Routine coagulation tests are not useful as a screening tool for the FII G20210A polymorphism.

BACKGROUND: The identification of prothrombin G20210A polymorphism (PT20210) is normally included in the thrombophilia laboratory panel and evaluated by DNA-based molecular analysis. To date, a routine coagulation test that helps to identify PT20210 carriers has not been set, in contrast to the FV Leiden mutation, for which a functional coagulation test, the Activated Protein C Resistance test (APCR), is available as a screening tool. More- over the molecular tests are expensive and are used inappropriately. The aim of the study is to characterize the effects of the prothrombin G20210A mutation on routine clotting assays in order to identify, if any, coagulation tests that can be used as a first-line cost-effective assay for prothrombin G20210A polymorphism. METHODS: Our cohort consisted of 80 PT20210 polymorphism carriers and 82 age and gender matched controls. All subjects were investigated for PT-INR, aPTT, dRVVT, FII (%), and Endogenous Thrombin Potential (EPT) parameters. RESULTS: In heterozygotes and wild-type, PT, aPTT, and dRVVT values were not significantly different. The plasma activity of Factor II (%), AUC TG (%), and C max (%) of EPT were significantly higher in heterozygotes than in controls (p < 0.0001, Mann-Whitney test). In the absence of oral anticoagulant therapy and/or heparin, lupus anticoagulants, and liver disease, the discriminating abilities of the FII, AUC TG, and C max (%) to separate properly the study population into carriers and controls were equal to 0.99 (95% CI 0.98 to 1.00); 0.97 (95% CI 0.94 to 0.99), and 0.84 (95% CI 0.77 to 0.90), respectively. CONCLUSIONS: All routine clotting assays performed in the present work are not useful as a screening tool for the G20210A prothrombin gene allele in a general population. Definitely, to date, the exclusive possible approach to identify the PT20210 mutation is molecular genetic testing, but unfortunately it is used inappropriately, contributing significantly to an uncontrolled waste of resources. It is mandatory to restrict the genetic thrombophilia test ordering to when it is actually recommended by the guidelines and to educate clinicians on the waste and danger of over-testing, particularly genetic tests, taking into account the fact that the PT20210 polymorphism is extremely variable (0.7 to 8% in Europe; 1.3-5% in the USA).

Hypovitaminosis D and response to cholecalciferol supplementation in patients with autoimmune and non-autoimmune rheumatic diseases.

Recent reports suggest a role of hypovitaminosis D in the pathogenesis of inflammatory autoimmune diseases (ARD); we investigated 25(OH)vitamin D plasma level before and after supplementation in ARD and NARD (non-ARD: osteoporosis and/or OA) patients. We retrospectively evaluated 572 consecutive clinical records of adult patients at immuno-rheumatology and rehabilitative units of our institution from January 2006 to October 2009. We excluded patients with vitamin D supplementation or renal failure, primary hyperparathyroidism, liver failure. We recorded 25(OH)vitamin D plasma concentration of 245 patients together with other clinical data. We then evaluated 25(OH)vitamin D plasma concentration of 100 (43 ARD and 57 NARD) patients previously included who underwent 750-1,000 UI/die 25(OH)vitamin D supplementation for at least 6 months. Appropriate statistical analysis was performed. The median 25(OH)vitamin D concentration was not significantly different between 119 ARD [33.4 (IQR 22.5-54.9) nmol/l] and 126 NARD patients 32.9 (IQR 18.7-50.2). In stepwise logistic regression, female sex (F:13.7), winter-spring season (F:5.6) and older age (F:5.3), but not ARD, predicted plasma 25(OH)vitamin D <75 nmol/l. Cholecalciferol supplementation increased 25(OH)vitamin D plasma concentration equally in both ARD and NARD; however, only 29/100 patients reached a plasma level ≥75 nmol/l without differences between ARD and NARD (χ(2) = n.s.). Hypovitaminosis D is common in rheumatic patients. Sex and age but not ARD are risk factors for this condition. 750-1,000 UI/die of cholecalciferol is not sufficient to normalize plasma level in these patients. Increase of plasma 25(OH)vitamin D after treatment is not influenced by the presence of an inflammatory autoimmune disease.

Superiority of a high loading dose of cholecalciferol to correct hypovitaminosis d in patients with inflammatory/autoimmune rheumatic diseases.

OBJECTIVE: To compare 3 different cholecalciferol supplementation regimens in patients with rheumatic diseases. METHODS: One hundred fifty-four patients who completed a 6-month course of cholecalciferol supplementation, of whom 111 had an autoimmune/inflammatory rheumatic disease (ARD) and 43 osteoarthritis (NARD), were retrospectively identified from a database of 872 consecutive adult patients who attended a tertiary level immuno-rheumatology clinic from 2007 to 2010. Patients with renal failure or primary hyperparathyroidism were excluded. Plasma 25-hydroxy vitamin D [25(OH)D] and parathyroid hormone (PTH) concentrations were evaluated at baseline and after completion of treatment with (i) a single oral dose of cholecalciferol 300,000 IU, followed by oral cholecalciferol 800-1000 IU daily for 6 months [high-dose loading treatment (HLT) group; n = 40]; (ii) a single oral dose of cholecalciferol 100,000 IU, followed by daily oral cholecalciferol as above [low-dose loading treatment (LLT) group; n = 30]; or (iii) daily oral cholecalciferol as above but without the loading dose [standard therapy (ST); n = 84]. RESULTS: The rates of serum 25(OH)D and PTH normalization (defined as values > 75 nmol/l and < 72.9 pg/ml, respectively) were as follows: HLT, 52.5% (95% CI 37.5-68.5) and 69.2% (95% CI 54.7-83.3); LLT, 36.7% (95% CI 19.7-54.3) and 53.8% (95% CI 36.2-71.8); ST, 31.0% (95% CI 21.1-40.9) and 35.0% (95% CI 14.1-55.9). All regimes increased 25(OH)D (p < 0.001) but only HLT reduced PTH (p < 0.01) in comparison to baseline. The ARD group had a similar 25(OH)D increase but a smaller PTH reduction than the NARD (p < 0.05). CONCLUSION: An HLT cholecalciferol regimen is needed to correct hypovitaminosis D of patients with rheumatic diseases, with superior 25(OH)D normalization and PTH suppression rates at 6 months.