Anticoagulant Reversal Handbook | Page 25

Pre-operative reversal urgent surgery in 12 – 18 hours . While oral vitamin K is an option for VKA reversal , its effects are slower and more unpredictable compared with the IV route . ⁸ As vitamin K is fat soluble , its absorption may be affected by a host of gastrointestinal or hepatobiliary conditions . ⁹

Pre-operative VKA reversal with factor replacement therapy for emergent surgery VKDFs can be replaced either with plasma or prothrombin complex concentrate ( PCC ). However , plasma is no longer the standard of care for emergent VKA reversal due to the availability of PCC . Transfusion of plasma requires ABO blood typing , thawing of frozen plasma , and long infusion times ( usually two to four hours ) resulting in significant delays in acheiving haemostatic levels . Plasma should be dosed at 15 – 30ml / kg ( 1000 – 2000ml ) to attain adequate factor levels and is often associated with volume overload , especially in elderly patients with cardiac diseases . Many patients are therefore given prophylactic diuretics . With a minimum of 30 minutes to transfuse each unit of plasma , the factor VII from the first unit ( half-life of approximately six hours ) will have decreased by the time plasma transfusion is completed , and INR correction is thus often incomplete . ¹⁰

PCCs are available in activated and non-activated forms . Activated PCC ( anti-inhibitor coagulant complex , Factor VIII Inhibitor Bypass Activity ( FEIBA ); Baxter , Deerfield , IL , USA ), contains primarily activated factor VII along with mainly non-activated factor II , factor IX , and factor X ; it is approved by the US Food and Drug Administration ( FDA ) for the treatment of haemophilia A and B patients with inhibitors . ¹¹ Non-activated PCCs are classified as 3-factor ( 3F ) or 4-factor ( 4F ) PCC . 4F-PCCs contain all VKDFs including PC and PS , whereas 3F-PCCs do not contain a significant amount of factor VII or natural anticoagulants PC and PS . As such , 3F-PCC is FDA-approved only for major bleeding episodes in haemophilia B due to its factor IX content , whereas 4F-PCC is approved for the urgent reversal of VKAs to treat major bleeding . ^{12 , 13} Several studies have shown superior efficacy of 4F-PCC compared with 3F-PCC for VKA

14 – 16 reversal , with similar safety profiles . PCC is reconstituted rapidly and can be infused in less than 15 minutes to

Table 1 : Recommendations for pre-operative VKA reversal

Minor dental , dermatologic , or cataract surgery

Minor surgical or invasive procedure

Moderate – major surgery

achieve an adequate correction of INR within 10 – 15 minutes . ^{17 , 18} PCCs do not carry the risk of transfusion-related acute lung injury and transfusion-associated circulatory overload that are associated with plasma transfusion . A multicentre randomised clinical trial comparing the efficacy of 4F-PCC and plasma for an urgent surgical or invasive procedure found 4F-PCC superior to plasma for both haemostatic efficacy and rapid INR reversal . The 4F-PCC group also had significantly faster reconstitution of VKDFs with much smaller volume . The two groups had a similar safety profile with respect to TEEs and late bleeding , but more fluid overload with plasma . ¹⁰

Dosing of PCC for major surgery Manufacturer-recommended dosing of 4F-PCC is determined by the patient ’ s

Recommendation

Elective

Urgent

Emergent

Elective

Urgent

Emergent

Low

Moderate – high

Low or moderate – high

Low or moderate – high

Low

Moderate – high

Low or moderate – high

Low or moderate – high a

Patients needing a surgical procedure in 12 – 18 hours ; ^b Patients needing a surgical procedure in < 12 hours

VKA cessation five days prior to the surgery

3mg IV vitamin K 12 – 18 hours prior to the procedure and hold dose of VKA prior to the procedure

3mg IV vitamin K 12 – 18 hours prior to the procedure and hold dose of VKA prior to the procedure

Consider 3mg IV vitamin K and low-dose PCC

VKA cessation five days prior to the surgery

3mg IV vitamin K 12 – 18 hours prior to the procedure and hold dose of VKA prior to the procedure

3mg IV vitamin K 12 – 18 hours prior to the procedure and hold dose of VKA prior to the procedure

3mg IV vitamin K and PCC

actual body weight in kg ( as opposed to ideal body weight ), up to a maximum 100kg , and pre-treatment INR ( Table 2 ). There is some evidence to support using lower weight-based doses of PCC , starting at 10 – 15IU / kg , or low fixed doses of 500 – 1500IU , with similar outcomes , lower thrombotic risk , and lower cost . ^{19 – 21} The practice at our own institution is to use fixed low doses of 500 , 1000 or 1500IU for patients with an LVAD or mechanical heart valve to reduce the risk of thromboembolic events , or a fixed high dose of 4000IU for intracranial haemorrhage to reverse VKA rapidly without waiting for body weight and INR values . ²² One should aim for a post-4F-PCC correction INR near normal ( ≤1.5 ) for patients who have major bleeding or are undergoing emergent surgery .

When clinically indicated , vitamin K 23 www . hospitalpharmacyeurope . com