Platelet reactivity and activated clotting time predict hemorrhagic site complications in patients with chronic coronary syndromes undergoing percutaneous coronary interventions.

BACKGROUND: Radial access is preferred in patients with chronic coronary syndromes (CCSs) treated with ad hoc percutaneous coronary intervention (PCI). Antithrombotic and antiplatelet treatment before PCI may affect outcomes at vascular access sites. QuikClot Radial is a kaolin-based band that may shorten hemostasis time. Using point-of-care testing, we investigated the effect of antithrombotic and antiplatelet treatment on access-site complications. METHODS: This prospective observational study included consecutive patients with CCS on chronic aspirin therapy referred for ad hoc PCI. The activated clotting time (ACT), global thrombosis test and VerifyNow P2Y 12 test were done sequentially after unfractionated heparin (UFH) and clopidogrel administration. Patients were monitored for radial artery patency, bleeding and local hematoma until discharge. RESULTS: We enrolled 40 patients [mean age, 68.8 ±â€…8.8 years; men, 30 (75%)] who received UFH (median dose, 8000 IU; interquartile range, 7000-9000 IU) and clopidogrel (600 mg). All radial arteries remained patent during follow-up. Local bleeding and hematomas were noted in 11 patients (27.5%) each. Patients with bleeding had lower mean platelet activity at 2 h [122.5 ±â€…51 platelet reactivity units (PRU) vs. 158.7 ±â€…43 PRU, P  = 0.04] and higher ACT (216.9 ±â€…40 s vs. 184.6 ±â€…28 s, P = 0.006) than patients without bleeding. An ACT >196 s at 2 h predicted bleeding or hematoma (AUC, 0.72; 95% CI, 0.56-0.85, P = 0.008). CONCLUSION: Lower platelet activity and higher ACT after PCI were associated with higher bleeding risk at a vascular access site. Point-of-care testing of ACT after the procedure may help identify patients with CCS undergoing PCI who are at higher risk of access-site bleeding.

Function and Biomarkers of the Blood-Brain Barrier in a Neonatal Germinal Matrix Haemorrhage Model.

Germinal matrix haemorrhage (GMH), caused by rupturing blood vessels in the germinal matrix, is a prevalent driver of preterm brain injuries and death. Our group recently developed a model simulating GMH using intrastriatal injections of collagenase in 5-day-old rats, which corresponds to the brain development of human preterm infants. This study aimed to define changes to the blood-brain barrier (BBB) and to evaluate BBB proteins as biomarkers in this GMH model. Regional BBB functions were investigated using blood to brain 14C-sucrose uptake as well as using biotinylated BBB tracers. Blood plasma and cerebrospinal fluids were collected at various times after GMH and analysed with ELISA for OCLN and CLDN5. The immunoreactivity of BBB proteins was assessed in brain sections. Tracer experiments showed that GMH produced a defined region surrounding the hematoma where many vessels lost their integrity. This region expanded for at least 6 h following GMH, thereafter resolution of both hematoma and re-establishment of BBB function occurred. The sucrose experiment indicated that regions somewhat more distant to the hematoma also exhibited BBB dysfunction; however, BBB function was normalised within 5 days of GMH. This shows that GMH leads to a temporal dysfunction in the BBB that may be important in pathological processes as well as in connection to therapeutic interventions. We detected an increase of tight-junction proteins in both CSF and plasma after GMH making them potential biomarkers for GMH.

Role of Complement Component 3 in Early Erythrolysis in the Hematoma After Experimental Intracerebral Hemorrhage.

Background and Purpose: Early erythrolysis occurs within the hematoma following intracerebral hemorrhage (ICH), and the release of erythrocyte cytoplasmic proteins such as hemoglobin and Prx2 (peroxiredoxin 2) can cause brain injury. Complement activation can induce erythrolysis. This study determined the function of complement component 3 (C3) in erythrolysis in hematoma and brain injury after ICH in mice. Methods: This study has 3 parts. First, ICH was induced in adult male C3-sufficient and deficient mice and animals were euthanized on days 1, 3, 7, and 28 for immunohistochemistry after magnetic resonance imaging and behavioral testing. Second, C3-sufficient and deficient mice with ICH were euthanized on day 1 for Western blot analysis. Third, C3-sufficient mice received injections of PBS and Prx2. Mice underwent both magnetic resonance imaging and behavioral tests on day 1 and were then euthanized. Brains were harvested for immunohistochemistry and Fluoro-Jade C staining. Results: Erythrolysis occurred in the hematoma in C3-sufficient and deficient mice on day 3 following ICH. C3-deficient mice had less erythrolysis, brain swelling, and neuronal degeneration in the acute phase and less brain atrophy in the chronic phase. There were fewer neurological deficits on days 3, 7, and 28 in C3-deficient mice. C3-deficient mice also had less extracellular Prx2 release. Moreover, Prx2 induced brain edema and brain injury and recruited macrophage scavenger receptor-1- and CD4-positive cells following ICH in mice. Conclusions: C3-deficient mice had less severe erythrolysis and brain injury following ICH compared with C3-sufficient mice. Prx2 released after erythrolysis can cause brain damage and neuroinflammation in mice.

Systemic inflammation status at admission affects the outcome of intracerebral hemorrhage by increasing perihematomal edema but not the hematoma growth.

Acute stress and inflammation responses are associated with worse outcomes in intracerebral hemorrhage (ICH) but the precise mechanisms involved are unclear. We evaluated the effect of neutrophil-to-lymphocyte ratio (NLR) in ICH outcome, with focus on hematoma expansion and early cerebral edema. In a retrospective study, we included all patients with primary ICH admitted to our center within 24-h from symptom onset from January 2014 to February 2015. We retrieved demographic and medical history data, Glasgow Coma Scale scores, blood cell counts, glucose, and C-reactive protein, and calculated NLR. We obtained hematoma volumes by computerized planimetry. Outcomes included independence at 90 days (modified Rankin scale 0-2), mortality at 30 days, significant hematoma expansion (> 33% or > 6 mL) and early cerebral edema causing significant midline shift (> 2.5 mm) at 24 h. We included 135 patients. NLR independently associated with independence at 90 days (adjusted odds ratio (aOR) 0.79, 95% CI 0.67-0.93, p = 0.006) significant cerebral edema (aOR 1.08, 95%CI 1.01-1.15, p = 0.016) but not hematoma expansion (aOR 0.99, 95%CI 0.94-1.04, p = 0.736). The severity of midline shift was positively correlated with NLR (adjusted beta = 0.08, 95% CI 0.05-0.11, p < 0.001). In ICH, an immediate and intense systemic inflammatory response reduces the likelihood of a better functional outcome at 90 days, which is more likely to be explained by perihematomal edema growth than due to a significant hematoma expansion. These findings could have implications in new treatment strategies and trial designs, which endpoints tend to target exclusively hematoma enlargement.

Prognostic significance of serum translocator protein in patients with spontaneous intracerebral hematoma：preliminary findings.

Background: The aim of this study was to measure the level of translocator protein (TSPO) in patients with intracerebral hematoma (ICH) and to determine whether TSPO can predict ICH outcomes.Method: Patients with ICH were recruited at Wujin Hospital Affiliated with Jiangsu University between January 2018 and May 2020. The level of TSPO and inflammatory factors were analyzed by enzyme-linked immunosorbent assay (ELISA). A receiver operating characteristic curve (ROC) analysis was applied to assess the accuracy of TSPO for predicting patient outcomes.Result: The median of TSPO was 2.26 ng/ml. The lower- (46 cases) and higher-(51 cases) TSPO groups were thus divided based on the median value. The perihematomal edema (PHE) volume in the lower TSPO group was 6.3 ± 1.3 ml which was significantly lower than that in higher-TSPO group (14.8 ± 3.5 ml) (p < 0.05). The serum level of the interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) in the higher-TSPO group was significantly higher than that in the lower TSPO group (p < 0.05). The Spearman's correlation found that TSPO concentrations significantly correlated with PHE volume, modified Rankin Scale score (MRS), IL-1ß, IL-6, TNF-α, and CRP concentrations. The area under the ROC (AUC), specificity, sensitivity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and Diagnostic Odds Ratio (DOR) of TSPO was 0.932, 82.1%, 89.9%, 5.02, 0.12, and 40.8, respectively, which was more reliable than other inflammatory factors.Conclusion: The TSPO may a reliable biomarker in predicting the prognosis of ICH patients.

Characterization of the cortisol response to traumatic hemorrhage and intra-abdominal contamination models in Cynomologus Macaques.

INTRODUCTION: Trauma, hemorrhage, and peritonitis have widely varying impacts on endocrine response in the injured patient. We sought to examine cortisol response in established non-human primate models of traumatic hemorrhage and intra-abdominal contamination. METHODS: Cynomologus Macaques were separated into two experimental groups, the polytrauma and hemorrhage model, involving a laparoscopic liver resection with uncontrolled hemorrhage, cecal perforation, and soft tissue excision; and the traumatic hemorrhage model, involving only liver resection and uncontrolled hemorrhage. Cortisol levels were measured pre-operatively, at the time of injury, and at regular intervals until post-operative day 1. RESULTS: Cortisol levels increased 600% from the pre-operative value in the polytrauma and hemorrhage model, with minimal changes (20%) in the hemorrhage only model. CONCLUSION: Cortisol levels increase dramatically in response to polytrauma and intra-abdominal contamination as compared to hemorrhage only. The lack of response in the hemorrhage only group may be due to relative adrenal insufficiency caused by the shock state or lack of enticing stimuli from fecal peritonitis.

Relationship of Serum Uric Acid to Hematoma Volume and Prognosis in Patients with Acute Supratentorial Intracerebral Hemorrhage.

BACKGROUND: Oxidative stress and inflammation play important roles in the neuronal injury caused by intracerebral hemorrhage (ICH). Uric acid (UA), an important natural antioxidant, might reduce the neuronal injury caused by ICH. Delineating the relationship between UA and ICH will enhance our understanding of antioxidative mechanisms in recovery from ICH. METHODS: We conducted a retrospective study of 325 patients with acute supratentorial ICH to investigate the relationship between serum UA levels and hematoma volumes and prognosis. A hematoma volume of ≥30 mL was defined as a large hematoma. An unfavorable outcome was defined as a modified Rankin scale score of 4-6 on day 30. RESULTS: The serum UA level was significantly lower in the patients with a large hematoma volume (median, 306 µmol/L; 25th to 75th percentile, 243-411 µmol/L) than in those with a small hematoma volume (median, 357 µmol/L; 25th to 75th percentile, 271-442 µmol/L; P = 0.012). Similarly, the unfavorable outcome group had had lower serum UA levels (median, 309 vs. 363 µmol/L; P = 0.009) compared with the favorable outcome group. The results of the multivariate logistic analysis indicated that a lower serum UA level was associated with a larger hematoma volume (odds ratio, 0.996; P = 0.006) and an unfavorable outcome (odds ratio, 0.997; P = 0.030). CONCLUSIONS: The results from the present study have indicated that in patients with acute supratentorial ICH, a low serum UA level might indicate that the patient has a large hematoma volume and might be a risk factor for a poor day 30 functional prognosis.

Lower total protein and absence of neuronavigation are novel poor prognostic factors of endoscopic hematoma removal for intracerebral hemorrhage.

OBJECTIVES: Endoscopic hematoma removal is widely performed for the treatment of intracerebral hemorrhage. We investigated the factors related to the prognosis of intracerebral hemorrhage after endoscopic hematoma removal. MATERIALS AND METHODS: From 2013 to 2019, we retrospectively analyzed 75 consecutive patients with hypertensive intracerebral hemorrhage who underwent endoscopic hematoma removal. Their characteristics, including neurological symptoms, laboratory data, and radiological findings were investigated using univariate and multivariate analysis. Complications during hospitalization, Glasgow Coma Scale (GCS) score on day 7, and modified Rankin Scale (mRS) score at 6 months were considered as treatment outcomes. RESULTS: The mean age of the patients (33 women, 42 men) was 71.8 (36-95) years. Mean GCS scores at admission and on day 7 were 10.3 ± 3.2 and 11.7 ± 3.8, respectively. The mean mRS score at 6 months was 3.8 ± 1.6, and poor outcome (mRS score ranging from 3 to 6 at 6 months) in 53 patients. Rebleeding occurred in 4 patients, and other complications in 15 patients. Multivariate analysis revealed that older age, hematoma in the basal ganglia, lower total protein level, higher glucose level, and absence of neuronavigation were associated with poor outcomes. Of the 75 patients, 9 had cerebellar hemorrhages, and they had relatively favorable outcomes compared to those with supratentorial hemorrhages. CONCLUSION: Several factors were related to the prognosis of intracerebral hemorrhage after endoscopic hematoma removal. Lower total protein level at admission and absence of neuronavigation were novel factors related to poor outcomes of endoscopic hematoma removal for intracerebral hemorrhage.

Circulating TIMP-1 is associated with hematoma volume in patients with spontaneous intracranial hemorrhage.

Matrix metalloproteinases (MMPs) are proteolytic zinc-endopeptidases regulated by tissue Inhibitors of matrix metalloproteinases (TIMPs). We evaluated the potential of MMPs and TIMPs as clinical tools for Intracranial Haemorrhage (ICH). Spontaneous non-traumatic ICH patients were recruited from two hospitals: Complejo Hospitalario de Navarra (CHN = 29) and Vall d´Hebron (VdH = 76). Plasmatic levels of MMP-1, -2, -7, -9, -10 and TIMP-1 and their relationship with clinical, radiological and functional variables were evaluated. We further studied the effect of TIMP-1 (0.05-0.2 mg/Kg) in an experimental tail-bleeding model. In CHN, TIMP-1 was associated with admission-hematoma volume and MMP-7 was elevated in patients with deep when compared to lobar hematoma. In VdH, admission-hematoma volume was associated with TIMP-1 and MMP-7. When data from both hospitals were combined, we observed that an increase in 1 ng/ml in TIMP-1 was associated with an increase of 0.14 ml in haemorrhage (combined ß = 0.14, 95% CI = 0.08-0.21). Likewise, mice receiving TIMP-1 (0.2 mg/Kg) showed a shorter bleeding time (p < 0.01). Therefore, the association of TIMP-1 with hematoma volume in two independent ICH cohorts suggests its potential as ICH biomarker. Moreover, increased TIMP-1 might not be sufficient to counterbalance MMPs upregulation indicating that TIMP-1 administration might be a beneficial strategy for ICH.

Intramuscular Hematoma as a Manifestation of IgA Vasculitis.

We describe an atypical pediatric case of immunoglobulin A vasculitis (IgAV), also referred to as Henoch-Schönlein purpura, in which formation of spontaneous hematoma of the paraspinal muscles developed. Spontaneous or unprovoked hematomas rarely occur in IgAV. These manifestations have not been described specifically in the pediatric literature as coinciding with IgAV. These findings are alarming for nonaccidental trauma, particularly in a patient without underlying blood dyscrasia. Our objective for this report is to highlight the possible association of muscular hematoma formation with IgAV and to help providers consider this association when trauma and hemophilia has been ruled out.

Suburothelial Hematomas Masquerading as Neoplasms in a Patient with Supra-Therapeutic INR.

Suburothelial hemorrhages (Antopol-Goldman lesions) are a rare but important condition. When unsuspected in a patient with a bleeding diathesis on anticoagulation therapy, computed tomography may lead to incorrect diagnoses of renal or transitional cell carcinoma resulting in inappropriate nephrectomy. We present a patient with supratherapeutic international normalized ratio and thigh hematoma who was found to have nonenhancing solid lesions of the bilateral renal pelves consistent with suburothelial hemorrhage. The patient's INR was controlled, and he was discharged with hematology follow-up 4 weeks later.

Association between Serum Lipid and Hematoma Expansion after Spontaneous Intracerebral Hemorrhage in Chinese Patients.

OBJECTIVES: Although several studies have shown that interventions to lower blood lipid concentration may reduce the risk of coronary arterial disease and ischemic stroke, the correlation between serum lipid levels and hemorrhagic stroke remains controversial. To clarify any possible association between serum lipid and hematoma expansion, we examined various serum lipid indices in patients with and without early hematoma expansion. METHODS: Data of 572 intracerebral hemorrhage (ICH) patients from the cerebral small vessel disease cohort of Peking Union Medical College Hospital were retrospectively analyzed. Patients who finished the baseline brain computed tomography (CT) examination within 6 h post-ictus and the follow-up CT within 48 h after initial CT were included in the study. Hematoma expansion was delimited as an enlargement of hemorrhage volume over 33% or 12.5 mL between baseline and subsequent CT. Both uni- and multivariate logistic regression analyses were conducted to explore the association between early hematoma growth and various serum lipid indices, including triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, ratios of LDL-C/HDL-C and LDL-C/TC, as well as other demographic and clinical features. RESULTS: Out of 157 patients included in the analysis, hematoma growth occurred in 45 (28.7%). Only higher baseline systolic blood pressure was found to be correlated with an increased risk of hematoma growth based on both univariate (odds ratio [OR] 1.014, 95% confidence interval [CI]: 1.002-1.026, P = .024) and multivariate logistic regression analyses (OR 1.022, 95%CI: 1.008-1.037, P = .003). No associations were detected between the various serum lipid indices examined and other clinical features with a likelihood of early hematoma growth between groups or within various subgroups defined by different characteristics including age, gender, baseline Glasgow Coma Scale score, systolic blood pressure, intraventricular extension, and hematoma location. CONCLUSIONS: No association between various indices of serum lipid and hematoma growth was identified among patients and subgroups with spontaneous ICH in the Chinese population; these findings may help to guide lipid management after ICH. However, further multi-centered, larger scale studies are expected to verify our results.

The relationship between low serum calcium level and intracerebral hemorrhage hematoma expansion: A protocol of systematic review and meta-analysis.

BACKGROUND: To investigate the relationship between intracerebral hemorrhage hematoma expansion with low serum calcium level. METHODS: We will search the following electronic bibliographic databases: MEDLINE, Embase, PubMed, The Cochrane Library, and Web of Science. All sources have to be searched from the earliest date until May 1, 2019. The quality of the included studies will assess by 2 evaluation members according to the Cochrane Collaboration network standard or the Newcastle-Ottawa Scale. The included studies will analysis by using RevMan 5.3 software. RESULTS AND CONCLUSION: This will be the first systematic review and meta-analysis to evaluate the association of hematoma following intracerebral hemorrhage with hypocalcemia. The study will provide more reliable, evidence-based data for clinical decision making. PROSPERO REGISTRATION NUMBER: CRD42019135956.

Prognostic models for neurological functional outcomes in aneurysmal subarachnoid hemorrhage patients with intracranial hematoma.

OBJECTIVES: Current guidelines paid little attention to a unique severe disease about intracranial hematoma owing to aneurysm rupture. We attempted to explore the predictive factors for prognosis in these poor patient population. PATIENTS AND METHODS: One hundred twenty-one aneurysmal subarachnoid hemorrhage combined with intracerebral hematoma patients discharged between 2013 and 2016 were reviewed in this retrospective study. Unfavorable outcome was defined as a modified Rankin Scale (mRS) score of 3, 4, 5, or 6 at 6 months. Multivariable logistic regression was performed to evaluate the association of unfavorable outcome with preoperative and postoperative clinical characteristics. RESULTS: Of 121 patients with intact follow-up data, 34 (28.10 %) had an unfavorable prognosis. The preoperative prognostic model included patients' age, respiratory rate, Hunt-Hess scale, red cell distribution width, and serum sodium at admission. The postoperative prognostic model included patients' age, respiratory rate, red cell distribution width, serum sodium, postoperative delayed cerebral ischemia, and pulmonary infection. Both preoperative and postoperative prognostic models had excellent discrimination with Area Under The Curve (AUC) of 0.864 (P < .001) and 0.898 (P < .001), respectively. CONCLUSION: In clinical practice, we should pay more attention to those old patients with worse admission Hunt-Hess score, presenting deep-slow respiratory and lower serum sodium. Reduction of postoperative delayed cerebral ischemia and pulmonary infection might improve outcomes after aneurysmal SAH with intracerebral hematoma.

A novel deletion involving exon 13 of factor VIII gene in a newborn with splenic hematoma.

Splenic hematoma is an exceptionally rare event in newborn period that usually occurs in concomitant birth trauma and bleeding disorder. This report presents a newborn case with severe hemophilia A, who had a splenic hematoma presented on the second day of life with severe anemia, abdominal distention, abdominal and scrotal ecchymosis. The patient was successfully treated medically with factor VIII concentrates without splenectomy. Molecular analysis of the factor VIII gene revealed a hemizygous deletion in exon 13.

The Monocyte-to-Lymphocyte Ratio at Hospital Admission Is a Novel Predictor for Acute Traumatic Intraparenchymal Hemorrhage Expansion after Cerebral Contusion.

PURPOSE: To explore the potential of monocyte-to-lymphocyte ratio (MLR) at hospital admission for predicting acute traumatic intraparenchymal hematoma (tICH) expansion in patients with cerebral contusion. Patients and Methods. This multicenter, observational study included patients with available at-hospital admission (baseline) and follow-up computed tomography for volumetric analysis (retrospective development cohort: 1146 patients; prospective validation cohort: 207 patients). Semiautomated software assessed tICH expansion (defined as ≥33% or 5 mL absolute growth). MLR was acquired from routine blood tests upon admission. We constructed two predictive models: basic combined model of clinical and imaging variables and MLR combined model of both MLR and other variables in the basic model. Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) were used to estimate the performance of MLR for predicting acute tICH expansion. RESULTS: MLR was significantly larger in patients with acute tICH expansion compared to those without acute tICH expansion (mean [SD], 1.08 [1.05] vs. 0.59 [0.37], P < 0.001). A nonlinear positive relationship between MLR and the incidence of acute tICH expansion was observed. Multivariate logistic regression indicated MLR as an independent risk factor for acute tICH expansion (odds ratio (OR), 5.88; 95% confidence interval (CI), 4.02-8.61). The power of the multivariate model for predicting acute tICH expansion was substantially improved with the inclusion of MLR (AUC 0.86 vs. AUC 0.74, P < 0.001), as was also observed in an external validation cohort (AUC 0.83 vs. AUC 0.71, P < 0.001). The net benefit of MLR model was higher between threshold probabilities of 20-100% in DCA. For clinical application, a nomogram derived from the multivariate model with MLR was introduced. In addition, MLR was positively associated with 6-month unfavorable outcome. CONCLUSION: MLR is a novel predictor for traumatic parenchymatous hematoma expansion. A nomogram derived from the MLR model may provide an easy-to-use tool for predicting acute tICH expansion and promoting the individualized treatment of patients with hemorrhagic cerebral contusion. MLR is associated with long-term outcome after cerebral contusion.

Spontaneous Rectus Sheath Hematoma: Factors Predictive of Conservative Management Failure.

PURPOSE: To evaluate radiographic, laboratory, and clinical factors associated with conservative management (CM) failure in spontaneous rectus sheath hematoma (RSH). MATERIALS AND METHODS: Retrospective review of 72 patients with spontaneous RSH between 2006 and 2017 was performed. Patients were initially managed conservatively and then divided into 2 groups based on decision to embolize. No differences were found between embolization (n = 32) and CM (n = 40) groups in age (67.5 vs 69.5 y; P = .79), sex (31% vs 38% male; P = .58), body mass index (27.7 vs 25.7 kg/m2; P = .20), or medical comorbidities. Univariate analyses compared initial hemoglobin level, change in hemoglobin level, coagulation parameters, transfusion requirements, hematoma volume, and active extravasation on computed tomographic (CT) angiography between groups. Multivariable logistic regression identified factors predictive of CM failure. A scoring system was then created to predict CM failure. RESULTS: CM failed in 32 of 72 patients. Multivariable regression identified active extravasation on CT angiography (P = .02), hematoma volume (P = .01), and packed red blood cell (pRBC) transfusion of ≥ 4 U (P = .03) as predictors of embolization. A scoring system using these factors along with maximum rate of hemoglobin decrease yielded a sensitivity of 100% and specificity of 98% in determining need for embolization. CONCLUSIONS: CM for RSH was more likely to fail in patients with active extravasation on CT angiography, larger hematoma volume, pRBC transfusion of ≥ 4 U, and higher rate of hemoglobin decrease. Using these parameters, a scoring system was created that achieved high sensitivity and specificity in identifying patients who would require embolization.