Rivaroxaban for the treatment of noncirrhotic splanchnic vein thrombosis: an interventional prospective cohort study.

Heparins and vitamin K antagonists are the mainstay of treatment of splanchnic vein thrombosis (SVT). Rivaroxaban is a potential alternative, but data to support its use are limited. We aimed to evaluate the safety and efficacy of rivaroxaban for the treatment of acute SVT. In an international, single-arm clinical trial, adult patients with a first episode of noncirrhotic, symptomatic, objectively diagnosed SVT received rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg daily for an intended duration of 3 months. Patients with Budd-Chiari syndrome and those receiving full-dose anticoagulation for >7 days prior to enrollment were excluded. Primary outcome was major bleeding; secondary outcomes included death, recurrent SVT, and complete vein recanalization within 3 months. Patients were followed for a total of 6 months. A total of 103 patients were enrolled; 100 were eligible for the analysis. Mean age was 54.4 years; 64% were men. SVT risk factors included abdominal inflammation/infection (28%), solid cancer (9%), myeloproliferative neoplasms (9%), and hormonal therapy (9%); 43% of cases were unprovoked. JAK2 V617F mutation was detected in 26% of 50 tested patients. At 3 months, 2 patients (2.1%; 95% confidence interval, 0.6-7.2) had major bleeding events (both gastrointestinal). One (1.0%) patient died due to a non-SVT-related cause, 2 had recurrent SVT (2.1%). Complete recanalization was documented in 47.3% of patients. One additional major bleeding event and 1 recurrent SVT occurred at 6 months. Rivaroxaban appears as a potential alternative to standard anticoagulation for the treatment of SVT in non-cirrhotic patients. This trial was registered at www.clinicaltrials.gov as #NCT02627053 and at eudract.ema.europa.eu as #2014-005162-29-36.

Acquired haemophilia A: Italian Consensus Recommendations on diagnosis, general management and treatment of bleeding.

BACKGROUND: Acquired haemophilia A (AHA) is a rare bleeding disorder due to autoantibodies to coagulation factor VIII that may be secondary to autoimmune diseases, cancer, drugs, pregnancy, infections, or be idiopathic. Recurrent bleeding, often severe, mostly in muscles and soft tissues, and isolated prolonged activated partial thromboplastin time (aPTT), in the absence of personal and family history of bleeding, are typical features that should raise the suspicion of AHA. Poor awareness of the disease results in diagnostic delays and inappropriate treatment. MATERIALS AND METHODS: The Italian Association of Haemophilia Centres (AICE) developed consensus recommendations in cooperation with the Italian Society on Thrombosis and Haemostasis (SISET). The document was shared with scientific societies of specialist physicians, laboratory professionals and pharmacists to spread knowledge about AHA and promote appropriate diagnosis/treatment. RESULTS: Ready availability of the aPTT mixing test is crucial, although diagnostic confirmation and optimal management require prompt referral of patients to specialised centres with rapidly available diagnostic and therapeutic facilities. If immediate referral is unfeasible, treatment must be undertaken early, under guidance of specialised centres or based on shared protocols. Recommendations about diagnosis, general management and, in bleeding patients, haemostatic therapy using bypassing agents or replacement treatment, including the recently available recombinant porcine factor VIII, are provided, considering the different clinical settings and laboratory facilities. DISCUSSION: This consensus document aims to improve the overall healthcare pathways for AHA, harmonise the management and therapeutic approaches to newly diagnosed patients and reduce the still relevant complications and mortality in this setting.

Emergency management in patients with haemophilia A and inhibitors on prophylaxis with emicizumab: AICE practical guidance in collaboration with SIBioC, SIMEU, SIMEUP, SIPMeL and SISET.

Emicizumab has been approved in several countries for regular prophylaxis in patients with congenital haemophilia A and FVIII inhibitors because it substantially reduces their bleeding risk and improves quality of life. However, although significantly less frequent, some breakthrough bleeds may still occur while on emicizumab, requiring treatment with bypassing or other haemostatic agents. Thrombotic complications have been reported with the associated use of activated prothrombin complex concentrates. In addition, when surgery/invasive procedures are needed while on emicizumab, their management requires multidisciplinary competences and direct supervision by experts in the use of this agent. Given this, and in order to expand the current knowledge on the use of emicizumab and concomitant haemostatic agents, and reduce the risk of complications in this setting, the Italian Association of Haemophilia Centres (AICE) here provides guidance on the management of breakthrough bleeds and surgery in emergency situations in patients with haemophilia A and inhibitors on emicizumab prophylaxis. This paper has been shared with other National Scientific Societies involved in the field.

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

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 <100×109/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<100×109/L and at 50% dose reduction for PLT ≥30<50×109/L. In acute VTE for PLT <30×109/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<100×109/L or over and at 50% dose reduction for PLT ≥30<50×109/L is considered appropriate. The discontinuation of full or reduced therapeutic dose of LMWH is recommended for PLT <30×109/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.

Khorana score and histotype predicts incidence of early venous thromboembolism in non-Hodgkin lymphomas. A pooled-data analysis of 12 clinical trials of Fondazione Italiana Linfomi (FIL).

Current data suggests that the risk of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) is comparable to that observed in patients with solid tumours, although more robust confirmatory analyses are required. With that in mind, we investigated the occurrence of VTE in a pooled analysis of 12 "Fondazione Italiana Linfomi" (FIL) prospective clinical studies. Specifically, we wished to assess the cumulative incidence of VTE in NHL patients, evaluate the predictive value of the Khorana Score (KS), and identify other potential risk factors for VTEs. Data for VTE occurrence were retrieved from study databases and pharmacovigilance reports. Our analysis includes 1717 patients from 12 prospective phase II and III trials, including newly diagnosed NHL. We observed 53 VTEs (any grade) in 46 patients, with 20 severe VTEs in 17 patients. The cumulative incidences for "all-grade" or grade ≥3 VTEs were 2.9 % (95 % CI: 2.1-3.8) and 1.1 % (95 % CI: 0.6-1.6), respectively. KS categories were positively associated with the risk of VTE of any grade, and with severe events (i. e. grade ≥3; Gray's test p-values = 0.048 and 0.012, respectively). Among NHL patients, those with diffuse large B-cell lymphoma (DLBCL) showed a greater risk of (any grade) VTE (HR: 3.42, 95 % CI: 1.32-8.84, p-value = 0.011). Our study indicates that 1) VTE is a relevant complication for NHL patients, 2) KS is predictive of VTE events and 3) DLBCL histotype is an independent risk factor for VTE incidence, for which preventative interventions could be considered.