The history of the traditional anticoagulants is marked by both perseverance and serendipity. Hirudin extracts from the medicinal leech were first used for parenteral anticoagulation in the clinic in 1909, but their use was limited due to adverse effects and difficulties in achieving highly purified extracts.The anticoagulant effect of heparin was discovered by McLean in 1915. Link identified dicumarol from spoiled sweet clover hay in 1939 as the causal agent of the sweet clover disease, a hemorrhagic disorder in cattle. Heparins and coumarins (i.e.: warfarin, phenprocoumon, acenocoumarol) have been the mainstay of anticoagulant therapy for more than 60 years.          
Prevention of  Venous thrombosis  is the main use  of oral anticoagulants while antiplatelets are useful in arterial thrombosis. The most common indication for the use of oral anticoagulation is atrial fibrillation, but they are also widely used to prevent a range of other thromboembolic complications, such as deep vein thrombosis, pulmonary embolisms and strokes from mechanical heart valves.
Oral anticoagulation therapy carries the inherent risk of haemorrhagic complications. Many patients receiving vitamin K antagonists have an international normalised ratio (INR) higher than the target of 2.0 to 3.0 for over 50% of the time, increasing their risk of bleeding; those with an INR within the therapeutic range may still be at risk. 
Major bleeding can occur at a number of sites, with gastrointestinal and urinary tract bleeds the most frequently observed, affecting approximately 1% to 4% of patients being treated with vitamin K antagonists per year . Intracranial haemorrhage (ICH) is less common, with reported annual risk ranging between 0.25% and 1% among patients receiving vitamin K antagonists  however, it is the most life-threatening of bleeds and is associated with a high mortality rate .
In the perioperative setting patients present with intractable bleeding due to trauma, emergency surgery necessitates rapid and safe reversal. Moreover, in patients without haemorrhage, rapid anticoagulant reversal may be required prior to immediate emergency surgery
There are a number of potential treatment options for anticoagulant reversal, including administration of vitamin K (oral or intravenous), human plasma products (for example, fresh frozen plasma (FFP)), prothrombin complex concentrates (PCCs; concentrates that contain coagulation factors II, VII, IX and X), or single coagulation factors such as activated recombinant factor VII (rFVIIa).

Vitamin K
Normalisation with vitamin K alone is slow to take effect because of the time required for hepatic de novo synthesis of vitamin K-dependent coagulation factors. After intravenous vitamin K administration, the INR falls within 4 hours, but this may be misleading as it is almost entirely due to a rise in factor VII. The more important rise in factor II takes approximately 24 hours , and correction of coagulation factor levels takes longer following oral vitamin K administration. The delayed effect of vitamin K on endogenous coagulation factors complements the immediate effect of PCC therapy, providing a rationale for co-administration of the two products. Most studies of vitamin K alone examine the restoration of INR to levels within the therapeutic zone in non-haemorrhagic, over-anticoagulated patients . In this situation, where there is no need for complete reversal, administration of vitamin K (1 to 2.5 mg) is recommended . When complete reversal of anticoagulation is needed – that is, prior to surgery or when INR is very high – a vitamin K dose of up to 5 mg is recommended . In patients with serious bleeding and elevated INR, the recommended dose of vitamin K is 10 mg . However, vitamin K therapy alone is inadequate during an emergency situation in which rapid cessation of bleeding or correction of INR is required . More rapid reversal can only be achieved by the supplementation of vitamin K-dependent clotting factors through the use of human plasma products, PCCs or rFVIIa.

Fresh frozen plasma
After a decrease in FFP consumption in the 1990s, probably due to HIV epidemics, the use of FFP has increased in recent years. In patients with haemorrhagic trauma, recent data suggest that, contrary to traditional beliefs and guidelines, early use of FFP may be associated with better patient outcome . Nevertheless, several audits have shown that the rate of inappropriate FFP transfusion remains high considering the fact that FFP is the most frequently implicated blood product in transfusion-related acute lung injury (TRALI) . Moreover, FFP continues to be used in patients who may be better treated with other strategies . FFP contains all vitamin K-dependent factors but there are no in vitro studies about its effectiveness in the reversal of vitamin K antagonists; all clinical studies are observational and all underline the longer time required by FFP to reverse INR 
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Prothrombin complex concentrates
Historically, PCCs were approved for the treatment of bleeding associated with haemophilia B, due to their inclusion of factor IX. Although this remains the case in some European countries, most now have a specific factor IX product for treatment of bleeding in haemophilia B. PCCs are now formulated and approved specifically for vitamin K deficiency. They generally contain a balance of coagulation factors II, VII, IX and X, with ratios designed to limit accumulation of factors with a long half-life, particularly factor II . PCCs often also include anticoagulants, such as Proteins C, S and Z and antithrombin III, to balance the opposing needs of haemorrhage control and thrombosis avoidance . PCCs approved for use in anticoagulant reversal include Beriplex® P/N (CSL Behring, Marburg, Germany) and Octaplex® (Octapharma, Vienna, Austria), which are widely available in Europe, and other country-specific formulations are available. The effectiveness of PCCs for reversal of anticoagulation has been reported in a number of clinical studies in patients with haemorrhage and those requiring emergency intervention . The rapid onset of action of PCCs makes them ideal for anticoagulant reversal in an emergency situation. However, there are no clinical data comparing the efficacy of different PCCs in the treatment of acute haemorrhage and only one in vitro study has attempted to describe possible differences between different PCCs, analysing reversal efficiency

Activated recombinant factor VII

rFVIIa was originally used for the treatment of bleeding in patients with trauma  and haemophilia; it is currently licensed for the treatment of haemophilia and Glanzmann's thrombasthenia. For the treatment of hemophilia, an alternative to rFVIIa is FEIBA (factor VIII inhibitor bypassing activity). This is essentially a PCC with activated coagulation factors, but it is not recommended for reversal of vitamin K antagonists. The use of rFVIIa for treating patients on vitamin K antagonist therapy who have life-threatening haemorrhage has been examined in a number of studies , but there is less clinical experience with rFVIIa than with PCCs in this setting. Comparative investigation of rFVIIa and PCCs is required to further elucidate differences in treatments and their relative contribution to improved prognosis. However, the high number of thrombotic events reported to the US Food and Drug Administration compared with the low incidence of case reports associated with PCC use for anticoagulation reversal, and the shorter half-life of rFVIIa (approximately 2 hours), which complicates the transition to the effect of vitamin K, suggest that there is not a strong enough argument to favour rFVIIa for reversal of oral anticoagulation 

Conclusion:
Supplementation of coagulation factors via the administration of PCCs provides effective correction of coagulation more rapidly than the alternative treatment options. Moreover, PCCs are associated with a reduced risk of pathogen transmission and volume overload compared with human plasma. Although PCCs are widely recommended in current guidelines, their use remains limited due to a lack of understanding of their clinical benefits. PCCs are an effective treatment for the cessation of severe bleeding and for rapid normalisation of INR in patients receiving vitamin K antagonists, and their use should be considered immediately at the time of presentation or diagnosis in emergency situations.