Time to therapeutic range (TtTR), anticoagulation control, and cardiovascular events in vitamin K antagonists–naive patients with atrial fibrillation

Background: Vitamin K antagonists (VKAs) reduce cardiovascular events (CVEs) in atrial fibrillation (AF) when a time in therapeutic range (TiTR) >70% is achieved. Factors affecting the time to achieve the TR (TtTR) are unknown. Methods: Prospective observational study including 1,406 nonvalvular AF patients starting VKAs followed for a mean of 31.3 months (3,690 patient/year); TiTR, TtTR, and SAMe-TT 2 R 2 score were calculated, and CVEs were recorded. Results: Median TtTR was 8.0 days (interquartile range 5.0-18.0). Patients with high TtTR (ie, >75th percentile) were more likely to be in AF than in sinus rhythm at entry (odds ratio [OR]: 1.423, P =.011). Median TiTR was 60.0%; low TiTR (below median) was associated with SAMe-TT 2 R 2 score (OR: 1.175, P =.001), high TtTR (>75th percentile, OR: 1.357, P =.017), and number of international normalized ratio checks (OR: 0.998, P =.049). We recorded 113 CVEs (3.1%/y), with a higher rate seen in patients with TtTR >75th percentile compared to those below (log-rank test, P =.006). A multivariable Cox regression analysis showed that SAMe-TT 2 R 2 score (hazard ratio [HR]: 1.331, P <.001), TtTR >75th percentile (HR: 1.505, P =.047), TiTR <70% (HR: 1.931, P =.004), number of international normalized ratio checks (HR: 0.988, P <.001), digoxin (HR: 1.855, P =.008), and proton-pump inhibitors (HR: 0.452, P <.001) were independently associated with CVEs. Conclusions: High TtTR is associated with poorer long-term quality of VKAs therapy. Patients with TtTR >18 days or with high SAMe-TT 2 R 2 score should be considered for treatment with non–vitamin K oral anticoagulants

The risk of myocardial infarction in patients with atrial fibrillation: an unresolved issue

[No abstract available

EFFECT OF ORAL DEFIBROTIDE ON TISSUE-PLASMINOGEN ACTIVATOR AND TISSUE-PLASMINOGEN ACTIVATOR INHIBITOR BALANCE

Defibrotide, a polydeoxyribonucleotide of mammalian origin, has been shown to reduce the blood level of the plasminogen activator inhibitor, and so to increase the activity of tissue plasminogen activator without any adverse effect. A randomized, double-blind, placebo-controlled study has been done in 22 patients, 14 with peripheral vascular disease, 6 with coronary heart disease and 2 with cerebrovascular disease. Patients were given defibrotide 400 mg b.d. or identical placebo for 30 days and the parameters of fibrinolysis were evaluated before and after the treatment. A significant increase in tissue plasminogen activator activity at rest and after venostasis was observed after defibrotide; tissue plasminogen activator antigen at rest and after venostasis was not affected by either treatment. Defibrotide significantly reduced plasminogen activator inhibitor activity and antigen at rest. Only one patient complained of gastric pain after placebo treatment. The study shows that defibrotide has profibrinolytic property and that it could be used to explore the role of plasminogen activator inhibitor in venous and arterial thrombosis

CLOTTING ABNORMALITIES IN CHRONIC LIVER-DISEASE

In patients with chronic liver disease (CLD), several clotting changes can be observed. The most frequent abnormality is the reduced synthesis of many clotting factors, including vitamin-K-dependent and vitamin-K-independent ones. A low platelet count is another frequent feature of patients with CLD, which, however, is not always associated with the prolongation of bleeding time. Hyperfibrinolytic syndrome is usually seen in patients with decompensated state, and may further deteriorate the clotting abnormalities and favor bleeding complications. The assessment of the clotting system may be a useful approach to evaluate liver function and predict prognosis of patients with CLD

INHIBITION OF TISSUE PLASMINOGEN-ACTIVATOR INHIBITOR BY DEFIBROTIDE IN ATHEROSCLEROTIC PATIENTS

Defibrotide, an antithrombotic drug, was previously shown to activate fibrinolysis. In order to elucidate the relationship between defibrotide treatment and fibrinolysis, ten atherosclerotic patients were given 1200 mg/day defibrotide intravenously for 7 days and then 400 mg/day intramuscularly for another 20 days. t-PA antigen assessed before and after venous occlusion was not affected by the treatment. Tissue PAI activity significantly decreased and t-PA activity, measured after venous occlusion, increased after 8 and 28 days of treatment; both these changes disappeared after defibrotide was discontinued. No particular side effects were detected throughout the investigation. The study suggests that defibrotide increases t-PA activity by reducing PAI activity

Specificity and sensitivity of diluted aPTT and anticardiolipin antibodies towards thrombosis and miscarriages in patients with systemic lupus erythematosus

In 36 patients suffering from systemic lupus erythematosus (SLE), lupus anticoagulant (LA), as assessed by aPTT and diluted aPTT, and anticardiolipin antibodies (aCL) were studied. 14 patients, had a clinical history complicated by thrombosis and/or miscarriages. Among patients with thrombosis LA was positive in 42% and in 100% of patients when assessed by aPTT and diluted aPTT respectively; aCL were positive in 85.7% of patients. Among patients without a clinical history of thrombosis, 1 had prolonged aPTT, 3 had prolonged diluted aPTT and 5 had aCL positivity. Diluted aPTT was more sensitive than aPTT and aCL (p less than 0.01) to thrombosis and miscarriages; specificity to thrombosis and miscarriages ranged from 77.3% for aCL and 86.4% for diluted aPTT to 95.5% for aPTT but not significant differences were found. The study suggests that LA, as assessed by a sensitive test like diluted aPTT, is strongly associated to thrombosis and should therefore be considered an important risk factor

IMPROVEMENT OF BLOOD-GAS LEVELS AFTER CALCIUM-HEPARIN TREATMENT IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY-DISEASE

[No abstract available

Reply to. "monitoring antivitamin K anticoagulants in antiphospholipid syndrome. a challenge in quality"

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Prognostic value of clotting and fibrinolytic systems in a follow-up of 165 liver cirrhotic patients. CALC Group.

One hundred sixty-five patients with cirrhosis diagnosed by needle liver biopsy were followed for 2 years to evaluate the relation between clotting factors and survival. Patients with spontaneous bacterial peritonitis, hepatic carcinoma, and cholestatic liver diseases were excluded. Patients were classified as A (n = 34), B (n = 75), or C (n = 56) according to Child-Pugh criteria. During the follow-up 45 patients died of liver failure or gastrointestinal hemorrhage. Nonsurvivor patients had significantly higher values of bilirubin and D-dimer, a marker of fibrinolysis in vivo, lower values of albumin, prothrombin activity, fibrinogen, prekallikrein, factor VII, and a more prolonged activated partial thromboplastin time than survivors. All these variables and Child-Pugh classification were significantly associated with survival in a univariate analysis. Multivariate analysis (Cox's model) showed that only prekallikrein and factor VII were independently predictors of survival. Ninety-three percent of patients with prekallikrein values < 32% died within 32 months of follow-up, whereas factor VII < 34% identified 93% of patients who died within 10 months of follow-up. This study suggests that factor VII is an early predictor of survival and may be a useful test to better identify cirrhotic patients who should be candidates for liver transplantation

Antiphospholipid syndrome and anticoagulation quality: A clinical challenge

BACKGROUND AND AIMS: Antiphospholipid Syndrome (APS) is often complicated by ischemic vascular events. Vitamin K Antagonists (VKAs) reduce the risk of recurrent thrombosis. Quality of VKAs treatment, as assessed by the Time in Therapeutic Range (TTR), has never been investigated in APS patients. METHODS: We performed a prospective observational study including 30 APS and 30 Atrial Fibrillation (AF) patients balanced by age and gender. All patients were treated with VKAs (INR target 2.5), and TTR was calculated. RESULTS: Median TTR of APS was 53.5% vs. 68% of AF patients (p = 0.001). A multivariable linear regression analysis confirmed that the presence of APS (vs. AF) was independently associated with a worse TTR (B: -14.067, 95% Confidence Interval -25.868/-2.266, p = 0.020). The weekly dosage of VKAs was significantly higher in APS than AF patients. CONCLUSIONS: APS patients disclose a lower quality of anticoagulation compared to those with AF, requiring higher doses of VKAs. The efficacy of non-vitamin K oral anticoagulants in this high-risk patients should be tested