Prothrombin complex concentrates to reverse warfarin-induced coagulopathy in patients with intracranial bleeding

Cabral, Katherine P.; Fraser, Gilles L.; Duprey, Jennifer; Gibbons, Beth A.; Hayes, Timothy L.; Florman, Jeffrey E.; Seder, David B.

doi:10.1016/j.clineuro.2012.07.006

Cited by 46 publications

(31 citation statements)

References 27 publications

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“…In anticoagulation reversal with PCC not being limited to VKA-ICH patients, thromboembolic complications associated to PCC administration have been reported in 1.8% in a meta-analysis and in 0.0-7.3% [23,[39][40][41][42][43] among observational cohort studies and randomizedcontrolled trials that included patients with VKA-related bleedings or prior to urgent surgical procedures. Evaluating specifically VKA-ICH patients, a retrospective study with 30 VKA-ICH patients treated with PCC reported a TE rate of 10% [40] .…”

Section: Discussionmentioning

confidence: 99%

Adverse Events Following International Normalized Ratio Reversal in Intracerebral Hemorrhage

Laible

Jenetzky

Beynon³

et al. 2016

Cerebrovasc Dis

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Background: Prothrombin complex concentrates (PCCs) are frequently used to reverse the effect of vitamin K antagonists (VKAs) in patients with non-traumatic intracerebral hemorrhage (ICH). However, information on the rate of thromboembolic events (TEs) and allergic events after PCC therapy in VKA-ICH patients is limited. Methods: Consecutive VKA-ICH patients treated with PCC at our institution between December 2004 and June 2014 were included into this retrospective observational study. We recorded international normalized ratio (INR) values before and after PCC treatment, baseline clinical characteristics including the premorbid modified Rankin Scale (pmRS) score, TE and allergic event that occurred during the hospital stay. All events were classified by 3 reviewers as being ‘related', ‘probably related', ‘possibly related', ‘unlikely related' or ‘not related' to treatment with PCC. To identify factors associated with TEs, log-rank analyses were applied. Results: Two hundred and five patients were included. Median INR was 2.8 (interquartile range (IQR) 2.2-3.8) before and 1.3 (IQR 1.2-1.4) after PCC treatment and a median of 1,500 IU PCC (IQR 1,000-2,500) was administered. Nineteen TEs were observed (9.3%); none were classified ‘related' but 9 were classified as ‘possibly' or ‘probably related' to PCC infusion (4.4%). One allergic reaction (0.5%), ‘unlikely related' to PCC, was observed. In the whole cohort, PCC doses >2,000-3,000 IU, ICH volumes >40 ml, National Institute of Health Stroke Scale values >10 and a pmRS >2 were associated with the development of TEs (p = 0.031, p = 0.034, p = 0.050 and p = 0.036, respectively). Conclusions: Overall, INR reversal with PCC appears safe. Though no clear relationship between higher PCC dosing and TEs was observed, PCC doses between >2,000 and 3,000 IU and higher morbidity at ICH onset were associated with TEs. Hence, individual titration of PCC to avoid exposure to unnecessarily high doses using point-of-care devices should be prospectively explored.

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Section: Discussionmentioning

confidence: 99%

Adverse Events Following International Normalized Ratio Reversal in Intracerebral Hemorrhage

Laible

Jenetzky

Beynon³

et al. 2016

Cerebrovasc Dis

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“…30 Prothrombin complex concentrate used with or without additional FFP has been shown to provide rapid reversal of the INR in neurosurgical patients and patients with trauma. [31][32][33][34] With effective rapid reversal strategies now available as well as the demonstrated ineffectiveness of plasma, a policy of prophylactic reversal of anticoagulation appears unwarranted.…”

Section: Discussionmentioning

confidence: 99%

Prophylactic Fresh Frozen Plasma Infusion is Ineffective in Reversing Warfarin Anticoagulation and Preventing Delayed Intracranial Hemorrhage After Falls

Reddy

Sharma

Grotts

et al. 2015

The Neurohospitalist

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Background: Elderly patients, with considerable fall risk, are increasingly anticoagulated to prevent thromboembolic disease. We hypothesized that a policy of prophylactic fresh frozen plasma (FFP) infusion in patients having falls would reverse vitamin K antagonists (VKAs) and that reversal would decrease delayed intracranial hemorrhage (ICH). Methods: A retrospective review of patients with trauma admitted to a level 2 community trauma center was performed from January 2010 until November 2012. Inclusion criteria were: ground level fall (GLF) with suspected head trauma, on VKA, an international normalized ratio (INR) of >1.5, and a negative head computed tomography (CT). Patients were transfused with FFP to a goal INR of <1.5 while observed. Patients were classified as reversed (REV) if the lowest INR achieved within 4 to 24 hours after initial INR was <1.5 or unreversed (NREV) if lowest INR achieved was >1.5. Chi-square and logistic regression were performed. Results: A total of 194 patients met the criteria. In all, 43 (22%) patients were able to be REV, and 151 (78%) patients remained NREV. Unreversed patients were male and younger (P < .05). There was no difference in mean FFP received. Unreversed patients had a higher initial INR of 3.0 compared to REV patients (2.5; P ¼ .018). One patient developed a delayed ICH and belonged to the REV group. Conclusion: The incidence of delayed hemorrhage was 0.5%. A strategy of prophylactic FFP infusion was ineffective in VKA reversal. We recommend against prophylactic infusion of FFP during a period of observation for patients on VKA with suspected head trauma and a negative initial CT.

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“…Randomized data do not yet support the clinical efficacy of rFVIIa in patients with ICH. 66,67 PCC + intravenous vitamin K is considered the first therapeutic choice by many authors 1,23,64,65,68 whereas others 22,69 include FFP in their recommendations; the rationale for this is that the only three types of PCC available in their country are 3PCC.…”

Section: Prothrombin Complex Concentratesmentioning

confidence: 99%

Emergency management of patients being treated with oral anticoagulants

Manzato

Franchini

2013

Ital J Med

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Vitamin K antagonists (VKA) are among the most widely prescribed drugs in the industrialized world. In fact, for decades, VKA have been the only orally available anticoagulant for the primary and secondary prevention of venous and arterial thrombotic events. Their efficacy has been widely demonstrated in a series of studies carried out in the 1990s. Since the incidences of atrial fibrillation and venous thromboembolism increase exponentially with age, the number of anticoagulated patients is destined to increase. This paper examines anticoagulation therapy management with particular attention to the use of VKA. but also a molecule of O 2 , one of CO 2 , and the reduced form of vitamin K (hydroquinone: KH2) which, in the reaction, is oxidized to vitamin K epoxide. Vitamin K epoxide can be re-used through its reduction first to vitamin K and then to reduced vitamin K by two enzyme systems: the first, vitamin K epoxide reductase, is completely inhibited by dicoumarols, while the second, vitamin K reductase, is only partially inhibited by dicoumarols. 3 The anticoagulant effect of VKA can, therefore, be overcome by even small doses of phytonadione (vitamin K). In Italy, two VKA are available: sodium warfarin (Coumadin) and acenocoumarol (Sintrom). Both are rapidly absorbed through the intestines, with peak blood concentrations being reached after 90 min, and, transported by albumin, accumulate in the liver where they are metabolized. The main difference between the two drugs is their half-lives. Warfarin is a racemic mixture of two isomers: R-warfarin has a halflife of 45 h, while S-warfarin, which is 2.7-3.8 times more potent than R-warfarin, has a half-life of 29 h. Acenocoumarol is also produced as a mixture of two isomers: the half-life of R-acenocoumarol is 9 h, while that of S-acenocoumarol is only 0.5 h. Traditionally, VKA treatment is monitored by measuring the prothrombin time expressed as an INR, which reflects the levels of three clotting factors (II, VII, X) of the four that are vitamin K-dependent. When treatment with VKA is started or suspended, the changes in the prothrombin time/INR reflect the changes in these aforementioned three factors which do, however, have notably different half-lives: 2-9 h for factor VII, 17-44 h for factor X and 60-72 h for factor II. In these situations, the prothrombin time does, therefore, reflect above all the levels of factor VII, while the antithrombotic effect of VKA is correlated with the concentration of factor II. 3Anticoagulant therapy is associated with a risk of bleeding for the entire duration of the treatment, independently of the drug used. Although it would be extremely useful to have clinical prediction parameters for estimating bleeding risk in patients on OAT, unfortunately, none of the available clinical prediction criteria has sufficient predictive accuracy and there have been no trials to evaluate the impact of their use on patients' outcomes. 11 The main variables that influence bleeding are the intensity and duration of the anticoagulation. ...

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Prothrombin complex concentrates to reverse warfarin-induced coagulopathy in patients with intracranial bleeding

Cited by 46 publications

References 27 publications

Adverse Events Following International Normalized Ratio Reversal in Intracerebral Hemorrhage

Adverse Events Following International Normalized Ratio Reversal in Intracerebral Hemorrhage

Prophylactic Fresh Frozen Plasma Infusion is Ineffective in Reversing Warfarin Anticoagulation and Preventing Delayed Intracranial Hemorrhage After Falls

Emergency management of patients being treated with oral anticoagulants

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