations, such as JAK2V617F, MPL and CALR enhance the thrombotic tendency of these patients. Despite the fact that the procoagulant state of patients with Essential thrombocythemia is greatly elucidated, their behavior after the cloat formation remains obscure, since their fibrinolytic system is less studied. In this small study we assessed the fibrinolytic system of 15 patients with ET, using a new test of global Thromboelastography, the TPA test. We cause fast activation of fibrinolysis using Tissue Factor Activator of Plasminogen (TPA) in whole blood. Patients with ET at diagnosis or with resistance to Aspirin display a resistance in fibrinolysis, which contributes to the thrombotic profile of this group of patients. The administration of Hydroxyurea seems to reduce the resistance to fibrinolysis, hence improves the procoagualant tendency

Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR?=?1.022, 95%CI 1.007?1.038 and OR?=?1.025, 95%CI 1.001?1.051, respectively), while thromboprophylaxis use was protective (OR?=?0.199, 95%CI 0.061?0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR?=?1.062, 95%CI 1.017-1.109 and OR?=?2.438, 95%CI 1.023-5.813, respectively). CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration

COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated

The evolving landscape of COVID‐19 and post‐COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations

Pregnancy Complications in a-Thalassemia (Hemoglobinopathy H): A Case Study.

Thalassemia intermedia (TI) is a clinical definition which represents a wide spectrum of thalassemia genotypes but mainly includes patients who do not require or only occasionally require transfusion. An uncommon case of a 32-year-old Greek woman, para 1, at the 22nd week + day 3 of gestation with thalassemia intermedia (she was splenectomized), where her pregnancy was complicated with portal vein thrombosis, splenic thrombosis, and partial HELLP, is described. This is a generally uncommon event in thalassemia intermedia. She had no transfusion as her hematologist consulted and she took anticoagulation therapy. Thus, we present for the first time in the literature a case of HbH a-thalassemia pregnant woman whose pregnancy was complicated with portal vein thrombosis, splenic vein thrombosis, and partial HELLP; she was treated with anticoagulation therapy and she had a successful outcome

Pregnancy Complications in a-Thalassemia (Hemoglobinopathy H): A Case Study

Thalassemia intermedia (TI) is a clinical definition which represents a wide spectrum of thalassemia genotypes but mainly includes patients who do not require or only occasionally require transfusion. An uncommon case of a 32-year-old Greek woman, para 1, at the 22nd week + day 3 of gestation with thalassemia intermedia (she was splenectomized), where her pregnancy was complicated with portal vein thrombosis, splenic thrombosis, and partial HELLP, is described. This is a generally uncommon event in thalassemia intermedia. She had no transfusion as her hematologist consulted and she took anticoagulation therapy. Thus, we present for the first time in the literature a case of HbH a-thalassemia pregnant woman whose pregnancy was complicated with portal vein thrombosis, splenic vein thrombosis, and partial HELLP; she was treated with anticoagulation therapy and she had a successful outcome

Serum ferritin levels in previously untreated classical Hodgkin lymphoma: correlations and prognostic significance

Serum ferritin (SF) is frequently elevated in classical Hodgkin lymphoma (cHL). We report on its prognostic significance in an unselected series of 529 cHL patients treated with state-of-the-art therapy. Higher baseline levels correlated with markers of advanced/aggressive disease. SF levels were significantly higher in male and older patients, those with high body mass index and mixed cellularity histology. The strongest correlation was recorded between SF and complement reactive protein (CRP) levels. Gender-specific SF cutoffs which provided the best discrimination in terms of freedom from progression (FFP) were identified. In multivariate analysis elevated SF levels, advanced stage and high lactate dehydrogenase (LDH) were independent prognostic factors of inferior FFP. SF also appears to retain independent prognostic significance for progression-free survival (PFS) but not for overall survival (OS). In conclusion, SF levels in cHL reflect disease activity and are associated with adverse patient outcomes

Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively). CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration