20th March 2024

Safe prescribing of Anticoagulants and Opioids

Anticoagulants, antibiotics, and opioids are commonly prescribed classes of medication in modern medicine. To prescribe these medications, one needs to consider several patient factors such as weight, platelet count and renal/liver function. There are many sources of information for support in prescribing such medications, and these can be divided into two broad categories which include local or national resources. Local resources can include guidelines produced by a hospital trust. Healthcare professionals such as pharmacists and microbiologists also form part of local resources and can help to prescribe appropriately. National resources include the British National Formulary (BNF) and the National Institute of Health and Care Excellence (NICE) guidelines.

Low molecular weight heparin

Some of the most used anticoagulants in modern medical practice include low molecular weight heparins (LMWHs) and vitamin K antagonists (VKAs), which include warfarin. LMWHs act on the final common pathway in the coagulation cascade. In normal physiology, activation of factor Xa will lead to conversion of prothrombin to thrombin. It is thrombin which is involved in converting fibrinogen into fibrin to help form a stable clot. The LMWHs activate antithrombin III which in turn binds to and inhibits factor Xa. As a result, prothrombin is not converted into thrombin and, in turn, fibrinogen is not converted to fibrin which is needed for clot formation. The LMWHs are cleared mainly by the renal system so must be cautiously prescribed in patients with renal failure. LMWHs are contraindicated in low platelet levels and local guidelines can give more information on when to suspend LMWHs when there is thrombocytopenia. Monitoring is not often required when LMWHs are prescribed. However, if needed, anti-Xa levels are used for monitoring.  The reversal agent for LMWHs is protamine sulfate. The main adverse effect of LMWHs is bleeding. Less common adverse effects include osteoporosis, spontaneous fractures, hypoaldosteronism. Heparin-induced thrombocytopenia (HIT) is a potentially devastating adverse effect where there is the development of antibodies against the heparin/platelet factor 4 complex. This leads to platelet activation, resulting in thrombocytopenia, but can also paradoxically cause potentially fatal arterial and venous thromboses. Part of the management would include switching to an alternative anticoagulant.

Warfarin

Warfarin competitively inhibits the vitamin K epoxide reductase complex 1 (VKORC1), an essential enzyme for activating vitamin K. It is vitamin K which is needed for the synthesis of clotting factors II, VII, IX and X as well as both proteins C and S. Therefore, if vitamin K levels are reduced the production of these clotting factors and proteins will be reduced leading to less clot formation. Warfarin is mainly excreted via the kidneys. Hence, prescribe cautiously in patients with renal dysfunction. Warfarin is monitored via INR. It is important to note that in the first few days of initiating warfarin therapy, it is prothrombotic, and hence, bridging therapy with LMWHs might be needed. In patients who have life-threatening haemorrhage or those with intracranial bleeding and on warfarin Prothrombin complex concentrate (PCC) can be used to rapidly reverse the anticoagulant effects. PCC is a plasma derived concentrate of vitamin K dependent clotting factors and proteins. Warfarin adverse effects include bleeding, purple toes and skin necrosis. Skin necrosis occurs as protein C production is reduced in the first few days of administration, leading to a prothrombotic state and thrombosis in venules. Warfarin can cross the placenta and has teratogenic properties. It is advised that warfarin be suspended during pregnancy and especially during the first and third trimesters. Patients on warfarin also need to be aware that certain foods can either inhibit or increase the anticoagulant effect of warfarin. For example, foods such as kale, green tea leaves, Brussel sprouts, and spinach contain vitamin K which can inhibit the anticoagulant effects of warfarin. Conversely, grapefruit juice and increased alcohol intake can increase the anticoagulant effects of warfarin.

Opioids

Opioids are widely used for analgesia in both palliative and non-palliative care settings. Patients who are approaching the end of their life may need additional opioids to control breakthrough pain (BTP). It is defined as an episode of severe exacerbation of longstanding pain in patients who have chronic conditions such as cancer. BTP doses are calculated as typically 1/10 to 1/6 of the total daily regular dose of opioids. There might be cases where the route of administration may need to be altered. For example, a patient who is at high risk of aspiration may need opioids administered subcutaneously.