To Anticoagulate or Not to Anticoagulate in COVID-19: Lessons after 2 Years.

A hypercoagulable state associated with coronavirus disease 2019 (COVID-19) has been well documented and is believed to be strongly supported by a proinflammatory state. The hypercoagulable state in turn results in increased incidence of arterial and venous thromboembolism (VTE) seen in hospitalized COVID-19 when compared with hospitalized non-COVID-19 patient cohorts. Moreover, patients with arterial or VTE and COVID-19 have higher mortality compared with COVID-19 patients without arterial or VTE. Prevention of arterial or VTE thus remains an essential question in the management of COVID-19 patients, especially because of high rates of reported microvascular and macrovascular thrombosis. This has prompted multiple randomized control trials (RCTs) evaluating different anticoagulation strategies in COVID-19 patients at various stages of the disease. Herein, we review findings from RCTs in the past 2 years of antithrombotic therapy in critically ill hospitalized patients, noncritically ill hospitalized patients, patients postdischarge from the hospital, and outpatients. RCTs in critically ill patients demonstrated therapeutic dose anticoagulation does not improve outcomes and has more bleeding than prophylaxis dose anticoagulant in these patients. Trials in noncritically ill hospitalized patients showed a therapeutic dose anticoagulation with a heparin formulation might improve clinical outcomes. Anticoagulation with a direct oral anticoagulant posthospital discharge may improve outcomes, although there is a large RCT in progress. Nonhospitalized COVID-19 patients have an insufficient burden of events to be candidates for antithrombotic therapy. Anticoagulation in pregnant and lactating patients with COVID-19, as well as antiplatelet therapy for COVID-19, is also reviewed.

Mechanisms and management of drug-induced hyperkalemia in kidney transplant patients.

Hyperkalemia is a common and potentially life-threatening complication following kidney transplantation that can be caused by a composite of factors such as medications, delayed graft function, and possibly potassium intake. Managing hyperkalemia after kidney transplantation is associated with increased morbidity and healthcare costs, and can be a cause of multiple hospital admissions and barriers to patient discharge. Medications used routinely after kidney transplantation are considered the most frequent culprit for post-transplant hyperkalemia in recipients with a well-functioning graft. These include calcineurin inhibitors (CNIs), pneumocystis pneumonia (PCP) prophylactic agents, and antihypertensives (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers). CNIs can cause hyperkalemic renal tubular acidosis. When hyperkalemia develops following transplantation, the potential offending medication may be discontinued, switched to another agent, or dose-reduced. Belatacept and mTOR inhibitors offer an alternative to calcineurin inhibitors in the event of hyperkalemia, however should be prescribed in the appropriate patient. While trimethoprim/sulfamethoxazole (TMP/SMX) remains the gold standard for prevention of PCP, alternative agents (e.g. dapsone, atovaquone) have been studied and can be recommend in place of TMP/SMX. Antihypertensives that act on the Renin-Angiotensin-Aldosterone System are generally avoided early after transplant but may be indicated later in the transplant course for patients with comorbidities. In cases of mild to moderate hyperkalemia, medical management can be used to normalize serum potassium levels and allow the transplant team additional time to evaluate the function of the graft. In the immediate post-operative setting following kidney transplantation, a rapidly rising potassium refractory to medical therapy can be an indication for dialysis. Patiromer and sodium zirconium cyclosilicate (ZS-9) may play an important role in the management of chronic hyperkalemia in kidney transplant patients, although additional long-term studies are necessary to confirm these effects.