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Oral Anticoagulation Reversal

Disease Management

Read time: 40 mins
Last updated:12th Mar 2020
This section of the Learning Zone provides information on the methods behind blood coagulation, how the body and drugs work to reverse coagulation, what diagnostic tests can be used to ascertain blood's ability to clot, the risks of anticoagulants and the burden of anticoagulant-associated bleeding.

There will be details of blood coagulation factors II, VII, IX and more; the coagulation cascade; haemorrhagic risk assessment, using the international normalised ratio; the factor Xa inhibitors rivaroxaban, edoxaban or apixaban; the factor IIa (thrombin) inhibitor dabigatran; the risks of warfarin treatment; current national and international guidelines; the use of fresh frozen plasma to reverse vitamin K antagonist (VKA) anticoagulation; plasma and rVIIA; and details of the anticoagulation reversal agents idarucizumab, andexanet alpha and ciraparantag are all included in this section.

Blood Coagulation

Blood coagulation involves the complex interaction of multiple factors resulting in the generation of an insoluble fibrin clot. Classically blood coagulation was considered to be a cascade involving two convergent pathways: the intrinsic (contact activation) pathway and the extrinsic (tissue factor) pathway. [Monroe and Hoffman 2006; Adams and Bird 2009; Alquwaizani et al., 2013] 

More recently, blood coagulation is considered to consist of phases, involving initiation, amplification, propagation and finally, clot stabilisation. [Monroe and Hoffman 2006; Adams and Bird 2009] {Figure 1}

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Anticoagulation

Coagulation is a rapid and tightly controlled process giving a response to tissue injury and allowing for repair to begin. However, in some acquired or inherited clinical disorders, the coagulation process is aberrantly activated, causing thrombosis. 

Patients needing anticoagulation therapy for the prevention or treatment of thrombosis have commonly been treated with the oral vitamin K antagonist warfarin, or parenterally with a heparin formulation [Harter et al., 2015]. 

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Diagnostic Tests

In patients taking oral vitamin K antagonist (VKA) anticoagulants, haemorrhagic risk is assessed by the international normalised ratio (INR) which standardises the prothrombin time (PT), 

with risk of bleeding increasing exponentially at INR values >5.0. {Figure 3} [Landefeld and Beyth 1993; Cannegieter 1995; Palareti 1996; Makris and Watson 2001]

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Bleeding Risks of Anticoagulants

As with all therapies, there are sometimes serious side effects. When treating with anticoagulation therapy, monitoring is essential to ensure that the anticoagulant effects are not detrimental to patients' health. Risk of haemorrhage is likely if there is a high level of anticoagulant within the blood stream. 

It is all about creating a fine pharmacokinetic balance, however if the patient is in danger of haemorrhage there are oral anticoagulation reversal treatments that should be administered urgently.

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Disease Burden and Treatment

Disease burden

A retrospective analysis of data from patients with AF treated from 2003 to 2007 in the USA showed that the mean costs of warfarin-associated bleeding were $41,903

for intracranial haemorrhage, and $40,586 and $24,347 for major and minor GI bleeding respectively. [Ghate et al., 2011]

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