Thrombosis in Acute Myeloid Leukemia: Pathogenesis, Risk Factors and Therapeutic Challenges.

OPINION STATEMENT: Prophylaxis and treatment of thrombosis in leukemic patients still represent a major challenge with several clinical questions yet to be solved. Indeed, the paucity of evidence makes the management of venous thromboembolic events difficult and not uniform. Due to thrombocytopenia, patients with acute myeloid leukemia (AML) are underrepresented in trials investigating prophylaxis and treatment of thrombosis in cancer, and prospective data are lacking. Likewise, the therapeutic approach with anti-coagulants in leukemic patients is inferred from guidelines originally developed in the solid cancer setting and clear recommendations in the thrombocytopenic population are limited. Importantly, the discrimination of patients at high risk of bleeding from those with a predominant risk of thrombosis remains extremely difficult with no predictive score validated so far. Thus, the management of thrombosis often relies on clinician experience, and it is tailored to the individual patient, constantly balancing thrombotic and hemorrhagic risks. Who would benefit from primary prophylaxis and how a thrombotic event should be appropriately treated are some of the unanswered questions that the future guidelines and trials should address. Moreover, a greater effort should be made to identify robust predictive factors able to guide clinicians in the management of this potential serious complication for AML patients.

Frequency and risk factors for thrombosis in acute myeloid leukemia and high-risk myelodysplastic syndromes treated with intensive chemotherapy: a two centers observational study.

The frequency of thrombosis in AML has been evaluated only in a few studies and no validated predictive model is currently available. Recently, DIC score was shown to identify patients at higher thrombotic risk. We aimed to evaluate the frequency of thromboembolism in AML patients treated with intensive chemotherapy and to assess the ability of genetic and clinical factors to predict the thrombotic risk. We performed a retrospective observational study including 222 newly diagnosed adult AML (210) and high-risk MDS (12), treated with intensive chemotherapy between January 2013 and February 2020. With a median follow-up of 44 months, we observed 50 thrombotic events (90% were venous, VTE). The prevalence of thrombosis was 22.1% and the 6-months cumulative incidence of thrombosis was 10%. The median time to thrombosis was 84 days and 52% of the events occurred within 100 days from AML diagnosis. Khorana and DIC score failed to stratify patients according to their thrombotic risk. Only history of a thrombotic event (p = 0.043), particularly VTE (p = 0.0053), platelet count above 100 × 109/L at diagnosis (p = 0.036) and active smoking (p = 0.025) significantly and independently increased the risk of thrombosis, the latter particularly of arterial events. AML genetic profile did not affect thrombosis occurrence. Results were confirmed considering only thromboses occurring within day 100 from diagnosis. DIC score at diagnosis, but not thrombosis, was independently associated with reduced survival (p = 0.004). Previous VTE, platelet count above 100 × 109/L and active smoking were the only factors associate with increased thrombotic risk in AML patients treated intensively, but further studies are needed to validate these results.

New Viscoelastic Hydrogel Hymovis MO.RE. Single Intra-articular Injection for the Treatment of Knee Osteoarthritis in Sportsmen: Safety and Efficacy Study Results.

Viscosupplementation by hyaluronic acid (HA) is recommended for non-surgical management of knee osteoarthritis (OA). This study investigated the efficacy and safety of a single i.a. (32 mg/4 ml) Hymovis MO.RE. injection, a new HA derivative hydrogel, for the treatment of adult regular sports players affected by knee OA arising from overuse injuries. Patients were prospectively enrolled if regularly practicing sports and diagnosed with Kellgren-Lawrence grade I-III OA. They received a single Hymovis MO.RE. intra-articular (i.a.) injection and were evaluated 30, 90, 180, and 360 days thereafter. The assessment involved measuring changes in knee function, pain, the activity of daily living (ADL), and quality of life (QOL) by using the Knee injury and Osteoarthritis Outcome Score (KOOS), GAIT analysis, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for knee pain (WOMAC A) and function (WOMAC C), and a visual analogue scale (VAS) pain score. The study involved thirty-one patients, 23 women and eight men, whose median age was 49. KOOS function subscore, as well as GAIT cadence and velocity, showed a statistically significant increase at each time-point after injection (p < 0.0001). WOMAC, KOOS pain, symptoms, ADL, and QOL scores also significantly improved at all control visits. No severe adverse events or treatment-related events were detected. A single Hymovis MO.RE. (32 mg/4 ml) intra-articular injection provides a rapid, lasting, and safe response in regular sports players affected by knee OA, possibly representing a viable therapeutic option for this demanding patient subgroup. Further investigations are necessary to confirm these findings.