Sandro Scarpelini

Abnormal Coagulation Tests Are Associated With Progression of Traumatic Intracranial Hemorrhage

BACKGROUNDnIntracranial hemorrhage (ICH) is common in traumatic brain injury (TBI) and a major determinant of death and disability. ICH commonly increases in size and coagulopathy has been implicated in such progression. We investigated the association between coagulopathy diagnosed by routine laboratory tests and ICH progression.nnnMETHODSnSubgroup post hoc analysis from a randomized controlled trial including adult patients with blunt severe TBI (Glasgow Coma Scale score <or=8) and repeat computerized tomography scans in 48 hours. Coagulopathy was defined as international normalized ratio >or=1.3, activated partial thromboplastin time >or=35, or platelet count (PLT) <or=100 x 10/L any time in the first 24 hours. Progression was any size increase or new ICH. TBI-associated coagulopathy was investigated measuring soluble tissue factor (TF) and d-dimer.nnnRESULTSnThe ICH progressed in 37 of 72 patients (51%), in 80% if any abnormal laboratory test (coagulopathic patients) versus 36% in noncoagulopathic (p = 0.0004). Abnormal international normalized ratio (odds ratio [OR] = 4.09; 95% confidence interval [CI] = 1.29-12.95; p = 0.017), PLT (OR = 12.59; 95% CI = 1.52-108.57; p = 0.019), head Abbreviated Injury Scale (AIS) (OR = 1.82; 95% CI = 1.15-2.88; p = 0.011) were significantly associated with progression (univariate analysis). In a multiple logistic regression, only head AIS (OR = 1.81; 95% CI 1.10-2.98; p = 0.0198) and PLT (OR = 11.8; 95% CI = 1.38-101.23; p = 0.024) correlated with progression. All patients with abnormal partial thromboplastin time experienced progression. ICH progression carried a 5-fold higher odds of death; 32% with progression died versus 8.6% without. Age, head AIS, Injury Severity Score, and d-dimer were also associated with mortality. Tissue factor was not associated with progression or mortality.nnnCONCLUSIONnThis study demonstrates an association between coagulopathy, diagnosed by routine laboratorial tests in the first 24 hours, with ICH progression; and ICH progression with mortality in patients with severe TBI. The causal relationship between coagulopathy and ICH progression will require further studies.

Prehospital resuscitation with hypertonic saline- dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients

BackgroundTraumatic brain injury (TBI) initiates interrelated inflammatory and coagulation cascades characterized by wide-spread cellular activation, induction of leukocyte and endothelial cell adhesion molecules and release of soluble pro/antiinflammatory cytokines and thrombotic mediators. Resuscitative care is focused on optimizing cerebral perfusion and reducing secondary injury processes. Hypertonic saline is an effective osmotherapeutic agent for the treatment of intracranial hypertension and has immunomodulatory properties that may confer neuroprotection. This study examined the impact of hypertonic fluids on inflammatory/coagulation cascades in isolated head injury.MethodsUsing a prospective, randomized controlled trial we investigated the impact of prehospital resuscitation of severe TBI (GCS < 8) patients using 7.5% hypertonic saline in combination with 6% dextran-70 (HSD) vs 0.9% normal saline (NS), on selected cellular and soluble inflammatory/coagulation markers. Serial blood samples were drawn from 65 patients (30 HSD, 35 NS) at the time of hospital admission and at 12, 24, and 48-h post-resuscitation. Flow cytometry was used to analyze leukocyte cell-surface adhesion (CD62L, CD11b) and degranulation (CD63, CD66b) molecules. Circulating concentrations of soluble (s)L- and sE-selectins (sL-, sE-selectins), vascular and intercellular adhesion molecules (sVCAM-1, sICAM-1), pro/antiinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL-10)], tissue factor (sTF), thrombomodulin (sTM) and D-dimers (D-D) were assessed by enzyme immunoassay. Twenty-five healthy subjects were studied as a control group.ResultsTBI provoked marked alterations in a majority of the inflammatory/coagulation markers assessed in all patients. Relative to control, NS patients showed up to a 2-fold higher surface expression of CD62L, CD11b and CD66b on polymorphonuclear neutrophils (PMNs) and monocytes that persisted for 48-h. HSD blunted the expression of these cell-surface activation/adhesion molecules at all time-points to levels approaching control values. Admission concentrations of endothelial-derived sVCAM-1 and sE-selectin were generally reduced in HSD patients. Circulating sL-selectin levels were significantly elevated at 12 and 48, but not 24 h post-resuscitation with HSD. TNF-α and IL-10 levels were elevated above control throughout the study period in all patients, but were reduced in HSD patients. Plasma sTF and D-D levels were also significantly lower in HSD patients, whereas sTM levels remained at control levels.ConclusionsThese findings support an important modulatory role of HSD resuscitation in attenuating the upregulation of leukocyte/endothelial cell proinflammatory/prothrombotic mediators, which may help ameliorate secondary brain injury after TBI.Trial registrationNCT00878631.

Clotting Factor Deficiency in Early Trauma-Associated Coagulopathy

BACKGROUNDnCoagulopathic bleeding is a leading cause of in-hospital death after injury. A recently proposed transfusion strategy calls for early and aggressive frozen plasma transfusion to bleeding trauma patients, thus addressing trauma-associated coagulopathy (TAC) by transfusing clotting factors (CFs). This strategy may dramatically improve survival of bleeding trauma patients. However, other studies suggest that early TAC occurs by protein C activation and is independent of CF deficiency. This study investigated whether CF deficiency is associated with early TAC.nnnMETHODSnThis is a prospective observational cohort study of severely traumatized patients (Injury Severity Score ≥ 16) admitted shortly after injury, receiving minimal fluids and no prehospital blood. Blood was assayed for CF levels, thromboelastography, and routine coagulation tests. Critical CF deficiency was defined as ≤ 30% activity of any CF.nnnRESULTSnOf 110 patients, 22 (20%) had critical CF deficiency: critically low factor V level was evident in all these patients. International normalized ratio, activated prothrombin time, and, thromboelastography were abnormal in 32%, 36%, and 35%, respectively, of patients with any critically low CF. Patients with critical CF deficiency suffered more severe injuries, were more acidotic, received more blood transfusions, and showed a trend toward higher mortality (32% vs. 18%, p = 0.23). Computational modeling showed coagulopathic patients had pronounced delays and quantitative deficits in generating thrombin.nnnCONCLUSIONSnTwenty percent of all severely injured patients had critical CF deficiency on admission, particularly of factor V. The observed factor V deficit aligns with current understanding of the mechanisms underlying early TAC. Critical deficiency of factor V impairs thrombin generation and profoundly affects hemostasis.

Hypoperfusion in severely injured trauma patients is associated with reduced coagulation factor activity.

BACKGROUNDnRecent studies have shown that acute traumatic coagulopathy is associated with hypoperfusion, increased plasma levels of soluble thrombomodulin, and decreased levels of protein C but with no change in factor VII activity. These findings led to the hypothesis that acute traumatic coagulopathy is primarily due to systemic anticoagulation, by activated protein C, rather than decreases in serine protease activity. This study was designed to examine the effect of hypoperfusion secondary to traumatic injury on the activity of coagulation factors.nnnMETHODSnPost hoc analysis of prospectively collected data on severely injured adult trauma patients presenting to a single trauma center within 120 minutes of injury. Venous blood was analyzed for activity of factors II, V, VII, VIII, IX, X, and XI. Base deficit from arterial blood samples was used as a marker of hypoperfusion.nnnRESULTSnSeventy-one patients were identified. The activity of factors II, V, VII, IX, X, and XI correlated negatively with base deficit, and after stratification into three groups, based on the severity of hypoperfusion, a statistically significant dose-related reduction in the activity of factors II, VII, IX, X, and XI was observed. Hypoperfusion is also associated with marked reductions in factor V activity levels, but these appear to be relatively independent of the degree of hypoperfusion. The activity of factor VIII did not correlate with base deficit.nnnCONCLUSIONSnHypoperfusion in trauma patients is associated with a moderate, dose-dependent reduction in the activity of coagulation factors II, VII, IX, X, and XI, and a more marked reduction in factor V activity, which is relatively independent of the severity of shock. These findings suggest that the mechanisms underlying decreased factor V activity--which could be due to activated protein C mediated cleavage, thus providing a possible link between the proposed thrombomodulin/thrombin-APC pathway and the serine proteases of the coagulation cascade--and the reductions in factors II, VII, IX, X, and XI may differ. Preservation of coagulation factor activity in the majority of normally and moderately hypoperfused patients suggests that aggressive administration of plasma is probably only indicated in severely hypoperfused patients. Markers of hypoperfusion, such as base deficit, might be better and more readily available predictors of who require coagulation support than international normalized ratio or activated partial thromboplastin time.

The Natural History of Trauma-related Coagulopathy: Implications for Treatment

BACKGROUNDnHemorrhage is a leading cause of death in trauma patients and coagulopathy is a significant contributor. Although the exact mechanisms of trauma-associated coagulopathy (TAC) are incompletely understood, hemostatic resuscitation strategies have been developed to treat TAC. Our study sought to identify which trauma patients develop TAC and the factors associated with its development, to describe the natural history of TAC, and to identify patients with TAC who may not require hemostatic resuscitation.nnnMETHODSnPatients with early coagulopathy (International Normalized Ratio >1.3) who were admitted directly from the scene within 1 hour of injury were identified in our institutional trauma registry. We analyzed these data for the presence of TAC, predictors of early and delayed TAC, and evolution of TAC during the first 24 hours of admission.nnnRESULTSnOf 2,473 patients, 290 (12%) had early TAC (International Normalized Ratio >1.3) and 271 (11%) developed delayed TAC. Multivariate analysis identified female gender (odds ratio [OR] 1.25 [1.11-1.41]), lower pH (OR 0.08 [0.015-0.47]), lower hemoglobin (OR 0.96 [0.95-0.97]), lower temperature (OR 0.82 [0.70-0.95]), and blunt mechanism (OR 0.49 [0.33-0.71]) as factors significantly associated with development of early TAC. Progression of early TAC occurred in 64%, and these patients had more severe abdominal injury and received more emergency room crystalloid. Of patients with early TAC who did not receive fresh frozen plasma, only 49% developed worsening coagulopathy. Patients with isolated intracranial hemorrhage had higher rates of bleeding progression (75% vs. 20%, p < 0.005) in the presence of early TAC.nnnCONCLUSIONSnTAC may appear in an early or delayed form and its presence and progression are associated with a number of identifiable factors. Although TAC commonly progresses, it also resolves spontaneously in many patients. Further research is required to identify which patients with TAC require hemostatic treatment, although those with intracranial hemorrhages seem to warrant aggressive therapy.

Recombinant factor VIIa and the surgical patient.

Purpose of reviewBleeding remains a challenge in surgery. A unique drug, recombinant factor VIIa, causes clotting exclusively at bleeding sites. Recombinant factor VIIa has recently been introduced to surgery where current evidence, consisting mostly of case reports, suggest remarkable safety and efficacy. The first randomized controlled trials are only now being published with less remarkable results. This manuscript summarizes the current evidence. Recent findingsIn trauma, a single randomized control trial suggests recombinant factor VIIa reduces bleeding and transfusion in blunt trauma, particularly in coagulopathic patients. In cardiac surgery, one randomized control trial, open-label studies and case reports suggest benefit in refractory bleeding. For liver surgery, randomized control trials do not support use in liver transplant or gastrointestinal bleeding. In neurosurgery, one randomized control trial demonstrated improved outcome in intracerebral hemorrhage. In urology, one randomized control trial demonstrated significant reduction in perioperative bleeding. For orthopedics, a single randomized control trial showed no benefit in pelvic/acetabular surgery. In obstetrics/gynecology, limited evidence suggests benefit in massive bleedings. SummaryCurrent evidence does not yet support recombinant factor VIIa as standard of care in surgery. However, the evidence indicates that recombinant factor VIIa should be used in intracerebral hemorrhage and massive perioperative or traumatic bleeding refractory to conventional therapies. For now, the bedside decision to use recombinant factor VIIa remains a matter of surgical judgment.

Temporal Distribution of Trauma Deaths : Quality of Trauma Care in a Developing Country

BACKGROUNDnExamination of the epidemiology and timing of trauma deaths has been deemed a useful method to evaluate the quality of trauma care.nnnOBJECTIVEnThe purpose of this study was to evaluate the quality of trauma care in a regional trauma system and in a university hospital in Brazil by comparing the timing of deaths in the studied prehospital and in-hospital settings to those published for trauma systems in other areas.nnnMETHODSnWe analyzed the National Health Ministers System of Deaths Information for the prehospital mortality and we retrospectively collected the demographics, timelines, and trauma severity scores of all in-hospital patients who died after admission through the Emergency Unit of Hospital das Clinicas de Ribeirao Preto between 2000 and 2001.nnnRESULTSnDuring the study period, there were 787 trauma fatalities in the city: 448 (56.9%) died in the prehospital setting and 339 (43.1%) died after being admitted to a medical facility. In 2 years, 238 trauma deaths occurred in the studied hospital, and we found a complete clinical set of data for 224 of these patients. The majority of deaths in the prehospital setting were caused by penetrating injuries (66.7%), whereas in-hospital mortality was mainly because of blunt traumas (59.1%). The largest number of in-hospital deaths occurred beyond 72 hours of stay (107 patients-47%).nnnCONCLUSIONnThe region studied showed some deficiencies in prehospital and in-hospitals settings, in particular in the critical care and short-term follow-up of trauma patients when compared with the literature. Particularly, the late mortality may be related to training and human resources deficiency. Based on the timeline of trauma deaths, we can suggest that the studied region needs improvements in the prehospital trauma system and in hospital critical care.

Pulmonary emboli after blunt trauma: Timing, clinical characteristics and natural history

BACKGROUNDnVenous thromboembolism (VTE) frequently complicates the recovery of trauma patients, and contributes to morbidity and mortality. Recent studies showed an increase in diagnosis of pulmonary embolism (PE) mainly in the early or immediate period after trauma. The clinical significance of those incidental PEs is unclear.nnnMETHODSnThe study cohort included all blunt trauma patients who had a contrast-enhanced CT of the chest performed as part of their initial trauma assessment from January 1, 2005 to January 31, 2007 in a large academic Canadian trauma centre. Patients diagnosed with PE at any point during admission were identified using our institutional trauma registry. All chest CT scans and electronic charts were reviewed. Patients were classified according to time of PE detection (immediate, early or late) and symptoms (asymptomatic or symptomatic). The clinical characteristics and hospital course of the patients who were diagnosed with immediate PE were described.nnnRESULTSn1259 blunt trauma patients were reviewed. Six patients presented with immediate PE (0.5%); nine patients were found to have early PE (0.7%) and 13 had late PE (1.0%). All six of the patients with immediate PE were classified as asymptomatic. Five of the nine patients with early PE were symptomatic and all 13 patients who developed late PE were symptomatic. Amongst the six patients with immediate PE, five survived 24h hospitalisation. Four of them were managed with prophylactic low molecular weight heparin and no other thromboembolic events were observed during admission or after discharge.nnnCONCLUSIONSnThe increased use of advanced CT technology in trauma patients has resulted in an increased diagnosis of incidental PEs that are asymptomatic. The clinical significance and management of these small, incidental PE are uncertain and further studies are needed to clarify the natural history of this controversial finding.

Abdominal compartment syndrome in trauma resuscitation

Purpose of review Swelling is inexorably linked to shock and resuscitation in trauma. In many forms, swelling complicates and interacts with traumatic injury to raise pressures in the abdomen, resulting in intraabdominal hypertension, which may overtly manifest as abdominal compartment syndrome (ACS) driving multiple organ failure. Despite renewed clinical interest in posttraumatic intraabdominal pressure, there remains a chiasm between knowledge of the risks and clinical interventions to mitigate them. This review provides a concise overview of definitions, risk factors, diagnosis and management using an illustrative trauma case. Recent findings Intraabdominal pressure commonly increases following trauma, wherein ACS may manifest earlier than generally appreciated and complicate other insults such as shock and hemorrhage. Contemporary resuscitation strategies may exacerbate intraabdominal hypertension, particularly massive crystalloid resuscitation. Although unproven, the recent transition to crystalloid restriction and high plasma resuscitation strategies may influence the prevalence of ACS. Nonetheless, aggressive intraabdominal pressure monitoring should be mandatory in the critically ill. Despite potential nonoperative options, decompressive laparotomy remains the only definitive but often morbid treatment. Summary ACS results from many dysfunctions acting in concert with each other in self-propagating vicious cycles. Starting with greater awareness, it is imperative that the growing knowledge should be translated into clinical practice.

Retrograde urethrocystography impairs computed tomography diagnosis of pelvic arterial hemorrhage in the presence of a lower urologic tract injury.

BACKGROUNDnThere is controversy about the appropriate sequence of urologic investigation in patients with pelvic fracture. Use of retrograde urethrography or cystography may interfere with regular pelvic CT scanning for arterial extravasation.nnnSTUDY DESIGNnWe performed a retrospective study at a regional trauma center in Toronto, Canada. Included were adult blunt trauma patients with pelvic fractures and concomitant bladder or urethral disruption who underwent initial pelvic CT before operation or hospital admission. Exposure of interest was whether retrograde urethrography (RUG) and cystography were performed before pelvic CT scanning. Main outcomes measures were indeterminate or false negative initial CT examinations for pelvic arterial extravasation.nnnRESULTSnSixty blunt trauma patients had a pelvic fracture and either a urethral or bladder rupture. Forty-nine of these patients underwent initial CT scanning. Of these 49 patients, 23 had RUG or conventional cystography performed before pelvic CT scanning; 26 had cystography after regular CT examination. Performing cystography before CT was associated with considerably more indeterminate scans (9 patients) and false negatives (2 patients) for pelvic arterial extravasation (11 of 23 versus 0 of 26, p < 0.001) compared with performing urologic investigation after CT. In the presence of pelvic arterial hemorrhage, indeterminate or false negative CT scans for arterial extravasation were associated with a trend toward longer mean times to embolization compared with positive scans (p=0.1).nnnCONCLUSIONSnExtravasating contrast from lower urologic injuries can interfere with the CT assessment for pelvic arterial extravasation, delaying angiographic embolization.