Rapid Warfarin Reversal in the Setting of Intracranial Hemorrhage: A Comparison of Plasma, Recombinant Activated Factor VII, and Prothrombin Complex Concentrate

Woo, Carolyn H.; Patel, Niraj; Conell, Carol; Rao, V.; Faigeles, Bonnie; Patel, Minal C.; Pombra, Jasmeen; Akins, Paul T.; Axelrod, Yekaterina; Ge, Ivy Y.; Sheridan, William F.; Flint, Alexander C.

doi:10.1016/j.wneu.2012.12.002

Cited by 62 publications

(36 citation statements)

References 23 publications

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“…In addition to administration of vitamin K which initiates synthesis of clotting factors in VKA-treated patients, administration of fresh frozen plasma, PCC and recombinant activated factor VII (rFVIIa) have been shown to restore haemostasis and correct INR. Although efficacy regarding improving outcomes in patients has not been proven, retrospective studies demonstrated that administration of these substances allow rapid correction of INR which may reduce mortality and morbidity in patients with tICH [19,20]. European Guidelines for the management of bleeding complications in trauma patients recommend the use of PCC for the emergency reversal of VKA [21].…”

Section: Discussionmentioning

confidence: 99%

Rivaroxaban and intracranial haemorrhage after mild traumatic brain injury: A dangerous combination?

Beynon

Potzy

Sakowitz

et al. 2015

Clinical Neurology and Neurosurgery

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Section: Discussionmentioning

confidence: 99%

Rivaroxaban and intracranial haemorrhage after mild traumatic brain injury: A dangerous combination?

Beynon

Potzy

Sakowitz

et al. 2015

Clinical Neurology and Neurosurgery

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“…40,47 In one of these studies, there was no difference in time to INR reversal with 3F-PCC or rFVIIa; however, there was an increased risk of INR rebound with rFVIIa. 40 Conversely, in the other study, INR ≤1.3 within 1 h was achieved by 5/6 (83%) evaluable patients treated with rFVIIa, compared with 1/5 (20%) of those treated with 3F-PCC, although this did not translate into a clinical benefit; hematoma expansion occurred in 3/15 (20%) and 1/9 (11%) of those treated with rFVIIa and 3F-PCC, respectively. 47 It should be noted that both these studies compared rFVIIa with 3F-PCC, and evidence from ICH and other settings suggests that VKA reversal with 3F-PCC is suboptimal.…”

Section: Dosingmentioning

confidence: 99%

Prothrombin Complex Concentrate for Vitamin K Antagonist-Associated Intracranial Hemorrhage　― Global Evidence and the Japanese Perspective ―

Yasaka

Brainsky

Toyoda

2017

Circ J

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Patients receiving vitamin K antagonists (VKAs) are at increased risk of bleeding. Intracranial hemorrhage (ICH) is a major cause of morbidity and mortality in this population, and is a particular concern among Japanese clinicians, given reports of an elevated risk of this bleeding type in patients of Asian ethnicity. Patients with VKA-associated ICH require rapid international normalized ratio (INR) reversal, and treatment guidelines suggest the use of prothrombin complex concentrates (PCCs) or plasma for this purpose. Although European and US guidelines recommend PCCs for the treatment of VKA-associated major bleeding, they do not make a specific recommendation in the setting of ICH, owing to the lack of comparative evidence. In contrast, Japanese guidelines recommend the use of PCCs rather than plasma for VKA reversal in patients with ICH; however, these agents are not currently licensed in Japan for this indication. Here we review the available evidence on the use of PCCs for the treatment of VKA-associated ICH, both globally and specifically in Japanese settings. Overall, the evidence reviewed here supports the use of PCC for rapid VKA reversal in these patients.

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“…The remainder of studies showed no difference in mortality, although they were likely underpowered to detect differences. 19,[22][23][24][25][26][27][28] There were no differences in the duration of hospital admission in 3 studies reporting this outcome. 22,23,29 One study showed an improvement in functional gains in patients receiving PCC versus plasma after warfarin-associated ICH as measured by the functional independence measure.…”

mentioning

confidence: 99%

“…In 7 studies, administration of PCC was associated with reduced time to INR correction (as defined in individual studies) compared with plasma. [22][23][24][25][26][27][28] Two studies showed reduced time from product administration to laboratory testing with PCC compared with plasma. 31,32 In 3 of 6 studies, the mean posttreatment INR was reduced significantly in patients receiving PCC compared with plasma.…”

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confidence: 99%

Plasma versus prothrombin complex concentrate for warfarin-associated major bleeding: a systematic review

Siegal

Savage

2015

Hematology

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Learning Objective• To compare the efficacy and adverse effects of prothrombin complex concentrate and plasma for rapid correction of vitamin K antagonist-associated hemorrhagic emergency Clinical vignetteA 78-year-old female presents to the emergency department with brisk hematochezia, fatigue, and tachycardia. She is receiving chronic oral anticoagulant therapy with warfarin as thromboprophylaxis for a mechanical mitral valve. International normalized ratio (INR) is 4.2. Red blood cell transfusion is ordered, and 10 mg of intravenous vitamin K is given. You are asked whether plasma or prothrombin complex concentrate is more effective for emergent reversal of her warfarin-associated coagulopathy.Warfarin is a vitamin K antagonist (VKA) that has been the mainstay of oral anticoagulant therapy for the prevention and treatment of thromboembolism. Bleeding is the major complication of anticoagulant therapy with rates of major warfarin-related bleeding up to 7% reported depending on the indication for anticoagulation and study design. [1][2][3][4][5] Warfarin use increases the risk of major bleeding by 0.3%-0.5%/year and intracranial hemorrhage (ICH) by 0.2%/year compared to controls in clinical trials. 1 Despite the availability of warfarin-reversal agents, warfarin-associated bleeding leads to significant morbidity and mortality, with case fatality rates of 8%-13%. 5-8 Death in hospital or within 7 days of discharge has been reported in 18% of warfarin-treated atrial fibrillation patients presenting with major bleeding. 9 In patients presenting with warfarin-associated ICH, high mortality rates of 54% and 64% have been reported at 30 days and 6 months, respectively. 10Although direct oral anticoagulants (DOACs) are now approved for several indications, warfarin use is expected to continue for patients who are stably managed on long-term warfarin therapy, conditions in which DOACs are not proven (eg, antiphospholipid antibody syndrome, mechanical heart valves), patients with severe renal failure (creatinine clearance Ͻ30 mL/min), and patients for whom DOACs are cost prohibitive.Warfarin-associated major bleeding complications require urgent reversal of coagulopathy. When given intravenously, the effect of vitamin K on warfarin coagulopathy is evident within 6 hours. Plasma contains all coagulation factors and will correct coagulation factor deficiency attributable to inadequate synthesis. Time to thaw frozen plasma (FP) may in some circumstances be a limitation, but large blood banks typically have a continuous stock of thawed plasma. The infusion time depends on vascular access and volume status of the patient. Fluid overload and mild allergic reactions are the most common adverse reactions to plasma (ϳ1 in 100 transfusions). Serious allergic and transfusion-related acute lung injury reactions are rare (ϳ1 in 10 000 transfusions). [11][12][13][14][15][16] Prothrombin complex concentrates (PCCs) are plasma-derived products containing vitamin K-dependent factors II, VII, IX, and X (4-factor PCC) or II, IX, and X (3-...

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Rapid Warfarin Reversal in the Setting of Intracranial Hemorrhage: A Comparison of Plasma, Recombinant Activated Factor VII, and Prothrombin Complex Concentrate

Cited by 62 publications

References 23 publications

Rivaroxaban and intracranial haemorrhage after mild traumatic brain injury: A dangerous combination?

Rivaroxaban and intracranial haemorrhage after mild traumatic brain injury: A dangerous combination?

Prothrombin Complex Concentrate for Vitamin K Antagonist-Associated Intracranial Hemorrhage　― Global Evidence and the Japanese Perspective ―

Plasma versus prothrombin complex concentrate for warfarin-associated major bleeding: a systematic review

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Rapid Warfarin Reversal in the Setting of Intracranial Hemorrhage: A Comparison of Plasma, Recombinant Activated Factor VII, and Prothrombin Complex Concentrate

Cited by 62 publications

References 23 publications

Rivaroxaban and intracranial haemorrhage after mild traumatic brain injury: A dangerous combination?

Rivaroxaban and intracranial haemorrhage after mild traumatic brain injury: A dangerous combination?

Prothrombin Complex Concentrate for Vitamin K Antagonist-Associated Intracranial Hemorrhage ― Global Evidence and the Japanese Perspective ―

Plasma versus prothrombin complex concentrate for warfarin-associated major bleeding: a systematic review

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Product

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Prothrombin Complex Concentrate for Vitamin K Antagonist-Associated Intracranial Hemorrhage　― Global Evidence and the Japanese Perspective ―