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Rediscovering the wound hematoma as a site of hemostasis during major arterial hemorrhage.

ABSTRACT: BACKGROUND:Treatments for major internal bleeding after injury include permissive hypotension to decrease the rate of blood loss, intravenous infusion of plasma or clotting factors to improve clot formation, and rapid surgical hemostasis or arterial embolization to control bleeding vessels. Yet, little is known regarding major internal arterial hemostasis, or how these commonly used treatments might influence hemostasis. OBJECTIVES:(i) To use a swine model of femoral artery bleeding to understand the perivascular hemostatic response to contained arterial hemorrhage. (ii) To directly confirm the association between hemodynamics and bleeding velocity. (iii) To observe the feasibility of delivering an activated clotting factor directly to internal sites of bleeding using a simplified angiographic approach. METHODS:Ultrasound was used to measure bleeding velocity and in vivo clot formation by elastography in a swine model of contained femoral artery bleeding with fluid resuscitation. A swine model of internal pelvic and axillary artery hemorrhage was also used to demonstrate the feasibility of local delivery of an activated clotting factor. RESULTS:In this model, clots formed slowly within the peri-wound hematoma, but eventually contained the bleeding. Central hemodynamics correlated positively with bleeding velocity. Infusion of recombinant human activated factor VII into the injured artery near the site of major internal hemorrhage in the pelvis and axillae was feasible. CONCLUSIONS:We rediscovered that clot formation within the peri-wound hematoma is an integral component of hemostasis and a feasible target for the treatment of major internal bleeding using activated clotting factors delivered using a simplified angiographic approach.

SUBMITTER: White NJ

PROVIDER: S-EPMC4777306 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Rediscovering the wound hematoma as a site of hemostasis during major arterial hemorrhage.

White N J NJ Mehic E E Wang X X Chien D D Lim E E St John A E AE Stern S A SA Mourad P D PD Rieger M M Fries D D Martinowitz U U

Journal of thrombosis and haemostasis : JTH 20151029 12

<h4>Background</h4>Treatments for major internal bleeding after injury include permissive hypotension to decrease the rate of blood loss, intravenous infusion of plasma or clotting factors to improve clot formation, and rapid surgical hemostasis or arterial embolization to control bleeding vessels. Yet, little is known regarding major internal arterial hemostasis, or how these commonly used treatments might influence hemostasis.<h4>Objectives</h4>(i) To use a swine model of femoral artery bleedi ...[more]

PMID: 26414624

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Project description:BackgroundAlthough arterial hemorrhage after pancreaticoduodenectomy (PD) is not frequent, it is fatal. Arterial hemorrhage is caused by pseudoaneurysm rupture, and the gastroduodenal artery stump and hepatic artery (HA) are frequent culprit vessels. Diagnostic procedures and imaging modalities are associated with certain difficulties. Simultaneous accomplishment of complete hemostasis and HA flow preservation is difficult after PD. Although complete hemostasis may be obtained by endovascular treatment (EVT) or surgery, liver infarction caused by hepatic ischemia and/or liver abscesses caused by biliary ischemia may occur. We herein discuss therapeutic options for fatal arterial hemorrhage after PD.AimTo present our data here along with a discussion of therapeutic strategies for fatal arterial hemorrhage after PD.MethodsWe retrospectively investigated 16 patients who developed arterial hemorrhage after PD. The patients' clinical characteristics, diagnostic procedures, actual treatments [transcatheter arterial embolization (TAE), stent-graft placement, or surgery], clinical courses, and outcomes were evaluated.ResultsThe frequency of arterial hemorrhage after PD was 5.5%. Pancreatic leakage was observed in 12 patients. The onset of hemorrhage occurred at a median of 18 d after PD. Sentinel bleeding was observed in five patients. The initial EVT procedures were stent-graft placement in seven patients, TAE in six patients, and combined therapy in two patients. The rate of technical success of the initial EVT was 75.0%, and additional EVTs were performed in four patients. Surgical approaches including arterioportal shunting were performed in eight patients. Liver infarction was observed in two patients after TAE. Two patients showed a poor outcome even after successful EVT. These four patients with poor clinical courses and outcomes had a poor clinical condition before EVT. Fourteen patients were successfully treated.ConclusionTranscatheter placement of a covered stent may be useful for simultaneous accomplishment of complete hemostasis and HA flow preservation.

Project description:ObjectiveHematoma enlargement (HE) is associated with clinical outcomes after supratentorial intracerebral hemorrhage (ICH). This study evaluates whether HE characteristics and association with functional outcome differ in deep versus lobar ICH.MethodsPooled analysis of individual patient data between January 2006 and December 2015 from a German-wide cohort study (RETRACE, I + II) investigating ICH related to oral anticoagulants (OAC) at 22 participating centers, and from one single-center registry (UKER-ICH) investigating non-OAC-ICH patients. Altogether, 1954 supratentorial ICH patients were eligible for outcome analyses, which were separately conducted or controlled for OAC, that is, vitamin-K-antagonists (VKA, n = 1186) and non-vitamin-K-antagonist-oral-anticoagulants (NOAC, n = 107). Confounding was addressed using propensity score matching, cox regression modeling and multivariate modeling. Main outcomes were occurrence, extent, and timing of HE (>33%/>6 mL) and its association with 3-month functional outcome.ResultsOccurrence of HE was not different after deep versus lobar ICH in patients with non-OAC-ICH (39/356 [11.0%] vs. 36/305 [11.8%], P = 0.73), VKA-ICH (249/681 [36.6%] vs. 183/505 [36.2%], P = 0.91), and NOAC-ICH (21/69 [30.4%] vs. 12/38 [31.6%], P = 0.90). HE extent did not differ after non-OAC-ICH (deep:+59% [40-122] vs. lobar:+74% [37-124], P = 0.65), but both patients with VKA-ICH and NOAC-ICH showed greater HE extent after deep ICH [VKA-ICH, deep: +94% [54-199] vs. lobar: +56% [35-116], P < 0.001; NOAC-ICH, deep: +74% [56-123] vs. lobar: +40% [21-49], P = 0.001). Deep compared to lobar ICH patients had higher HE hazard during first 13.5 h after onset (Hazard ratio [HR]: 1.85 [1.03-3.31], P = 0.04), followed by lower hazard (13.5-26.5 h, HR: 0.46 [0.23-0.89], P = 0.02), and equal hazard thereafter (HR: 0.96 [0.56-1.65], P = 0.89). Odds ratio for unfavorable outcome was higher after HE in deep (4.31 [2.71-6.86], P < 0.001) versus lobar ICH (2.82 [1.71-4.66], P < 0.001), and only significant after small-medium (1st volume-quarter, deep: 3.09 [1.52-6.29], P < 0.01; lobar: 3.86 [1.35-11.04], P = 0.01) as opposed to large-sized ICH (4th volume-quarter, deep: 1.09 [0.13-9.20], P = 0.94; lobar: 2.24 [0.72-7.04], P = 0.17).InterpretationHE occurrence does not differ among deep and lobar ICH. However, compared to lobar ICH, HE after deep ICH is of greater extent in OAC-ICH, occurs earlier and may be of greater clinical relevance. Overall, clinical significance is more apparent after small-medium compared to large-sized bleedings.

Project description:Trazodone is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors (SARIs). The drug is approved and marketed in several countries worldwide for the treatment of major depressive disorder (MDD) in adult patients. In clinical studies, trazodone has demonstrated comparable antidepressant activity to other drug classes, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs). Moreover, the SARI action of trazodone may overcome the tolerability issues that are often associated with second-generation antidepressants such as SSRIs (i.e. insomnia, anxiety and sexual dysfunction). Recent focus has been placed on the development of a new prolonged-release once-a-day formulation of trazodone (TzCOAD), which may provide improved tolerability over the conventional immediate-release formulation of trazodone. Clinical studies have led to the recent approval in the USA of TzCOAD (as Oleptro™; Angelini Labopharm LLC, Princeton, NJ, USA), which may see resurgence of interest in the drug for the management of patients with MDD. Although trazodone is approved for the treatment of depression, evidence supports the use of low-dose trazodone as an off-label hypnotic for the treatment of sleep disorders in patients with MDD. The most common adverse effects reported with trazodone are drowsiness (somnolence/sedation), headache, dizziness and dry mouth. Other events reported, albeit with low incidence, include orthostatic hypotension (particularly in elderly patients or those with heart disease), minimal anticholinergic activity, corrected QT interval prolongation and torsade de pointes, cardiac arrhythmias, and rare occurrences of priapism and suicidal ideation. Overall, trazodone is an effective and well tolerated antidepressant (SARI) with an important role in the current treatment of MDD both as monotherapy and as part of a combination strategy. Trazodone is effective in controlling a wide range of symptoms of depression, while avoiding the negative effects on sleep seen with SSRI antidepressants. The recently approved prolonged-release formulation should provide further optimization of this antidepressant and may be useful for enabling an appropriate therapeutic dose to be administered with improved patient compliance.

Project description:BACKGROUND:Hematoma expansion (HE) after intracerebral hemorrhage (ICH) is associated with worse outcome. Lobar ICHs are known to have better outcomes compared to deep ICH; however, it is unclear whether there are HE differences between these locations. We sought to investigate the hypothesis that lobar ICH has less HE compared to deep ICH. METHODS:Primary ICH patients admitted between 2009 and 2016 were included in a prospective single-center ICH cohort study. Patients with preceding anticoagulant use, coagulopathy on admission labs, or presenting after 24?h from symptom onset were excluded. Lobar and deep ICH patients with baseline and follow-up computed tomography (CT) (within 24?h of admission CT) were evaluated. HE was defined primarily as relative growth >?33% given expected baseline hematoma volume differences between locations. Other commonly utilized definitions of HE: >?6 mL, and >?33% or >?6 mL, were additionally assessed. Multivariable logistic regression was used to assess the association of ICH location with HE while adjusting for previously identified covariates of HE. RESULTS:There were 59 lobar and 143 deep ICH patients analyzed. Lobar ICH patients had significantly larger baseline hematoma volumes, lower admission systolic blood pressure, and longer times to admission CT compared to deep ICH. Multivariable logistic regression revealed an association of lobar ICH with lower odds of HE (>?33%) [odds ratio (OR) 0.32; 95% confidence interval (CI) 0.11-0.93; p?=?0.04] compared to deep ICH after adjusting for baseline ICH volume, blood pressure, and time to CT. Secondary analysis did not identify an association of lobar ICH with HE defined as >?6 mL (adjusted OR 1.44; 95% CI 0.59-3.50; p?=?0.41) or >?33% or >?6 mL (adjusted OR 0.71; 95% CI 0.29-1.70; p?=?0.44). CONCLUSION:We identified less HE in lobar compared to deep ICH. The use of absolute growth thresholds in defining HE may be limited when assessing groups with largely different baseline hematoma sizes. Further study is required to replicate our findings and investigate mechanisms for HE differences between lobar and deep ICH locations.

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Rediscovering the wound hematoma as a site of hemostasis during major arterial hemorrhage.

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Rediscovering the wound hematoma as a site of hemostasis during major arterial hemorrhage.

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