Worsening Of Hemorrhage Research Articles

Abstract WP227: Deep Medullary Vein Thrombosis in Neonates

Introduction: Deep medullary vein(DMV) thrombosis is a rare cause of neurological damage noted in both term and preterm infants. Although their incidence in children is not know, DMV thrombosis can occur isolated or in association with cerebral sinovenous thrombosis (CSVT). The spectrum of parenchymal radiological findings in DMV thrombosis includes edema and hemorrhage of variable extent. No clinical trials or definite treatment algorithms are available for DMV thrombosis in neonates. The choice of antithrombotic therapy is therefore based on the experience of the single centers or on indications extrapolated from available guidelines on CSVT. Aims: There are limited guidelines for the management of DMV thrombosis in literature. Recently published systematic review in neonates found a total of only 75 cases in literature. In none of these cases treatment options were described. We aim to present a single institute experience describing 3 cases of neonatal DMV thrombosis and different management methods. Methods and findings: Between July-August 2023, we prospectively studied 3 neonates with deep medullary vein thrombosis as evidenced by characteristic hemorrhage noted on MRI. For the 1st patient no anticoagulation was initially started given co-morbid conditions and critical illness. However, repeat imaging showed worsening of hemorrhage, thereby indicating progression of thrombosis resulting in venous hemorrhage. Pt was therefore stared on AC with LMWH. No worsening hemorrhage was noted thereafter. For the 2nd patient, AC was not started & no progression of thrombosis was noted. For the 3rd patient AC was started from a cardiac standpoint and no worsening in hemorrhage was noted. Observation: 1. Anticoagulation in patient with progression of DMV thrombosis did not worsen existing hemorrhage and prevented further propagation of clot. 2. No anticoagulation did not result in worsening of thrombosis and it likely self resolved in the absence of other comorbid conditions. 3. Anticoagulation used for a different indication did not worsen existing intraparenchymal hemorrhage. Next steps: 1. To conduct a retrospective chart review on a larger cohort of patients. This will help future studies and management options for this rare condition.

Fluctuations in Detection Indicators and Their Significance for the Diagnosis of Early Pressure Injury in Rat Models.

The aim of this study was to identify the most meaningful diagnostic indicator for distinguishing blanchable erythema (BE) and stage 1 pressure injury (early PI) in an in vivo (rat) model. A prospective case-control design was used to complete a horizontal and vertical comparison of detection indicators during the process of fading of BE or the deterioration of early PI into ulcer in rat models. The sample comprised 5 hairless rats with 20 injuries, of which 10 were BE and the other 10 were early PI. Data were collected at Nagano College of Nursing in 2020 in Nagano, Japan. The BE and PI rat models were established by subjecting the dorsal skin of a hairless rat to compression between 2 neodymium magnets for 45 minutes and 3.45 hours, respectively. The affected skin was observed based on the following: (1) photography, (2) hardness, (3) temperature, (4) moisture, and (5) spectrophotometric (a* value and ultraviolet [UV] reflectance) measurements. All measurements of BE were performed at the beginning to 60 minutes after decompression, and those for early PI were performed until 48 hours after decompression. Multiple BE factors, such as the degree of erythema (macroscopy and a* value), hardness, temperature, and moisture, were found to have unstable fluctuations. Only UV reflectance gradually decreased from 6 hours and decreased significantly at 48 hours after decompression (P = .001 vs 1 hour). In contrast to early PI, erythema in BE obviously faded within 10 minutes. Study findings indicate that a continuous decrease in UV reflectance can reflect the worsening of hemorrhage in early (stage 1) PI. In contrast, other indicators including photography, skin hardness, temperature, and moisture fluctuated and did not prove predictive for PI progression. The obvious fading of erythema in BE a short time after decompression can be used for clinical observations.

Thrombectomy for Large‐Vessel Occlusion With Pretreatment Intracranial Hemorrhage

Background Many patients treated with endovascular thrombectomy (EVT) in clinical practice would not have qualified for inclusion in the initial clinical trials demonstrating benefit for EVT, yet likely will benefit from reperfusion. One such subset for which data are sparse is patients with emergent large‐vessel occlusion and concomitant intracranial hemorrhage (ICH). The objective of this report is to document patients who underwent thrombectomy for large‐vessel occlusion in the presence of concomitant ICH and evaluate their clinical characteristics and outcomes. Methods We retrospectively reviewed prospectively collected patient records at 4 comprehensive stroke centers from 2012 to 2019. Patients were identified who had pre‐EVT ICH. Data collected included baseline patient demographics and laboratory values, stroke characteristics, ICH radiographic variables, antiplatelet/anticoagulant/thrombolytic medication use, and procedural factors. The primary safety outcome was any worsening of ICH on neuroimaging obtained 24 hours after EVT. Results Eight patients were identified who underwent thrombectomy with concomitant ICH. The mean age was 71.9 years (range, 37–90). Median National Institutes of Health Stroke Scale score was 25 (interquartile range, 16.5–28.8), and 5 (63%) received tissue plasminogen activator. All patients underwent EVT and had mTICI2B or greater reperfusion. In 7 patients (88%), the initial ICH remained stable on postprocedure imaging. In 1 patient who received intravenous antiplatelet agents during thrombectomy, the hemorrhagic transformation was radiographically increased but without clinical correlate or mass effect. Conclusions In a multi‐institution evaluation of 8 patients with ICH at the time of thrombectomy, 1 patient had radiographic worsening of hemorrhage, and no patient experienced clinical worsening related to hemorrhage progression. These findings suggest that thrombectomy may be safe in this population.

Predictors of Early Neurological Deterioration Following Intravenous Thrombolysis: Difference between Risk Factors for Ischemic and Hemorrhagic Worsening.

Background:Prevention of early neurological deterioration (END) is becoming an important therapeutic target in acute ischemic stroke management. The aim of the study is to ascertain the causes and predictors of early neurological deterioration following thrombolysis and determine the predictive value of IScore.Methods:In this single center prospective study, we analyzed clinical, imaging and outcome data in 168 patients thrombolyzed intravenously ≤4.5 hours from onset of stroke. Early neurological deterioration was defined as worsening ≥2 points in the NIHSS score at 24 hours.Results:END occurred in 34 patients (20%) and caused significantly worse short term outcome. Ischemic END (ENDi) (n = 23) was twice as common as symptomatic hemorrhage (ENDh) (n = 11). Ischemia progression (n = 15) was the most common cause. Early malignant edema was another major cause. On multivariate analysis, significant predictors (p <.05) were proximal artery occlusion [all END (p <.001), ENDi and ENDh], previous ischemic insults (all END) and raised diastolic blood pressure (ENDh). ENDi was more common in those with carotid artery occlusion, large vessel disease and previous ischemic insults. ENDh was more common in those with raised diastolic blood pressure and NIHSS-ASPECTS mismatch. For patients with NIHSS <14, IScore >105 and for NIHSS ≥14, IScore >175 was associated with higher risk of END.Conclusion:END occurs in one fifth of patients after intravenous thrombolysis; ENDi outnumbers ENDh. Proximal artery occlusion is a major predictor for END. Potentially modifiable risk factors include admission hyperglycemia and elevated blood pressures. Distinct factors characterize ENDh and ENDi and can guide prevention and management strategies. IScore identifies patients at risk for END.

Patterns of Intracranial Hemorrhage in Pediatric Patients with Facial Fractures.

Intracranial hemorrhage (ICH) is a potentially fatal injury accompanying fractures of the cranium and facial skeleton. When occurring at a young age, ICH can lead to developmental delay, cerebral palsy, epilepsy, and death. It is therefore important for clinicians to recognize the presence of ICH early, and understand the factors that affect its prognosis. In this study, we aim to identify diagnostic and prognostic signs for ICH in pediatric facial fracture patients by examining aspects of patient presentation, concomitant injuries, and fracture patterns. Data were collected for all radiologically diagnosed facial fractures between January 2000 and December 2012 at a level I trauma center in Newark, NJ. This was then further refined to include only patients 18 years of age or younger who had a documented ICH. Patient age, Glasgow coma scale (GCS) on presentation, fracture location, type of hemorrhage, and certain aspects of management were collected from these records. Data were then analyzed by either Pearson chi-square test or a t-test to determine significant relationships. A total of 285 pediatric patients were found to have sustained a facial fracture during this time period, 67 of which had concomitant ICH; 46 of these patients were male and 21 were female, with average ages of 14.26 and 9.52 (p < 0.01), respectively. Causes of injury included motor vehicle accidents, pedestrians struck, assault, falls, gunshot injuries, and sports-related injuries. All patients who suffered injuries as a result of violent crimes (assault and gunshot injuries) were male. Although nearly all fracture patterns were significantly associated with the presence of ICH, mandibular fractures showed a significant negative association with the presence of ICH. In addition, patients who received surgical intervention were significantly younger than those who did not (7.7 vs. 13.7, p < 0.05). The GCS was significantly lower in patients who underwent ICP (intracranial pressure) monitoring or EVD (external ventricular drain) placement, suffered intraventricular hemorrhage, experienced worsening of hemorrhage on repeat imaging, and suffered fatal injuries. Our data also showed a significant association between the need for intubation in the emergency department and fatality. Because the consequence of ICH can be life threatening, proper diagnosis and management are imperative. The purpose of this study is to describe patterns associated with ICH in pediatric facial fracture patients to promote early recognition of the injury and understanding of poor prognostic signs.

Administration of 4-Factor Prothrombin Complex Concentrate as an Antidote for Intracranial Bleeding in Patients Taking Direct Factor Xa Inhibitors

Direct factor Xa inhibitors rivaroxaban and apixaban are efficacious alternatives to warfarin and confer a lower risk of spontaneous intracranial hemorrhage (ICH); however, they lack a validated reversal strategy. We evaluated the efficacy and safety of 4-factor prothrombin complex concentrate (PCC) administration on rivaroxaban- and apixaban-mediated coagulopathy in patients with traumatic and spontaneous ICH. Retrospective review of patients presenting with traumatic and spontaneous ICH and concurrent use of rivaroxaban or apixaban. Demographic factors, reason for anticoagulation, hemorrhage type and location, Glasgow coma scale score, and when appropriate, ICH score, were included. Patient charts were reviewed for in-hospital mortality, thromboembolic events, pulmonary complications, worsening of hemorrhage, hemorrhagic complications after neurosurgical intervention, and 90-day modified Rankin scale score. Eighteen patients met inclusion criteria; 16 used rivaroxaban and 2 used apixaban. Eight patients presented with traumatic ICH, 8 with hemorrhagic stroke, 1 with subarachnoid hemorrhage, and 1 patient with tumoral hemorrhage. Mean Glasgow coma scale score was 12.6 (range, 6-15) and mean ICH score was 2.3 (range, 0-4). After reversal with PCC, 1 patient (5.6%) demonstrated worsening of ICH on follow-up head computed tomography. PCCs were administered before emergent placement of an external ventricular drain in 1 individual, with no hemorrhagic complications. Six patients (33.3%) experienced in-hospital mortality: family withdrew care in 4 and 2 died due to pneumonia. There was 1 (5.6%) thromboembolic complication. Favorable outcomes at 90 days were seen in 6 patients (33.3%). Despite no studies demonstrating the efficacy of 4-factor PCC administration for reversal of coagulopathy in patients on direct factor Xa inhibitors, our early experience demonstrates it to be safe, yet potentially reducing hemorrhagic complications and hematoma expansion in this critically ill population.

Anticoagulant therapy in head injury-associated cerebral sinovenous thrombosis in children.

Head injury is a risk factor for cerebral sinovenous thrombosis (CSVT) in children. Literature concerning head injury-associated CSVT (HIA-CSVT) is scarce. Data supporting safety and efficacy of anticoagulant therapy (ACT) in childhood CSVT is emerging. However, intracranial hemorrhage (ICH) occurs frequently in children with HIA-CSVT at diagnosis making initiation of ACT controversial due to the fear of worsening of ICH. We conducted a retrospective descriptive review of a consecutive cohort of children with HIA-CSVT from 1998 to 2012. Twenty patients (14 males, mean age 7 years) with HIA-CSVT were identified. Most (19/20 [95%]) had significant ICH at diagnosis. None received ACT at diagnosis. Fourteen (70%) were later (median 7 days post-trauma, range 2-48 days) treated with ACT due to CSVT persistence (nine) and propagation (five), despite ICH in 13. None of the treated patients, including the 13 with pre-existing ICH, had significant worsening of hemorrhage. Three (21%) treated patients had minor asymptomatic extension of their hemorrhage and further ACT was withheld. No patient died while on ACT. No patient experienced CSVT propagation on ACT. Clinical outcomes were normal (no neurologic deficits) in 5/20(25%), mild neurological deficits in 10/20(50%), and moderate-severe neurological deficits in 5/20(25%). Small sample size did not permit assessment of the effect of ACT on outcome. Anticoagulant therapy is safe in selected children with HIA-CSVT. ICH is not an absolute contraindication to ACT in children with HIA-CSVT.

Abstract WP412: Anticoagulant Therapy in Head Injury-associated Cerebral Sinovenous Thrombosis in Children

Background - Head injury is a rare risk factor associated with cerebral sinovenous thrombosis (CSVT). Literature concerning head injury-associated CSVT (HIA-CSVT) is scarce. There is emerging data to support the safety and efficacy of anti-coagulant therapy (ACT) in childhood CSVT. However, intracranial hemorrhage (ICH), which is seen frequently in children with HIA-CSVT at diagnosis, makes initiation of ACT controversial due to the fear of extension of pre-existing ICH. boldMethods - We conducted a retrospective review of a consecutive cohort of children with HIA-CSVT from 1998-2009. Results - Seventeen patients (11 males, mean age 7-years) with HIA-CSVT were identified. Most [16/17 (94%)] had significant ICH at diagnosis. None received ACT at diagnosis. 12/17 (71%) were later treated with ACT due to CSVT persistence (8) and propagation (4) despite ICH in 11. None of the 12 treated patients, including the 11 with pre-existing ICH, had significant worsening of hemorrhage on ACT. Three (25%) of the 12 treated patients had minor extension of their hemorrhage; further ACT was withheld in these patients due to physician preference. No patient died on ACT. No patient experienced CSVT propagation on ACT. Neurological outcome was normal in 3/17 (18%), mildly abnormal in 9/17 (53%) and moderate-severely abnormal in 5/17 (29%). Due to small sample size, influence of ACT on clinical and recanalization outcome could not be measured. Conclusions - Anticoagulant therapy is safe in selected children with HIA-CSVT. Head injury is not an absolute contraindication to ACT in children with HIA-CSVT.

Symptomatic intracerebral hematomas in posterior circulation stroke patients anticoagulated with heparin

A lot of clinicians use heparin in patients with posterior circulation stroke. Frequency and risk factors of symptomatic intracerebral hematoma (ICH) in posterior circulation infarct patients anticoagulated with unfractionated heparin are not known. To determine the incidence and the risk factors of the heparin-related ICH in posterior circulation infarct patients, we retrospectively reviewed the clinical features of 37 patients who had acute posterior circulation infarct and received intravenous heparin after they underwent brain computed tomographic scans and diffusion-weighted imaging (DWI). Follow-up brain scans were obtained at any time if clinical symptoms worsened. Volumes of acute posterior circulation infarction were calculated on DWI. Of 37 patients, four (10.8%) developed symptomatic ICH during heparin infusion. The location of ICH was cerebellum in all the hemorrhagic worsening patients. We found that the size of an acute infarction calculated on DWI is the risk factor of symptomatic ICH during intravenous heparin therapy in patients with posterior circulation infarct. Until a large prospective study is performed, it may be prudent to avoid heparin infusion in patients with large posterior circulation infarct documented on DWI.

Heparin in acute stroke with atrial fibrillation: clinical relevance of very early treatment.

The risk-benefit ratio of early vs late heparinization for acute stroke with nonvalvular atrial fibrillation remains unsettled. To clarify the relationship between timing to heparinization and functional outcome in acute cardioembolic stroke. Consecutive case series. Referral center. In 231 patients with stroke and nonvalvular atrial fibrillation, intravenous or subcutaneous heparin administered with the goal of achieving an activated partial thromboplastin time (APTT) 1.5 to 2.0 times control values. Delay to the initiation of heparin therapy was less than 6 hours from the onset of symptoms in 74 patients and between 6 and 48 hours in 157 patients. Functional outcome (Rankin scale) was assessed 9 +/- 3 (mean +/- SD) days from stroke onset using multivariate analysis and including in the model treatment delay, risk factors (eg, age, hypertension, diabetes, hypercholesterolemia, previous stroke, and heart disease), initial neurological severity, and baseline computed tomographic findings (eg, early signs of infarction and white matter abnormalities). Clinical symptoms on admission (Mathew score) and baseline radiological findings were evaluated in all subjects. The bleeding rate was assessed on subsequent computed tomographic (CT) scans (obtained 7 +/- 2 days after stroke). The relationship between APTT ratios and stroke recurrence or hemorrhagic worsening was also tested. Functional outcome at hospital discharge and incidence of early recurrent strokes and bleeding complications. Mortality (9%), hemorrhagic worsening (3.4%), and early stroke recurrence (2.1%) occurred in the hospital. Complete recovery was associated with age younger than 70 years (odds ratio [OR], 0.21; 95% confidence interval [CI], 0.05-0.70), a baseline Mathew score higher than 74 (OR, 11.5; 95% CI, 4.95-26.70), normal baseline CT findings (OR, 8.86; CI, 3.99-19.60), and early heparinization (OR, 1.7; 95% CI, 1.10-2.50). Targeted APTT ratios were achieved at 24 hours in fewer than 50% of patients. Whereas stroke recurrence was associated with lower mean APTT ratios, higher mean APTT ratios were observed in patients with symptomatic bleeding, especially on the day of bleeding. Age, admission stroke severity, blood pressure, and baseline CT findings did not predict hemorrhagic worsening. Delaying anticoagulation in alert patients with stroke and nonvalvular atrial fibrillation is not endorsed by the initial severity of symptoms or the early signs of infarction on CT scan. Functional recovery is improved the sooner heparin is administered. These findings suggest that heparin also has therapeutic properties. However, close APTT monitoring is warranted to lessen the incidence of untoward complications.

Early anticoagulation after large cerebral embolic infarction: a safety study.

To assess whether hemorrhage after early anticoagulation in nonseptic embolic infarction is related to clinical severity and infarction size. Explicit clinical criteria and timing of anticoagulation after large embolic infarctions are unknown. Out of 171 patients receiving anticoagulation between July 1992 and December 1993, 83 patients with hemispheric embolisms received heparin within 72 hours from onset (activated partial thromboplastin time [aPTT] 1.5 times control value). Stratified by age and sex, a "high-risk" group (46 patients) was defined as those having stroke symptoms involving three or more CNS domains, Mathew Scale score < or = 74, or hemorrhagic infarction on initial CT, and a "low-risk" group (37 patients) as those having stroke symptoms involving fewer than three cortical domains, or Mathew Scale score > 74, and CT showing no blood. Loss of consciousness, seizures, or history of bleeding were exclusion criteria. Repeated CTs (100%) and MRIs (36%) detailed infarctions according to standard maps and evaluated all unexplained clinical worsening. Prior to therapy, high-risk patients had more severe clinical deficits (p < 0.01), larger infarctions on CT (p < 0.01), and more mass effect (p < 0.01). Hemorrhagic conversion (26% in the high-risk group versus 22% in the low-risk group) and hemorrhagic worsening (4% in the high-risk group versus 13% in the low-risk group) were unrelated to admission clinical severity or infarction size, but they were related to an excessive prolongation of the aPTT (p < 0.01). Infarction size and clinical severity in alert patients with nonseptic embolic stroke carries no additional bleeding complications after early anticoagulation. If anticoagulants are deemed necessary, treatment delay seems unjustified. However, rigorous monitoring of the aPTT is strongly advised to keep the level at 1.5 to 2 times control values.

Cardioembolic stroke, early anticoagulation, and brain hemorrhage. Cerebral Embolism Study Group

Brain hemorrhage is a feared complication of early anticoagulation therapy in patients with cardioembolic brain infarction. We describe nine patients with cardioembolic stroke who experienced clinical deterioration associated with computed tomography-documented hemorrhagic transformation. The clinical features of these nine patients combined with 15 previously reported cases were analyzed to determine factors associated with hemorrhagic worsening. Patient age, embolic source, and intensity of anticoagulation were not associated with hemorrhagic worsening. Large infarct size and initiation of anticoagulation after early (less than 12 hours) computed tomography were associated with hemorrhagic transformation and clinical worsening in patients who received anticoagulation therapy.