- Email: [email protected]
HMGB1 Expression on Platelet-Derived Microparticles Promotes Deep Vein Thrombosis
Vol. 223, No. 4S1, October 2016
Scientific Forum Abstracts
S153
outcomes as higher-energy mechanisms in geriatric patients who sustain pelvic fractures.
centrifugation and analyzed by Nanosight quantification and flow cytometry.
METHODS: We retrospectively reviewed pelvic fractures between 2005 and 2015. Geriatric (65 years) and young (18-64 years) patient characteristics, mechanism of injury, and outcomes (including any complications and death) were assessed, specifically noting isolated pelvic fractures (IPF). The psoas:L3 diameter index on CT scan was used as a surrogate measure of frailty.
RESULTS: Activated murine platelets generated microparticles that expressed more HMGB1 compared with unstimulated platelets (fluorescence-activated cell sorting median fluorescence intensity [FACS MFI] 9847 vs 1792, p<0.01). Recombinant HMGB1, administered via tail vein injection, led to a significant increase in DVT compared with control (25.3 vs 11.6 mg, p<0.05). HMGB1 PF4 mice have a decreased clot burden (CNTL 12.5 vs HMGB1 PF4 7.3 mg, p<0.05). Importantly, platelet-derived microparticles are significantly elevated in trauma patients compared with healthy volunteers (FACS MFI 2903 vs 1537, p<0.01).
RESULTS: Overall, 600 geriatric and 1,098 young patients sustained pelvic fractures. IPF occurred in 53.5% geriatric (IPFGeri) and 21.3% young patients (IPF-Young). IPF-Geri, when compared with IPF-Young, were less often motor vehicle crashes (6.2% vs 40.2%; p<0.001) but were noted to have no difference in need for ICU (8.7% vs 6.4%; p¼0.3), blood transfusion (14% vs 9.8%; p¼0.2) or VIR (3.4% vs 5.1%; p¼0.4). Within IPF-Geri patients, comparing fall from standing (FFS) with all other mechanisms, FFS patients were older (84 0.5 years vs 77.3 1 years; p<0.01), more likely female (86.8% vs 53.4%; p<0.01), and had more severe frailty (0.35 [interquartile range (IQR) 0.28-0.43] vs 0.41 [IQR¼0.3-0.53; p¼0.02]). In regression analysis adjusting for age, sex, and frailty, patients who sustained FFS compared with all other mechanisms, were just as likely to need critical care interventions (odds ratio 0.6; 95% CI 0.2-1.34) and suffer from complications (odds ratio 0.75; 95% CI 0.25-2.3). CONCLUSIONS: There are no trivial mechanisms in the vulnerable and frail geriatric trauma population. Our data underscore that complications, including death, are just as likely to occur in fall from standing compared with other higher-energy mechanisms. Collapse is as catastrophic as collision. HMGB1 Expression on Platelet-Derived Microparticles Promotes Deep Vein Thrombosis Mitchell R Dyer, MD*, Qiwei Chen, Matthew D Neal, MD, Sebastian Vogel, MD University of Pittsburgh Medical Center, Pittsburgh, PA INTRODUCTION: Deep vein thrombosis (DVT) is a common and highly morbid complication after trauma. The damage-associated molecular pattern molecule, high-mobility group box 1 (HMGB1), is recognized to be involved in the inflammatory response after trauma, and recently, platelet-derived HMGB1 has been found to be a key mediator of microvascular thrombosis after trauma. Activated platelets are known to upregulate HMGB1 and also generate microparticles that have pro-thrombotic activity. We hypothesized that HMGB1 expression on platelet-derived microparticles is a key regulator in the development of DVT in a murine model. METHODS: We generated transgenic mice lacking HMGB1 specifically on platelets (HMGB1 PF4) and subjected them to a model of deep vein thrombosis involving inferior vena cava ligation. Clots were harvested and quantified for size and weight. Platelet-derived microparticles were isolated from trauma patients by differential
CONCLUSIONS: HMGB1 is released from platelets via microparticles after trauma and substantially increases thrombus burden in a murine model of DVT. Impact of Circle of Willis Anatomy in Blunt Cerebrovascular Injury-Related Stroke Charles P Shahan, MD, Timothy C Fabian, MD, FACS, Richard I Gray, MD, MBA, Martin A Croce, MD, FACS University of Tennessee Health Science Center, Memphis, TN INTRODUCTION: Cerebral vascular anatomy, specifically, the circle of Willis (COW), plays an unstudied role in the development of stroke after blunt cerebrovascular injury (BCVI) (carotid and vertebral arteries). Variant anatomy is very common, and certain variants such as persistent fetal circulation (enlarged posterior communicating artery) may improve collateralization between the anterior (carotid) and posterior (vertebral) circulations. Identifying patients at increased stroke risk may allow tailored anticoagulation, the mainstay of therapy. This study constitutes the first attempt to identify vascular anatomy patterns associated with stroke, with the hypothesis that normal COW anatomy would protect against stroke. METHODS: Radiographic images from patients with BCVIrelated stroke from 2005 to 2014 were identified. Stroke patients were compared with injury-matched, nonstroke controls. Normal COW anatomy was defined as presence of all vessels without hypoplasia. RESULTS: Of 457 BCVI patients, 22 (4.8%) BCVI-related stroke patients and matched controls were reviewed. Nine (41%) stroke patients and 2 (9%) controls had normal COW anatomy (odds ratio 7.1, 95% CI 1.28-33.3). Persistent fetal circulation was found in 6 controls and 1 stroke patient, resulting in a 7.9-fold decreased risk of stroke with this variant (odds ratio 0.13, 95% CI 0.0031.26). CONCLUSIONS: Cerebral vascular anatomy has a role in BCVIrelated stroke. Normal COW anatomy is not protective, and the increased collateral flow provided by persistent fetal circulation is likely protective. The identification of high-risk patients may allow for more selective anticoagulation in this multiply injured trauma
Scientific Forum Abstracts
S153
outcomes as higher-energy mechanisms in geriatric patients who sustain pelvic fractures.
centrifugation and analyzed by Nanosight quantification and flow cytometry.
METHODS: We retrospectively reviewed pelvic fractures between 2005 and 2015. Geriatric (65 years) and young (18-64 years) patient characteristics, mechanism of injury, and outcomes (including any complications and death) were assessed, specifically noting isolated pelvic fractures (IPF). The psoas:L3 diameter index on CT scan was used as a surrogate measure of frailty.
RESULTS: Activated murine platelets generated microparticles that expressed more HMGB1 compared with unstimulated platelets (fluorescence-activated cell sorting median fluorescence intensity [FACS MFI] 9847 vs 1792, p<0.01). Recombinant HMGB1, administered via tail vein injection, led to a significant increase in DVT compared with control (25.3 vs 11.6 mg, p<0.05). HMGB1 PF4 mice have a decreased clot burden (CNTL 12.5 vs HMGB1 PF4 7.3 mg, p<0.05). Importantly, platelet-derived microparticles are significantly elevated in trauma patients compared with healthy volunteers (FACS MFI 2903 vs 1537, p<0.01).
RESULTS: Overall, 600 geriatric and 1,098 young patients sustained pelvic fractures. IPF occurred in 53.5% geriatric (IPFGeri) and 21.3% young patients (IPF-Young). IPF-Geri, when compared with IPF-Young, were less often motor vehicle crashes (6.2% vs 40.2%; p<0.001) but were noted to have no difference in need for ICU (8.7% vs 6.4%; p¼0.3), blood transfusion (14% vs 9.8%; p¼0.2) or VIR (3.4% vs 5.1%; p¼0.4). Within IPF-Geri patients, comparing fall from standing (FFS) with all other mechanisms, FFS patients were older (84 0.5 years vs 77.3 1 years; p<0.01), more likely female (86.8% vs 53.4%; p<0.01), and had more severe frailty (0.35 [interquartile range (IQR) 0.28-0.43] vs 0.41 [IQR¼0.3-0.53; p¼0.02]). In regression analysis adjusting for age, sex, and frailty, patients who sustained FFS compared with all other mechanisms, were just as likely to need critical care interventions (odds ratio 0.6; 95% CI 0.2-1.34) and suffer from complications (odds ratio 0.75; 95% CI 0.25-2.3). CONCLUSIONS: There are no trivial mechanisms in the vulnerable and frail geriatric trauma population. Our data underscore that complications, including death, are just as likely to occur in fall from standing compared with other higher-energy mechanisms. Collapse is as catastrophic as collision. HMGB1 Expression on Platelet-Derived Microparticles Promotes Deep Vein Thrombosis Mitchell R Dyer, MD*, Qiwei Chen, Matthew D Neal, MD, Sebastian Vogel, MD University of Pittsburgh Medical Center, Pittsburgh, PA INTRODUCTION: Deep vein thrombosis (DVT) is a common and highly morbid complication after trauma. The damage-associated molecular pattern molecule, high-mobility group box 1 (HMGB1), is recognized to be involved in the inflammatory response after trauma, and recently, platelet-derived HMGB1 has been found to be a key mediator of microvascular thrombosis after trauma. Activated platelets are known to upregulate HMGB1 and also generate microparticles that have pro-thrombotic activity. We hypothesized that HMGB1 expression on platelet-derived microparticles is a key regulator in the development of DVT in a murine model. METHODS: We generated transgenic mice lacking HMGB1 specifically on platelets (HMGB1 PF4) and subjected them to a model of deep vein thrombosis involving inferior vena cava ligation. Clots were harvested and quantified for size and weight. Platelet-derived microparticles were isolated from trauma patients by differential
CONCLUSIONS: HMGB1 is released from platelets via microparticles after trauma and substantially increases thrombus burden in a murine model of DVT. Impact of Circle of Willis Anatomy in Blunt Cerebrovascular Injury-Related Stroke Charles P Shahan, MD, Timothy C Fabian, MD, FACS, Richard I Gray, MD, MBA, Martin A Croce, MD, FACS University of Tennessee Health Science Center, Memphis, TN INTRODUCTION: Cerebral vascular anatomy, specifically, the circle of Willis (COW), plays an unstudied role in the development of stroke after blunt cerebrovascular injury (BCVI) (carotid and vertebral arteries). Variant anatomy is very common, and certain variants such as persistent fetal circulation (enlarged posterior communicating artery) may improve collateralization between the anterior (carotid) and posterior (vertebral) circulations. Identifying patients at increased stroke risk may allow tailored anticoagulation, the mainstay of therapy. This study constitutes the first attempt to identify vascular anatomy patterns associated with stroke, with the hypothesis that normal COW anatomy would protect against stroke. METHODS: Radiographic images from patients with BCVIrelated stroke from 2005 to 2014 were identified. Stroke patients were compared with injury-matched, nonstroke controls. Normal COW anatomy was defined as presence of all vessels without hypoplasia. RESULTS: Of 457 BCVI patients, 22 (4.8%) BCVI-related stroke patients and matched controls were reviewed. Nine (41%) stroke patients and 2 (9%) controls had normal COW anatomy (odds ratio 7.1, 95% CI 1.28-33.3). Persistent fetal circulation was found in 6 controls and 1 stroke patient, resulting in a 7.9-fold decreased risk of stroke with this variant (odds ratio 0.13, 95% CI 0.0031.26). CONCLUSIONS: Cerebral vascular anatomy has a role in BCVIrelated stroke. Normal COW anatomy is not protective, and the increased collateral flow provided by persistent fetal circulation is likely protective. The identification of high-risk patients may allow for more selective anticoagulation in this multiply injured trauma