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.

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.

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.

Atorvastatin enhances angiogenesis to reduce subdural hematoma in a rat model.

BACKGROUND AND PURPOSE: Statins are active in reducing plasma lipids, suppressing inflammation and promoting angiogenesis. Because angiogenesis is critical for the absorbance of subdural hematoma (SDH), we hypothesize that atorvastatin promotes angiogenesis to enhance hematoma absorption. METHODS: SDH was induced in adult Wistar rats and treated with 3mg/kg, 8mg/kg of atorvastatin, or vehicle saline daily for 7days. The treated rats were examined for the level of CD34+/CD133+ endothelial progenitor cells (EPCs) in the circulation by flow cytometry, hematoma volumes by magnetic resonance imaging (MRI), and changes in cognitive functions. We also examined angiogenesis in the hematoma wall by transmission electronic microscopy and immunohistochemistry for the expression of vascular endothelial growth factor (VEGF), matrix metalloprotease 9 (MMP 9) and angiopoietin. RESULTS: SDH volume was significantly reduced and neurological deficits improved in rats receiving the low dose atorvastatin compared to those receiving either the high dose of atorvastatin or saline. Consistent with these outcome measures, the low dose atorvastatin increased the expression of angiopoient-1 and VEGF and reduced MMP9 expression in the connective tissue of the SDH wall, resulting in an increased vascular density and enhanced vascular maturation. CONCLUSIONS: The low-dose atorvastatin is effective in reducing SDH and improving neurological deficits in a rat model, primarily by promoting angiogenesis and vascular maturation.

Uso de fator protrombínico no tratamento de hematoma subdural espontâneo: relato de caso / Prothrombin Factor Use in the Treatment of Spontaneous Subdural Haematoma: Case Report

A warfarina é amplamente utilizada na condução de pacientes com patologias cardiovasculares, apesar do risco de sangramentos potencialmente graves. Quando tais sangramentos ocorrem, é necessária rápida reversão da anticoagulação. No presente relato descreve-se um paciente que desenvolveu hematoma subdural espontâneo associado ao uso de warfarina, necessitando intervenção cirúrgica emergencial. É dada ênfase aos mecanismos de produção deste fenômeno e à sua condução clínica.

Warfarin is widely used on the treatment of cardiovascular pathology, although there are risks of potentially lethal bleeding. When such bleeding occurs, it is imperative a rapid reversal of anticoagulation. A case of a spontaneous subdural hematoma during the use of warfarin and requiring emergent surgical treatment is reported. Emphasis is given to the mechanisms of this phenomenon and its clinical conduction.

A rare case of chronic myeloid leukemia with acquired von Willebrand disease presenting as subdural hematoma.

We report a case of a 32-year-old lady with chronic myeloid leukemia (CML) on Imatinib for the past four years and in complete clinical, hematological and molecular remission who presented to us with sudden onset of headache, vomiting and diplopia following self discontinuation of Imatinib for a month. Investigations were suggestive of chronic phase CML (CML-CP) with massive thrombocytosis and magnetic resonance imaging (MRI) of the brain revealed subdural hematoma. Coagulation studies confirmed the diagnosis of Acquired von Willebrand disease (AvWD) 2A because of thrombocytosis. The patient also tested positive for mutation T315I in bcr-abl gene. Treatment of the patient with high dose of Imatinib and hydroxyurea led to normalisation of platelet counts, reversal of coagulation defect and subsidence of symptoms. The present case highlights the importance of diagnosis of AvWD to determine the cause of bleeding in CML and distinguish it from Imatinib-induced bleeding, as prompt treatment with Imatinib can achieve reversal of the condition.

Bilateral subdural hemorrhage as a possible adverse event of gefitinib in a patient with non-small cell lung cancer.

Gefitinib, a selective inhibitor of epidermal growth factor receptor tyrosine kinase is an effective agent used in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Adverse drug reactions were frequently observed in the skin, gastrointestinal tract, and liver, but they were generally mild in severity and reversible. Therefore, gefitinib has been regarded as a relatively safe agent. As a serious adverse effect, however, acute lung injury has been reported. The present report describes a patient with NSCLC who developed bilateral subdural hemorrhage as a possible adverse drug reaction after gefitinib therapy. We expect that this case may provide a reference for clinicians being involved in the treatment with gefitinib.

[Subdural hematomas in infants and children of early age].

The article focuses on clinical presentation, pathophysiology and course of infantile subdural hematomas. Diagnostic procedures and surgical technique are described. Authors demonstrated results of minimally invasive surgical treatment of infantile subdural hematomas.

[Effectiveness of adjuvant corticosteroid therapy for chronic subdural hematoma: a retrospective study of 198 cases]. / Efficacité de la corticothérapie dans le traitement adjuvant des hématomes sous-duraux chroniques. Etude rétrospective sur 198 cas.

BACKGROUND AND PURPOSE: Adjuvant treatments can be proposed in addition to surgery for patients with chronic subdural hematoma (CSDH) in order to improve the postoperative outcome. According to the survey published in 2001 by the Neurosurgery French Society, 38% of French neurosurgeons use adjuvant corticosteroid therapy after surgery. Does this adjuvant corticosteroid therapy have an effect on the postoperative outcome of CSDH? METHODS: A retrospective trial was performed on patients who were surgically treated for CSDH between January 1998 and July 2002 in the Nice Department of Neurosurgery. Corticosteroid therapy was initiated just after surgery and maintained for one month. Part of the patients were not given corticosteroids enabling a comparison of two groups: "corticosteroid therapy" versus "no corticosteroid therapy". RESULTS: One hundred and ninety-eight patients were included in the trial, 142 patients in the "corticosteroid therapy" group and 56 patients in the "no corticosteroid therapy" group. The difference in survival between the two groups was significant in favor of the group give corticosteroids. A multivariate analysis was carried out which confirmed the beneficial effect of the corticosteroid therapy on survival of the operated patients. Their risk of death was threefold less than those not given this treatment (p=0.006). CONCLUSIONS: This study highlighted a protective effect of postoperative corticosteroid therapy on patient survival. This effect persisted at multivariate analysis. However, due to skews inherent in retrospective studies, a multicentric prospective randomized trial is being prepared in our institution to confirm these results.

Non-surgical management of intracranial subdural hematoma complicating spinal anesthesia.

We report the case of a 29 year-old woman who presented a symptomatic intracranial subdural hematoma developing shortly after spinal anesthesia. The patient was fully conscious at clinical onset, and thus we treated her conservatively with an epidural autologous blood patch and close neurological observation. Given the clinical improvement the possibility of surgery was discauded in agreement with the neurosurgical team. Most cases of subdural hematoma appearing after spinal anesthesia are treated with surgery. In the present case the subdural hemorrhage was detected at our hospital 20 days after the anesthetic procedure, and given the excellent state of consciousness, we choosed a conservative management.

Subdural hematomas during CML therapy with imatinib mesylate.

Seven of one hundred twenty-one patients with chronic myeloid leukemia (CML) treated with imatinib mesylate developed subdural hematomas. All had advanced disease and were treated initially at a dose of 600 mg per day. Three patients had thrombocytopenia (platelet < 10 x 10(9)/l), one had leukocytosis (white blood cell count > 150 x 10(9)/l) and three had neither around the time of diagnosis of the subdural hematomas. Four patients required surgical evacuation. One patient, in blast crisis, died as a consequence of the subdural hematoma. Three patients survived but died of progressive CML. The remaining three patients having recommenced imatinib, are alive and well, and one has achieved a major cytogenetic response. Subdural hematomas must be considered even in mildly symptomatic patients receiving imatinib regardless of their peripheral blood counts. Patients who survive can be cautiously restarted on imatinib. Further studies are required to study the potential relationship between imatinib mesylate and subdural hematomas.

The use of recombinant activated factor VII to reverse warfarin-induced anticoagulation in patients with hemorrhages in the central nervous system: preliminary findings.

OBJECT: In this report the authors describe the use of the hemostatic agent recombinant activated factor VII (rFVIIa) in the perioperative treatment of hemorrhages in the central nervous system that are associated with warfarin therapy. METHODS: Two patients sustained hemorrhages within the spinal canal, and the other two had acute intracranial subdural hematomas. All patients had normal platelet counts, activated partial thromboplastin times, and fibrinogen levels, and all received fresh frozen plasma in conjunction with rFVIIa. The initial international normalized ratios (INRs) ranged from 1.9 to 5.6. Each dose of rFVIIa was 1200 microg, ranging from 16 to 22 microg/kg of body weight. Two patients received two perioperative doses of rFVIIa; the others required just one dose before surgery. The INR normalized within 2 hours of administration of rFVIIa in all patients. There were no thromboembolic complications, and surgical blood loss was less than 100 ml for all operations. CONCLUSIONS: This clinical experience indicates that rFVIIa may be safe and effective as the initial hemostatic agent for rapid reversal of orally administered anticoagulation medications in patients who require urgent neurosurgical intervention.

[Neurological complications after roller coaster rides: an emerging new risk?]. / Le mal des montagnes russes. Emergence d'un nouveau risque?

OBJECTIVE: To describe neurological complications occurring after roller-coaster rides. PATIENTS AND METHODS: We report 6 cases of complications occurring after roller-coaster rides and analyze published data. RESULTS: Complications seen our patients included 5 cervicoencephalic arterial dissections, one with brainstem dysfunction due to extending syringobulbia. Reported data include one cervicoencephalic arterial dissection, one case of carotid artery occlusion, 3 cases of subdural hematoma, one with subarachnoid hemorrhage, one with cerebrospinal fluid leak, and one with Brown-Séquard syndrome secondary to an enterogenous cyst of the spinal cord. In all patients, pain was the first symptom experienced. In 71.4% of cases, it occurred immediately after the trauma. Marfanís syndrome may be the only risk factor identifiable prior to exposure. The mechanisms of most complications are poorly understood but are likely to involve sudden head and neck flexion-extension movements. CONCLUSION: Neurological complications occurring after roller-coaster rides are highly uncommon, but may leave invalidating sequelae or be fatal. Clinicians should be aware of these complications so these patients can be given proper care early, particularly at the stage when pain is the only sign. Early management could help limit the consequences of these complications.

Management of haemophilia in patients with high-titre inhibitors: focus on the evolution of activated prothrombin complex concentrate AUTOPLEX T.

Numerous therapeutic strategies have been applied to the management of patients with inhibitors to factors VIII or IX. Different treatment approaches are analysed including prothrombin complex concentrates (PCCs), activated prothrombin complex concentrates (aPCCs), porcine factor VIII concentrate, inhibitor neutralization, immune tolerance therapy, immunosuppressive regimens and recombinant factor VIIa. Clinical data are reported in the analysis of several treatments. PCCs and aPCCs have gained widespread acceptance as the standard first-line approach for patients with inhibitors. The aPCC AUTOPLEX T has achieved a high response rate with a low level of thrombotic events. Four case studies are presented in which AUTOPLEX T has been used successfully. Administration of platelet concentrate or, in elective surgery, waiting for inhibitor levels to decline are useful adjuncts to some treatments. The optimal treatment depends on the patient's inhibitor status--low responder (minimal or no increase in inhibitor levels upon administration of replacement clotting factor) or high responder (replacement clotting factor generates inhibitor production). A suggested algorithm for treating high-responder inhibitor patients is presented.

Local coagulofibrinolysis in the postsurgical recovery of patients with chronic subdural haematoma.

Postoperative recovery of patients with chronic subdural haematoma (CSH) was investigated by comparing pre- and postoperative coagulant and fibrinolytic activity in the haematoma contents of 15 patients with SCH. Patients in this study were treated draining the haematoma cavity without irrigation, a procedure dubbed the closed drainage. Haematomas were collected during, and 24 hrs after, surgery. Postoperative fibrinolytic activity was lower than that observed pre-operatively. In particular, levels of tissue plasminogen activator activity (TPA), and fibrin and fibrinogen degradation products (FDP) all decreased. In contrast, coagulant activity increased postoperatively. This paper will discuss the role of local coagulofibrinolysis in the postoperative recovery of CSH patients.

[Chronic subdural hematoma following advanced cancer: report of three cases].

Three cases of chronic subdural hematoma (CSH) following advanced cancer are reported. Case 1. A 54-year-old male patient was referred to our clinic in a semicomatose state. Bilateral CSH was evacuated through a pair of burr holes, and consciousness was recovered. However, subependymal hemorrhage occurred at the third ventricle 6 days after the operation. Hematological examination revealed thrombocytopenia. He died 12 days after operation because of hemorrhage in the lung. Postmortem examination disclosed metastatic adenocarcinoma of unknown origin to the dura mater, lymph nodes, lung and bone marrow. Case 2. A 50-year-old male patient who was diagnosed as having gastric cancer was referred to our clinic in a state of deep coma. CT scan revealed CSH and putaminal hemorrhage at the left side. Hematological examination revealed disseminated intravascular coagulation (DIC). After the subdural hematoma was evacuated, the putaminal hematoma enlarged and hemorrhagic infarction at the left temporo-occipital lobes occurred. He died 2 days after operation. Autopsy was not carried out, but histological examination revealed poorly differentiated malignant cells in the outer membrane of the subdural hematoma. Case 3. A 53-year-old female patient who had a history of gastric cancer operated on 4 years ago was admitted to our clinic complaining of headache and vomiting. CT scan revealed bilateral subdural hematoma. Following a pair of burr-holes and irrigation of the hematoma, hemorrhage recurred alternatively at the left side on the 6th and at the right side on the 27th day after the operation. Hematological examination revealed DIC, and bone marrow puncture disclosed metastasis of the adenocarcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

[Chronic subdural hematoma occurring in patients with senile dementia: report of 4 cases].

Four cases are presented of male patients over 63 years of age. Preceding head injuries relating to chronic subdural hematoma (CSH) were noted in 2 patients. Suspected clinical signs of CSH were disturbance of consciousness and mono- or hemiparesis. Surgery, a burr-hole technique for external drainage, was performed in 2 patients, and nonsurgical treatment by intravenous administration of glycerol was carried out in the remaining 2 patients. After the treatment, 3 patients returned to the previous demented state, and one who had been treated nonsurgically died of pneumonia. Disappearance or marked reduction of the hematoma was demonstrated by follow-up CT scans in all patients. The signs induced by CSH in a patient with senile dementia may be misunderstood as an aggravation of senile dementia. Nonsurgical treatment with osmotic perfusions for CSH may be considered as a treatment of first choice in a patient with advanced senile dementia, unless he shows advanced mass effect of the hematoma on CT.