Effect of Three-Day Atorvastatin Administration on Coagulation Factors in Patients With Prior Venous Thromboembolism and Healthy Subjects: A Preliminary Study.

ABSTRACT: Statins exert antithrombotic effects, which might contribute to reduced risk of venous thromboembolism (VTE). Rosuvastatin 20 mg/d administered for 4 weeks has been reported to decrease coagulation factors (F) VII, FVIII, and FXI in VTE patients. Moreover, in accordance with recent registry data in non-VTE subjects, statins usage was associated with lower FXI. We investigated whether 3 doses of a statin decrease coagulation factors activity and if such changes can alter fibrin clot properties in VTE patients and healthy subjects. We enrolled 28 consecutive first-ever prior VTE patients after 6 months of anticoagulation and 25 healthy controls well-matched for demographics and lipid profiles (aged 44 [interquartile range 34-51] years) in an interventional nonrandomized study. Before and after 3 doses of atorvastatin 40 mg/d, activity of FVII, FVIII, FIX, and FXI was measured, along with fibrin clot properties, including permeability (Ks) and clot lysis using 3 various assays. After a 3-day statin administration, we observed the decrease of FVII (by 6.2%, P = 0.046) and FXI (by 8.6%, P = 0.044), irrespective of low-density lipoprotein cholesterol reduction (by 24%, P < 0.001), whereas other coagulation factors remained unaltered. Reduction of FVII and FXI activity was inversely correlated with Ks alterations (R = -0.292, P = 0.034 and R = -0.335, P = 0.014, respectively). After adjustment for age, studied group, and fibrinogen level, the reduction of FXI was independently associated with an increase of fibrin clot permeability (B = -0.084, P = 0.027). In conclusion, a 3-day 40 mg atorvastatin administration is sufficient to reduce FVII and FXI activity in our pilot study, which is associated with favorable fibrin clot properties modification.

Autoimmune polyendocrine syndrome type 2 in patient with severe allergic asthma treated with omalizumab.

Asthma therapy with monoclonal antibodies is a promising and effective approach for those with a severe and refractory type of disease. Although such a targeted therapy is considered to be safe, unusual complications may occur. We present a case of a 45 year-old female patient with severe allergic asthma and chronic spontaneous urticaria, who developed autoimmune polyendocrine syndrome type 2 (APS-2) after 26 months of omalizumab administration. The patient was diagnosed with primary adrenal insufficiency (Addison's disease) and Hashimoto's thyroiditis accompanied by autoimmune atrophic gastritis. According to our knowledge this is the first description of APS-2 that developed in conjunction with omalizumab treatment, although we have no evidence that the observed phenomenon indicated a cause-effect relationship to omalizumab.

Atorvastatin favorably modulates proinflammatory cytokine profile in patients following deep vein thrombosis.

BACKGROUND: Venous thromboembolism (VTE) has been shown to be associated with inflammation. Statins that might reduce VTE risk have been found to exert anti-inflammatory properties in patients at cardiovascular risk. We sought to investigate whether anti-inflammatory effects of atorvastatin can be observed in VTE patients. MATERIALS AND METHODS: Atorvastatin 40 mg/d was given for 3 days to 26 consecutive VTE patients following discontinuation of anticoagulant therapy and 25 controls. We evaluated interleukin (IL)-1b, IL-6, IL-8, IL-10, soluble P-selectin and von Willebrand factor (vWF) antigen in peripheral venous blood. RESULTS: The VTE patients displayed higher C-reactive protein (p=0.013), IL-1b (p=0.03), IL-8 (p=0.03) and vWF (p<0.0001) compared with the controls. In VTE patients atorvastatin decreased IL-6 (p=0.0003), IL-8 (p=0.003) and P-selectin (p<0.0001), but increased IL-10 (p=0.001), with no association with C-reactive protein or cholesterol-lowering effects. Atorvastatin reduced IL-1b (p=0.01), IL-6 (p=0.03) and P-selectin (p=0.002) in controls. Residual venous thrombosis was associated with elevated IL-6 and P-selectin, whereas patients with proximal deep vein thrombosis showed elevated P-selecitn prior to and following statin administration (all p<0.05). CONCLUSION: A 3-day administration of atorvastatin reduces inflammation without decrease in C-reactive protein in VTE patients.

Architecture of a native mitral valve thrombus in a patient with hypereosinophilic syndrome.

A 27-year-old male with a six-year history of hypereosinophilic syndrome (HES) presented with a native mitral valve thrombus, despite therapeutic oral anticoagulation. The thrombus was removed, the mitral valve replaced, and subsequent oral anticoagulation maintained at a higher level (INR 3.5). The patient developed two recurrences of mitral valve thrombosis requiring urgent reoperations, and died shortly after the second intervention. A scanning electron microscopy analysis of the native mitral valve thrombus removed during the first cardiac surgery revealed tightly packed thin fibrin strands forming fuzzy irregular structures, with areas of an almost solid fibrin clot. The fibrin networks indicated a heightened thrombin generation, and may account for a diminished susceptibility to intrinsic fibrinolysis. In conclusion, the unfavorably altered compact structure of the fibrin-rich thrombus, which formed despite adequate anticoagulation, might in part explain the recurrent valvular thrombosis. It may also represent a novel prothrombotic mechanism that operates in HES.

Switching from acenocoumarol to warfarin in patients with unstable anticoagulation and its effect on anticoagulation control.

INTRODUCTION: Unstable oral anticoagulation increases the risk of thrombotic events and bleedings. Acenocoumarol use has been reported to be associated with two-fold higher risk for instability of anticoagulation control compared to warfarin administration. OBJECTIVES: The aim of the study was to evaluate the effect of introducing warfarin on anticoagulation control in patients with a variable response to acenocoumarol. PATIENTS AND METHODS: Sixty-eight subjects treated with acenocoumarol for 5 months or more and displaying intraindividual variability of international normalized ratio (INR) results were switched to warfarin. Unstable anticoagulation was defined as a failure to achieve a target INR within the preceding 3 months, i.e. > or = 50% of 8 or more INR values below 2 or above 3.5. Patients with stable anticoagulation (<20% of out-of-range INRs), matched for age, gender, and anticoagulation indications, served as a reference group. RESULTS: Patients with unstable anticoagulation on acenocoumarol had higher body mass index (p<0.01) and serum C-reactive protein levels (p<0.01) compared to stable counterparts. The transition factor between acenocoumarol and warfarin was 1.8 (95% CI 1.69-1.96). The percentage time within the target INR range in patients with unstable anticoagulation was 40.2% at baseline and increased to 60.4% following 6 months on warfarin therapy (p<0.05). The number of subjects with <20% of out-of-range INRs among individuals switched from acenocoumarol to warfarin was 22 (32.4%) vs. 63 (92.6%) in patients on stable anticoagulation after 6 months of follow-up (p<0.001). CONCLUSIONS: Switching acenocoumarol to warfarin in patients with unstable anticoagulation can improve anticoagulation control.

Anti-Ku autoantibodies: series of 5 cases.

Autoantibodies directed against nuclear protein Ku are infrequently detected. If present, they are found in high titers in patients with connective tissue overlap syndromes. This article describes 5 patients with anti-Ku antibodies in whom systemic lupus erythematosus, Sjögren's syndrome, idiopathic lung fibrosis or scleroderma - polymyositis overlap syndrome were diagnosed. Interestingly, signs and symptoms of transient cranial neuropathy involving trigeminal and facial nerves were reported by 3 patients. Cranial nerve neuropathy has not been described in patients with anti-Ku autoantibodies previously.

[Mycophenolate mofetil maintenance therapy in lupus nephritis]. / Mykofenolan mofetylu w leczeniu podtrzymujacym u chorych z nefropatia toczniowa.

INTRODUCTION: The aim of this study was to assess clinical efficacy and changes in immunological parameters during maintenance therapy with mycophenolate mofetil (MMF) in patients with lupus nephritis. METHODS: Patients (n = 7) with systemic lupus erythematosus (SLE) and proliferative nephropathy confirmed by renal biopsy, in whom disease remission was induced with intravenous cyclophosphamide, received MMF (2 x 500 mg daily) for 3 months. Clinical and immunological parameters as well as drug tolerance were assessed before, and after 1 and 3 months of MMF therapy. RESULTS: MMF therapy lead to a decrease in disease activity index (SLEDAI), and maintenance of previously achieved reduction of proteinuria, improvement of renal function and immunological parameters. These changes were associated with decrease in the number of activated T cells and increase in B cells. The titer of anti-dsDNA antibodies was reduced in 5 out of 7 patients. CONCLUSIONS: Mycofenolate mofetil is effective in the maintenance therapy oflupus nephritis. A 3-month MMF treatment allows for sustained beneficial immunological profile achieved in induction therapy.

[Non-Hodgkin lymphomas as a cause of persistent fever in internal medicine wards--a series of cases]. / Chloniaki nieziarnicze jako przyczyna uporczywych goraczek na oddzialach chorób wewnetrznych--seria przypadków.

Patients with a suspicion of non-Hodgkin lymphoma (NHL) represent a diagnostic challenge for clinicians, because they may present with a variety of symptoms. We present a series of 5 patients in whom persistent fever was one of the earliest symptoms of NHL.