The initial treatment of haemodynamically stable patients with pulmonary embolism (PE) has dramatically changed since the introduction of low molecular weight heparins (LMWHs). With the recent discovery of the direct oral anticoagulant drugs (DOACs), initial treatment of PE will be simplified even further. In several large clinical trials it has been demonstrated that DOACs are not inferior to standard therapy for the initial treatment of PE, and because of their practicability they are becoming the agents of first choice. However, many relative contraindications to DOACs were exclusion criteria in the clinical trials. Therefore, LMWHs will continue to play an important role in initial PE treatment and in some cases there still is a role for unfractionated heparin (UFH). In this review we will give an overview of the biophysical, pharmacokinetic and pharmacodynamic properties of anticoagulants currently available for the initial management of PE. In addition, we will provide a comprehensive overview of the indications for the use of UFH, LMWHs and DOACs in the initial management of PE from a pharmacokinetic/-dynamic point of view.

The hypercoagulable state observed in COVID-19 could be responsible for morbidity and mortality. In this retrospective study we investigated whether therapeutic anticoagulation prior to infection has a beneficial effect in hospitalized COVID-19 patients. This study included 1154 COVID-19 patients admitted to 6 hospitals in the Netherlands between March and May 2020. We applied 1:3 propensity score matching to evaluate the association between prior therapeutic anticoagulation use and clinical outcome, with in hospital mortality as primary endpoint. In total, 190 (16%) patients used therapeutic anticoagulation prior to admission. In the propensity score matched analyses, we observed no associations between prior use of therapeutic anticoagulation and overall mortality (risk ratio 1.02 [95% confidence interval; 0.80-1.30]) or length of hospital stay (7.0 [4-12] vs. 7.0 [4-12] days, P = .69), although we observed a lower risk of pulmonary embolism (0.19 [0.05-0.80]).

The hypercoagulable state observed in COVID-19 could be responsible for morbidity and mortality. In this retrospective study we investigated whether therapeutic anticoagulation prior to infection has a beneficial effect in hospitalized COVID-19 patients. 1154 COVID-19 patients admitted to 6 hospitals in the Netherlands between March and May 2020 were included. We applied 1:3 propensity score matching to evaluate the association between prior therapeutic anticoagulation use and clinical outcome, with in hospital mortality as primary endpoint. 190 (16%) patients used therapeutic anticoagulation prior to admission. In the propensity score matched analyses, we observed no associations between prior use of therapeutic anticoagulation and overall mortality (RR 1.02 (95% CI; 0.80-1.30) or length of hospital stay (7.0 [4-12] vs 7.0 {4-12] days, p=0.69), although we observed a lower risk of pulmonary embolism (RR 0.19 (95% CI; 0.05-0.80). This study shows that prior use of therapeutic anticoagulation is not associated with improved clinical outcome in hospitalized COVID-19 patients.

orIgInAl ArtIclePurpose. Guidelines of the Dutch Association of General Practitioners (NHG) dictate the evalu ation, treatment, and referral process of pa tients with stable chest pain syndromes (CPS). Adherence to this guideline was assessed in a consecutive group of patients referred to our hospital. Methods. We retrospectively studied the records of 296 subjects referred to our outpatient de partment in 2007 for evaluation of stable CPS. Referral letters were checked for complete ness (past and present history, mentioning of risk factors for cardiovascular disease, physical exam ination, listing of medication) and used to judge adherence to the guideline. In a subset of patients, additional information regarding the referral process was gathered by telephone in terview. Results. The referral letter was complete in only 67 patients (23%); items most often not reported were physical examination (63%) and cardiovascular risk factors (62%). Judging from the referral letter, 23 patients (8%) were evalu ated in accordance with the NHG guideline prior to their referral. In patients in whom the final diagnosis of angina pectoris was made by the cardiologist, this was 20%. Seventy nine pa tients were contacted by telephone after their work up by the cardiologist; 36 of them (44%) reported being referred at their first visit to their primary physician, while 14 (18%) were referred at their own request. Conclusion.Prior to referral, only a minority of patients with stable CPS were evaluated and treated in accordance with NHG guidelines. Furthermore, their referral letter was often in complete. (Neth Heart J 2010;18:178 82.)

Background Co-trimoxazole is an antibiotic combination used for the treatment of Pneumocystis jirovecii pneumonia, amongst others. Co-trimoxazole is known to increase serum potassium. For this reason, Dutch guidelines advise serum potassium monitoring in high-risk patients. Objective This study aimed to determine average serum potassium rise after administration of intravenous co-trimoxazole in hospitalized patients, compared to intravenous ceftriaxone. This study also aimed to determine adherence to Dutch guidelines by measuring the incidence of serum potassium monitoring in these patients. Setting Five departments of the Canisius Wilhelmina Hospital, a teaching hospital in Nijmegen, the Netherlands. Method Data was collected and compared from patients that received intravenous co-trimoxazole (n = 66) and intravenous ceftriaxone (n = 132) in the period of November 2008-November 2017. For each patient using co-trimoxazole, two patients using ceftriaxone were included in a paired fashion. Baseline and follow-up potassium were collected, if available. Additionally, it was tested if serum potassium was measured around the initiation of antibiotic therapy. Main outcome measure Changes in serum potassium where obtainable in 30 patients using cotrimoxazole and 40 patients using ceftriaxone. When compared to ceftriaxone, administration of intravenous co-trimoxazole was associated with a significant mean increase in serum potassium (+ 0.55 mmol/l, 95% CI 0.29-0.80, p < 0.001). After correction for confounders (baseline potassium, estimated glomerular filtration rate 30 to < 60, the presence of haematological malignancies and the usage of corticosteroids), this effect shrunk noticeably, but remained significant (+ 0.28 mmol/l, 95% CI 0.03-0.53, p = 0.031). Results The incidence of hyperkalemia at follow-up was 20% in the cotrimoxazole group, compared to 5% in the ceftriaxone group. Despite this, serum potassium was often not measured in patients using intravenous cotrimoxazole, being 76% at baseline and 55% in the period of 48-120 h after antibiotic therapy initiation, compared to 87% and 34% in the ceftriaxone group respectively. Conclusion Adherence to Dutch guidelines was poor as serum potassium monitoring was often not performed. As intravenous co-trimoxazole usage is associated with a significant increase in mean serum potassium, monitoring is strongly recommended.