Laboratory Monitoring of Direct Oral Anticoagulants (DOACs)

The introduction of direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban, provides safe and effective alternative to previous anticoagulant therapies. DOACs directly, selectively, and reversibly inhibit factors IIa or Xa. The coagulation effect follows the plasma concentration–time profile of the respective anticoagulant. The short half-life of a DOAC constrains the daily oral intake. Because DOACs have predictable pharmacokinetic and pharmacodynamic responses at a fixed dose, they do not require monitoring. However in specific clinical situations and for particular patient populations, testing may be helpful for patient management. The effect of DOACs on the screening coagulation assays such as prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) is directly linked to reagent composition, and clotting time can be different from reagent to reagent, depending on the DOAC’s reagent sensitivity. Liquid chromatography–mass spectrometry (LC-MS/MS) is considered the gold standard method for DOAC measurement, but it is time consuming and requires expensive equipment. The general consensus for the assessment of a DOAC is clotting or chromogenic assays using specific standard calibrators and controls. This review provides a short summary of DOAC properties and an update on laboratory methods for measuring DOACs.

A randomised comparison of increase in serum 25-hydroxyvitamin D concentration after 4 weeks of daily oral intake of 10 μg cholecalciferol from multivitamin tablets or fish oil capsules in healthy young adults

Many types of vitamin supplements are available on the market, but little is known about whether cholecalciferol obtained from fat-containing capsules differs in bioavailability from that of solid tablets. Our objective was to test whether 4 weeks of daily supplementation with 10 μg cholecalciferol given as a fish oil capsule produces a larger increase in serum 25-hydroxyvitamin D (s-25(OH)D) concentration compared with the same dose of cholecalciferol given as a multivitamin tablet. A total of seventy-four healthy subjects aged 19–49 years were initially included and fifty-five of these completed the study and fulfilled the inclusion criteria. After completing a self-administered questionnaire about diet and sunshine exposure and having a non-fasting venous blood sample drawn, participants were randomised to receive daily multivitamin tablets (n 28) or fish oil capsules (n 27), each containing equal doses of cholecalciferol. A second blood sample was drawn after 28 d. Mean baseline s-25(OH)D was 40·3 (sd 22·0) nmol/l in the multivitamin group and 48·5 (24·8) nmol/l in the fish oil group. When controlling for baseline s-25(OH)D, mean 4-week increase in s-25(OH)D was 35·8 (95 % CI 30·9, 40·8) nmol/l in the multivitamin group and 32·3 (95 % CI 27·3, 37·4) nmol/l in the fish oil group; the mean difference was 3·5 (95 % CI − 3·6, 10·6) nmol/l (P = 0·33). The results were unaltered by statistical adjustment for BMI, ethnic background, age and sex. We conclude that fish oil capsules and multivitamin tablets containing 10 μg cholecalciferol administered over a 4-week period produced a similar mean increase in s-25(OH)D concentration.

Estimation of the total daily oral intake of NDMA attributable to drinking water

Disinfection with chlorine and chloramine leads to the formation of many disinfection by-products including N-Nitrosodimethylamine (NDMA). Because NDMA is a probable human carcinogen, public health officials are concerned with its occurrence in drinking water. The goal of this study was to estimate NDMA concentrations from exogenous (i.e., drinking water and food) and endogenous (i.e., formed in the human body) sources, calculate average daily doses for ingestion route exposures and estimate the proportional oral intake (POI) of NDMA attributable to the consumption of drinking water relative to other ingestion sources of NDMA. The POI is predicted to be 0.02% relative to exogenous and endogenous NDMA sources combined. When only exogenous sources are considered, the POI was predicted to be 2.7%. The exclusion of endogenously formed NDMA causes the POI to increase dramatically, reflecting its importance as a potentially major source of exposure and uncertainty in the model. Although concentrations of NDMA in foods are small and human exposure to NDMA from foods is quite low, the contribution from food is predicted to be high relative to that of drinking water. The mean concentration of NDMA in drinking water would need to increase from 2.1 × 10−3 μg/L to 0.10 μg/L, a 47-fold increase, for the POI to reach 1%, relative to all sources of NDMA considered in our model, suggesting that drinking water consumption is most likely a minor source of NDMA exposure.

Influence of method of conservation of lucerne on factors associated with voluntary intake in sheep

This experiment measured the voluntary intake and rate of eating of sheep fed lucerne (Medicago sativa) that had been conserved as sun-dried material or as silage at 3 different DM contents (29.2, 33.1, and 51.2%). Changes in rumen osmolality and palatability due to diet were measured. Palatability was assessed by introducing feed directly into the rumen and measuring the subsequent oral intake. Eight sheep with rumen fistulae were used in two 4 x 4 latin squares, which allowed for adjustment for carryover effects. There was no significant (P<0.05) difference between voluntary intakes of lucerne conserved as sundried material and as silages of various DM contents (mean intake 1189 g DM/day). The lack of difference in intake was attributed to the high quality of fermentation of the silages. Rate of eating was also generally similar for all diets. Evidence from measurements of palatability and rumen osmolality support these observations. Palatability appeared not to influence the voluntary intake of any of the diets, because the sheep reduced their daily oral intake by an amount similar to that introduced into the rumen. Under normal feeding conditions, rumen osmolality was also similar for all feeds and was relatively consistent for the 9 h immediately after the start of feeding. While rumen osmolality per se may affect voluntary intake, the lack of response reported here for changes in osmolality due to diet support the lack of response reported for feed consumption.

Nutritional Consequences of Large Intestinal Function in Health

The nutritional contribution of human colonic function has been poorly appreciated. As well as absorbing the equivalent of a daily oral intake of sodium and water, other minerals can be absorbed. Up to 10% of energy requirements may come from carbohydrate entering the colon, fermentation to short chain fatty acids that are absorbed being intermediate steps. The role of the large intestine in nitrogen and fat metabolism is unknown, as is its contribution to vitamin supplies.