Analysis of Hemostatic Effect and Safety of Local Spray Treatment With Hemocoagulase Bothrops Atrox for Injection After Resection of Colon Polyps.

Context: Postoperative bleeding after resection of colon polyps (CPs) is an extremely common adverse event with endoscopic treatment. Hemocoagulase Bothrops Atrox (HBA) is a newly discovered hemostatic substance that contains thrombin-like and coagulation kinase-like enzymes. However, research is lacking about its use for the treatment of intestinal polyps. Objective: The study intended to examine the hemostatic efficacy and safety of a local spray treatment with HBA, derived from HBA for injection, after CP resection, to provide a new hemostatic method, support HBA's use, and provide evidence for clinical decision making. Design: The research team performed a randomized controlled study. Setting: The study took place at the Affiliated Hospital of Hebei University in Baoding, Hebei, China. Participants: Participants were 200 patients with CP who received treatment at the hospital between December 2020 and December 2022. Intervention: The research team divided participants into two groups with 100 participants each, an intervention group and a control group, using the random number expression method. For hemostasis, the intervention group received a local spray treatment that used HBA for injection, and the control group received metal-clip closure or electrocoagulation. Outcome Measures: The research team measured: (1) the hemostatic efficacy; (2) clinical outcomes-time to hemostasis, hemostasis rate, rebleeding rate, and incidence of late postoperative bleeding; (3) at baseline and at 24h postintervention, the coagulation function-prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB); (4) at baseline and at 24h postintervention, PLT parameters-platelet count (PLT), procalcitonin (PCT), and mean platelet volume (MPV); (5) economic effects-total number of participants with hemostasis, hospital days, and total hospital costs; and (6) adverse reactions. Results: The total hemostatic efficacy for the intervention group was significantly higher than that of the control group (P = .027), and the time to hemostasis was significantly shorter (P < .001) and the hemostasis rate, rebleeding rate, and incidence of late postoperative bleeding were all significantly lower than those of the control group, at P = .009, P = .009, and P = .048, respectively. In addition, the intervention group's postoperative PT, TT, APTT, FIB, and MPV were all significantly lower than those of the control group (all P < .05), while its PLT and PCT were significantly higher than those of the control group (both P < .05). The intervention group's total number of participants with hemostasis, participants with hemostasis, hospital days, and total cost were significantly lower than those of the control group (all P < .05), while no significant difference existed between the groups in the incidence of adverse effects (P > .05). Conclusions: HBA has an excellent hemostatic effect on intestinal polypectomy, with convenient use and high safety. In the future, popularizing the use of HBA in the treatment of intestinal polypectomy can not only effectively guarantee the postoperative safety of patients but also could reduce their economic burden and improve the quality of clinical medical services.

Factor Xa Inhibitor-Related Intracranial Hemorrhage: Results From a Multicenter, Observational Cohort Receiving Prothrombin Complex Concentrates.

BACKGROUND: Since the approval of the oral factor Xa inhibitors, there have been concerns regarding the ability to neutralize their anticoagulant effects after intracranial hemorrhage (ICH). Multiple guidelines suggest using prothrombin complex concentrates (PCCs) in these patients on the basis of research that includes a limited number of patients with ICH. Given this, we aimed to evaluate the safety and efficacy of PCCs for factor Xa inhibitor-related ICH in a large, multicenter cohort of patients. METHODS: This was a multicenter, retrospective, observational cohort study of patients with apixaban- or rivaroxaban-related ICH who received PCCs between January 1, 2015, and March 1, 2019. The study had 2 primary analysis groups: safety and hemostatic efficacy. The safety analysis evaluated all patients meeting inclusion criteria for the occurrence of a thrombotic event, which were censored at hospital discharge or 30 days after PCC administration. Patients with intracerebral, subarachnoid, or subdural hemorrhages who had at least 1 follow-up image within 24 hours of PCC administration were assessed for hemostatic efficacy. The primary efficacy outcome was the percentage of patients with excellent or good hemostasis on the basis of the modified Sarode criteria. Secondary outcomes included an evaluation of in-hospital mortality, length of stay, infusion-related reactions, and thrombotic event occurrence during multiple predefined periods. RESULTS: A total of 663 patients were included and assessed for safety outcomes. Of these, 433 patients met criteria for hemostatic efficacy evaluation. We observed excellent or good hemostasis in 354 patients (81.8% [95% CI, 77.9-85.2]). Twenty-five (3.8%) patients had a total of 26 thrombotic events, of which 22 occurred in the first 14 days after PCC administration. One patient had documentation of an infusion-related reaction. For the full cohort of patients, in-hospital mortality was 19.0%, and the median intensive care unit and hospital lengths of stay were 2.0 and 6.0 days, respectively. CONCLUSIONS: Administration of PCCs after apixaban- and rivaroxaban-related ICH provided a high rate of excellent or good hemostasis (81.8%) coupled with a 3.8% thrombosis rate. Randomized, controlled trials evaluating the clinical efficacy of PCCs in patients with factor Xa inhibitor-related ICH are needed.

Transarterial chemoembolization for unresectable hepatocellular carcinoma: A comparison of the efficacy and safety of 2 embolic agents.

The aim of this study was to compare the efficacy and safety of 2 different embolic agents, namely gelatin sponge particle (GSP) and Lipiodol, for transarterial chemoembolization (TACE) of unresectable hepatocellular carcinoma (HCC).We retrospectively reviewed 87 consecutive patients with unresectable HCC who underwent Lipiodol TACE with lobaplatin and 87 consecutive patients with unresectable HCC who underwent GSP TACE with lobaplatin between January 2013 and June 2017 in our institution as the initial treatment. Both groups were compared considering the clinical and laboratory outcomes and imaging findings before and after TACE. Tumor response and adverse events were also evaluated.There was significant difference in the rate of complete and overall response between the groups (P = .029 and .001, respectively), specifically when the tumor size was >5 cm (P = .001). The disease control rate was significantly better in the GSP group than in the Lipiodol group (94.3% vs. 86.4%, P = .011). The response differences in higher stages were significant between the 2 groups (P = .035 and .007, respectively). The grades of adverse events were also significantly different between the groups (P = .000).GSP-as an embolic agent in TACE for HCC-could significantly increase the rate of tumor response 1 month after treatment, especially in large tumors, without any significant increase in severe adverse events, when compared to Lipiodol.

Identification of certain Panax species to be potential substitutes for Panax notoginseng in hemostatic treatments.

Panax notoginseng (Burkill) F. H. Chen ex C. H. Chow (P. notoginseng) is a highly valued Chinese materia medica having a hemostatic effect and mainly used for the treatment of trauma and ischemic cardiovascular diseases. Stringent growth requirements, weak resistance to insect pests and plant diseases, arsenic contamination and continuous cropping constitute hurdles to further increases in the agricultural production of P. notoginseng. This review focuses on the traditional uses (based on traditional Chinese medicine theory), major chemical components, biological activities, pharmacological properties, geographical distributions and historical development of taxonomy of P. notoginseng and its related species in Panax genus, including Panax japonicus C. A. Meyer (P. japonicus), Panax japonicus C. A. Meyer var. major (Burkill) C. Y. Wu et K. M. Feng (P. japonicus var. major) and Panax japonicus C. A. Meyer var. bipinnatifidus (Seem.) C. Y. Wu et K. M. Feng (P. japonicus var. bipinnatifidus) are reviewed. This review sheds light on the origin herbs of Zhujieshen (ZJS) and Zhuzishen (ZZS), e.g., P. japonicas var japonicas, P. japonicus var. major and P. japonicus var. bipinnatifidus could be used as a substitute for P. notoginseng as hemostatic herbs.

Controllable vitamin K deficiency under high-dose oral menatetrenone administration - a case report.

Vitamin (V) K deficiency may cause severe bleeding tendencies, which necessitates extreme caution. We report a case of a 30-year-old man diagnosed with VK deficiency of unknown etiology. He was treated with intravenous menatetrenone three times a week in an outpatient setting for about 1 year and 9 months. Eventually, he developed an allergic reaction to intravenous menatetrenone and was under steroid therapy. In order to reduce his hospital visits and discontinue steroid use, the pharmacist proposed to change the method of menatetrenone administration from intravenous to oral (high dose). The change in treatment method has greatly improved the patient's quality of life.

[Comparative evaluation of effectiveness and safety of the local hemostatic agents in the experiment].

Comparative evaluation of effectivennes and safety of the local hemostatic agents in the experiment. On the model side damage the femoral artery of pigs we performed a comperative test of modern local hemostatic agents (LHA): bandages on the basis of chitosan <> (TG), eGemofleks Combat> (GC), (GB) bandages on kaolin-based <> (CG), and the usual bandage 10 cm x 3 m (control group). 25 animals were divided equally into 5 groups. After 45 seconds of bleeding from 6-mm side wound of femoral artery was used LHA with a three-minute external compression and wound edges approximation. In the case of the continuation-bleeding wounds performed re-tamponade with the second package of the LHA. Hemostasis after applying the first packet never recorded in the CG group, occurred in I out of 5 animals in the groups TG and GC, 2 of 5 animals in the group GB and the control group (p>0,05). Application of two packages LHA in the TG group, GB and the control group was effective in 3 of 5 animals and in groups CG and GC - in 2 of 5 animals (p>0,05). Mortality did not differ significantly between the groups. Thus, the conventional bandage wound with ordinary tamponade in this model is not less effective than current LHA.

Four-factor prothrombin complex concentrate for life-threatening bleeds or emergent surgery: A retrospective evaluation.

PURPOSE: Previous trials investigating usage of four-factor prothrombin complex concentrate (4F-PCC) excluded patients with various thrombotic risk factors. The objective of this study was to evaluate the safety and effectiveness of 4F-PCC in a real-world setting based on an institutional protocol that does not have strict exclusion criteria. METHODS: This was a retrospective study of adult patients who received 4F-PCC. The primary outcome was a confirmed thromboembolism within 14 days after 4F-PCC administration. Secondary outcomes included international normalized ratio (INR) correction to <1.5 at first draw and incidence of INR rebound for patients undergoing reversal of warfarin and hemostatic effectiveness for patients experiencing a bleed. RESULTS: Ninety-three patients received 4F-PCC. Sixty-three (67.7%) were reversed for bleeding and 30 (32.3%) for surgery. Eleven patients (11.8%) developed a thromboembolism within 14 days. The median (interquartile range) time to event was 5 (2-7) days. Significant risk factors were heparin-induced thrombocytopenia (P= .01) and major surgery within 14 days (P= .02), as well as the presence of >6 thrombotic risk factors (P= .01). For patients post-warfarin reversal, 45/63 (71.4%) achieved INR correction at first draw, 55/63 (87.3%) achieved INR correction within 24 hours, and 14/55 (25.5%) experienced INR rebound. Of these 14 patients, 8 (57.1%) did not receive concomitant vitamin K. CONCLUSIONS: 4F-PCC was associated with a notable thromboembolic risk. All patient-specific risk factors should be considered prior to administration. 4F-PCC remains a useful agent for warfarin reversal. Lack of concomitant vitamin K may contribute to INR rebound.

Half-life extended factor VIII for the treatment of hemophilia A.

Prophylactic infusion of factor VIII (FVIII) prevents joint bleeding and other hemorrhages in patients with hemophilia A. Conventional FVIII concentrates have a short half-life, with an average of about 12 h in adults, ranging in individual patients between 6 and 24 h, and even shorter in younger children. Therefore, effective prophylaxis requires frequent intravenous injection, usually three times per week or every other day. Several technologies are currently under investigation to extend the half-life of FVIII, including Fc fusion (Eloctate, Elocta, efmoroctocog alfa), addition of polyethylene glycol (turoctocog alfa pegol [N8-GP], BAY 94-9027, BAX 855), and a single-chain construct (CSL627). This review summarizes characteristics of products in clinical development and discusses their potential benefits.

Effects of hemostatic agents on shear bond strength of orthodontic brackets.

OBJECTIVES: The aim of this study was to determine the effects of blood contamination and hemostatic agents on shear bond strength (SBS) of brackets and bond failure. MATERIALS AND METHODS: The study material consisted of 57 freshly extracted human premolar and randomly divided into four groups: Group I, control group (n0 = 14); Group II, contamination with blood (n = 13); Group III, contamination with epinephrine ( n = 14); and Group IV, contamination with Ankaferd blood stopper (ABS) ( n = 16). After the bracket bonding procedure, all bonded teeth thermal cycled in deionized water at 5 ± 2°C to 55 ± 2°C for 500 cycles. SBS was applied using a universal test machine. RESULTS: According to Kruskal-Wallis test significant differences were found among the groups P < 0.05. Furthermore, significant differences were recorded between groups with Mann-Whitney U statistical test with Bonferroni correction (P = 0.0083). CONCLUSIONS: Examples contaminated with blood showed a statistically significant lower in vitro SBS than those contaminated with epinephrine, ABS, and control groups. CLINICAL SIGNIFICANCE: In impacted tooth surgical operations, blood contamination poses a substantial risk of bond failure in bonding attachments applications to the impacted teeth. Epinephrine and ABS may be used on surgical exposed impacted teeth operation for the prevention of blood contamination.

Treatment of hemorrhagic radiation-induced proctopathy with a 4% formalin application under perianal anesthetic infiltration.

AIM: To evaluate the results of hemorrhagic radiation proctopathy treatment with a 4% formalin application. METHODS: A prospective study was performed. Over a three-year period, 38 patients underwent 4% formalin application under perianal anesthetic infiltration for hemorrhagic radiation proctopathy. All patients included in the study were irradiated for prostate cancer. The patients ranged in age from 56-77 years (average 70 ± 5 years). All of the patients were referred for formalin therapy after noninvasive management had failed. Twenty-four (63.2%) patients underwent a single application, 10 (26.3%) patients underwent 2 applications, and 4 (10.5%) patients underwent 3 applications. RESULTS: Two to 36 mo (average 12 ± 3 mo) following treatment, 34 patients were interviewed (four were lost to follow-up). Twenty (58.8%) subjects reported complete cure, 8 (23.5%) subjects reported significant improvement, and 6 (17.7%) subjects reported no change. One patient (who underwent a colostomy at a regional hospital with no specialized services available for previous bleeding episodes from radiation proctopathy) was cured, and the colostomy was closed. One patient (2.6%) developed rectal mucosal damage after the second application. CONCLUSION: A 4-min application of 4% formalin for hemorrhagic radiation-induced proctopathy under perianal anesthetic infiltration in patients who have received external radial radiation therapy for prostate cancer is simple, reasonably safe, inexpensive, generally well tolerated, and effective.

A new hemostatic agent (Ankaferd Blood Stopper(®)) in tubeless percutaneous nephrolithotomy: a prospective randomized study.

PURPOSE: The present study evaluates the efficiency and reliability of a hemostatic agent ABS (Ankaferd Blood Stopper(®)) in tubeless percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: A total of 90 patients were divided into two subgroups. The first group had ABS applied during the intervention, whereas the control group underwent regular tubeless PCNL in this prospective randomized study. Age, stone size, operative time, postoperative hemoglobin change, renal parenchyma thickness, postoperative ureteral catheter removal time, access number, nephroscope time, blood transfusion rate, serum creatinine change, complication rate, visual analogue scale (VAS), and hospitalization time were compared between the two groups. RESULTS: Preoperative and postoperative data obtained from both groups were compared. No statistically meaningful differences were found related to variables of mean age, stone size, access number, serum creatinine change, operative time, renal parenchyma thickness, VAS scores, and hospitalization period. Whereas the nephroscope time (minutes) was longer in the ABS group (Group 1 [G1]:3, 33±1, 72 vs G2:2, 62±1, 43, P=0.035), hemoglobin (Hb) decrease, and urine clarity time were statistically lower compared with the control group. Hb decrease was (mg/dL) (G1: 1.40±1.04 vs G2: 1.84±1.15, P=0.034), and urine clarity time was (hour) (G1: 9.60±5.50 vs G2: 11.95±4.71, P=0.012), respectively. Complications were encountered in three (6.6%) patients of the ABS group and in four (8.8%) of the control group. CONCLUSION: ABS is an efficient and reliable hemostatic agent in tubeless PCNL. Comparative studies are needed, however, with other hemostatic agents that might be applied in tubeless PCNL.

Transcatheter arterial embolization of acute arterial bleeding in the upper and lower gastrointestinal tract with N-butyl-2-cyanoacrylate.

PURPOSE: To assess the clinical utility and safety of transcatheter arterial embolization with N-butyl-2-cyanoacrylate (NBCA) for urgent control of acute arterial bleeding in the upper and lower gastrointestinal tract. MATERIALS AND METHODS: Therapeutic NBCA embolization was performed in 37 patients (39 cases; mean age, 67.8 years) with acute upper (n = 16) or lower (n = 23) gastrointestinal tract bleeding after endoscopic management had failed. Transcatheter arterial embolization was performed using 1:1 to 1:5 mixtures of NBCA and iodized oil. The most common etiologies of bleeding were colonic diverticulosis (n = 13), malignancy (n = 11), and benign ulcer (n = 7). Coagulopathy was present in 11 patients, and 23 patients were hemodynamically unstable before NBCA embolization. Histologic examination for bowel ischemia was also performed in five patients who underwent excision of the lesion after NBCA embolization. RESULTS: The technical success rate was 100%. Recurrent bleeding occurred in two patients. Complete hemostasis was achieved in all 11 patients with coagulopathy. Ulcers induced by transcatheter arterial embolization were noted in 6 of 20 patients who underwent endoscopic examination; the ulcers were successfully treated with conservative measures. Histologic examination revealed that despite inflammatory reactions in and around the vessels, no intestinal necrosis secondary to NBCA embolization was found. Hepatic abscess occurred in two cases, and ischemia of the lower limb occurred in one case; these complications were managed by percutaneous drainage and bypass surgery. CONCLUSIONS: Transcatheter arterial embolization with NBCA is a good treatment option with a high rate of complete hemostasis and a low recurrent bleeding rate, even in patients with coagulopathy.

Transcatheter arterial embolization with N-butyl cyanoacrylate for acute life-threatening gastroduodenal bleeding uncontrolled by endoscopic hemostasis.

PURPOSE: To investigate the feasibility, efficacy, and safety of transcatheter arterial embolization with N-butyl cyanoacrylate (NBCA) for gastroduodenal nonvariceal bleeding uncontrolled by endoscopic hemostasis. MATERIALS AND METHODS: Between January 2006 and December 2011, a total of 317 patients underwent emergent endoscopic therapy for nonvariceal gastroduodenal bleeding, but hemostasis was not achieved in 20 cases. Emergent surgery was performed immediately following endoscopy in two patients. Arteriography was performed in the remaining 18 patients, and embolization with NBCA was performed in 15 patients (mean age, 71.3 y) in whom the bleeding site was detected on arteriography. For embolization, NBCA was mixed with iodized oil at a ratio of 1:1.5-1:4, and no other embolic material was used in the procedure. Technical and clinical success rates, recurrent bleeding, procedural time, complications, and clinical outcomes were determined for each procedure. RESULTS: Embolization with NBCA was technically and clinically successful in all procedures, without major complications. No patient receiving embolization with NBCA experienced recurrent bleeding or required further treatment after the one-session procedure. All patients were discharged after clinical improvement. The time between puncture of the femoral artery and completion of embolization ranged from 25 to 240 minutes (mean, 66 min), and the time between the microcatheter reaching the ultimate catheter location selected for embolization and hemostasis ranged from 142 to 550 seconds (mean, 322s). CONCLUSIONS: In this limited series, embolization with NBCA was found to be a safe, feasible, and effective treatment for gastroduodenal arterial bleeding when endoscopic hemostasis had failed.

Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects.

Vitamin K is required for the carboxylation of Gla-proteins in the liver (coagulation factors) and extra-hepatic tissues, such as bone (osteocalcin, OC), and arterial wall (matrix Gla-protein, MGP). Although the coagulation factors are essentially fully carboxylated under normal conditions, 10-40 % of OC and MGP remains undercarboxylated. We were therefore interested to study the dose-response effects of extra intake of menaquinones on the carboxylation of the extra-hepatic Gla-proteins. A total of forty-two healthy Dutch men and women aged between 18 and 45 years were randomised into seven groups to receive: placebo capsules or menaquinone-7 (MK-7) capsules at a daily dose of 10, 20, 45, 90, 180 or 360 µg. Circulating uncarboxylated OC (ucOC), carboxylated OC (cOC) and desphospho-uncarboxylated MGP were measured by ELISA. The ucOC:cOC ratio was calculated from circulating ucOC and cOC values. Endogenous thrombin potential and peak height were determined by calibrated automated thrombography. To increase the statistical power, we collapsed the treatment groups into three dosage groups: placebo, low-dose supplementation (doses below RDA, Commission Directive 2008/100/EC), and high-dose supplementation (doses around RDA, Commission Directive 2008/100/EC). MK-7 supplementation at doses in the order of the RDA (Commission Directive 2008/100/EC) increased the carboxylation of circulating OC and MGP. No adverse effects on thrombin generation were observed. Extra MK-7 intake at nutritional doses around the RDA (Commission Directive 2008/100/EC) improved the carboxylation of the extra-hepatic vitamin K-dependent proteins. Whether this improvement contributes to public health, i.e. increasing the protection against age-related diseases needs further investigation in specifically designed intervention trials.

Effects of a new hemostatic agent Ankaferd Blood Stopper(®)on the intraocular tissues in rat model.

PURPOSE: To investigate the histopathological changes due to administration of Ankaferd Blood Stopper(®) (ABS) into intraocular tissues by an anterior chamber and intravitreal injections. METHODS: Twenty Wistar albino rats were divided into four equal groups. Group 1 was injected 0.01 mL ABS into anterior chamber. Group 2 was injected intravitreal 0.02 mL ABS. Groups 3 and 4, which were used as controls, were injected into the anterior chamber and intravitreal 0.01 mL and 0.02 mL balanced salt solution (BSS), respectively. At 2, 5, 10, 15 and 20 days after injection, the eyes were examined under an operating microscope and were subsequently enucleated for histopathological examination. RESULTS: Ophthalmic examination of the rats prior to enucleation revealed ocular complications ranging from conjunctival hyperemia to corneal perforation in group 1 and increased conjunctival hyperemia and discharge in group 2. No physical and histopathological anomalies were detected in groups 3 and 4. All eyes in group 1 showed mixed type inflammatory cell reaction, foreign-body reaction, stromal congestion, disintegration of the collagen fibers and loss of the epithelium of the posterior wall in the iris and ciliary body were observed histopathologically. All eyes in group 2 showed disintegration and separation of the retina, brown pigment accumulation and mixed type inflammatory cell reaction. CONCLUSION: Our results indicate that the commercially available form of ABS solution exerts a toxic effect on intraocular tissues. We consider that the intraocular use of different concentrations, rather than multiple time point of ABS should be investigated.

Postoperative adhesions after application of topical hemostatic agents: outcomes in a rat partial nephrectomy model.

OBJECTIVE: To compare 3 kinds of topical hemostatic agents in terms of adhesive strength, control of hemorrhage, and postoperative intra-abdominal adhesions in an experimental partial nephrectomy (PN) model. METHODS: A total of 27 Wistar rats were divided into 5 groups. PN was performed in 6 rats (control group) with the conventional technique, in which the lower pole of the kidney was excised and sutured after hilar control. In 5 rats, oxidized cellulose was placed over the excised part of the kidney following conventional technique. In 6 rats, the hemostatic plant extract was used without hilar control. In 5 rats, the hemostatic agent chitosan was used without hilar control. As a sham group, 5 rats underwent a laparotomy and handling of the renal pedicle without the removal of renal pole. On the tenth day after the operation, the degree of adhesions to the operated kidney were evaluated. Histopathological evaluation was also performed by a blinded pathologist. RESULTS: Mean warm ischemia times for control and oxidized cellulose groups were 4.85 ± 0.75 and 4.28 ± 1.28 minutes, respectively (P = .662). Wound healing was excellent in all groups except in 1 rat in the chitosan group. Chitosan was associated with significantly higher intestinal and peritoneal adhesion scores, although histopathologically comparable scores were revealed. CONCLUSION: In our rat model, chitosan and the hemostatic plant extract were as effective as conventional suturing in achieving hemostasis even without hilar control. Warm ischemia was eliminated and PN time was significantly decreased. The use of oxidized cellulose was not associated with higher scores of adhesion, suppuration, or hematoma.

Evaluation of a haemostatic agent in rabbits.

Topical hemostatic agents are applied locally to areas of injured vascular endothelium to control local bleeding. Ankaferd Blood Stopper (ABS) has gained approval in Turkey and Bosnia-Herzegovina as a topical haemostatic agent for external post-surgical and post-dental surgery bleeding. The safety of topical use of ABS has been demonstrated in numerous in vitro and in vivo animal models, as well as in a clinical Phase I trial in humans. ABS, besides its haemostatic activity, also has in vitro anti-infectious and anti-neoplastic effects. To assess potential detrimental effects of intravenous administration of ABS into intact systemic circulation in a rabbit experimental model, one milliliter of ABS was administered intravenously into the systemic circulation of twelve rabbits which were included in the study via the marginal ear vein. Animals were observed for 1 hr before euthanasia was performed by administering 40 mg of intracardiac suxamethonium chloride. In the event of death (cardiopulmonary arrest) before the end of the planned observation period of 60 minutes, time of death was recorded and histopathological examination of the liver and spleen was commenced. Ten rabbits were alive by the end of the planned observation period, without showing any clear signs of discomfort, whereas two animals died within five minutes after systemic administration of intravenous ABS. Postmortem histopathological examination of the livers and spleens of all animals' revealed findings consistent with hepatic venous outflow obstruction. Systemic intravascular administration of ABS into intact vascular endothelium should never be performed in any setting. Further experimental and clinical studies on this liquid hemostatic agent should proceed by accepting ABS as purely a topical haemostatic agent, to be applied solely to areas of injured vascular endothelium.

Blood-brain barrier breakdown and repair by Src after thrombin-induced injury.

OBJECTIVE: Thrombin mediates the life-threatening cerebral edema that occurs after intracerebral hemorrhage. Therefore, we examined the mechanisms of thrombin-induced injury to the blood-brain barrier (BBB) and subsequent mechanisms of BBB repair. METHODS: Intracerebroventricular injection of thrombin (20U) was used to model intraventricular hemorrhage in adult rats. RESULTS: Thrombin reduced brain microvascular endothelial cell (BMVEC) and perivascular astrocyte immunoreactivity-indicating either cell injury or death-and functionally disrupted the BBB as measured by increased water content and extravasation of sodium fluorescein and Evans blue dyes 24 hours later. Administration of nonspecific Src family kinase inhibitor (PP2) immediately after thrombin injections blocked brain edema and BBB disruption. At 7 to 14 days after thrombin injections, newborn endothelial cells and astrocytes were observed around cerebral vessels at the time when BBB permeability and cerebral water content resolved. Delayed administration of PP2 on days 2 through 6 after thrombin injections prevented resolution of the edema and abnormal BBB permeability. INTERPRETATION: Thrombin, via its protease-activated receptors, is postulated to activate Src kinase phosphorylation of molecules that acutely injure the BBB and produce edema. Thus, acute administration of Src antagonists blocks edema. In contrast, Src blockade for 2 to 6 days after thrombin injections is postulated to prevent resolution of edema and abnormal BBB permeability in part because Src kinase proto-oncogene members stimulate proliferation of newborn BMVECs and perivascular astrocytes in the neurovascular niche that repair the damaged BBB. Thus, Src kinases not only mediate acute BBB injury but also mediate chronic BBB repair after thrombin-induced injury.

Efficacy of transarterial embolization with arsenic trioxide oil emulsion in a rabbit VX2 liver tumor model.

PURPOSE: To investigate the anticancer activity of transarterial embolization with arsenic trioxide (As(2)O(3)) oil emulsion, as well as its hepatic and renal toxicity, in a rabbit VX2 liver model. MATERIALS AND METHODS: VX2 carcinomas were grown in rabbit livers, followed by transarterial embolization with high-dose As(2)O(3) (5 mg/kg with 0.2 mL Lipiodol, n = 7), low-dose As(2)O(3) (1 mg/kg with 0.2 mL Lipiodol, n = 7), or control (0.2 mL Lipiodol, n = 7). The growth ratios and residual viable proportions of the tumors were estimated by multi-detector row computed tomography and histopathologic examination, respectively. Hepatic and renal toxicity was evaluated by means of blood biochemical analysis. RESULTS: The growth ratios of the tumors differed significantly among the three groups (P = .008). The high-dose As(2)O(3) group showed significantly lower tumor growth ratios than the control group (mean +/- SD, 14.8% +/- 78.6 vs 794.0% +/- 156.2; P = .008). The residual viable proportions of the tumors were significantly lower in the high-dose (9.5% +/- 8.8) and low-dose (13.0% +/- 9.1) As(2)O(3) groups than in the control group (44.5% +/- 5.2; P < .017). Blood chemical concentrations indicating hepatic and renal toxicity did not differ among the three groups before or after transarterial embolization (P > .05). CONCLUSIONS: Transarterial embolization with As(2)O(3) iodized oil emulsion in rabbit VX2 liver tumors has anticancer effects without significant increase in hepatic and renal toxicity.