Anti-CD47 antibody administration via cisterna magna in proper dosage can reduce perihematomal cell death following intracerebral hemorrhage in rats.

OBJECTIVE: The secondary injury caused by RBC autolysis after intracerebral hemorrhage (ICH) can be reduced by increasing the efficiency of microglia (MG)/macrophages (Mø) phagocytizing red blood cells (RBCs). CD47 is an important regulator of MG/Mø phagocytosis. This study aims to clarify whether anti-CD47 antibody administrated into the cisterna magna after ICH can transfer to the hematoma site, promote MG/Mø gathering to phagocytize RBCs and ultimately reduce cell death. METHODS: Forty male Wistar rats were divided into sham, ICH, low-dosage (group A, 0.3 µg), medium-dosage (group B, 0.9 µg) and high-dosage (group C, 1.8 µg) anti-CD47 antibody groups. For the rats in group A, B and C, anti-CD47 antibody solution was administrated into the cisterna magna at 10 min after ICH. Brain tissue was harvested 3 days after the operation. Western blotting was performed to detect the expression of Caspase-3 and Bcl-2. Immunofluorescence was performed to detect the CD68 expression. TUNEL was performed to detect the cell death. RESULTS: The hematoma of the ICH rats was located in the basal ganglia, with a good homogeneity of hematoma volume. Low-dosage anti-CD47 antibody in group A had no effects on the perihematomal CD68 (P = 0.338), Caspase-3 (P = 0.769), Bcl-2 (P = 0.176) expression and cell death (P = 0.698), compared with the ICH group. CD68 and Bcl-2 expression increased and Caspase-3 expression decreased significantly in group B (P < 0.001 for all) and group C (P < 0.001 for all). The increase of CD68 expression in group C was greater than that in group B (P < 0.01) by a large margin, while there was no difference for Bcl-2 (P = 0.908) and Caspase-3 (P = 0.913) expression between the 2 groups. Compared with the ICH group, medium-dosage of anti-CD47 antibody in group B significantly reduced the number of TUNEL-positive cells (P < 0.005), but not for group C (P = 0.311). CONCLUSION: The results suggested that anti-CD47 antibody administration into the cisterna magna in proper dosage (0.9 µg) can effectively reach the hematoma, induce more MG/Møs to gather around the hematoma, and reduce cell death in perihematomal brain tissue. The results of this study has provided a basic theory for improving the efficiency of MG/Mø phagocytizing RBCs and hematoma clearance after ICH by administrating anti-CD47 antibody via the cisterna magna.

Low Risk of Traumatic Intracranial Hematoma Expansion with Factor Xa Inhibitors without Andexanet Reversal.

BACKGROUND: Andexanet alfa, a novel anticoagulation reversal agent for factor Xa inhibitors, was recently approved. Traumatic intracranial hemorrhage presents a prime target for this drug. The Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors study established the efficacy of andexanet alfa in reversing factor Xa inhibitors. However, the association between anticoagulation reversal and traumatic intracranial hemorrhage progression is not well understood. The objective of this study was to determine progression rates of patients with traumatic intracranial hemorrhage on factor Xa inhibitors prior to hospitalization who were managed without the use of andexanet alfa. METHODS: A retrospective cohort study was performed between 2016 and 2019 at a single institution. An institutional traumatic brain injury (TBI) registry was queried. Patients with recorded use of apixaban or rivaroxaban <18 hours before injury were included. The primary study outcome was <35% increase in hemorrhage volume or thickness on repeated head computed tomography (CT) scans. RESULTS: We identified 25 patients meeting the inclusion criteria. Two patients were excluded because of a lack of necessary CT data. Twelve patients (52%) were receiving apixaban, and 11 were (48%) on rivaroxaban. On admission CT scan, 14 patients had subdural hematoma, 6 had traumatic intraparenchymal hemorrhage, and 3 had subarachnoid hemorrhage. Anticoagulation reversal was attempted in 17 patients (74%), primarily using 4-factor prothrombin complex concentrate. Twenty patients (87%) were adjudicated as having excellent or good hemostasis on repeat imaging. CONCLUSIONS: Our results indicate that patients on factor Xa inhibitors with complicated mild TBI have a similar intracranial hemorrhage progression rate to patients who are not anticoagulated or anticoagulated with a reversible agent. The hemostatic outcomes in our cohort were similar to those reported after andexanet alfa administration.

Interventional Ultrasound Assisted Early Local Hemostatic Drug Therapy in Traumatic Intracerebral Hemorrhage.

This article aims to test a minimally invasive interventional approach by real-time transcranial contrast-enhanced ultrasound (CEUS) through a small bur hole to achieve an early local hemostatic drug therapy in a novel traumatic intracerebral hematoma (ICH) model of pigs with hemostatic abnormalities. The effects of hemostasis in the hemocoagulase atrox (HA) injection group and saline injection group groups were observed by transcranial CEUS at three time points: 0 s, 10 s, 2nd. We successfully established a novel traumatic ICH model of pigs with hemostatic abnormalities by the methods of interventional ultrasound techniques and observed the effect of hemostasis by using HA in a local injection method with the assistance of minimally invasive interventional ultrasound technique. At 0 s, four pigs (100%) were observed that active bleeding was significantly weakened, and the range of hematoma became smaller in the HA group. At 10 s, four pigs (100%) were observed that active bleeding became much weaker, and the range of hematoma became further smaller in the HA group. At 2nd, zero pigs (0/4, 0%) were observed that active bleeding could be clearly identified and four pigs (100%) with ICH could also be observed in the HA group. We believe this useful technique could minimize the invasiveness and be operated at the bedside, which would bring much more benefits for traumatic ICH patients.

Improving Survival with Tranexamic Acid in Cerebral Contusions or Traumatic Subarachnoid Hemorrhage: Univariate and Multivariate Analysis of Independent Factors Associated with Lower Mortality.

BACKGROUND: Fall with head injury is a pervasive challenge, especially in the aging population. Contributing factors for mortality include the development of cerebral contusions and delayed traumatic intracerebral hematoma. Currently, there is no established specific treatment for these conditions. OBJECT: This study aimed to investigate the impact of independent factors on the mortality rate of traumatic brain injury with contusions or traumatic subarachnoid hemorrhage. METHODS: Data were collected from consecutive patients admitted for cerebral contusions or traumatic subarachnoid hemorrhage at an academic trauma center from 2010 to 2016. The primary outcome was the 30-day mortality rate. Independent factors for analysis included patient factors and treatment modalities. Univariate and multivariate analyses were conducted to identify independent factors related to mortality. Secondary outcomes included thromboembolic complication rates associated with the use of tranexamic acid. RESULTS: In total, 651 consecutive patients were identified. For the patient factors, low Glasgow Coma Scale on admission, history of renal impairment, and use of warfarin were identified as independent factors associated with higher mortality from univariate and multivariate analyses. For the treatment modalities, univariate analysis identified tranexamic acid as an independent factor associated with lower mortality (P = 0.021). Thromboembolic events were comparable in patients with or without tranexamic acid. CONCLUSION: Tranexamic acid was identified by univariate analysis as an independent factor associated with lower mortality in cerebral contusions or traumatic subarachnoid hemorrhage. Further prospective studies are needed to validate this finding.

Acute ethanol administration results in a protective cytokine and neuroinflammatory profile in traumatic brain injury.

Ethanol intoxication is a common comorbidity in traumatic brain injury. To date, the effect of ethanol on TBI pathogenic cascades and resulting outcomes remains debated. A closed blunt weight-drop murine TBI model has been implemented to investigate behavioral (by sensorimotor and neurological tests), and neuro-immunological (by tissue cytokine arrays and immuno-histology) effects of ethanol intoxication on TBI. The effect of the occurrence of traumatic intracerebral hemorrhage was also studied. The results indicate that ethanol pretreatment results in a faster and better recovery after TBI with reduced infiltration of leukocytes and reduced microglia activation. These outcomes correspond to reduced parenchymal levels of GM-CSF, IL-6 and IL-3 and to the transient upregulation of IL-13 and VEGF, indicating an early shift in the cytokine profile towards reduced inflammation. A significant difference in the cytokine profile was still observed 24h post injury in the ethanol pretreated mice, as shown by the delayed peak in IL-6 and by the suppression of GM-CSF, IFN-γ, and IL-3. Seven days post-injury, ethanol-pretreated mice displayed a significant decrease both in CD45+ cells infiltration and in microglial activation. On the other hand, in the case of traumatic intracerebral hemorrhage, the cytokine profile was dominated by KC, CCL5, M-CSF and several interleukins and ethanol pretreatment did not produce any modification. We can thus conclude that ethanol intoxication suppresses the acute neuro-inflammatory response to TBI, an effect which is correlated with a faster and complete neurological recovery, whereas, the presence of traumatic intracerebral hemorrhage overrides the effects of ethanol.

Effects of Deferoxamine Mesylate on Hematoma and Perihematoma Edema after Traumatic Intracerebral Hemorrhage.

Deferoxamine mesylate can cross the blood-brain barrier and reduce iron accumulation in nervous tissue; moreover, it has a variety of neuroprotective functions in addition to complexing with iron ions. Such iron chelators are expected to become a new treatment option for intracerebral hemorrhage. This study evaluated the effects of deferoxamine mesylate on hematoma and edema absorption after traumatic intracerebral hemorrhage (TICH), and it provides clinical evidence for TICH treatment with deferoxamine mesylate. Patients with isolated TICH, confirmed by head computed tomography, were enrolled prospectively from January 2013 to December 2016. Patients were divided non-randomly into an experimental or control group as decided by the attending neurosurgeon. Patients in the experimental group received intravenous deferoxamine mesylate (20 mg/kg daily) from the day of admission for 5 consecutive days. We evaluated the impact of deferoxamine mesylate on the change in edema volume and the absorption of hematoma volume using a propensity score-matched analysis. In total, 190 patients were included. After matching, 94 patients were included in the final analysis (47 per group); no variable differed significantly between the two groups. The hematoma volume on the 7th day in the control group was higher than that at the same time-point in the experimental group (9.4 ± 7.2 vs. 5.2 ± 4.8 mL; p = 0.001). There was no difference in hematoma volume on Day 1 (12.6 ± 7.8 vs. 12.8 ± 6.4 mL; p = 0.896), Day 3 (12.4 ± 7.4 vs. 11.4 ± 4.9 mL; p = 0.442), and Day 14 (3.2 ± 3.0 vs. 2.5 ± 2.6 mL; p = 0.215) between the groups. The absorption of hematoma volume between the 1st and 3rd days and the 1st and 7th days in the experimental group was higher than that during the same periods in the control group. The edema volumes on the 3rd, 7th, and 14th days in the control group were higher than those at the same time-points in the experimental group. There was no difference in edema volume on the 1st day. The changes in edema volume between the 1st and 3rd days, the 1st and 7th days, and the 1st and 14th days in the control group were higher than those during the same periods in the experimental group. Deferoxamine mesylate may accelerate hematoma absorption and inhibit edema after TICH; however, further investigation is required to reach definitive conclusions.

The effect of tranexamic acid in traumatic brain injury: A randomized controlled trial.

PURPOSE: Traumatic brain injury (TBI) is a leading cause of death and disability. Intracranial hemorrhage (ICH) secondary to TBI is associated with a high risk of coagulopathy which leads to increasing risk of hemorrhage growth and higher mortality rate. Therefore, antifibrinolytic agents such as tranexamic acid (TA) might reduce traumatic ICH. The aim of the present study was to investigate the extent of ICH growth after TA administration in TBI patients. METHODS: This single-blind randomized controlled trial was conducted on patients with traumatic ICH (with less than 30 ml) referring to the emergency department of Vali-Asr Hospital, Arak, Iran in 2014. Patients, based on the inclusion and exclusion criteria, were divided into intervention and control groups (40 patients each). All patients received a conservative treatment for ICH, as well as either intravenous TA or placebo. The extent of ICH growth as the primary outcome was measured by brain CT scan after 48 h. RESULTS: Although brain CT scan showed a significant increase in hemorrhage volume in both groups after 48 h, it was significantly less in the TA group than in the control group (p = 0.04). The mean total hemorrhage expansion was (1.7 ± 9.7) ml and (4.3 ± 12.9) ml in TA and placebo groups, respectively (p < 0.001). CONCLUSION: It has been established that TA, as an effective hospital-based treatment for acute TBI, could reduce ICH growth. Larger studies are needed to compare the effectiveness of different doses.

Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair).

BACKGROUND: Preterm infants suffering from intraventricular hemorrhage (IVH) are at increased risk for neurodevelopmental impairment. Observational data suggest that recombinant human erythropoietin (rEPO) improves long-term cognitive outcome in infants with IVH. Recent studies revealed a beneficial effect of early high-dose rEPO on white matter development in preterm infants determined by magnetic resonance imaging (MRI). OBJECTIVES: To summarize the current evidence and to delineate the study protocol of the EpoRepair trial (Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants). METHODS: The study involves a review of the literature and the design of a double-blind, placebo-controlled, multicenter trial of repetitive high-dose rEPO administration, enrolling 120 very preterm infants with moderate-to-severe IVH diagnosed by cranial ultrasound in the first days of life, qualitative and quantitative MRI at term-equivalent age and long-term neurodevelopmental follow-up until 5 years of age. RESULTS AND CONCLUSIONS: The hypothesis generated by observational data that rEPO may improve long-term cognitive outcomes of preterm infants suffering from IVH are to be confirmed or refuted by the randomized controlled trial, EpoRepair.

Dabigatran bleed risk with closed head injuries: are we prepared?

OBJECT: The direct thrombin inhibitor dabigatran has recently been approved in the US as an alternative to warfarin. The lack of guidelines, protocols, and an established specific antidote to reverse the anticoagulation effect of dabigatran potentially increases the rates of morbidity and mortality in patients with closed head injury (CHI). Confronted with this new problem, the authors reviewed their initial clinical experience. METHODS: The authors retrospectively reviewed all cases of adult patients (age ≥ 18 years) who sustained CHI secondary to ground-level falls and who presented to the authors' provisional regional Level I trauma center between February 2011 and May 2011. The authors divided these patients into 3 groups based on anticoagulant therapy: dabigatran, warfarin, and no anticoagulants. RESULTS: Between February 2011 and May 2011, CHIs from ground-level falls were sustained by 5 patients while on dabigatran, by 15 patients on warfarin, and by 25 patients who were not on anticoagulants. The treatment of the patients on dabigatran at the authors' institution had great diversity. Repeat CT scans obtained during reversal showed 4 of 5 patients with new or expanded hemorrhages in the dabigatran group, whereas the warfarin group had 3 of 15 (p = 0.03). The overall mortality rate for patients sustaining CHI on dabigatran was 2 (40%) of 5, whereas that of the warfarin group was 0 (0%) of 15 (p = 0.05). CONCLUSIONS: It is critical for physicians involved in the care of patients with CHI on dabigatran to be aware of an elevated mortality rate if no treatment protocol or guideline is in place. The authors will soon implement a reversal management protocol for patients with CHI on dabigatran at their institution in an attempt to improve efficacy and safety in their treatment approach.

[Comparative study of himantane and amantadine effects in experimental intracerebral posttraumatic hematoma].

Effects of the novel antiparkinsonian drug himantane and amantadin were studied in rats with intracerebral posttraumatic hematoma. Drugs were administered first at 3.5 hours after surgery and then for 4 consecutive days. Effects were registered on days 1, 3, 7 and 14 after surgery. It was shown that both drugs significantly decreased mortality and improved motor activity, exploratory behavior and memory. Amantadin was more effective in tests for motor activity and exploratory behavior. Himantane 5 mg/kg i.p demonstrated the more pronounced activity in restoring memory. The results obtained testify for neuroprotective properties of the novel antiparkinsonian drug himantane.

[Neuroprotective effect of recombinant human erythropoietin-loaded poly(lactic-co-glycolic) acid nanoparticles in rats with intracerebral posttraumatic hematoma].

The neuroprotective activity of recombinant human erythropoietin (rhEPO) loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been observed in rats with model intracerebral post-traumatic hematoma (hemorrhagic stroke). It is established that rhEPO-loaded PLGA nanoparticles produce a neuroprotective effect in rats with hemorrhagic stroke, which is manifested by reduced number of lethal outcomes and animals with neurological disorders. Treatment with rhEPO-loaded PLGA prevented amnesia of passive avoidance reflex (PAR), which was produced by the hemorrhagic stroke, and reduced the area of brain damage caused by the intracerebral hematoma. These effects were recorded during one-week observation period. Native rhEPO exhibited a similar, but much less pronounced effect on the major disorders caused by the model hemorrhagic stroke in rats.

Fibroblast growth factors preserve blood-brain barrier integrity through RhoA inhibition after intracerebral hemorrhage in mice.

Fibroblast growth factors (FGFs) maintain and promote vascular integrity; however whether FGFs protect the blood-brain barrier (BBB) after intracerebral hemorrhage (ICH) remains unexplored. In this present study, we hypothesized that exogenous FGF administration attenuates brain injury after ICH, specifically by preserving endothelial adherens junctions, therefore reducing vasogenic brain edema and attenuating neurofunctional deficits in mice subjected to experimental ICH. Acid fibroblast growth factor (FGF1) or basic fibroblast growth factor (FGF2) was administered intracerebroventricularly (ICV) at 0.5 h after intrastriatal injection of bacterial collagenase (cICH) or autologous whole blood (bICH). Fibroblast growth factor receptor (FGFR) inhibitor PD173074 and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 were additionally administered with FGF2. The selective Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK) inhibitor Y27632 was independently administered at 0.5 h after cICH. Brain water content and neurofunctional deficits were evaluated at 24 and 72h after ICH induction. Evans blue extravasation as well as Western blot analysis for the quantification of activated FGFR, Akt, Ras-related C3 botulinum toxin substrate 1 (Rac1), Ras homolog gene family member A (RhoA) and adherens junction proteins (p120-catenin, ß-catenin and VE-cadherin) were conducted at 72 h post-cICH. FGF treatment reduced perihematomal brain edema and improved neurofunctional deficits at 72 h after experimental ICH (p<0.05, compared to vehicle); however, FGFR and PI3K inhibition reversed these neuroprotective effects. Exogenous FGF2 increased activated FGFR, Akt, and Rac1 but reduced activated RhoA protein expression at 72 h after cICH (p<0.05, compared to vehicle), which was reversed by FGFR and PI3K inhibition. Y27632 treatment reduced brain injury at 72 h after cICH (p<0.05, compared to vehicle) and increased the expression of catenins (p120-catenin, ß-catenin). In conclusion, our findings suggest that exogenous FGF treatment reduced RhoA activity via FGFR-induced activation of the PI3K-Akt-Rac1 signaling pathway, thus preserving BBB integrity, and therefore attenuating secondary brain injury after experimental ICH in mice.

Neuroprotective properties of afobazole in repeated hemorrhagic stroke modeling in aged rats.

Intraperitoneal administration of afobazole in a dose of 0.1 mg/kg over 2 weeks after repeated modeling of intracerebral post-traumatic hematoma reduces animal mortality, decreases motor coordination disturbances, and improves learning and memory processes in rats.

Haemostatic drugs for traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability. Intracranial bleeding is a common complication of TBI, and intracranial bleeding can develop or worsen after hospital admission. Haemostatic drugs may reduce the occurrence or size of intracranial bleeds and consequently lower the morbidity and mortality associated with TBI. OBJECTIVES: To assess the effects of haemostatic drugs on mortality, disability and thrombotic complications in patients with traumatic brain injury. SEARCH STRATEGY: We searched the electronic databases: Cochrane Injuries Group Specialised Register (3 February 2009), CENTRAL (The Cochrane Library 2009, Issue 1), MEDLINE (1950 to Week 3 2009), PubMed (searched 3 February 2009 (last 180 days)), EMBASE (1980 to Week 4 2009), CINAHL (1982 to January 2009), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to January 2009), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to January 2009). SELECTION CRITERIA: We included published and unpublished randomised controlled trials comparing haemostatic drugs (antifibrinolytics: aprotinin, tranexamic acid (TXA), aminocaproic acid or recombined activated factor VIIa (rFVIIa)) with placebo, no treatment, or other treatment in patients with acute traumatic brain injury. DATA COLLECTION AND ANALYSIS: Two review authors independently examined all electronic records, and extracted the data. We judged that there was clinical heterogeneity between trials so we did not attempt to pool the results of the included trials. The results are reported separately. MAIN RESULTS: We included two trials. One was a post-hoc analysis of 30 TBI patients from a randomised controlled trial of rFVIIa in blunt trauma patients. The risk ratio for mortality at 30 days was 0.64 (95% CI 0.25 to 1.63) for rFVIIa compared to placebo. This result should be considered with caution as the subgroup analysis was not pre-specified for the trial. The other trial evaluated the effect of rFVIIa in 97 TBI patients with evidence of intracerebral bleeding in a computed tomography (CT) scan. The corresponding risk ratio for mortality at the last follow up was 1.08 (95% CI 0.44 to 2.68). The quality of the reporting of both trials was poor so it was difficult to assess the risk of bias. AUTHORS' CONCLUSIONS: There is no reliable evidence from randomised controlled trials to support the effectiveness of haemostatic drugs in reducing mortality or disability in patients with TBI. New randomised controlled trials assessing the effects of haemostatic drugs in TBI patients should be conducted. These trials should be large enough to detect clinically plausible treatment effects.

Deferoxamine reduces intracerebral hematoma-induced iron accumulation and neuronal death in piglets.

BACKGROUND AND PURPOSE: Our previous studies found that deferoxamine reduces intracerebral hemorrhage (ICH)-induced brain injury in rats. The current study examined whether deferoxamine reduces brain injury in a piglet ICH model. METHODS: Pigs received an injection of autologous blood into the right frontal lobe. Deferoxamine (50 mg/kg, IM) or vehicle was administered 2 hours after ICH and then every 12 hours up to 7 days. Animals were killed 3 or 7 days later to examine iron accumulation, white matter injury, and neuronal death. RESULTS: ICH resulted in development of a reddish perihematomal zone, and iron accumulation, ferritin upregulation, and neuronal death within that zone. Deferoxamine reduced the perihematomal reddish zone, white matter injury, and the number of Perls', ferritin, and Fluoro-Jade C-positive cells. CONCLUSIONS: Iron accumulation occurs in the piglet brain after ICH. Deferoxamine reduces ICH-induced iron buildup and brain injury in piglets.

Neuroleptic malignant syndrome in traumatic brain injury patients treated with haloperidol.

BACKGROUND: Haloperidol, which is commonly used to treat agitation in critically ill patients, has been associated with the development of neuroleptic malignant syndrome (NMS). The purpose of this manuscript was to review the literature describing NMS and haloperidol use in patients sustaining a traumatic brain injury (TBI) since these patients may be at greater risk for NMS. METHODS: A computerized search of MEDLINE was conducted (1966-May 2008) to identify all publications in which haloperidol was related to NMS in patients with a TBI. The references of these manuscripts were reviewed for additional literature. RESULTS: Nine case reports describe the development of NMS in patients with TBI treated with haloperidol for agitation. Cumulative haloperidol doses before the onset of NMS ranged from 10 mg to at least 210 mg. Most of these patients received high dose (> or =30 mg) haloperidol. Four patients received haloperidol parenterally. On diagnosis, of NMS, haloperidol was discontinued in five cases, and all were given supportive care and pharmacologic treatment. Patients were discharged with improved, but diminished functional capacity. CONCLUSION: Development of NMS in TBI patients treated with haloperidol should be a concern for clinicians since these patients may be at greater risk for this adverse event; especially if the patient is receiving haloperidol at high doses parenterally. Future studies are needed to evaluate the incidence and increased risk of adverse events in patients sustaining a TBI and receiving haloperidol especially since haloperidol is being used more frequently in the critically ill patients.

Management of prehospital antiplatelet and anticoagulant therapy in traumatic head injury: a review.

Trauma and emergency department clinicians encounter a growing number of patients admitted with traumatic head injury on prehospital antithrombotic therapies. These patients appear to be at increased risk of developing life-threatening intracranial hemorrhage. It is imperative that trauma clinicians understand the mechanism and duration of commonly prescribed outpatient antithrombotics in order to appropriately assess and treat patients who develop intracranial hemorrhage. This review summarizes current literature on the morbidity and mortality associated with premorbid non-steroidal anti-inflammatory drugs, aspirin, clopidogrel, warfarin, and heparinoids in the setting of traumatic head injury, and also examines the current strategies for reversal of these therapies.

A promising new alternative for the rapid reversal of warfarin coagulopathy in traumatic intracranial hemorrhage.

BACKGROUND: Internationally, Factor IX complex (FIX complex) has been used to correct warfarin-induced coagulopathy. We present our experience with 28 patients using FIX complex. METHODS: A retrospective chart review was conducted between November 2002 and July 2006 on patients with warfarin-induced coagulopathy. We recorded the dose and timing of FIX complex, serial international normalized ratios (INRs), early adverse events, and patient outcome. RESULTS: Twenty-eight patients met criteria. The mean INR on admission was 5.1, and after FIX complex infusion was reduced significantly to 1.9 (P = .008). Eleven patients had a repeat INR drawn within 30 minutes after FIX complex infusion. The mean time to correction was 13.5 minutes. There were no early thrombotic events or allergic reactions. CONCLUSIONS: FIX complex results in an immediate reversal of coagulopathy within 15 minutes after administration. Its use should be considered as an alternative treatment to fresh-frozen plasma and recombinant Factor VIIa. Prospective randomized trials are needed to confirm these findings.