1,720,985 research outputs found
IMMUNE THROMBOTIC THROMBOCYTOPENIC PURPURA: PATHOPHYSIOLOGY, DIAGNOSIS AND OPEN ISSUES.
No full textImmune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and ischemic end organ injury due to microvascular platelet-rich thrombi. iTTP pathophysiology is based on a severe ADAMTS13 deficiency, the specific von Willebrand factor (vWF)-cleaving protease, due to anti-ADAMTS13 autoantibodies. Early diagnosis and treatment reduce the mortality. Front-line therapy includes daily plasma exchange (PEX) with fresh frozen plasma replacement and immunosuppression with corticosteroids. Caplacizumab is recently added to the front-line therapy. Caplacizumab is a nanobody that binds to the A1 domain of vWF, blocking the interaction of ultra-large vWF multimers with the platelet, and thereby preventing the formation of platelet-rich thrombi. Caplacizumab reduces mortality due to ischemic events, refractoriness and exacerbations after PEX discontinuation. Until now, the criteria for response to treatment mainly took into account the normalization of platelet count and discontinuation of PEX, now with the use of caplacizumab, leading to rapid normalization of platelet count, it has been necessary to redefine the response criteria, taking into account also the underlying autoimmune disease. Monitoring of ADAMTS13 activity is important to identify cases with low value of activity (<10IU/L), requiring the optimization of immunosuppressive therapy with addition of rituximab. Rituximab is effective in patients with refractory disease or relapsing disease, currently the use of rituximab has expanded, both in front line treatment, and during follow-up as pre-emptive approach. Some patients do not achieve an ADAMTS13 remission following the acute phase despite steroids and rituximab treatment, requiring an individualized immunosuppressive approach to prevent clinical relapse. In iTTP, there is an increased risk of venous thrombotic events (VTEs) as well as arterial thrombotic events and most occur after platelet normalization. Until now, there is no consensus on the use of pharmacological thromboprophylaxis in patients on caplacizumab, because the drug is known to increase bleeding-risk
Severe Thrombotic Complications in Congenital Afibrinogenemia: A Pathophysiological and Management Dilemma
No full textCongenital afibrinogenemia (CA) is a disease characterized by a complex pathophysiology, involving both the procoagulant and fibrinolytic systems, as well as platelet activity. Although hemorrhagic diathesis represents the most frequent clinical presentation of this disorder, severe thrombotic events can occur. It is not yet clear if these events are strictly related to the disease itself or to the fibrinogen replacement therapy. Different hypotheses on the pathophysiological mechanisms have been proposed. It is well known that fibrinogen/fibrin has a role in the downregulation of thrombin generation in plasma. In the absence of circulating fibrinogen, this "antithrombin" activity is missing and plasma thrombin levels rise; this excess of thrombin could promote clotting of the infused fibrinogen, initiating the thrombotic process. Furthermore, the observation of impaired plasmin generation in the plasma of CA patients has raised the hypothesis of a fibrinolytic system deficiency. We report the case of a CA male patient who at the age of 36 years experienced an arterial thrombosis in his left lower limb. Despite an aggressive medical treatment with low-molecular-weight heparin, fibrinolytic and antiplatelet agents, the arterial thrombosis progressed to the obstruction of the whole left arterial district and the patient underwent the amputation of the left lower limb. This case demonstrates the complexity of pathophysiology and clinical management of a "so-called" bleeding disorder as CA
True vs. false immune-mediated thrombotic thrombocytopenic purpura exacerbations: a clinical case in the caplacizumab era
No full textAcquired thrombotic thrombocytopenic purpura (aTTP) is a medical emergency requiring urgent plasma exchange and immunosuppressive agents. Recently, the therapeutic options have been expanded by the approval of a novel anti-von Willebrand factor (vWF) nanobody, caplacizumab, inhibiting vWF-platelet aggregation. Here, we present a rare case of a patient affected by immune-mediated TTP (iTTP) reporting ischemic stroke caused by a real iTTP exacerbation during caplacizumab administration and subsequent pancytopenia caused by cytomegalovirus (CMV) infection that mimicked another iTTP exacerbation. The case is a real-life example of a not-frequent iTTP exacerbation in the caplacizumab era and of the new management issues arising with the introduction of the new drugs in clinical practice, highlighting the need of new comprehensive response criteria and treatment guidelines
Risk of secondary hypogammaglobulinaemia after Rituximab and Fludarabine in indolent non-Hodgkin lymphomas: a retrospective cohort study
No full textThe occurrence of secondary hypogammaglobulinemia (SH) after chemo-immunotherapy represents a potential side effect in patients with indolent non-Hodgkin lymphomas (iNHL). Few data are available on SH occurring after chemotherapy and/or Rituximab (R). We retrospectively investigated the incidence and the risk factors for SH and infectious complications in patients with iNHL after chemo-immunotherapy. Two hundred and sixty six patients treated between 1993 and 2011 were studied. Patients with a basal hypogammaglobulinemia or a monoclonal component were excluded. The incidence of SH was 2.2×1000 person-years (95% CI 1.6-2.9). Exposure to Fludarabine-based schedules (Fbs)±R was associated with a hazard ratio (HR) of 18.1 (95% CI: 4.3-77.0). Conversely, exposure to CHOP±R or CVP±R was not a risk factor (HR 0.3, 95% CI: 0.1-0.8; HR 0.3, 95% CI: 0.08-1.4, respectively). The role of R was studied comparing cohorts differing only for R; no differences were found comparing R-CHOP/R-CVP versus CHOP/CVP (HR 1.07, 95% CI: 0.38-3.05) and R-Fbs versus Fbs (HR 2.07, 95% CI: 0.62-6.99). Autologous stem cell transplantation (ASCT) is also a risk factor (HR: 5.2, 95% CI 2.1-13.0). SH patients presented a high risk for pneumonia development (HR 7.07 95% CI: 2.68-18.44). We recommend monitoring of serum immunoglobulins in an attempt to reduce the probability of infection after Fbs or ASCT
Reduced transmission of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) in patients with haematological malignancies hospitalized in an Italian hospital during the COVID-19 pandemic
Full text linkObjectives: During the lockdown that started in Italy on 10 March 2020 to address the COVID-19 pandemic,
aggressive procedures were implemented to prevent SARS-CoV-2 transmission in SARS-CoV-2-negative patients
with haematological malignancies. These efforts progressively reduced Klebsiella pneumonia carbapenemase-
producing K. pneumoniae (KPC-KP) spread among these patients. Here we evaluated the potential effects of
measures against COVID-19 that reduced KPC-KP transmission.
Patients and methods: We analysed KPC-KP spread among 123 patients with haematological malignancies,
hospitalized between March and August 2020, who were managed using measures against COVID-19. Their
outcomes were compared with those of 80 patients hospitalized during the preceding 4 months (November
2019–February 2020).
Results: During March–August 2020, 15.5% of hospitalized patients were KPC-KP positive, compared with 52.5%
in November 2019–February 2020 (P , 0.0001); 8% and 27.5% of patients in these two groups were newly KPC-
KP positive, respectively (P " 0.0003). There were eight new KPC-KP-positive patients during January 2020 and
none during June 2020. The weekly rate of hospitalized KPC-KP-positive patients decreased from 50% during
March 2020 to 17% during August 2020. Four KPC-KP bloodstream infections (BSIs) were experienced by 123
patients (3%) in March–August 2020, and seven BSIs (one fatal) by 80 patients (8%) in November 2019–February
2020 (P " 0.02). Consumption and expense of ceftazidime/avibactam administered to KPC-KP-positive patients
significantly decreased in March–August 2020.
Conclusions: Aggressive strategies to prevent SARS-CoV-2 transmission were applied to all hospitalized patients,
characterized by high levels of KPC-KP endemicity and nosocomial transmission. Such measures prevented
SARS-CoV-2 infection acquisition and KPC-KP horizontal transmission. Reduced KPC-KP spread, fewer associated
clinical complications and decreased ceftazidime/avibactam consumption represented unexpected ‘collateral
benefits’ of strategies to prevent COVID-19
Autologous stem cell transplantation in favorable-risk acute myeloid leukemia: single-center experience and current challenges
No full textBackground Autologous stem cell transplantation (ASCT) has gained growing consideration as a treatment option for favorable-risk acute myeloid leukemia (FR-AML) in first complete remission (CR1), compared with chemotherapy. Materials and Methods We report the long-term outcomes of 117 consecutive patients with FR-AML fit for intensive chemotherapy diagnosed in our center between 1999 and 2020, who underwent ASCT. Results Sixty-five of the 117 were eligible for intensive post-remission treatment, and 42 of those 65 received ASCT. Median follow up was 132 months. Overall survival (OS) and disease-free survival (DFS) were 75% and 76%. Higher doses of CD34 + stem cell infusions negatively impacted DFS in multivariate analysis. Core-binding factor (CBF) leukemia was an independent prognostic factor for improved DFS. No differences based on pre-transplant measurable residual disease (MRD) were observed. In CBF leukemia, 10-year DFS is 72% for MRD-positive patients versus 100% for MRD negative patients. Conclusions ASCT is effective and safe in FR-AML patients. In CBF leukemia, ASCT provides excellent results regardless of achievement of bone marrow MRD negativity. In NPM1-mutated/FLT3-wild type (mNPM1) AML, early molecular response seems to have more impact on prognosis. Prospective investigation of the role of gemtuzumab ozogamicin in this setting is ongoing
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Covid-19 vaccination in patients with immune-mediated thrombotic thrombocytopenic purpura: a single-referral center experience
Full text linkCases of immune-mediated thrombotic thrombocytopenic purpura (iTTP) following the
administration of vaccines have been described in literature 1-2. Recently, de novo and relapsed iTTP have been reported during SARS-Cov-2 infection3-5 and after the vaccine, mainly with adenoviral and rarely with messenger mRNA vaccines6-11. The French Reference Center for Thrombotic Microangiopathies conducted a large multicenter retrospective study to investigate the possible link between COVID-19 vaccine and the new-onset or recurrence of iTTP. Results showed that vaccination does not trigger relapse in these patients, particularly if they are regularly monitored and do not have low ADAMTS13 enzyme activity12. Similar results were described by the Vaccine Adverse Event Reporting System (VAERS), the US passive surveillance system for adverse events after immuniziation13. COVID-19 vaccine did not increase the risk of de novo or relapsed iTTP, except in individuals in hematologic remission with extremely low ADAMTS13 activity (<20%)12-13.
We report here our single-center experience in 33 patients with preexisting iTTP, followed at our Institute, who received regular mRNA COVID-19 vaccinatio
Benefits and Safety of Empiric Antibiotic Treatment Active Against KPC-K. pneumoniae in Febrile Neutropenic Patients with Acute Leukemia Who are Colonized with KPC-K. pneumoniae. A 7-Years Retrospective Observational Cohort Study
No full textPURPOSE: To evaluate the benefits and safety of the empiric antibiotic treatment (EAT) active against KPC-K. pneumoniae in febrile neutropenic patients with acute leukaemia (AL) who are colonised by KPC-K. pneumoniae. PATIENTS AND METHODS: A 7-year (2013–2019) retrospective observational cohort study was conducted at the Haematology, Sapienza Rome University (Italy) on 94 febrile neutropenia episodes (FNE) in AL patients KPC-K. pneumoniae carriers treated with active EAT. RESULTS: Eighty-two (87%) FNE were empirically treated with antibiotic combinations [38 colistin-based and 44 ceftazidime-avibactam (CAZAVI)-based], 12 with CAZAVI monotherapy. Successful outcomes were observed in 88/94 (94%) FNE, 46/49 (94%) microbiologically documented infections, and 24/27 (89%) gram-negative bloodstream infections (GNB-BSI). Mortality due to infective causes was 4.2% (2.1% within 1 week). KPC-K. pneumoniae infections caused 28/94 FNE (30%) and KPC-K. pneumoniae-BSI was documented in 22 FNE (23.4%) (85% of GNB-BSI), in all cases patients received active EAT, and 21 survived. KPC-K.pneumoniae-BSI mortality rate was 4.5%. CAZAVI-based EAT showed better results than colistin-based EAT (55/56 vs 33/38, p = 0.037), overall and without EAT modification (41/56 vs 20/38, p = 0.02). Empirical combinations including CAZAVI were successful in 98% of cases (43/44 vs 33/38 for colistin-based EAT, p = 0.01), without modifications in 82% (36/44 vs 20/28, p = 0.02). All deaths occurred in patients treated with colistin-based EAT (4/38 vs 0/56, p = 0.02). CAZAVI-containing EAT was the only independent factor for an overall successful response (HR 0.058, CI 0.013–1.072, p = 0.058). Nephrotoxicity occurred in 3(8%) patients undergoing colistin-based EAT (none in those undergoing CAZAVI-based EAT, p = 0.02). CONCLUSION: KPC-K. pneumoniae infections are frequent in colonised AL patients with FNE. EAT with active antibiotics, mainly CAZAVI-based combinations, was effective, safe, and associated with low overall and KPC-K. pneumoniae-BSI-related mortality
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