Thrombotic and Hemorrhagic Issues Associated with Myeloproliferative Neoplasms.

Thrombotic and hemorrhagic complications are related to a significant rate of morbidity and mortality in patients with myeloproliferative neoplasms (MPNs), they are therefore called "thrombohemorrhagic" syndromes. Several clinical factors, such as age and presence of cardiovascular comorbidities are responsible for thrombotic complications. High blood counts, platelet alterations, presence of JAK2 mutation and possibly of other CHIP mutations such as TET2, DNMT3A, and ASXL1, procoagulant microparticles, NETs formation, endothelial activation and neo-angiogenesis are some of the parameters accounting for hypercoagulability in patients with myeloproliferative neoplasms. Bleeding complications emerge as a result of platelet exhaustion. They can be also linked to a functional deficiency of von Willebrand factor, when platelet counts rise above 1000G/L. The mainstay of management consists on preventing hemostatic complications, by antiplatelet and/or anticoagulant treatment and myelosuppressive agents in high-risk patients.Circumstances related to a high thrombohemorrhagic risk, such as pregnancy and the perioperative period, prompt for specific management with regards to anticoagulation and myelosuppression treatment type. In order to apply a patient-specific treatment strategy, there is a need for a risk score assessment tool encompassing clinical parameters and hemostasis biomarkers.

Derivation and Validation of a Predictive Score for Disease Worsening in Patients with COVID-19.

The prospective observational cohort study COMPASS-COVID-19 aimed to develop a risk assessment model for early identification of hospitalized COVID-19 patients at risk for worsening disease. Patients with confirmed COVID-19 (n = 430) hospitalized between March 18 and April 21, 2020 were divided in derivation (n = 310) and validation (n = 120) cohorts. Two groups became evident: (1) good prognosis group (G-group) with patients hospitalized at the conventional COVID-19 ward and (2) Worsening disease group (W-group) with patients admitted to the intensive care unit (ICU) from the emergency departments. The study end point was disease worsening (acute respiratory failure, shock, myocardial dysfunction, bacterial or viral coinfections, and acute kidney injury) requiring ICU admission. All patients were routinely evaluated for full blood count, prothrombin time, fibrinogen, D-dimers, antithrombin (AT), and protein C activity. Data from the first hospitalization day at the conventional ward or the ICU were analyzed. Cardiovascular risk factors and comorbidities were routinely registered. Obesity, hypertension, diabetes and male gender, increased fibrinogen and D-dimers, thrombocytopenia, AT deficiency, lymphopenia, and an International Society on Thrombosis and Haemostasis (ISTH) score for compensated disseminated intravascular coagulation score (cDIC-ISTH) ≥5 were significant risk factors for worsening disease. The COMPASS-COVID-19 score was derived from multivariate analyses and includes obesity, gender, hemoglobin, lymphocyte, and the cDIC-ISTH score (including platelet count, prothrombin time, D-dimers, AT, and protein C levels). The score has a very good discriminating capacity to stratify patients at high and low risk for worsening disease, with an area under the receiver operating characteristic curve value of 0.77, a sensitivity of 81%, and a specificity of 60%. Application of the COMPASS-COVID-19 score at the validation cohort showed 96% sensitivity. The COMPASS-COVID-19 score is an accurate clinical decision-making tool for an easy identification of COVID-19 patients being at high risk for disease worsening.

Lobectomy and postoperative thromboprophylaxis with enoxaparin improve blood hypercoagulability in patients with localized primary lung adenocarcinoma.

BACKGROUND: Patients with lung adenocarcinoma undergoing surgery are in high risk for VTE and receive routine post-operative thromboprophylaxis with LWMH. AIM: We investigated markers of hypercoagulability in patients with primary localized adenocarcinoma and the modifications induced by lobectomy and postoperative administration of enoxaparin. MATERIALS AND METHODS: Patients suffering from localised primary lung adenocarcinoma (n=15) scheduled for lobectomy were studied. The control group consisted of 15 healthy age and sex-matched individuals. Blood was collected before anaesthesia induction and after surgery, at several intervals until the 7th post-operative day. Samples were assessed for thrombin generation, phosphatidylserin expressing platelet derived microparticles expressing (Pd-MP/PS(+)), tissue factor activity (TFa), FVIIa and TFPI levels, procoagulant phospholipid dependent clotting time and anti-Xa activity. RESULTS: At baseline, patients showed increased thrombin generation and Pd-MP/PS(+). After lobectomy thrombin generation significantly decreased. Administration of enoxaparin attenuated thrombin generation. In about 50% of samples collected post-operatively an increase of thrombin generation occurred despite the presence of the expected anti-Xa activity in plasma. At the 7th post-operative day, 3 out of 15 patients showed a significant increase of thrombin generation. CONCLUSION: In patients with localized lung adenocarcinoma, hypercoagulability is characterized by high thrombin generation and increased concentration of Pd-MP/PS(+). Tumor mass resection is related with attenuation of thrombin generation, which is inhibited by postoperative thromboprophylaxis with enoxaparin. The response to enoxaparin is not predicted by the concentration of the anti-Xa activity in plasma. The assessment of thrombin generation during prophylaxis with enoxaparin allows to identify patients with high residual plasma hypercoagulability.