Venous thromboembolism and major bleeding in severe and critical COVID-19 hospitalized patients.

Venous thromboembolism (VTE) and major bleeding (MB) are life-threatening complications described in COVID-19 hospitalized patients and they can be considered as two sides of the same coin. This retrospective study aims to evaluate the risk factors for VTE and MB in COVID-19 patients admitted to two Italian hospitals. The medical records of all COVID-19 patients (males 139; 62.3%, mean age 67.2±13.6 years, body weight 88.2±20.6 kg) hospitalized from March 11th to July 31st, 2020 to the Federico II University Hospital and to Sea Hospital, Naples, Italy, were analyzed. The COVID-19 patients were classified into four groups: COVID-19 patients developing VTE and/or MB, COVID-19 patients developing only VTE, COVID-19 patients developing only MB, and COVID-19 patients not developing neither VTE nor MB. During the hospitalization, 53 COVID-19 patients (24.7%; males 40; 75.5%, mean age 67.2±13.6 years, weight 88.2±20.6 kg) developed VTE, 33 COVID-19 patients (15.3 %; males 17; 51.5, mean age 67.3±14.9 years, weight 74.1±14.3 kg) developed MB, and 129 COVID-19 patients not developed neither TVP nor MB. No parameters to identify severe COVID-19 complicated by VTE and/or MB were found. However, some clinical and biochemical parameters can be evaluated to predict the risk of MB in order to modify the treatment and take prompt action to reduce mortality.

Spontaneous Muscle Hematoma in Patients with COVID-19: A Systematic Literature Review with Description of an Additional Case Series.

Coagulation abnormalities, thrombosis, and endothelial dysfunction have been described in COVID-19 patients. Spontaneous muscle hematoma (SMH) is a rare complication in COVID-19. The aims of this study are to: (1) perform a systematic review of the literature to better define the clinical SMH characteristics, (2) describe the prevalence and the clinical characteristics of SMH in COVID-19 patients referring to a Department of Internal Medicine (IM) (Federico II University of Naples), a Department of Sub-Intensive Care Medicine (SIM) (Ospedale Del Mare), and a Department of Intensive Care Unit (ICU) (Federico II University). The systematic review was performed according to PRISMA criteria. The local prevalence of SMH in COVID-19 was evaluated retrospectively. The medical records of all COVID-19 patients referring to IM and ICU from March 11th, 2020, to February 28th, 2021 were examined for SMH occurrence. In our retrospective analysis, we describe 10 cases of COVID-19 patients with SMH not previously reported in literature, with a prevalence of 2.1%. The literature review, inclusive of our case series, describes a total of 50 SMHs in COVID-19 patients (57.4% males; mean age 68.8 ± 10.0 years). The SMH sites were ileo-psoas, vastus intermedius, gluteus, sternocleidomastoid, and pectoralis major muscles. Males developed SMH earlier than females (9.5 ± 7.8 vs. 17.1 ± 9.7 days). Ileo-psoas hematoma was more frequent in males (69.2 vs. 30.8%), while pectoralis major hematoma occurred only in females. The in-hospital mortality rate of SMH in COVID-19 patients was 32.4%. SMH is a rare but severe complication in COVID-19 hospitalized patients, associated with high mortality. A gender difference seems to be present in the clinical presentation of the disorder.

Arterial Thrombosis in Cancer Patients: An Update.

Cancer is associated with an increased incidence of both venous thromboembolism (VTE) and arterial thrombosis (cardiovascular events and ischemic stroke). Cancer-associated arterial thrombotic events are less well studied than VTE, but increasingly recognized, particularly in specific malignancies and in association with specific anticancer therapies. The pathogenesis of arterial thrombotic events in cancer is complex and involves generation of tumor-associated procoagulant factors and a variety of alterations in platelet function as well as in the coagulation and fibrinolytic systems, and endothelial injury and dysfunction, that combine to produce hypercoagulability. The multifactorial interaction between this prothrombotic state, the individual cardiovascular risk, advanced age and presence of comorbidities, and the specific neoplasm characteristics and therapy, may induce the vascular events. Recent studies based on population databases and prospective or retrospective analyses with prolonged follow-up highlight that cancer patients experience an increased (approximately 1.5-2-fold) risk of both cerebrovascular and cardiovascular events compared with noncancer individuals, which peaks in the time period of the diagnosis of cancer but may persist for years. Beyond the type of cancer, the risk reflects the tumor burden, being higher in advanced stages and metastatic cancers. The occurrence of arterial thromboembolic events is also associated with increased overall mortality. We here present an update of the pathophysiology, risk factors, clinical evidence, and treatment considerations on cancer-associated arterial thrombosis, in the light of the need for specific multidisciplinary prevention and surveillance strategies in this setting, in the frame of cardio-oncology approaches.

Venous Thromboembolism in COVID-19 Compared to Non-COVID-19 Cohorts: A Systematic Review with Meta-Analysis.

BACKGROUND: A high incidence of venous thromboembolism (VTE) is reported in hospitalized COVID-19 patients, in particular in patients admitted to the intensive care unit (ICU). In patients with respiratory tract infections, including influenza A (H1N1), many studies have demonstrated an increased incidence of thromboses, but evidence is lacking regarding the risk difference (RD) of the occurrence of VTE between COVID-19 and non-COVID-19 patients. METHODS: In this systematic review with meta-analysis, we evaluated the RD of the occurrence of VTE, pulmonary embolism (PE), and deep venous thrombosis (DVT) between COVID-19 and other pulmonary infection cohorts, in particular H1N1, and in an ICU setting. We searched for all studies comparing COVID-19 vs. non-COVID-19 regarding VTE, PE, and DVT. RESULTS: The systematic review included 12 studies and 1,013,495 patients. The RD for VTE in COVID-19 compared to non-COVID-19 patients was 0.06 (95% CI 0.11-0.25, p = 0.011, I2 = 97%), and 0.16 in ICU (95% CI 0.045-0.27, p = 0.006, I2 = 80%). The RD for PE between COVID-19 and non-COVID-19 patients was 0.03 (95% CI, 0.006-0.045, p = 0.01, I2 = 89%). The RD for PE between COVID-19 and non-COVID-19 patients was 0.021 in retrospective studies (95% CI 0.00-0.04, p = 0.048, I2 = 92%) and 0.11 in ICU studies (95% CI 0.06-0.16, p < 0.001, I2 = 0%). CONCLUSIONS: The growing awareness and understanding of a massive inflammatory response combined with a hypercoagulable state that predisposes patients to thrombosis in COVID-19, in particular in the ICU, may contribute to a more appropriate strategy of prevention and earlier detection of the thrombotic events.

Combined Oral Fentanyl Citrate and Midazolam as Premedication for Bone Marrow Aspiration and Biopsy in Patients with Hematological Malignancies: A Randomized, Controlled and Patient-Blinded Clinical Trial.

Bone marrow aspiration and biopsy (BMAB) is a painful procedure, and the routinely used local infiltration anesthesia (LIA) with lidocaine is unable to provide pain relief during the most uncomfortable phases. The primary endpoint of the present randomized, patient-blinded trial was to evaluate the efficacy of an opioid and benzodiazepine combination plus LIA (sedoanalgesia) in patients undergoing BMAB for hematological malignancies. The secondary endpoint was the safety of the procedure in an outpatient setting. Ancillary assessments were anticipatory anxiety related to pain recall in the event of re-biopsy, and adequacy of bone tissue harvested. Patients were randomly assigned to one of 2 arms to receive either sedoanalgesic placebo plus LIA (standard group) or oral fentanyl citrate 200 µg plus oral midazolam 5 mg plus LIA (combo group) during BMAB. Pre-procedural anxiety and procedural pain were assessed according to the Numerical Rating Scale (NRS: 0-10), dividing the time of the procedure into five intervals (T0, T1, T2a, T2b and T3) and evaluating the degree of discomfort at each time (T) in both groups. One hundred and sixteen patients were eligible for the study. At T2b (time of biopsy) and T3 (time after biopsy), a significantly lower perception of pain was registered in the combo group. Moreover, there were no significant sedoanalgesia-related side-effects. Finally, histological specimens were higher in quality in the combo group. Sedoanalgesia was highly effective in reducing pain during biopsy, diminished anticipatory anxiety in patients undergoing re-biopsy and led to fewer non-diagnostic specimens being harvested.