Impact of Antithrombotic Medications and Reversal Strategies on the Surgical Management and Outcomes of Traumatic Acute Subdural Hematoma.

OBJECTIVE: Careful hematologic management is required in surgical patients with traumatic acute subdural hematoma (aSDH) taking antithrombotic medications. We sought to compare outcomes between patients with aSDH taking antithrombotic medications at admission who received antithrombotic reversal with patients with aSDH not taking antithrombotics. METHODS: Retrospective review identified patients with traumatic aSDH requiring surgical evacuation. The cohort was divided based on antithrombotic use and whether pharmacologic reversal agents or platelet transfusions were administered. A 3-way comparison of outcomes was performed between patients taking anticoagulants who received pharmacologic reversal, patients taking antiplatelets who received platelet transfusion, and patients not taking antithrombotics. Multivariable regressions, adjusted for injury severity, further investigated associations with outcomes. RESULTS: Of 138 patients who met inclusion criteria, 13.0% (n = 18) reported taking anticoagulants, 16.7% (n = 23) reported taking antiplatelets, and 3.6% (n = 5) reported taking both. Patients taking antiplatelets who received platelet transfusion had longer intraoperative times (P = 0.040) and higher rates of palliative care consultations (P = 0.046) compared with patients taking anticoagulants who received pharmacologic reversal and patients not taking antithrombotics. Across groups, no significant differences were found in frequency of in-hospital intracranial hemorrhage and venous thromboembolism, length of hospital stay, rate of inpatient mortality, or follow-up health status. In multivariable analysis, intraoperative time remained longest for the antiplatelets with platelet transfusion group. Other outcomes were not associated with patient group. CONCLUSIONS: Among surgical patients with traumatic aSDH, those taking antiplatelet medications who receive platelet transfusions experience longer intraoperative procedure times and higher rates of palliative care consultation. Comparable outcomes were observed between patients receiving antithrombotic reversal and patients not taking antithrombotics.

The implications of antithrombotic agents on subdural hematoma evacuation: what does "reversal" truly entail?

OBJECTIVE: The optimal perioperative management of antithrombotic therapy (ATT) in patients requiring urgent neurosurgical intervention for subdural hematoma (SDH) is poorly understood. The delicate equilibrium of effective hemostasis while preventing thrombosis is complex and relies on numerous factors such as indication for and type of ATT, medical comorbidities, and extent of neurological injury. This study aimed to analyze the impact of ATT and reversal strategies on surgical outcomes to highlight current challenges in the management of these high-risk patients. METHODS: The authors performed a retrospective surgical cohort analysis of 100 patients undergoing urgent SDH evacuation at a level I trauma center between March 2020 and May 2021. The patients were first stratified into two cohorts based on preoperative ATT use and then further segregated by receipt of reversal agents. Statistical analysis included the chi-square test, Welch two-sample t-test, and multivariate logistic regression. The primary outcome was mortality. Secondary endpoints included radiographic SDH reexpansion, revision surgery, improvement in preoperative neurological deficits, and incidence of thromboembolism. A crossover cohort was secondarily analyzed in patients for whom ATT was interrupted for a minimum duration equal to effective drug metabolism. Finally, ATT reinitiation patterns were examined. RESULTS: Of 100 patients, 48% received ATT, 54.2% of whom were given reversal agents. ATT use was significantly associated with decreased rates of postoperative neurological improvement (p = 0.023) with trends toward increased mortality (p = 0.078), SDH reexpansion (p = 0.12), and need for revision surgery (p = 0.10). Patient crossover revealed a 4 times greater likelihood of death in patients without ATT interruption prior to surgery (p = 0.040) without an observable impact on secondary outcomes. ATT reversal contributed no improvement in outcomes other than a decreased intensive care unit length of stay when adjusted for in-hospital mortality (p = 0.014). The rate of postoperative thromboembolism following ATT reversal was 11.5%. ATT reinitiation was highly variable, occurring in 59.5% of patients, with median times of 17 and 15 days for antiplatelets and anticoagulants, respectively. CONCLUSIONS: Use of preoperative ATT portends poor clinical outcomes following nonelective SDH evacuation regardless of attempts to reverse these medications with replacement blood products. This study further reinforces the critical need for judicious use of ATT and optimization of reversal strategies in high-risk patient populations as best guided by multidisciplinary teams and evolving clinical practice guidelines.

Long-term outcomes after traumatic brain injury in elderly patients on antithrombotic therapy.

INTRODUCTION: Elderly patients receiving antithrombotic treatment have a significantly higher risk of developing an intracranial hemorrhage when suffering traumatic brain injury (TBI), potentially contributing to higher mortality rates and worse functional outcomes. It is unclear whether different antithrombotic drugs carry a similar risk. OBJECTIVE: This study aims to investigate injury patterns and long-term outcomes after TBI in elderly patients treated with antithrombotic drugs. METHODS: The clinical records of 2999 patients ≥ 65 years old admitted to the University Hospitals Leuven (Belgium) between 1999 and 2019 with a diagnosis of TBI, spanning all injury severities, were manually screened. RESULTS: A total of 1443 patients who had not experienced a cerebrovascular accident prior to TBI nor presented with a chronic subdural hematoma at admission were included in the analysis. Relevant clinical information, including medication use and coagulation lab tests, was manually registered and statistically analyzed using Python and R. In the overall cohort, 418 (29.0%) of the patients were treated with acetylsalicylic acid before TBI, 58 (4.0%) with vitamin K antagonists (VKA), 14 (1.0%) with a different antithrombotic drug, and 953 (66.0%) did not receive any antithrombotic treatment. The median age was 81 years (IQR = 11). The most common cause of TBI was a fall accident (79.4% of the cases), and 35.7% of the cases were classified as mild TBI. Patients treated with vitamin K antagonists had the highest rate of subdural hematomas (44.8%) (p = 0.02), hospitalization (98.3%, p = 0.03), intensive care unit admissions (41.4%, p < 0.01), and mortality within 30 days post-TBI (22.4%, p < 0.01). The number of patients treated with adenosine diphosphate (ADP) receptor antagonists and direct oral anticoagulants (DOACs) was too low to draw conclusions about the risks associated with these antithrombotic drugs. CONCLUSION: In a large cohort of elderly patients, treatment with VKA prior to TBI was associated with a higher rate of acute subdural hematoma and a worse outcome, compared with other patients. However, intake of low dose aspirin prior to TBI did not have such effects. Therefore, the choice of antithrombotic treatment in elderly patients is of utmost importance with respect to risks associated with TBI, and patients should be counselled accordingly. Future studies will determine whether the shift towards DOACs is mitigating the poor outcomes associated with VKA after TBI.

Successful treatment of subdural hemorrhage and retinal hemorrhage in childhood-onset systemic lupus erythematosus associated with thrombocytopenia: Case report.

INTRODUCTION: Thrombocytopenia (TP) is a common complication of childhood-onset systemic lupus erythematosus (SLE), and can range from mild to life-threatening. However, severe TP with multiple hemorrhagic complications is very rare and often predicts a poor prognosis. We describe a 12-year-old Chinese girl who had a history of idiopathic thrombocytopenic purpura who developed SLE that presented as subdural hemorrhage and retinal hemorrhage because of severe TP. PATIENT CONCERNS: A 12-year-old girl was admitted into our hospital because of fever, purpura, and gum bleeding lasting for 12 days. She had a history of idiopathic thrombocytopenic purpura 2 years ago previously. DIAGNOSIS: SLE was diagnosed according to American College of Rheumatology classification criteria. Subdural hemorrhage and retinal hemorrhage were diagnosed based on brain MRI and funduscopy. Severe TP was defined as platelet count <20 × 109/L. INTERVENTIONS: She was treated first with intravenous immunoglobulin, but it was not efficacious. High-dose methylprednisolone showed short-term efficacy. Then, she was given a glucocorticoid and cyclosporine A plus mycophenolate mofetil. OUTCOMES: Fever, purpura, and gum bleeding were resolved before hospital discharge. Subdural hemorrhage and left hemorrhagic retinopathy were improved remarkably. She had a durable response to refractory TP with no adverse effects during >1-year follow-up. CONCLUSION: Isolated TP may be an early symptom of childhood-onset SLE . A child with severe TP is prone to develop life-threatening hemorrhagic complications. Glucocorticoids and combined immunosuppressive drugs had a durable response to refractory TP in this patient with no adverse effects.

Ketamine for empiric treatment of cortical spreading depolarization after subdural hematoma evacuation.

BACKGROUND: It is widely known that some patients surgically treated for subdural hematoma (SDH) experience neurologic deficits not clearly explained by the acute brain injury or known sequelae like seizures. There is increasing evidence that cortical spreading depolarization (CSD) may be the cause. A recent article demonstrated that CSD occurred at a rate of 15 % and was associated with neurological deterioration in a subset of patients following chronic subdural hematoma evacuation. Furthermore, CSD can lead to ischemia leading to worsening neurologic deficits. CSD is usually detected on electrocorticography (ECoG) and needs cortical strip electrode placement with equipment and expertise that may not be readily available. CASE DESCRIPTION: We report three cases of patients with subdural hematoma (SDH) not undergoing ECoG in whom CSD was suspected to be the cause of their neurologic deficits post evacuation. Extensive workup including neuroimaging and electroencephalography (EEG) were inconclusive. Patients were subsequently treated with ketamine infusion and had resultant neurological recovery. CONCLUSIONS: Ketamine infusion can help reverse neurologic deficits in patients with SDH in whom the deficits are not explained by neuroimaging or electrographic seizure. CSD is a known phenomenon that can result in neurological injury and must remain in the differential diagnosis of such patients. Though only limited cases are discussed (n = 3), this small case series provides the basis for conducting clinical trials evaluating the efficacy of ketamine in improving functional outcome in brain-injured patients demonstrating evidence of CSD.

Successful dabigatran reversal after subdural hemorrhage using idarucizumab in a mobile stroke unit: A case report.

RATIONALE: Idarucizumab is a specific reversal agent for patients with bleeding related to the anticoagulant dabigatran. There are no prior descriptions of Idarucizumab administration in the prehospital setting for intracranial hemorrhage. PATIENT CONCERNS: An 82-year-old woman treated with dabigatran for atrial fibrillation developed acute focal weakness. This led to activation of emergency medical services and assessment in the mobile stroke unit (MSU). DIAGNOSIS: Computed tomography of the brain performed in the MSU revealed an acute subdural hematoma. INTERVENTIONS: The patient was treated with Idarucizumab in the MSU. OUTCOMES: The subdural hematoma was treated with a burr hole evacuation and the patient was discharged to a rehabilitation facility without residual focal neurological deficits. LESSONS: Idarucizumab can be used safely and effectively to treat dabigatran-associated intracranial hemorrhage in the prehospital setting.

Factor Xa Inhibitor-Related Intracranial Hemorrhage: Results From a Multicenter, Observational Cohort Receiving Prothrombin Complex Concentrates.

BACKGROUND: Since the approval of the oral factor Xa inhibitors, there have been concerns regarding the ability to neutralize their anticoagulant effects after intracranial hemorrhage (ICH). Multiple guidelines suggest using prothrombin complex concentrates (PCCs) in these patients on the basis of research that includes a limited number of patients with ICH. Given this, we aimed to evaluate the safety and efficacy of PCCs for factor Xa inhibitor-related ICH in a large, multicenter cohort of patients. METHODS: This was a multicenter, retrospective, observational cohort study of patients with apixaban- or rivaroxaban-related ICH who received PCCs between January 1, 2015, and March 1, 2019. The study had 2 primary analysis groups: safety and hemostatic efficacy. The safety analysis evaluated all patients meeting inclusion criteria for the occurrence of a thrombotic event, which were censored at hospital discharge or 30 days after PCC administration. Patients with intracerebral, subarachnoid, or subdural hemorrhages who had at least 1 follow-up image within 24 hours of PCC administration were assessed for hemostatic efficacy. The primary efficacy outcome was the percentage of patients with excellent or good hemostasis on the basis of the modified Sarode criteria. Secondary outcomes included an evaluation of in-hospital mortality, length of stay, infusion-related reactions, and thrombotic event occurrence during multiple predefined periods. RESULTS: A total of 663 patients were included and assessed for safety outcomes. Of these, 433 patients met criteria for hemostatic efficacy evaluation. We observed excellent or good hemostasis in 354 patients (81.8% [95% CI, 77.9-85.2]). Twenty-five (3.8%) patients had a total of 26 thrombotic events, of which 22 occurred in the first 14 days after PCC administration. One patient had documentation of an infusion-related reaction. For the full cohort of patients, in-hospital mortality was 19.0%, and the median intensive care unit and hospital lengths of stay were 2.0 and 6.0 days, respectively. CONCLUSIONS: Administration of PCCs after apixaban- and rivaroxaban-related ICH provided a high rate of excellent or good hemostasis (81.8%) coupled with a 3.8% thrombosis rate. Randomized, controlled trials evaluating the clinical efficacy of PCCs in patients with factor Xa inhibitor-related ICH are needed.

Non-Traumatic Subdural Hemorrhage and Risk of Arterial Ischemic Events.

Background and Purpose- The risk of arterial ischemic events after subdural hemorrhage (SDH) is poorly understood. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction among patients with and without nontraumatic SDH. Methods- We performed a retrospective cohort study using claims data from 2008 through 2014 from a nationally representative sample of Medicare beneficiaries. The exposure was nontraumatic SDH. Our primary outcome was an arterial ischemic event, a composite of acute ischemic stroke and acute myocardial infarction. Secondary outcomes were ischemic stroke alone and myocardial infarction alone. We used validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes to identify our predictor and outcomes. Using Cox regression and corresponding survival probabilities, adjusted for demographics and vascular comorbidities, we computed the hazard ratio in 4-week intervals after SDH discharge. We performed secondary analyses stratified by strong indications for antithrombotic therapy (composite of atrial fibrillation, peripheral vascular disease, valvular heart disease, and venous thromboembolism). Results- Among 1.7 million Medicare beneficiaries, 2939 were diagnosed with SDH. In the 4 weeks after SDH, patients' risk of an arterial ischemic event was substantially increased (hazard ratio, 3.6 [95% CI, 1.9-5.5]). There was no association between SDH diagnosis and arterial ischemic events beyond 4 weeks. In secondary analysis, during the 4 weeks after SDH, patients' risk of ischemic stroke was increased (hazard ratio, 4.2 [95% CI, 2.1-7.3]) but their risk of myocardial infarction was not (hazard ratio, 0.8 [95% CI, 0.2-1.7]). Patients with strong indications for antithrombotic therapy had increased risks for arterial ischemic events similar to patients in the primary analysis, but those without such indications did not demonstrate an increased risk for arterial ischemic events. Conclusions- Among Medicare beneficiaries, we found a heightened risk of arterial ischemic events driven by an increased risk of ischemic stroke, in the 4 weeks after nontraumatic SDH. This increased risk may be due to interruption of antithrombotic therapy after SDH diagnosis.

Subdural Catheter Injection of Tissue Plasminogen Activator for Residual Hematoma Post Drainage of Acute-on-Chronic Subdural Hematoma: Novel Case Report of 2 Patients.

BACKGROUND: Residual hematoma after operative management of acute subdural hematoma contributes to reoperation and is cited as a reason for deferment of less invasive drainage strategies. Although local antithrombolytic therapy has been studied in intracerebral hemorrhage and chronic subdural hematoma, to date there are no reports of recombinant tissue plasminogen activator for residual hematoma post drainage for acute subdural hematoma. CASE DESCRIPTION: Two patients presented with altered mental status secondary to acute-on-chronic subdural hematomas and underwent emergent craniotomies. The first, a 78-year-old man, had poor subdural drain output and deteriorated with seizures and evidence of new acute subdural hematoma formation. Recombinant tissue plasminogen activator was injected through the subdural catheter on postoperative day 3. The second patient, a 64-year-old male, received recombinant tissue plasminogen activator postoperatively. Subsequently, both experienced good subdural drainage, clinical and radiologic improvement, and successful discharge to a skilled nursing facility. CONCLUSIONS: Subdural thrombolytic therapy can improve hematoma evacuation. A potential implication of this is facilitation of minimally invasive options such as twist-drill craniotomy, previously deferred due to inadequate evacuation. However, there is a paucity of evidence and more research is needed to substantiate the safety and efficacy, refine this technique, and guide patient selection.

Intravenous Tranexamic Acid for Subdural and Epidural Intracranial Hemorrhage: Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Recovery of patients with traumatic brain injury largely depends on the reduction in secondary brain damage. The present study aims at investigating the effect of Tranexamic Acid (TXA) administration within the first hours of brain trauma in the emergency department (ED). METHODS: This randomized, double-blind, placebo-controlled clinical trial was carried out in patients with subdural and epidural hemorrhage. Patients with any type of bleeding were assigned into two groups of TXA and 0.9% normal saline as placebo. The rate of intracranial hemorrhage after surgery was assessed by CT-scan and amount of hemoglobin (Hb) was measured immediately before surgery and after 6 hours of surgery. RESULTS: A total of 80 participants were randomly assigned into four groups of 20 people. There was a significant difference in the mean of intraoperative bleeding during surgery in patients receiving TXA and placebo in both SDH (Subdural hematoma) and EDH (Epidural Hemorrhage) groups (P= 0.012). The Hb drop amount had no significant difference with placebo (P< 0.0001). No complications were observed in any of the intervention and control groups during the study as well. CONCLUSION: The use of TXA may reduce bleeding, however, based on the results of this study, such effect was not statistically significant in controlling the epidural and subdural hemorrhage, but clinical trials with a higher sample size are suggested for further investigation in this regard.

Does the Presence of Subdural Hemorrhage Increase the Risk of Intracranial Hemorrhage Expansion after the Initiation of Antithrombotic Medication?

Patients with traumatic intracranial hemorrhage (ICH) with a clinical indication for antithrombotic medication present a clinical dilemma, burdened by the task of weighing the risks of hemorrhage expansion against the risk of thrombosis. We sought to determine the effect of subdural hemorrhage on the risk of hemorrhage expansion after administration of antithrombotic medication. Medical records of 1626 trauma patients admitted with traumatic ICH between March 1, 2008, and March 31, 2013, to a Level I trauma center were retrospectively reviewed. The pharmacy database was queried to determine which patients were administered anticoagulant or antiplatelet medication during their hospitalization, leaving a sample of 97 patients that met inclusion criteria. Patients presenting with subdural hemorrhage were compared with patients without subdural hemorrhage. Demographic data, clinically significant expansion of hematoma, postinjury day of initiation, and mortality were analyzed. A total of 97 patients met inclusion criteria with 55 patients in the subdural hemorrhage group and 42 in the other ICH group. There were no significant differences in age, gender, injury severity score, admission Glasgow coma score, or mean hospital day of antithrombotic administration between the groups. Patients with subdural hemorrhage had a significantly higher rate of ICH expansion (9.1 vs 0%, P = 0.045). There was no difference in overall hospital mortality between the two groups. Incidence of ICH expansion was higher in patients with subdural hemorrhage. It may be prudent to use special caution when administering antiplatelet or anticoagulant medication in this group of patients after injury.

Use of Prothrombin Complex Concentrate for Warfarin Reversal Before the Performance of an Epidural Blood Patch in a Patient With Cortical Vein Thrombosis and Subdural Hematoma: A Case Report.

Compared to conventional therapy, several studies with prothrombin complex concentrate (PCC) have recently demonstrated its superior efficacy in rapidly replacing vitamin K-dependent factors for patients with life-threatening hemorrhage. We present a novel use of PCC in a patient with intracranial hypotension, who had received warfarin for treatment of cortical vein thrombosis. However, after anticoagulation, she proceeded to develop bilateral subdural hematomas with descent of cerebellar tonsils. Given the possibility of an occult dural puncture during labor analgesia, an epidural blood patch was performed after administration of PCC and normalization of coagulation parameters, with prompt improvement of the patient's headache.

A systematic review of epileptic seizures in adults with subdural haematomas.

BACKGROUND: Posttraumatic epileptic seizures (PTS) are a serious complication in patients with subdural haematoma (SDH). However, to date, several studies have shown discordances about SDH-associated seizures in terms of incidence, risk factors and prophylactic antiepileptic treatment. OBJECTIVE: The aim of this study was to analyse the incidence, risk factors of PTS and the role of prophylactic antiepileptic treatment in patients with SDH. DATA SOURCES: A systematic literature review examining PTS in patients with SDH was performed using PubMed gateway, Cochrane Central Register of Controlled Trials, and Excerpta Medica dataBASE between September 1961 and February 2016. Search terms included subdural haematoma, seizure, epilepsy, prophylactic antiepileptic drugs, anticonvulsive medication, and risk factors. DATA SELECTION: Human-based clinical studies focusing on epileptic seizures in patients with SDH. DATA EXTRACTION AND SYNTHESIS: PRISMA statements were used for assessing data quality. Two independent reviewers extracted data from included studies and disagreement was solved by consensus. Twenty-four studies were identified for inclusion into the study. RESULTS: Overall incidence of early PTS (ePTS) and late PTS (lPTS)/2 years was 28% and 43% in acute SDH (aSDH) whereas the incidence of e- and lPTS was lower in chronic SDH (cSDH; 5.3% vs. 10%). Overall risk factors for PTS in patients with aSDH were: 24h postoperative Glasgow Coma Score (GCS) score below 9 (OR 10.5), craniotomy (OR 3.9), preoperative GCS below 8 (OR 3.1). In patients with cSDH the risk factors were alcohol abuse (OR 14.3), change of mental status (OR 7.2), previous stroke (OR 5.3) and density of haematoma in computer tomography (OR 3.8). Age, sex, haematoma size/side and midline shifts were not significant risk factors for PTS in both types of SDH. In prevention of PTS phenytoin and levetiracetam showed similar efficacy (OR 1.3), whereas levetiracetam was associated with significantly lower adverse effects (OR 0.1). LIMITATIONS: Most of the studies were of retrospective nature with a small sample size. Due to the inclusion criteria, some studies had to be excluded and that might lead to selection bias. CONCLUSIONS: PTS are a serious complication in patients with SDH, particularly in aSDH. The "prophylactic use" of antiepileptic drugs might be beneficial in patients with cumulative risk factors.

Lupus anticoagulant - hypoprothrombinemia syndrome: a rare cause of intracranial bleeding.

: We report a 14-year-old girl who presented with subdural hematoma and a deranged coagulation profile suggestive of an inhibitor. Investigations revealed prothrombin deficiency along with positivity for antiphospholipid antibodies, which improved with steroid therapy. Bleeding diathesis in children and adolescents commonly results from thrombocytopenia, platelet function disorders, or coagulation factor deficiency; whereas bleeding because of coagulation factor inhibitors are extremely rare in this age group. This case also highlights the uncommon presentation of antiphospholipid antibody syndrome, as they often present with thrombosis or pregnancy complications rather than bleeding.

Tranexamic Acid for Recurring Subdural Hematomas Following Surgical Evacuation: A Clinical Case Series.

Background Chronic subdural hematomas (SDHs) are commonly encountered in neurosurgery. Optimal management of SDHs remains a significant challenge. Current treatment options generally include supportive care or surgical intervention. A significant proportion of patients have surgery; however, the reoperation rate is considered high. There are also cases in which additional surgical procedures would carry significant morbidity, and as a result, there is a need for nonsurgical medical therapies. We describe the use of tranexamic acid (TXA) as a nonsurgical option for the treatment of recurrent SDHs following surgery. Methods Patients were identified as candidates for potential TXA therapy and followed prospectively. The decision to administer TXA was made on the basis of history, presentation, and prognosis after further surgical intervention. Data collected included patient imaging, treatment administered, and both radiologic and clinical outcomes. Results Three patients underwent surgical evacuation of a chronic SDH (two via burr hole washout and one via craniotomy). All patients had recurrence identified on subsequent imaging. Two patients had poorer predicted outcomes if additional surgical intervention was necessary, and one refused additional surgical intervention. TXA was administered, in the same dosing and scheduled course, to all patients. Complete resolution was observed on imaging, and in the case of the patient who was symptomatic, clinical improvement was also noted. Conclusion TXA may be considered for the treatment of recurrent SDHs following surgical evacuation in patients for whom additional surgery would add significant morbidity.