Publications by authors named "Monica Carpenedo"

31 Publications

Practical Recommendations for the Management of Patients with ITP During the COVID-19 Pandemic.

Mediterr J Hematol Infect Dis 2021 1;13(1):e2021032. Epub 2021 May 1.

Istituto di Ematologia "Seràgnoli", IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

The current COVID-19 pandemic requires revisiting our current approach to major blood disorders, including ITP (Immune Thrombocytopenia), stirring up the production of several disease-specific practical guidelines. This report describes an updated version of consensus-based practical guidelines on the management of ITP, adapted to the Italian health system and social context. It highlights the role of the hematologist in offering guidance for choosing differentiated approaches in relation to specific circumstances and is intended to provide them with a useful tool for sharing the decision-making process with their patients. Probably, the greatest risk to avoid for a patient with suspected, ongoing or relapsed ITP - that is not severe enough to place him or her at risk for major bleeding - is to be infected in non-hospital and hospital healthcare settings. This risk must be carefully considered when adapting the diagnostic and therapeutic approach. More in detail, the document first addresses the appropriate management for COVID-19 negative patients with newly diagnosed ITP or who experience a relapse of previous ITP, according to first and second lines of treatment and then the management of COVID-19 positive patients according to their severity, from paucisymptomatic to those requiring admission to Intensive Cure Units (ICU). The pros and cons of the different treatments required to correct platelet count are discussed, as are some specific situations, including chronic ITP, splenectomy, thromboembolic complication and anti COVID-19 vaccination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4084/MJHID.2021.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114883PMC
May 2021

Real-world use of thrombopoietin receptor agonists in elderly patients with primary immune thrombocytopenia.

Blood 2021 Apr 22. Epub 2021 Apr 22.

(Institute of Hematology, Bologna, Italy.

The efficacy and safety of thrombopoietin-receptor agonists (TRAs) in elderly patients with primary immune thrombocytopenia (ITP) is uncertain. In 384 ITP patients treated with TRAs when aged ≥60 years, we investigated TRAs response and switch, thrombotic/hemorrhagic risk, and sustained responses off-treatment (SROT). After 3 months, 82.5% and 74.3% of eltrombopag and romiplostim-treated patients achieved a response, respectively (p=0.09); 66.7% maintained the response (median follow-up: 2.7 years). Eighty-five (22.2%) patients switched to the alternative TRA; while no cross-toxicity was observed, 83.3% of resistant patients had a response after the switch. During TRA, 34 major thromboses (3 fatal) and 14 major hemorrhages (none fatal) occurred in 18 and 10 patients, respectively, and were associated with thrombosis history (SHR: 2.04, p=0.05) and platelet count <20x109/L at TRA start (SHR: 1.69, p=0.04), respectively. A recurrent event occurred in 15.6% of patients surviving thrombosis, in all cases but one during persisting TRA treatment (incidence rate: 7.7 per 100 patient-years). All recurrences occurred in the absence of adequate antithrombotic secondary prophylaxis. Sixty-two (16.5%) responding patients discontinued TRA; 53 (13.8%) patients maintained SROT, which was associated with TRA discontinuation in complete response (p<0.001). Very old age (≥75, 41.1%) was associated with more frequent TRAs start in persistent/acute phase but not with response or thrombotic/hemorrhagic risk. TRAs are effective in elderly ITP patients, with no fatal haemorrhages and with SROT in a significant portion of patients; in patients with thrombosis history caution is warranted and a careful risk/benefit balance should be carried out.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2021010735DOI Listing
April 2021

Eltrombopag second-line therapy in adult patients with primary immune thrombocytopenia in an attempt to achieve sustained remission off-treatment: results of a phase II, multicentre, prospective study.

Br J Haematol 2021 Apr 22;193(2):386-396. Epub 2021 Feb 22.

Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.

Up to 30% immune thrombocytopenia (ITP) patients achieve a sustained remission off-treatment (SROT) after discontinuation of thrombopoietin receptor agonists (TPO-RAs). Factors predictive of response are lacking. Patients aged ≥18 years with newly diagnosed or persistent ITP were treated with eltrombopag for 24 weeks. Primary end-point was SROT: the proportion of responders that were able to taper and discontinue eltrombopag maintaining the response during a period of observation (PO) of six months. Secondary end-points included the association between some immunological parameters (TPO serum levels, cytokines and lymphocyte subsets) and response. Fifty-one patients were evaluable. Primary end-point was achieved in 13/51 (25%) treated patients and 13/34 (38%) patients who started the tapering. Baseline TPO levels were not associated with response at week 24 nor with SROT. Higher baseline levels of IL-10, IL-4, TNF-α and osteopontin were negative factors predictive of response (P = 0·001, 0·008, 0·02 and 0·03 respectively). This study confirms that SROT is feasible for a proportion of ITP patients treated with eltrombopag. Some biological parameters were predictive of response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.17334DOI Listing
April 2021

Best quality indicator of vitamin K antagonist therapy to predict mortality and bleeding in haemodialysis patients with atrial fibrillation.

Blood Transfus 2020 Dec 3. Epub 2020 Dec 3.

School of Medicine and Surgery, University of Milan-Bicocca, Milan.

Background: There is a high prevalence of atrial fibrillation (AF) in patients undergoing haemodialysis. Oral anticoagulant therapy with vitamin K antagonists (VKAs) is the only accepted treatment for the prevention of thromboembolism in haemodialysis patients with AF. However, in this population, the risk of bleeding is greatly increased. The aim of the study was to evaluate the ability of treatment quality indicators of VKA therapy to predict mortality and bleedings in a population of haemodialysis patients with AF.

Materials And Methods: A total of 129 patients were included in this cohort study. Deaths and bleeding events were recorded during a follow-up of 4 years. In all patients, International Normalized Ratio (INR) values were assessed at least once a month. Time in therapeutic range (TTR) and INR variability, as measured by the standard deviation of INR, were updated at each INR measurement. A Cox model with time-dependent co-variates and sandwich variance was applied.

Results: During follow-up, 71 patients died and 55 bleeding episodes occurred in 31 patients. INR variability was the only indicator associated with both mortality (hazard ratio [HR]=1.67, 95% confidence interval [CI] 1.12; 2.49, p=0.012) and bleeding (HR=2.85, 95% CI: 1.71; 4.75, p=0.0001). HR of mortality was higher in patients with INR >3 (HR=2.06, 95% CI: 1.09; 3.88, p=0.0259) than in subjects in therapeutic range 2
Discussion: Our study suggests that, in haemodialysis patients with AF taking VKAs, INR variability is the quality indicator that best predicts clinical outcomes. In this population, if more treatment quality indicators are considered together, it may become easier to identify patients at particularly high risk of bleeding and death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2450/2020.0217-20DOI Listing
December 2020

IgE monoclonal gammopathy: The clinical relevance to perform the immunofixation using IgE antisera.

Int J Lab Hematol 2020 10 14;42(5):e237-e239. Epub 2020 Jul 14.

Department of Laboratory Medicine, University of Milano-Bicocca, Azienda Socio Sanitaria Territoriale di Monza ASST-Monza, Desio Hospital, Desio, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijlh.13285DOI Listing
October 2020

Low levels of ADAMTS-13 with high anti-ADAMTS-13 antibodies during remission of immune-mediated thrombotic thrombocytopenic purpura highly predict for disease relapse: A multi-institutional study.

Am J Hematol 2020 08 21;95(8):953-959. Epub 2020 May 21.

Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening immune-mediated thrombotic microangiopathy. Daily therapeutic plasma exchange (TPE) and the optimized use of rituximab have strikingly improved the outcome of this disease, however the rate of disease recurrence remains high. Specific predictors of relapse in patients in remission can be relevant for an optimal patient management. In this study, we aimed to identify predictive variables of disease relapse in a multicenter cohort of 74 out of 153 iTTP patients. They were tested at different time points during remission for the levels of ADAMTS-13 activity and autoantibody, and did not receive pre-emptive treatment for ADAMTS-13 activity deficiency during remission. The results showed that the association of ADAMTS13 activity ≤20% with a high anti-ADAMTS-13 titer at remission, and the time to response to first line treatment ≥13 days, were independent predictive factors of disease relapse. In addition, the use of rituximab in patients with exacerbation or refractoriness to TPE was significantly associated with reduced relapse rate. By Cox regression analysis, patients with ADAMTS-13 activity ≤20% plus anti-ADAMTS13 antibody titer ≥15 U/mL at remission had an increased risk of relapse (HR 1.98, CI 95% 1.087-3.614; P < .02). These findings may help to outline more personalized therapeutic strategies in order to provide faster and sustained responses to first-line iTTP treatment and prevent relapses in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.25845DOI Listing
August 2020

A randomized double-blind trial of 3 aspirin regimens to optimize antiplatelet therapy in essential thrombocythemia.

Blood 2020 07;136(2):171-182

Hematology Project Foundation, Vicenza, Italy.

Essential thrombocythemia (ET) is characterized by abnormal megakaryopoiesis and enhanced thrombotic risk. Once-daily low-dose aspirin is the recommended antithrombotic regimen, but accelerated platelet generation may reduce the duration of platelet cyclooxygenase-1 (COX-1) inhibition. We performed a multicenter double-blind trial to investigate the efficacy of 3 aspirin regimens in optimizing platelet COX-1 inhibition while preserving COX-2-dependent vascular thromboresistance. Patients on chronic once-daily low-dose aspirin (n = 245) were randomized (1:1:1) to receive 100 mg of aspirin 1, 2, or 3 times daily for 2 weeks. Serum thromboxane B2 (sTXB2), a validated biomarker of platelet COX-1 activity, and urinary prostacyclin metabolite (PGIM) excretion were measured at randomization and after 2 weeks, as primary surrogate end points of efficacy and safety, respectively. Urinary TX metabolite (TXM) excretion, gastrointestinal tolerance, and ET-related symptoms were also investigated. Evaluable patients assigned to the twice-daily and thrice-daily regimens showed substantially reduced interindividual variability and lower median (interquartile range) values for sTXB2 (ng/mL) compared with the once-daily arm: 4 (2.1-6.7; n = 79), 2.5 (1.4-5.65, n = 79), and 19.3 (9.7-40; n = 85), respectively. Urinary PGIM was comparable in the 3 arms. Urinary TXM was reduced by 35% in both experimental arms. Patients in the thrice-daily arm reported a higher abdominal discomfort score. In conclusion, the currently recommended aspirin regimen of 75 to 100 once daily for cardiovascular prophylaxis appears to be largely inadequate in reducing platelet activation in the vast majority of patients with ET. The antiplatelet response to low-dose aspirin can be markedly improved by shortening the dosing interval to 12 hours, with no improvement with further reductions (EudraCT 2016-002885-30).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2019004596DOI Listing
July 2020

Management of elderly patients with immune thrombocytopenia: Real-world evidence from 451 patients older than 60 years.

Thromb Res 2020 01 21;185:88-95. Epub 2019 Nov 21.

Institute of Hematology "L. and A. Seràgnoli", Sant'Orsola-Malpighi University Hospital, Bologna, Italy.

Introduction: Primary Immune thrombocytopenia (ITP) in the elderly is a major clinical challenge which is increasingly frequent due to global ageing population.

Materials And Methods: To describe baseline ITP features, management, and outcome, a centralized electronic database was established, including data of 451 patients aged ≥60 years that were treated from 2000 onwards and were observed for ≥1 year (total observation of 2704 patient-years).

Results: At ITP diagnosis, median age was 71.1 years (age ≥ 75: 42.8%); 237 (53.9%) patients presented with haemorrhages (grade ≥ 3: 7.5%). First-line therapy included prednisone (82.9%), dexamethasone (14.6%), thrombopoietin-receptor agonists (TRAs, 1.3%), and oral immunosuppressive agents (1.1%). Prednisone starting dose ≥1 mg/kg/d (p = .01) and dexamethasone 40 mg/d (p < .001) were mainly reserved to patients aged 60-74, who were more treated with rituximab (RTX, p = .02) and splenectomy (p = .03) second-line. Overall response rates to first and second-line therapies were 83.8% and 84.5%, respectively, regardless of age and treatment type/dose. A total of 178 haemorrhages in 101 patients (grade ≥ 3: n. 52, 29.2%; intracranial in 6 patients), 49 thromboses in 43 patients (grade ≥ 3: n. 26, 53.1%) and 115 infections in 94 patients (grade ≥ 3: n. 23, 20%) were observed during follow-up. Incidence rates of complications per 100 patient-years were: 4.5 (haemorrhages, grade ≥ 3: 1.7), 1.7 (thromboses, grade ≥ 3: 0.9), and 3.9 (infections, grade ≥ 3: 0.7). TRAs use were associated with reduced risk of bleeding and infections, while cardiovascular risk factors (particularly, diabetes) significantly predicted thromboses and infections.

Conclusions: Age-adapted treatment strategies are required in elderly and very elderly patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2019.11.026DOI Listing
January 2020

Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia.

Ther Adv Hematol 2019 9;10:2040620719837906. Epub 2019 May 9.

ASST San Gerardo Hospital, Monza, Italy.

Primary immune thrombocytopenia (ITP) is a bleeding disorder that conventionally has been treated with steroids or other immunosuppressive treatments. The introduction of thrombopoietin receptor agonists (TPO-RAs), which increase platelet production, dramatically changed the treatment landscape for ITP by providing patients with well-tolerated, long-term treatment options. Two TPO-RAs, eltrombopag and romiplostim, have been approved in the United States and European Union for the treatment of ITP. Some patients do not benefit from the first TPO-RA they receive, so it is assumed that the alternate TPO-RA would have the same outcome. However, eltrombopag and romiplostim have distinct pharmacodynamic and pharmacokinetic properties and may have different tolerability and efficacy in individual patients with ITP. Published retrospective studies showed that >75% of patients who switched to the alternate TPO-RA maintained or achieved a response with the new treatment. Notably, most patients who switched due to lack of efficacy with the first TPO-RA responded to the alternate TPO-RA, which demonstrates an absence of cross-resistance between the two drugs. Therefore, switching to the alternate TPO-RA if the first TPO-RA fails to demonstrate a response should be considered before the use of a less-preferable option.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2040620719837906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515841PMC
May 2019

Platelet cut-off for anticoagulant therapy in thrombocytopenic patients with blood cancer and venous thromboembolism: an expert consensus.

Blood Transfus 2019 05 24;17(3):171-180. Epub 2018 Oct 24.

Alessandria.

Background: Management of venous thromboembolism (VTE) in patients with haematologic malignancies and thrombocytopenia is clinically challenging due to the related risks. No prospective studies or clinical trials have been carried out and, therefore, no solid evidence on this compelling issue is available.

Methods: Given this, an expert panel endorsed by the Gruppo Italiano Malattie Ematologiche dell'Adulto Working Party on Thrombosis and Haemostasis was set up to produce a formal consensus, according to the RAND method, in order to issue clinical recommendations about the platelet (PLT) cut-off for safe administration of low molecular weight heparin (LMWH) in thrombocytopenic (PLT <100×10/L) adult patients with haematologic malignancies affected by acute (<1 month) or non-acute VTE.

Results: In acute VTE, the panel suggests safe anticoagulation with LMWH at therapeutic doses for PLT between ≥50<100×10/L and at 50% dose reduction for PLT ≥30<50×10/L. In acute VTE for PLT <30×10/L, the following interventions are recommended: positioning of an inferior vena cava (IVC) filter with prophylactic LMWH administration and platelet transfusion. In non-acute VTE, anticoagulation with LMWH at therapeutic doses for PLT between ≥50<100×10/L or over and at 50% dose reduction for PLT ≥30<50×10/L is considered appropriate. The discontinuation of full or reduced therapeutic dose of LMWH is recommended for PLT <30×10/L, both in acute and non-acute VTE.

Discussion: We suggest using dose-adjusted LMWH according to PLT to optimise anticoagulant treatment in patients at high bleeding risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2450/2018.0143-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596377PMC
May 2019

The Aspirin Regimens in Essential Thrombocythemia (ARES) phase II randomized trial design: Implementation of the serum thromboxane B assay as an evaluation tool of different aspirin dosing regimens in the clinical setting.

Blood Cancer J 2018 06 1;8(6):49. Epub 2018 Jun 1.

Institute of Hematology "L. and A. Seràgnoli", S. Orsola-Malpighi Hospital, Bologna, Italy.

Once-daily (od), low-dose aspirin (75-100 mg) is recommended to reduce the thrombotic risk of patients with essential thrombocytemia (ET). This practice is based on data extrapolated from other high-risk patients and an aspirin trial in polycythemia vera, with the assumption of similar aspirin pharmacodynamics in the two settings. However, the pharmacodynamics of low-dose aspirin is impaired in ET, reflecting accelerated renewal of platelet cyclooxygenase (COX)-1. ARES is a parallel-arm, placebo-controlled, randomized, dose-finding, phase II trial enrolling 300 ET patients to address two main questions. First, whether twice or three times 100 mg aspirin daily dosing is superior to the standard od regimen in inhibiting platelet thromboxane (TX)A production, without inhibiting vascular prostacyclin biosynthesis. Second, whether long-term persistence of superior biochemical efficacy can be safely maintained with multiple vs. single dosing aspirin regimen. Considering that the primary study end point is serum TXB, a surrogate biomarker of clinical efficacy, a preliminary exercise of reproducibility and validation of this biomarker across all the 11 participating centers was implemented. The results of this preliminary phase demonstrate the importance of controlling reproducibility of biomarkers in multicenter trials and the feasibility of using serum TXB as a reliable end point for dose-finding studies of novel aspirin regimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41408-018-0078-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992153PMC
June 2018

Alternate use of thrombopoietin receptor agonists in adult primary immune thrombocytopenia patients: A retrospective collaborative survey from Italian hematology centers.

Am J Hematol 2018 01 9;93(1):58-64. Epub 2017 Nov 9.

Hematology and Oncology Department, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan.

Sequential use of the TPO-RAs romiplostim and eltrombopag in ITP patients failing either agent was retrospectively evaluated to assess efficacy and impact of clinical characteristics on outcome. Patients were grouped into 5 categories: efficacy issues: 1 TPO-RA failure; loss of response; non-efficacy issues: platelet fluctuations; patient's preference; adverse event development. Either one TPO-RA sequence was analyzed at 3 month and at last follow-up. 106/546 patients on TPO-RA underwent switch and 65% achieved, regained or maintained a short- term response independent of switch sequence, gender or age; lower response rates were associated with lines of previous therapy; disease duration lowers probability to respond. Clinically, patients switched for efficacy issue did not differ from those switched for non-efficacy issues. Response was achieved/regained in 57.8% of patients switched for efficacy issues, the lowest response rates were observed in non-responders to 1 TPO-RA; 80% of patients switched for non-efficacy issues maintained a response. Platelet fluctuation resolved in 44.4%. Of the 49 patients evaluable for long-term outcome, 27 were in response on therapy; 16 discontinued the TPO-RA for reasons other than efficacy, while only 6 were non responders. We confirm the efficacy of TPO-RA switch; once achieved, response to the 2 TPO-RA seems durable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.24935DOI Listing
January 2018

Rituximab in immune thrombocytopenia: gender, age, and response as predictors of long-term response.

Eur J Haematol 2017 Apr 20;98(4):371-377. Epub 2017 Jan 20.

Department of Hematology, Azienda Sanitaria Universitaria Integrata S. Maria della Misericordia, Udine, Italy.

Objectives: To evaluate the efficacy of a salvage treatment with rituximab (RTX) in adults with primary immune thrombocytopenia (ITP), in terms of short-term response and long-term response (LTR, i.e., probability to achieve and maintain response) and to identify biological and clinical predictors of response.

Methods: We retrospectively evaluated the outcome of patients with primary ITP treated with standard dosage RTX (375 mg/m × 4) as salvage therapy in five Italian centers. One hundred and three patients, median age of 46 yr, were included. The median period of observation was 59 months.

Results: Response (R) and complete response (CR) were documented in 57 (55%) and 37 (36%) patients, respectively. Patients younger than 40 yr had a higher probability to achieve CR (P = 0.025). Younger women (age < 40 yr) had a significantly higher probability to achieve R and CR (P = 0.039 and P = 0.009, respectively). The estimated LTR rate was 36% and 31% after 48 and 72 months, respectively; female sex (P = 0.033) and younger age (P = 0.021) were associated with better LTR. Younger women had the highest LTR rate (P = 0.006). Response duration was associated with the obtainment of CR after RTX (CR vs. partial response, P = 0.002).

Conclusions: The effect of RTX salvage treatment appears higher in younger women, with LTR rate possibly approaching that of splenectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejh.12839DOI Listing
April 2017

Clinical relevance of antiplatelet antibodies and the hepatic clearance of platelets in patients with immune thrombocytopenia.

Blood 2016 10 6;128(17):2183-2185. Epub 2016 Sep 6.

Department of Hematology and Oncology, Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2016-03-708388DOI Listing
October 2016

Health-related quality of life and burden of fatigue in patients with primary immune thrombocytopenia by phase of disease.

Am J Hematol 2016 Oct 14;91(10):995-1001. Epub 2016 Jul 14.

Department of Cellular Biotechnologies and Hematology, University of Rome "Sapienza", Rome, Italy.

The main objective of this study was to compare health-related quality of life (HRQOL) of primary immune thrombocytopenia (pITP) patients with that of general population, overall, and by patient group (i.e., newly diagnosed, persistent, and chronic patients). Fatigue was also investigated as a secondary objective. Overall, 424 adult patients were enrolled in a multicenter observational study and the control group consisted of a representative sample from the general population. Propensity score matching plus further multivariate linear regression adjustment was used to compare HRQOL outcomes between pITP patients and general population. Mean age of patients was 54 years. Of those with HRQOL assessment, 99 patients (23.6%) were newly diagnosed, 53 (12.6%) were persistent, and 268 (63.8%) were chronic pITP patients. Comparison by patient group versus their respective peers in the general population revealed greater impairments in persistent pITP patients. Persistent pITP patients reported clinically meaningful impairments in physical functioning (-15; 95% CI -24.1 to -5.8; P = 0.002), social functioning (-15.3; 95% CI -25.5 to -5.1; P = 0.004), role physical (-28.4; 95% CI -43.1 to -13.7; P < 0.001), role emotional (-23.9; 95% CI -40.1 to -7.7; P = 0.004), and mental health scales (-11.3; 95% CI -21.2 to -1.4; P = 0.026) of the SF-36 questionnaire. Higher fatigue severity was associated with lower physical and mental HRQOL outcomes. Our findings suggest that the burden of the disease and treatment might depend on the disease phase and that persistent pITP patients are the most vulnerable subgroup. Am. J. Hematol. 91:995-1001, 2016. © 2016 Wiley Periodicals, Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.24463DOI Listing
October 2016

Thrombopoietin receptor agonists for preparing adult patients with immune thrombocytopenia to splenectomy: results of a retrospective, observational GIMEMA study.

Am J Hematol 2016 May 4;91(5):E293-5. Epub 2016 Apr 4.

Clinica Ematologica, DISM, a O U S. M. Misericordia, Udine, Italy.

In patients with immune thrombocytopenia (ITP) refractory to corticosteroids and intravenous immunoglobulins (IVIG), splenectomy may result at higher risk of peri-operative complications and, for this reason, potentially contraindicated. The thrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag have shown high therapeutic activity in primary ITP, but data of efficacy and safety regarding their use in preparation for splenectomy are missing. Thirty-one adult patients, median age 50 years, with corticosteroids and/or IVIG refractory persistent and chronic ITP who were treated with TPO-RAs (romiplostim= 24; eltrombopag= 7) with the aim to increase platelet count and allow a safer execution of splenectomy were retrospectively evaluated. Twenty-four patients (77%) responded to the use of TPO-RAs with a median platelet count that increased from 11 × 10(9) /L before starting TPO-RAs to 114 × 10(9) /L pre-splenectomy, but a concomitant treatment with corticosteroids and/or IVIG was required in 19 patients. Twenty-nine patients underwent splenectomy while two patients who responded to TPO-RAs subsequently refused surgery. Post-splenectomy complications were characterized by two Grade 3 thrombotic events (1 portal vein thrombosis in the patient with previous history of HCV hepatitis and 1 pulmonary embolism), with a platelet count at the time of thrombosis of 260 and 167 × 10(9) /L, respectively and one Grade 3 infectious event. TPO-RAs may represent a therapeutic option to improve platelet count and reduce the risk of peri-operative complications in ITP candidates to splenectomy. An increased risk of post-splenectomy thromboembolic events cannot be ruled out and thromboprophylaxis with low-molecular weight heparin is generally recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.24341DOI Listing
May 2016

Response loss and development of neutralizing antibodies during long-term treatment with romiplostim in patients with immune thrombocytopenia: a case series.

Eur J Haematol 2016 Jul 4;97(1):101-103. Epub 2016 Feb 4.

Hematology and Oncology Department, Ospedale Niguarda Cà Granda, Milano, Italy.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts resulting from both immune-mediated platelet destruction and inappropriate bone marrow platelet production. Therefore, in patients with ITP failing immunosuppressants/splenectomy, an alternative approach is to enhance platelet production stimulating thrombopoiesis. Studies on the development of recombinant thrombopoietins (rhTPO) were halted as a minority of patients developed an autoantibody that neutralized pegylated rhTPO and also cross-reacted with and neutralized endogenous TPO resulting in thrombocytopenia. Clinical use of romiplostim, a second-generation TPO-RAs, has shown that during long-term treatment, it may elicit the development of neutralizing antibodies to this agent resulting in acute thrombocytopenia. In our case series of 47 primary adult patients with ITP treated with romiplostim, 28 of 47 are evaluable for response loss. Among these, we observed eight patients who either progressively (3 of 8) or abruptly (5 of 8) lost response which accounts for a prevalence of 28.5%. Neutralizing antibody testing could be performed in 4 of 8 patients and 3 of 4 tested positive. These antibodies did not cross-react with endogenous TPO and retesting of 2 patients at 9 and 7 months yielded a negative result. At follow-up, 5 of 8 patients - including the 3 patients with neutralizing antibodies - went into long-term complete response when switched to a different therapy while 3 of 8 patients never regained a response on subsequent lines of therapy. Response loss does not seem to be so rare an event during romiplostim administration (28.5% in our series) and in a minority of patients, it can be associated with development of drug neutralizing antibodies. Although recognized by the manufacturer as a possible adverse event ensuing during romiplostim administration, development of neutralizing antibody in everyday clinical practice has so far not been specifically addressed in reports on romiplostim use outside controlled studies. Unfortunately, testing for these antibodies requires adhesion to strict procedures which is not easily accomplished in everyday clinical practice. This complexity represents a significant drawback in extending antibody testing to all patients who lose response to romiplostim.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejh.12733DOI Listing
July 2016

Recurrent Thrombotic Events after Discontinuation of Vitamin K Antagonist Treatment for Splanchnic Vein Thrombosis: A Multicenter Retrospective Cohort Study.

Gastroenterol Res Pract 2015 5;2015:620217. Epub 2015 Oct 5.

Department of Hematology, Hemostasis and Thrombosis Center, S. Bortolo Hospital, 36100 Vicenza, Italy.

It is generally recommended that patients with splanchnic vein thrombosis (SVT) should receive a minimum of 3 months of anticoagulant treatment. However, little information is available on the long-term risk of recurrent thrombotic events. The aim of this study was to evaluate the risk of venous and arterial thrombosis after discontinuation of vitamin K antagonist (VKA) in SVT patients. Retrospective information from a cohort of SVT patients treated with VKA and followed by 37 Italian Anticoagulation Clinics, up to June 2013, was collected. Only patients who discontinued VKA and did not receive any other anticoagulant drug were enrolled in this study. Thrombotic events during follow-up were centrally adjudicated. Ninety patients were included: 33 unprovoked SVT, 27 SVT secondary to transient risk factors, and 30 with permanent risk factors. During a median follow-up of 1.6 years, 6 venous and 1 arterial thrombosis were documented, for an incidence of 3.3/100 patient-years (pt-y). The recurrence rate was highest in the first year after VKA discontinuation (8.2/100'pt-y) and in patients with permanent risk factors (10.2/100'pt-y). Liver cirrhosis significantly increased the risk of recurrence. In conclusion, the rate of recurrent vascular complications after SVT is not negligible, at least in some patient subgroups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/620217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609867PMC
October 2015

Feasibility of romiplostim discontinuation in adult thrombopoietin-receptor agonist responsive patients with primary immune thrombocytopenia: an observational retrospective report in real life clinical practice.

Hematol Rep 2015 Feb 24;7(1):5673. Epub 2015 Feb 24.

Hematology and Transplant Unit , A.O. San Gerardo, University of Milan Bicocca ; Milan, Italy.

Thrombopoietin mimetics are new treatment options for patients with immune throm-bocytopenia (ITP). Because of their mechanism of action, long-term administration was envisioned in order to maintain effective thrombopoiesis. We report on 30 romiplostim treated patients: 13/27 responders (48%) achieved stable platelet counts on a mean romiplostim dose of 2.43 µg/kg and were able to stop romiplostim after a mean of 44.3 weeks (range 12-122) on therapy with sustained response maintained at a mean of 26 months (range 12-52). No bleeding events occurred during the observational period. No specific patient's features nor pattern of early response seemed to predict for sustained response. However, patients achieving safe platelet counts at lower dosages are probably worth a try of therapy tapering and discontinuation. Our observations support feasibility of romiplostim safe suspension in a relevant proportion of ITP patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/hr.2015.5673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378205PMC
February 2015

Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients.

Blood 2014 Nov 16;124(19):2930-6. Epub 2014 Sep 16.

Unità Operativa Oncoematologia, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy;

The clinical outcome, response to treatment, and occurrence of acute complications were retrospectively investigated in 308 primary autoimmune hemolytic anemia (AIHA) cases and correlated with serological characteristics and severity of anemia at onset. Patients had been followed up for a median of 33 months (range 12-372); 60% were warm AIHA, 27% cold hemagglutinin disease, 8% mixed, and 5% atypical (mostly direct antiglobulin test negative). The latter 2 categories more frequently showed a severe onset (hemoglobin [Hb] levels ≤6 g/dL) along with reticulocytopenia. The majority of warm AIHA patients received first-line steroid therapy only, whereas patients with mixed and atypical forms were more frequently treated with 2 or more therapy lines, including splenectomy, immunosuppressants, and rituximab. The cumulative incidence of relapse was increased in more severe cases (hazard ratio 3.08; 95% confidence interval, 1.44-6.57 for Hb ≤6 g/dL; P < .001). Thrombotic events were associated with Hb levels ≤6 g/dL at onset, intravascular hemolysis, and previous splenectomy. Predictors of a fatal outcome were severe infections, particularly in splenectomized cases, acute renal failure, Evans syndrome, and multitreatment (4 or more lines). The identification of severe and potentially fatal AIHA in a largely heterogeneous disease requires particular experienced attention by clinicians.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2014-06-583021DOI Listing
November 2014

Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria phenotype in patients with splanchnic vein thrombosis.

Thromb Res 2014 Jun 1;133(6):1052-5. Epub 2014 Apr 1.

Department of Hematology, Ospedale S. Bortolo, Vicenza, Italy.

Introduction: Splanchnic vein thrombosis (SVT) is a serious complication in patients with paroxysmal nocturnal hemoglobinuria (PNH). Mutant PNH clones can be associated with an increased risk of SVT even in the absence of overt disease, but their prevalence in non-selected SVT patients remains unknown.

Materials And Methods: Patients with objective diagnosis of SVT and without known PNH were tested for the presence of PNH clone using high-sensitivity flow cytometric analysis.

Results: A total of 202 SVT patients were eligible, 58.4% were males, mean age was 54.6years (range 17-94), site of thrombosis was portal in 103 patients, mesenteric in 67, splenic in 37, and supra-hepatic in 10. SVT was associated with JAK2 V6167F in 28 of 126 (22.2%) screened patients, liver cirrhosis in 15.3% patients, recent surgery in 10.9%, and myeloproliferative neoplasm in 10.6%, whereas in 34.6% of patients neither permanent nor transient risk factors were detected. None of the patients had a clearly demonstrable PNH clone, but in two patients (0.99%, 95% CI 0.17-3.91) we observed very small PNH clones (size 0.014% and 0.16%) confirmed in two independent samples. One patient had portal vein thrombosis and no associated risk factors, the second had superior mesenteric vein thrombosis and inflammatory bowel disease.

Conclusions: Very small PNH clones can be detected in patients with SVT and no clinical manifestations of disease. Future studies are needed to explore the potential role of this finding in the pathogenesis of SVT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2014.03.044DOI Listing
June 2014

Patient preferences and willingness to pay for different options of anticoagulant therapy.

Intern Emerg Med 2013 Apr 28;8(3):237-43. Epub 2012 Aug 28.

Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, IRCCS Ca' Granda Maggiore Policlinico Hospital Foundation, Via Pace 9, 20122, Milan, Italy.

New anticoagulant drugs alternative to vitamin K antagonists are currently under clinical evaluation. Patient's preferences should be considered in the development of new therapeutic strategies. Our study aim was to elicit patient preferences, and estimate their willingness to pay for the different treatment options. A Discrete Choice Experiment was administered to patients consecutively attending an anticoagulation clinic, either on stable oral anticoagulant therapy, or during their first visit at the time of starting therapy. Six treatment characteristics were analysed: route and number of medication administrations, frequency of monitoring, risk of some minor bleeding, the amount of attention required for drug/food interactions, requirement for dose adjustment, and out-of-pocket treatment cost. Relationships between patient's preferences and their characteristics were analysed. 255 patients participated (55 % men, with a mean age 64 years; 35.7 % on stable therapy). A statistically significant importance was attributed to all but two characteristics (the amount of attention required for interaction with other drugs/food and for dose adjustment.) Monthly patient willingness to pay was 79 for tablets versus injections; 41 for once-daily versus twice-daily tablets, 25 for drugs without risk of minor bleeding events and 20 for once-monthly versus twice-monthly monitoring. Patients on stable therapy considered more important the amount of attention required for drug/food interactions than did the starters. Younger or working patients considered the reduction of monitoring frequency more important than did the older or not working patients (retired, housewives). This study elicited preferences from patients on oral anticoagulant therapy with a simple and well established method, which allows to obtain information warranted for planning optimal healthcare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11739-012-0844-3DOI Listing
April 2013

Prevention of venous thromboembolism in patients with cancer: guidelines of the Italian Society for Haemostasis and Thrombosis (SISET)(1).

Thromb Res 2012 May 2;129(5):e171-6. Epub 2011 Oct 2.

Cattedra ed UO di Ematologia con trapianto, Dipartimento di Medicina Interna e Specialistica, Azienda Ospedaliera Universitaria Policlinico di Palermo, Via del Vespro 127, 90127 Palermo, Italy.

Background: Prevention of venous thromboembolism (VTE) in cancer patients remains controversial in most clinical settings.

Purpose: The Italian Society for Haemostasis and Thrombosis (SISET) commissioned a project to develop clinical practice guidelines for the prevention of VTE in patients with malignancy.

Methods: Key questions concerning the prevention of VTE in patients with malignancy were formulated by a multidisciplinary working group consisting of experts in clinical medicine and research. After a systematic review and discussion of the literature, recommendations were formulated and graded according to the supporting evidence. For those questions for which the literature search did not find any definitive answers (due to absence of evidence, low quality evidence and/or contradictory evidence), a formal consensus method was used instead to issue clinical recommendations.

Results: The search for "VTE prevention" resulted in 1021 citations; 69 articles were selected and 24 were used for drafting clinical recommendations. Four areas were graded A to C: 1) Need of prevention (pharmacological and/or mechanical) in cancer patients undergoing major abdominal or pelvic surgery and in 2) those with an acute medical disease requiring hospitalization and who are bedridden. Avoid prevention in 3) cancer patients with a central venous catheter and 4) those on chemotherapy, radiotherapy or hormonal therapy, except patients with multiple myeloma treated with thalidomide/lenalidomide plus high-dose dexamethasone, and those with gastrointestinal or lung cancer. Six areas were considered to be clinically important, but lacked evidence from the literature and thus required a formal consensus (grade D): 1) need of prevention during chemo- radiotherapy or hormonal therapy in patients with previous VTE; 2) optimal duration of pharmacological prevention in patients who are hospitalized/bedridden for acute medical illness; 3) optimal duration of pharmacological prevention in patients undergoing major surgery other than abdominal and pelvic; 4) optimal duration of pharmacological prevention in myeloma patients receiving thalidomide plus dexamethasone; 5) presence of cerebral metastasis as a contraindication to pharmacological prevention; 6) prevention in cancer patients undergoing surgery by laparoscopic procedures lasting>30min.

Conclusion: Results of the systematic literature review and an explicit approach to consensus techniques have led to recommendations for the most clinically important issues in the prevention of VTE in cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2011.09.002DOI Listing
May 2012

From Vaquez to Dameshek through JAK…2 much for polycythemia vera to be feared?

Intern Emerg Med 2010 Oct 9;5(5):371-3. Epub 2010 Sep 9.

Hematology and Bone Marrow Transplantation Unit, San Gerardo Hospital, University of Milan Bicocca, Via Pergolesi 33, Monza, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11739-010-0454-xDOI Listing
October 2010

Attitudes to prescribing compression stockings for patients with acute DVT: the MASTER registry.

J Thromb Thrombolysis 2009 Nov 10;28(4):389-93. Epub 2009 Mar 10.

Department of Medicine, Azienda Ospedaliera Ospedale Civile di Vimercate, Via Cesare Battisti 23, 20059, Vimercate, Milan, Italy.

Unlabelled: Compression therapy is still not widely used for patients with deep vein thrombosis (DVT). This report provides information on Italian doctors' use of elastic stockings (ES) after acute DVT and identifies some predictors of prescription.

Material And Methods: The MASTER multicenter registry collected information about clinical characteristics and management of patients with venous thromboembolism (VTE). In patients with objectively confirmed acute VTE, information about clinical presentation, diagnostic methods, temporary and permanent risk factors, pre-event prophylaxis and treatment, including ES prescription, were captured by an electronic data network at the time of the index event.

Results: Of 2119 patients enrolled, 1913 had DVT, 1772 in the legs; 1277 were prescribed ES at hospital discharge. The following conditions were associated with more frequent prescription: edema, in-hospital management, known thrombophilia; younger age. In multivariate analysis these factors all remained significantly associated with more frequent use of ES.

Conclusions: Italian clinicians' attitudes to prescribing ES still appear suboptimal. Special attention is needed for patients treated at home, where organizational problems can interfere with the use of ES.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11239-009-0316-4DOI Listing
November 2009

D-dimer before chemotherapy might predict venous thromboembolism.

Blood Coagul Fibrinolysis 2009 Apr;20(3):170-5

Department of Medicine, Azienda Ospedaliera Ospedale Civile di Vimercate, Vimercate, Italy.

To see whether D-Dimer levels can identifying patients at high risk of venous thrombotic events and establish the best benefit/risk-of-bleeding ratio. Current guidelines do not recommend routine prophylaxis against venous thromboembolism (VTE) in cancer patients receiving chemotherapy, but the risk increases about 6.5-fold because of this treatment. D-dimer was measured at baseline in 124 cancer patients scheduled for their first chemotherapy. VTE events, including symptomatic episodes of deep vein thrombosis or pulmonary embolism or both, were recorded during the first 6 months of therapy, and asymptomatic deep vein thrombosis was revealed by compression ultrasonography at baseline and after 90 and 180 days. During follow-up, there were 11 episodes of VTE (8.9%). Mean D-dimer values were higher in patients with VTE (2195 +/- 1382 vs. 695 +/- 1039 ng/ml, (P < 0.001). On grouping D-dimer values in tertiles, only 2.4% (confidence interval, 0.9-5.7%) in the first (<262 ng/ml) and second tertiles (262-650 ng/ml) suffered a deep vein thrombosis/pulmonary embolism event as compared with 22% (confidence interval, 9-34%) in the third (>650 ng/dl) (P = 0.003). The VTE-free interval was significantly shorter in the third tertile than in the first (P = 0.0218, log-rank test; relative risk for third vs. first tertile, 11.0; 95% confidence interval, 1.4-81.3; P = 0.0033). Multivariate analysis found that only baseline D-dimer concentrations were correlated with the subsequent development of VTE. Baseline D-dimer values in cancer patients scheduled for chemotherapy might be used to select those at low risk of VTE, most likely to be safe without prophylaxis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MBC.0b013e32831bc2deDOI Listing
April 2009

The impact of antithrombotic prophylaxis on infectious complications in cancer patients with central venous catheters: an observational study.

Blood Coagul Fibrinolysis 2009 Jan;20(1):35-40

Department of Oncology, Desio Hospital, Azienda Ospedaliera Ospedale Civile di Vimercate, Milan, Italy.

Infections in cancer patients after implantation of a central venous device (CVD) are not infrequent and are potentially serious. The possibility of limiting this complication with antithrombotic drugs is still debated. For this observational study, we recorded the routine management of CVD in cancer patients in 18 oncology centers in Lombardy (northern Italy), assessing the effect of antithrombotic prophylaxis on catheter-related infections. Out of 1410 patients enrolled, 451 received antithrombotic prophylaxis continuously after implantation of the central line. During a median follow-up of 30 months, 57 catheter-related infections were reported in the 1390 patients seen at least once at follow-up visits (4.1% of the whole series), giving an overall incidence of 0.10 infections per 1000 catheter days. This complication was significantly more frequent among patients with an indwelling central venous catheter, or peripherally inserted catheter, than among those with a port device, and the group not given antithrombotic prophylaxis had 0.14 infective complications/1000 CVD days compared with 0.05/1000 CVD days (odds ratio 2.4; 95% confidence interval 1.7-5.0) for those treated. Antithrombotic prophylaxis protected against infections at the catheter exit site and track but not against systemic infections. Confirming earlier evidence, this study found a reduction in catheter-related infections in patients given antithrombotic prophylaxis. However, this reduction, reflecting local infections, seems unlikely to be one of the mechanisms explaining the lower mortality among our patients treated with anticoagulants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MBC.0b013e32831bc2f8DOI Listing
January 2009

Retrievable vena cava filters: a review.

Curr Opin Hematol 2006 Sep;13(5):351-6

Thrombosis Center, Emergency Department, Hospital of Piacenza, Piacenza, Italy.

Purpose Of Review: To examine the current literature regarding retrievable inferior vena cava filters and to discuss the appropriate indications for their clinical use.

Recent Findings: Permanent filters have been shown to be effective, but have a number of long-term complications such as filter thrombosis or migration. Indications for their placement should be accurately evaluated, especially in patients with a long life expectancy, or in whom the period of contraindication to anticoagulation is short. On the other hand, temporary filters are difficult to manage and their maximum implantation time is often insufficient to solve the clinical problem leading to their placement. Four different retrievable filters recently received approval for temporary insertion. Recent data suggest that the use of these filters may be related to a low rate of pulmonary embolism and insertion complications. Nevertheless, no randomized clinical trials have been performed, and the only available data refer to retrospective or prospective studies.

Summary: Retrievable filters are a new generation of filter that offers the attractive possibility of being left in place permanently or being removed after quite a long period when they become unnecessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.moh.0000239707.63168.eeDOI Listing
September 2006