Rajesh Patel

Women’s views on and adherence to low-molecular-weight heparin therapy during pregnancy and the puerperium

Summary.  Background: Non‐adherence to prescribed medication represents a significant factor associated with treatment failure. Pregnant women identified at risk of venous thromboembolism are increasingly being prescribed low‐molecular‐weight heparin (LMWH) during pregnancy and the puerperium. It is important to understand women’s views on and adherence to LMWH during pregnancy and the puerperium, so that women gain maximum benefit from the treatment. Objectives: To monitor women’s adherence to enoxaparin, when prescribed during pregnancy and the puerperium, and explore their beliefs about the enoxaparin therapy prescribed. Patients/Methods: A prospective cohort study involving 95 nullparous and multiparous women prescribed enoxaparin for recognized antenatal indications. Adherence to enoxaparin was assessed through self‐completion of a diary, additionally verified through laboratory tests. An adapted beliefs about medication questionnaire was administered to women during their pregnancy. Results: Women were highly adherent to enoxaparin: antenatally, mean percentage adherence 97.92%; postnatally, mean percentage adherence 93.37% (paired t‐test, P = 0.000). In the cohort of women we followed, their perceived necessity for enoxaparin therapy outweighed any concerns they had regarding enoxaparin antenatally, necessity‐concerns differential 2.20. In some women, however, this perceived necessity does decrease postnatally. Conclusions: Our results suggest that most women prescribed enoxaparin are highly adherent to their therapy during the antenatal period and that women’s antenatal beliefs about enoxaparin are able to predict a decrease in postnatal adherence. Our results have important clinical implications, particularly when women are initiated on LMWH just during the postnatal period.

Managing direct oral anticoagulants in patients undergoing dentoalveolar surgery

Our objective was to describe our experience of managing a cohort of adult patients prescribed direct oral anticoagulants (DOACs) undergoing dentoalveolar procedures between November 2012 and May 2016. Prior to conducting a procedure a formal assessment was made of each patients anticoagulation treatment. A specific plan was then formulated, balancing the risk of bleeding with the risk of thrombosis. Patients received a telephone consultation one week following treatment to assess any post-operative bleeding. Eighty-two patients underwent 111 oral surgical procedures, the majority of which were dental extractions. In the case of 35 (32%) procedures, advice was given to omit the DOAC, either before or after treatment. There was no bleeding following the majority of procedures. Persistent bleeding followed 15 (13.5%) procedures, of which 7 (6.3%) procedures required specific intervention. The majority of patients prescribed DOACs can undergo dentoalveolar procedures safely. Important considerations when planning treatment are: (i) when the patient usually takes their dose of DOAC, (ii) the time the procedure is performed and, (iii) when the DOAC is taken post-procedure. In our experience, if these factors are considered carefully, omission of DOAC doses is unlikely to be required for most patients.

Prophylaxis with low-dose low molecular weight heparin during pregnancy and the puerperium: is it effective? A rebuttal.

See also Roeters Van Lennep JE,Meijer E, Klumper FJCM, Middeldorp JM, Bloemenkamp KWM, Middeldorp S. Prophylaxis with low‐dose low molecular weight heparin during pregnancy and postpartum: is it effective? J Thromb Haemost 2011; 9: 473–80; Roeters van Lennep JE, Meijer E, Klumper FJCM, Middeldorp JM, Bloemenkamp KWM, Middeldorp S. Prophylaxis with lowdose low molecular weight heparin during pregnancy and the puerperium: is it effective? Reply to a rebuttal by J. P. Patel, R. K. Patel, J. G. Davies, and R. Arya. This issue, pp 1272–3.

The use of an exclusion-based risk-assessment model for venous thrombosis improves uptake of appropriate thromboprophylaxis in hospitalized medical patients

BACKGROUND Venous thromboembolism is a common condition in hospitalized medical patients. Numerous studies have demonstrated that low molecular weight heparin significantly reduces this risk but, despite this, the use of thromboprophylaxis remains poor. AIM To evaluate the use of an exclusion based risk-assessment model (RAM) for venous thrombosis in improving the uptake of appropriate thromboprophylaxis in hospitalized medical patients. DESIGN A survey with a subsequent audit cycle of three separate audits over 36 months. METHODS 497 hospitalized patients with acute medical conditions on general medical wards were audited at a secondary care centre in London, UK. The survey and subsequent audits were performed by reviewing the notes and medication charts of medical patients, prior to the launch of the RAM and at 12, 28 and 36 months following its introduction. RESULTS Prior to launching the RAM, 49% of hospitalized medical patients received appropriate thromboprophylaxis. This did not change 12 months after the RAM was introduced but increased significantly to 71% following formal education of the health care professionals involved in thromboprophylaxis prescription. This improvement was maintained as demonstrated by a subsequent audit 8 months later (75.9%). CONCLUSION The introduction of a simple exclusion-based RAM for venous thrombosis in medical patients significantly improved delivery of thromboprophylaxis. The successful uptake of the RAM appears to have been dependent on direct education of those health carers involved in its use. A similar exclusion-based model used nationally could have a significant impact on the burden of VTE currently experienced in the UK.

Experiences of vocational trainees on their preparation and application for vocational training

Objectives To report the experiences of vocational trainees on the level of undergraduate preparation for the vocational training application process and their experiences of the application system. Method A self-completed postal questionnaire distributed to all graduates undertaking vocational training in 2004. Results Of the 62% responding, nearly three quarters felt that they were given inadequate guidance and preparation for vocational training during their undergraduate studies. Shortcomings included help on preparing their curriculum vitae, interview techniques and guidance on choosing practices. There was a wide variation between the undergraduate schools. The application process itself was also felt to have major shortcomings. Conclusion Current arrangements for the transition between the undergraduate and vocational training education systems have shortcomings. These shortcomings could be addressed by dental schools, recognising undergraduate need in these areas by working more closely with the deaneries and those responsible for vocational training.

The impact of body weight on rivaroxaban pharmacokinetics

Essentials The optimal dosing strategy of rivaroxaban for patients at the extremes of body weight is not known. A pharmacokinetic study was conducted based in real‐world patients in a London teaching hospital. In the cohort of patients studied, weight on its own did not impact significantly on rivaroxaban pharmacokinetics. A larger study with patients in the weight categories of interest from the real‐world population is required to further clarify the situation.

Re: Pregnancy outcomes in women with mechanical prosthetic heart valves – a prospective descriptive population‐based study using the United Kingdom Obstetric Surveillance System (UKOSS) data collection system

Sir, We read with interest the study by Vause and colleagues on the reported outcomes of pregnant women with mechanical heart valves in situ in theUK over a 2year period. We agree with the accompanying editorials to this paper that the poor maternal and fetal outcomes are disheartening and that, given the low number of womenwithmechanical heart valves, their management should be undertaken in units where women can receive expert care. In Vause’s study, 41 women (71%) weremanagedwith lowmolecular weight heparin throughout pregnancy, with the authors reporting large variation in the frequency of monitoring and the target levels aimed for. The gravid state has a significant impact on the pharmacokinetics of LMWH. It iswell recognised that the glomerular filtration rate increases by ~50%by the end of the first trimester and is maintained throughout the remainder of pregnancy, and that the intravascular plasma volume increases by up to 60% during the gravid state. These changes will directly impact on the clearance and volume of distribution of LMWH due to their significant renal excretion and their distribution being largely confined to the intravascular space. Therefore, one would predict a significantly higher clearance of LMWH during the first trimester of pregnancy, where clearance changes dominate; however, as changes in the volumeof distributionbegin to takehold, this will begin to rebalance over the course of pregnancy, and the elimination half-life of LMWH will begin to be prolonged, having been reduced earlier on in pregnancy. We have developed a pharmacokinetic model for enoxaparin during the antenatal period. This demonstrates that as pregnancy progresses, if a woman is given the same dose of LMWH throughout pregnancy, a gradual increase in the trough concentration is observed during pregnancy, illustrating the prolongation of the half-life of enoxaparin. Others have reported similar findings. Given this and those fromoutcomespapers likeVause and colleagues, there is a clear need to be aggressive with LMWH dosing during the first trimester to ensure therapeutic anticoagulation, and a careful evaluation of dosing in the third trimester to prevent bleeding. Although not routinely recommended by international societies, we are of the opinion that trough anti-Xa monitoring has a role in this setting. Trough anti-Xa levels will provide clinicians with an indication of howquickly the LMWH is being cleared and arguably is more informative than a peak level. Vause and colleagues’ paper highlights the real challenge clinicians are faced with when women with mechanical heart valves present at the clinic. The lack of consensus has led to wide variation on how women are managed. We call on international societies from the cardiology, obstetric and haematology disciplines to provide unified guidelines for this patient population, with clearer guidance on dosing and monitoring of LMWH, with real consideration of the role of trough antiXa monitoring, so this high-risk group receives optimal and standardised management, and informative evaluation studies can be performed.&

Does IgA antibody against β2 glycoprotein I increase cardiovascular risk in hemodialysis patients

Cardiovascular disease is the most common cause of mortality in patients with chronic kidney disease on hemodialysis. In addition to a high prevalence of traditional cardiovascular risk factors, other specific factors, including uremia and chronic inflammation, seem to contribute to the excess cardiovascular mortality. The findings of Serrano et al. point to a link between IgA antibodies against β2 glycoprotein I and cardiovascular events in renal dialysis patients.

Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non‐valvular atrial fibrillation from the RE‐LY trial: a rebuttal

See also Liesenfled K‐H, Lehr T, Dansirikul C, Reilly PA, Connolly SJ, EzekowitzMD, Yusuf S,Wallentin L, Haertter S, Staab A. Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non‐valvular atrial fibrillation from the RE‐LY trial. J Thromb Haemost 2011; 9: 2168–75; and Liesenfeld K‐H, Lehr T, Dansirikul C, Reilly PA, Connolly SJ, Ezekowitz MD, Yusuf S, Wallentin L, Haertter S, Staab A. Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with on‐valvular atrial fibrillation from the RE‐LY trial: reply to a rebuttal. This issue, pp 502–4.

Clinical experience of prescribing dabigatran etexilate with dronedarone – the role of therapeutic drug monitoring.

To the Editor: The current summary of product characteristics for dabigatran states that concomitant treatment with dronedarone is contraindicated. This recommendation is based on the studies that demonstrate that when dabigatran etexilate and dronedarone are administered together, an increase in dabigatran Area under the curve (AUC)0–N and Peak concentration (Cmax) is seen: AUC0–N from 1160 ng