Bleeding Events in Patients 75 Years of Age and Older Under Long-term Anticoagulant Therapy: A Real-life Study.

OBJECTIVE: To investigate the risk of bleeding events in older patients under oral anticoagulant with a 4-year survey of a catchment area with 197,722 inhabitants of whom 15,267 were on warfarin and 10,397 on direct oral anticoagulants (DOACs). METHODS: Patients presented to the Emergency Department with major bleeding were enrolled and stratified according to age ≥75 years and ongoing warfarin or DOACs. Primary endpoint was 1-month death. RESULTS: Out of 1919 major bleeding, those of patients ≥75 years of age were 1127 (59%) versus 792 (41%) <75 years of age, P < 0.0001. In patients ≥75 years of age, brain hemorrhage accounted for 612 (54%) patients, gastrointestinal hemorrhage for 301 (27%), hematuria for 104 (9%), and other hemorrhage for 108 (10%). In patients ≥75 years of age, those on warfarin accounted for 175 versus 53 on DOACs, without difference of Charlson Comorbidity Index (5.25 ± 1.92 versus 5.09 ± 1.61; P = 0.5824). One-month death in patients ≥75 of age versus <75 years of age accounted for 77 (4.0%) versus 20 (1.0%); P < 0.0001. One-month death in patients ≥75 of age on DOACs was very low, without difference versus <75 years and within DOACs. Among DOACs, absolute bleeding events showed differences as follows: 3 bleeding events for edoxaban versus 21 for dabigatran; P < 0.001; versus 16 for rivaroxaban, P = 0.006; and versus 13 for apixaban, P = 0.02. CONCLUSIONS: Major bleeding and 1-month death accounted for higher percentage in patients ≥75 years of age and in patients receiving warfarin. Among DOACs, edoxaban presented the lowest absolute rate of hemorrhage among the 4 available DOACs, without difference in mortality.

Role of Hypertension and Other Clinical Variables in Prognostication of Patients Presenting to the Emergency Department With Major Bleeding Events.

BACKGROUND: Clinical variables including hypertension could be linked with major bleeding events and death beyond vitamin K antagonist (warfarin) or direct oral anti-coagulants (DOACs) treatment strategy. METHODS: Subgroup analysis of major bleeding (primary endpoint) associated with clinical variables, site of bleeding, ongoing antithrombotics, reversal treatment or blood transfusion, outcomes (secondary endpoints) was performed in patients with bleeding events submitted to hard 5:1 propensity-score matching for hypertension. RESULTS: Enrolled patients were 2,792 (mean age, 65.6 ± 19.9 years) during 2-year survey including 166,000 visits, of 200,000 inhabitants catchment area; 8,239 patients received warfarin and 3,797 DOACs. Hypertension account for 1,077 (39%) patients; major bleeding for 474 (17%); death for 29 (1%), and 72 (3%) on 1-month and 1-year, respectively. Hypertension, age, glucose, cancer, ischemic vascular disease, and CHA2D2VASc score were more likely to link with major bleeding. On multivariate analysis, only age (odds ratio [OR], 1.02; P < 0.001), CHA2DS2VASc score ≥ 2 (OR, 2.14; P = 0.001), and glucose (OR, 1.01; P = 0.005) were predictors of major bleeding. Kaplan-Meier analysis demonstrated patients with hypertension as compared with patients without showed 60% versus 20% death on 1-month (P < 0.001). Warfarin compared with DOACs was more likely to present with major bleeding (0.7% versus 0.2%; OR, 2.8; P = 0.005). Receiver operator characteristics analysis showed high value (0.61) of age and glucose over creatinine and systolic arterial pressure (P = NS). CONCLUSIONS: Four in 10 patients with major bleeding showed hypertension; of these 8 in 10 will die within 1 month. Warfarin compared with DOACs was more likely to present with major bleeding.

The practical management of intracerebral hemorrhage associated with oral anticoagulant therapy.

Oral anticoagulant-associated intracerebral hemorrhage is increasing in incidence and is the most feared complication of therapy with vitamin K1 antagonists. Anticoagulant-associated intracerebral hemorrhage has a high risk of ongoing bleeding, death, or disability. The most important aspect of clinical management of anticoagulant-associated intracerebral hemorrhage is represented by urgent reversal of coagulopathy, decreasing as quickly as possible the international normalized ratio to values ≤1·4, preferably ≤1·2, together with life support and surgical therapy, when indicated. Protocols for anticoagulant-associated intracerebral hemorrhage emphasize the immediate discontinuation of anticoagulant medication and the immediate intravenous administration of vitamin K1 (mean dose: 10-20 mg), and the use of prothrombin complex concentrates (variable doses calculated estimate circulating functional prothrombin complex) or fresh-frozen plasma (15-30 ml/kg) or recombinant activated factor VII (15-120 µg/kg). Because of cost and availability, there is limited randomized evidence comparing different reversal strategies that support a specific treatment regimen. In this paper, we emphasize the growing importance of anticoagulant-associated intracerebral hemorrhage and describe options for acute coagulopathy reversal in this setting. Additionally, emphasis is placed on understanding current consensus-based guidelines for coagulopathy reversal and the challenges of determining best evidence for these treatments. On the basis of the available knowledge, inappropriate adherence to current consensus-based guidelines for coagulopathy reversal may expose the physician to medico-legal implications.

Serum levels of proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor alpha in mixed cryoglobulinemia.

OBJECTIVE: No single previous study has evaluated serum levels of the proinflammatory cytokines interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha (TNFalpha) in patients with hepatitis C virus-associated mixed cryoglobulinemia (HCV-MC). This study was undertaken to evaluate serum levels of these cytokines in patients with HCV-MC. METHODS: Serum IL-1beta, IL-6, and TNFalpha were assayed in 43 patients with HCV-MC, in 43 sex- and age-matched patients with chronic HCV without cryoglobulinemia, and in 43 sex- and age-matched controls. RESULTS: HCV-MC patients showed significantly higher mean IL-1beta, IL-6, and TNFalpha levels than did the controls (P<0.01) or the HCV patients (P

CXCL10 and CCL2 chemokine serum levels in patients with hepatitis C associated with autoimmune thyroiditis.

To evaluate CXCL10 and CCL2 in patients with hepatitis C virus chronic infection in presence/absence of autoimmune thyroiditis (AT). CXCL10 was significantly higher in: (1) patients with AT than controls without AT (control 1) (P < 0.001; ANOVA); (2) patients with hepatitis C infection than control 1 and patients with AT (P < 0.001); (3) patients with hepatitis C virus chronic infection and AT (HCV+AT) than control 1 and patients with AT (P < 0.001) and hepatitis C (P = 0.004). By defining a high CXCL10 level as a value >218 pg/mL, 2% of control 1, 14% of patients with AT, 68% of patients with hepatitis C infection, 81% of HCV+AT had high CXCL10 (P < 0.0001; chi-square). CCL2 was similar in control 1 and patients with AT. CCL2 was significantly higher in: (1) patients with hepatitis C infection than control 1 (P = 0.04; ANOVA); (2) HCV+AT than patients with AT (P = 0.03) and control 1 (P = 0.02); no difference was observed between HCV with or without AT. Our study demonstrates: (1) higher circulating CXCL10 and CCL2 in patients with hepatitis C virus chronic infection than in controls; (2) higher CXCL10 in HCV+AT than in patients with hepatitis C infection, suggesting a stronger Th1 immune response in these patients.

Thyroid cancer in HCV-related chronic hepatitis patients: a case-control study.

OBJECTIVE: The present study prospectively investigated prevalence and features of thyroid cancer in patients with hepatitis C virus-related chronic hepatitis (HCV+) in comparison to two samples from the general population with different iodine intake. DESIGN: We studied the prevalence of thyroid cancer in 308 unselected HCV+ patients in comparison to two population-based, gender- and age-matched control groups: 1) 616 subjects from an iodine deficient area; 2) 616 subjects from an iodine-sufficient area. Thyroid status was assessed by measurement of circulating thyroid hormones and autoantibodies, thyroid ultrasonography, and when indicated, fine-needle aspiration cytology. MAIN OUTCOME: Circulating thyrotropin, anti-thyroglobulin, and anti-thyroperoxidase antibodies levels, and the prevalence of hypothyroidism were significantly higher in HCV+ patients (p < 0.001 for all). Six patients with papillary thyroid cancer were detected among HCV+ patients, whereas no case was observed in control 1 (p = 0.001), and only one case was observed in control 2 (p = 0.003). In HCV+ patients 83% with thyroid cancer had evidence of thyroid autoimmunity vs 31% of the other HCV+ patients (p = 0.02). CONCLUSIONS: These data suggest a high prevalence of thyroid papillary cancer in HCV+ patients, overall in presence of thyroid autoimmunity; careful thyroid monitoring is indicated during the follow-up of these patients.

Thyroid disorders in chronic hepatitis C.

PURPOSE: To explore the association of hepatitis C virus (HCV) infection with thyroid disorders. METHODS: We investigated the prevalence of thyroid disorders in 630 consecutive patients with chronic hepatitis due to HCV infection; all patients were free of cirrhosis and hepatocarcinoma, and were not on interferon treatment. Also included were a control group of 389 subjects from an iodine-deficient area, another control group of 268 persons living in an area of iodine sufficiency, and 86 patients >40 years of age with chronic hepatitis B. Levels of thyroid-stimulating hormone (TSH), free thyroxine (T(4)), and triiodothyronine (T(3)), as well as anti-thyroglobulin and anti-thyroid peroxidase antibodies, were measured. RESULTS: Mean TSH levels were higher (P = 0.001), and free T(3) and free T(4) levels were lower (P <0.0001), in patients with chronic hepatitis C than in all other groups. Patients with chronic hepatitis C were more likely to have hypothyroidism (13% [n = 82]), anti-thyroglobulin antibodies (17% [n = 108]), and anti-thyroid peroxidase antibodies (21% [n = 132]) than were any of the other groups. CONCLUSION: Both hypothyroidism and thyroid autoimmunity are more common in patients with chronic hepatitis C-even in the absence of cirrhosis, hepatocellular carcinoma, or interferon treatment-than in normal controls or those with chronic hepatitis B infection.