Recommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran and rivaroxaban.

Dabigatran, apixaban, and rivaroxaban have been approved for primary and secondary stroke prevention in patients with atrial fibrillation. However, questions have arisen about how to manage emergency situations, such as when thrombolysis would be required for acute ischemic stroke or for the managing intracranial or gastrointestinal bleedings. We summarize the current literature and provide recommendations for the management of these situations. Peak plasma levels of the direct oral anticoagulants (DOACs) apixaban, dabigatran, or rivaroxaban are observed about 2-4 h after intake. Elimination of dabigatran is mainly dependent on renal function. Consequently, if renal function is impaired, there is a risk of drug accumulation that is highest for dabigatran followed by rivaroxaban and then apixaban and thus dosing recommendations are different. To date, no bedside tests are available that reliably assess the anticoagulatory effect of DOACs, nor are specific antidotes available. We recommend performing the following tests if DOAC intake is unknown: dabigatran-associated bleeding risk is minimized or can be neglected if thrombin time, Hemoclot test, or Ecarin clotting time is normal. Apixaban and rivaroxaban effects can be ruled out if findings from the anti-factor Xa activity test are normal. High plasma levels of DOAC are also mostly excluded if PTT and PTZ are normal four or more hours after DOAC intake. However, normal values of global coagulation tests are not sufficient if thrombolysis is indicated for treating acute stroke. The decision for or against thrombolysis is an individual decision; in these cases, thrombolysis use is off-label. In case of bleeding, prothrombin complex concentrates seems to be the most plausible treatment. For severe gastrointestinal bleeding with life-threatening blood loss, the bleeding source needs to be identified and treated by invasive measures. Use of procoagulant drugs (antifibrinolytics) might also be considered. However, there is very limited clinical experience with these products in conjunction with DOAC.

Bicyclo[3.2.1]-DNA, a new DNA analog with a rigid backbone and flexibly linked bases: pairing properties with complementary DNA.

BACKGROUND: The structural and conformational variety in nucleic acid complexes is largely controlled by the sugar-phosphate backbone. In order to modulate specific features such as strength or selectivity of complex formation by designing nucleotide analogs, a deeper understanding of the relationship between mononucleotide structures and the properties of their oligomers is necessary. One approach involves comparing the properties of DNA analogs displaying well defined modifications in their backbone structure with those of natural DNA and RNA. RESULTS: We have designed and synthesized a new DNA analog, 'bicyclo[3.2.1]-DNA', which has a rigid phosphodiester backbone that emulates a B-DNA-type conformation, to which the nucleobases are attached via a flexible open-chain linker. A UV-melting curve analysis shows that bicyclo[3.2.1]-DNA forms stable duplexes with complementary DNA, although generally with lower Tm values than pure DNA duplexes. Duplex formation is strictly constrained to antiparallel complementary sequences, and base-mismatch discrimination is slightly enhanced compared to pure DNA duplexes. In addition, bicyclo[3.2.1]-DNA sequences are resistant to a 3'-exonuclease. CONCLUSIONS: The furanose unit present in natural nucleosides is not necessary for a competent and stable phosphodiester-based pairing system, provided that the backbone is conformationally constrained. The information for the preference of antiparallel strand association in B-DNA is not merely a consequence of bases being attached to a specific side of the furanose unit, but is also encoded in the backbone itself. Furthermore, conformational flexibility in the base-pairing region does not lead to a loss of selectivity in base-pair formation.

Comparison of A-scan device accuracy.

A-scan biometry is recognized as a useful aid in predicting intraocular lens power. Measurements are reported to be accurate to better than +/- 0.1 mm. Three biometry devices were compared in examinations of 159 persons, each examination being repeated several times. Axial length averaged 23.77 mm when measured by the immersion technique; applanation and modified applanation techniques yielded 0.1 mm and 0.3 mm shorter distances, respectively. Measured values of axial lengths did not have the same probability of being measured, even if they were close together. Results were not distributed in smooth Gaussian curves; on the contrary, clusters of values, on the pattern of our choice of ultrasound wavelength, were seen even when biometry was performed with electronic gates in the devices. Retest reliability decreased when short distances in the anterior segment of the eye were measured. Measurements of lens thickness were less readily reproducible in cataractous lenses than in healthy young eyes; anterior chamber depth, on the other hand, was measured more reliably in cataract patients. This last finding may have resulted in part from uncertainties about ultrasound velocity in the cataractous lens and in part from accommodation. In cataract patients, axial length was measured most reproducibly by the immersion technique; it was measured less accurately in young healthy eyes with a modified applanation device.

[The reliability of ultrasound biometry]. / Untersuchungen zur Reliabilität ultrasonographischer Biometrien.

Preoperative ultrasonic biometry is indispensible in cataract surgery in order to calculate the power of the intraocular lens to be implanted. Various authors have suggested that the accuracy of the measurements could be improved by performing biometry several times and basing the calculation of the lens on the mean value. The problem of the retest reliability of ultrasonic measurements was investigated in 99 young subjects with healthy eyes and 60 cataract patients. Biometry was performed three times consecutively in each mode using three different scanners and different coupling techniques. A comparison of the consecutive measurements showed good agreement (between r = 0.96 and r = 0.99) in regard to axial length and hence very good retest reliability. The accuracy of the repeat measurements was approximately the same with all three coupling methods used. The correlation coefficients of retest measurements of anterior chamber depth and lens thickness were much lower (r = 0.78 to r = 0.96). This may be explained by differences in handling of the probes, in the test modes, and in the physical conditions on which the measurements are based. In view of the good reproducibility of axial length measurements the authors consider one carefully performed biometry more valuable for preoperative calculation of lens power than the mean of several measurements.

[Flattening of the anterior chamber and myopic results in sulcus fixation of posterior chamber lenses]. / Vorderkammerabflachung und Myopisierung bei sulkusfixierten Hinterkammerlinsen.

Ultrasonographic biometry was performed in 56 patients immediately after implantation of a posterior chamber intraocular lens to measure the position of the lens. A modified applanation method was used to avoid injury to the scleral suture. Ten months later, 44 of these patients were examined by the same method. The anterior chamber depth was found to have decreased from 4.26 mm (s = 0.39 mm) in the immediate postoperative period to 4.2 mm ten months later. However, axial length, at 23.28 mm postoperatively and 23.34 mm at follow-up, and mean corneal refraction (43.28 D and 43.34 D, respectively) were practically unchanged. There was a shift in the spheric equivalent of refraction from postoperative emmetropia (mean -0.07 D) to slight myopia (mean -0.76 D) at follow-up. This mean myopization of 0.69 D corresponded to the tendency toward a shallower anterior chamber. Shrinkage and fibrosis of the posterior capsule, reduced elasticity of the polypropylene loops, flattening of the cornea and axial changes are discussed as possible causes. The tendency toward myopization should be taken into account when calculating the power of sulcus-fixated posterior chamber lenses.