Balloon-Assisted Thrombin Injection of a Profunda Femoral Pseudoaneurysm Using Radial Access.

The profunda femoral artery is an uncommon location for a pseudoaneurysm and is technically challenging to resolve with traditional techniques, such as ultrasound-guided compression or thrombin injection, owing to its deep anatomical location. Balloon-assisted thrombin injection (BATI) is a technique that has been shown to be effective using contralateral access for technically difficult pseudoaneurysms in high-risk surgical patients. We report a case of BATI using radial access in a patient with a profunda femoral artery pseudoaneurysm.

Intra-Sac Injection of Thrombin During Endovascular Aneurysm Repair to Remedy Type II Endoleak and Promote Sac Shrinkage.

PURPOSE: To evaluate the safety and effectiveness of intra-sac thrombin injection to remedy type II endoleaks (T2ELs) during endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: 224 cases abdominal aortic aneurysm (AAA) were treated with EVAR. For the 52 cases of intra-operative type II endoleaks and 8 cases of ruptured AAAs, after the grafts were deployed, thrombin was injected into the aneurysm sac through a preset catheter. The occurrence of endoleaks post-EVAR were followed up with by Computed Tomography (CT) angiogram. The diameter and the volume of the aneurysm sac were also measured. Endpoints included incidence of T2ELs, AAA sac shrinkage and re-intervention rate and all-cause mortality. RESULTS: The overall technical success rate was 100%. Fifty-two patients were followed up with for 9-56 (median 24) months. No serious complications were observed during follow-up. The incidence of endoleak was 5.8% (3/52) during follow-up. The maximum diameter of the aneurysm decreased from 61.1 ± 14.2 mm to 53.7 ± 10.6 mm, 47.9 ± 8.3 mm and 43.7 ± 7.2 mm (87.9%, 78.4% and 71.5% of pre-EVAR) at the 6-month, 1-year and 2-year follow-up, respectively (P < .05). The volume of the aneurysm sac shrank from 236.2 ± 136.2 cm3 to 202.6 ± 114.1 cm3, 155.6 ± 68.4 cm3 and 129.7 ± 52.4 cm3 (85.8%, 65.9%, and 54.9% of pre-EVAR) at the 6-month, 1-year and 2-year follow-up, respectively (P < .05). The rate of various endoleaks was 5.8% (3/52) and the re-intervention rate was 1.9% (1/52) in this research. CONCLUSIONS: Clinical outcomes show that intra-sac injection of thrombin during EVAR is safe and may be effective in remedying small amount and low-velocity endoleaks and promoting shrinkage of the aneurysm sac.

Thrombin and Thrombin-Incorporated Biomaterials for Disease Treatments.

Thrombin, a coagulation-inducing protease, has long been used in the hemostatic field. During the past decades, many other therapeutic uses of thrombin have been developed. For instance, burn treatment, pseudoaneurysm therapy, wound management, and tumor vascular infarction (or tumor vasculature blockade therapy) can all utilize the unique and powerful function of thrombin. Based on their therapeutic effects, many thrombin-associated products have been certificated by the Food and Drug Administration, including bovine thrombin, human thrombin, recombinant thrombin, fibrin glue, etc. Besides, several thrombin-based drugs are currently undergoing clinical trials. In this article, the therapeutic uses of thrombin (from the initial hemostasis to the latest cancer therapy), the commercially available drugs associated with thrombin, and the pros and cons of thrombin-based therapeutics (e.g., adverse immune responses related to bovine thrombin, thromboinflammation, and vasculogenic "rebounds") are summarized. Further, the current challenges and possible future research directions of thrombin-incorporated biomaterials and therapies are discussed. It is hoped that this review may provide a valuable reference for researchers in this field and help them to design safer and more effective thrombin-based drugs for fighting against various intractable diseases.

[Effect of recombinant human thrombin for hemostasis in liver resection: a randomized controlled phase â ¢ clinical trial].

Objective: To evaluate the hemostatic efficacy, safety and immunogenicity of recombinant human thrombin in the treatment of liver wounds that still ooze after conventional surgical hemostasis. Methods: A multicenter, stratified randomized, double-blind, placebo-controlled phase Ⅲ trial with a planned enrollment of 510 subjects at 33 centers, with a 2∶1 randomization to the thrombin group versus the placebo group. An interim analysis will be conducted after approximately 70% of the subjects have completed the observation period. The primary efficacy endpoint was the rate of hemostasis within 6 minutes at the point of bleeding that could be evaluated. Safety analysis was performed one month after surgery, and the positive rates of anti-drug antibody (ADA) and neutralizing antibody were evaluated. Results: At the interim analysis, a total of 348 subjects had been randomized and received the study drug (215 were male and 133 were female). They were aged 19-69 (52.9±10.9)years. Among them, 232 were in the thrombin group and 116 were in the placebo group, with balanced and comparable demographics and baseline characteristics between the two groups. The hemostasis rate at 6 minutes was 71.6% (95%CI:65.75%-77.36%) in the thrombin group and 44.0% (95%CI: 34.93%-53.00%) in the placebo group, respectively (P<0.001). No grade≥3 drug-related adverse events and no drug-related deaths were reported from the study.No recombinant human thrombin-induced immunologically-enhanced ADA or immunologically-induced ADA was detected after topical use in subjects. Conclusion: Recombinant human thrombin has shown significant hemostatic efficacy and good safety in controlling bleeding during liver resection surgery, while also demonstrating low immunogenicity characteristics.

Bothrops venom-induced hemostasis disorders in the rat: Between Scylla and Charybdis.

Hemostasis impairment represents the most threatening consequence of Viperidae envenoming, notably with Bothrops genus. In the French departments of America, B. atrox envenomation in French Guiana may lead to bleeding while B. lanceolatus envenomation in Martinique to thrombosis. Bleeding related to B. atrox envenomation is attributed to vascular damage mediated by venom metalloproteinases and blood uncoagulable state resulting from thrombocytopenia and consumptive coagulopathy. Thrombosis related to B. lanceolatus envenomation are poorly understood. We aimed to compare the effects of B. atrox and B. lanceolatus venoms in the rat to identify the determinants of the hemorrhagic versus thrombotic complications. Viscoelastometry (ROTEM), platelet count, plasma fibrinogen, thrombin generation assay, fibrinography, endothelial (von Willebrand factor, ADAMTS13 activity, ICAM-1, and soluble E-selectin), and inflammatory biomarkers (IL-1ß, IL-6, TNF-α, MCP-1, and PAI-1) were determined in blood samples obtained at H3, H6, and H24 after the subcutaneous venom versus saline injection. In comparison to the control, initial fibrinogen consumption was observed with the two venoms while thrombocytopenia and reduction in the clot amplitude only with B. atrox venom. Moreover, we showed an increase in thrombin generation at H3 with the two venoms, an increase in fibrin generation accompanied with hyperfibrinogenemia at H24 and an increase in inflammatory biomarkers with B. lanceolatus venom. No endothelial damage was found with the two venoms. To conclude, our data support two-sided hemostasis complications in Bothrops envenoming with an initial risk of hemorrhage related to platelet consumption and hypocoagulability followed by an increased risk of thrombosis promoted by the activated inflammatory response and rapid-onset fibrinogen restoration.

Silica nanoparticles trigger phosphatidylserine exposure in red blood cells and induce thrombosis risk.

Silica nanoparticles (SiNPs) have attracted increasing attention for their health effects due to the increased risk of exposure to human bodies via diverse routes. Considering that SiNPs enter the circulatory system and inevitably encounter red blood cells (RBCs), it is necessary to investigate their risk of causing erythrocytotoxicity. In this study, three sizes of SiNPs (SiNP-60, SiNP-120, and SiNP-200) were tested for their effects on mouse RBCs. The results showed that SiNPs could induce hemolysis, morphological changes, and phosphatidylserine (PS) exposure in RBCs in a particulate size-related manner. Further investigations on the underlying mechanism indicated that SiNP-60 exposure increased intracellular reactive oxidative species (ROS) generation and subsequently caused the phosphorylation of p38 and ERK1/2 in RBCs. The addition of antioxidants or inhibitors of mitogen-activated protein kinase (MAPK) signaling significantly attenuated PS exposure in RBCs and ameliorated SiNP-induced erythrocytotoxicity. Moreover, ex vivo assays using platelet-rich plasma (PRP) showed that SiNP-60-induced PS exposure in RBCs could trigger thrombin-dependent platelet activation. The contrary evidence from the assays of PS blockage and thrombin inhibition further confirmed that SiNP-60-induced platelet activation was dependent on PS externalization in RBCs, concomitantly with thrombin formation. These findings revealed the procoagulant and prothrombotic effects of SiNPs through the regulation of PS externalization in RBCs, and may be of great help in bridging the knowledge gap on the potential cardiovascular hazards of particulate silica from both artificial and naturally occurring origins.

Comparison of three different treatment methods for traumatic and Iatrogenic peripheral artery pseudoaneurysms.

OBJECTIVE: To compare the efficacy of open surgery (OS), endovascular interventions (EIs), and ultrasound-guided thrombin injection (UGTI) for the treatment of peripheral arterial pseudoaneurysms (PAs). METHODS: From January 1, 2001, to February 10, 2021, 38 patients diagnosed with traumatic and iatrogenic PAs treated with OS, EI, and UGTI were retrospectively analyzed. There were 18 females and 20 males, with an age of 56.47 ± 14.08 years (range,17-87 years). Anesthesia modality, operation duration, blood transfusion, duration of hospital stay, primary and secondary success rates, and complication rate were used to evaluate the surgical outcomes. RESULTS: There were 11 cases under regional anesthesia and 4 under general anesthesia in OS group, 9 under regional anesthesia and 1 under general anesthesia in EI group, and no regional or general anesthesia was required in UGTI group. There was no significant differences between any two groups (χ2  = 39.80, p < 0.05). The blood tranfusion amount (units) were 3.6 ± 6.0, 0.8 ± 2.5, 0.0 ± 0.0 for OS, EI, and UGTI groups, respectively, with significant difference between OS and UGTI groups (F = 3.03, p < 0.05). The operation duration (minutes) of OS, EI, and UGTI groups were 80.0 ± 41.9, 56.0 ± 8.4, and 22.7 ± 5.3, respectively, with significant difference between any two groups (F = 15.69, p < 0.05). The duration of hospital stay (days) were 47.7 ± 39.0, 31.5 ± 17.6, and 16.3 ± 9.5, repectively, with significant difference between any two groups (F = 47.73, p < 0.05). The primary clinical success rates were 80% (12/15), 90% (9/10), and 92.3% (12/13) in OS,EI, and UGTI groups, respectively, with no significant difference between any two groups (χ2  = 0.34, p > 0.05). The secondary clinical success rates were 100% for all three groups. The overall complication rates of OS, EI, and UGTI groups were 20% (3/15), 10% (1/10), and 7.7% (1/13), respectively, with no significant difference between any two groups (χ2  = 1.00, p > 0.05). The infection rates were 13.3% (2/15), 10% (1/10), and 0% (0/13) in OS, EI, and UGTI groups respectively, with no significant difference between any two groups (χ2  = 1.80, p > 0.05). The reintervention rates were 6.7% (1/15), 0% (0/10), 7.7% (1/13) in OS, EI, and UGTI groups, respectively, with no significant difference between two groups (χ2  = 0.95, p > 0.05). Neuralgia was relieved in all patients. CONCLUSIONS: OS, EI, and UGTI are efficacious and safe options for the treatment of appropriate patients with traumatic and iatrogenic PAs. UGTI would be considered as a first-line therapy for this condotion.

Efficacy and Safety of a Thrombin-Containing Collagen-Based Hemostatic Agent in Spinal Surgery: A Randomized Clinical Trial.

OBJECTIVE: When common hemostatic methods, such as suturing, cautery, and compression, fail to arrest bleeding during surgery, various local hemostatic agents are used. We aimed to evaluate the hemostatic efficacy and safety of CollaStat (Dalim Tissen Co. Ltd., Seoul, Korea), a novel thrombin-containing, collagen-based topical haemostatic agent used in spinal surgery, by comparing it with Floseal (Baxter Healthcare, Deerfield, Illinois, USA). METHODS: We performed a randomized controlled trial in 78 patients who underwent spinal surgery. The participants were randomly assigned to either an intervention group (use of CollaStat) or a control group (use of Floseal). We compared successful haemostasis rate, time to hemostasis, length of hospital stay, amount of fluid drainage, and rate of adverse events between the 2 groups. RESULTS: The hemostasis success rate was 94.87% in the intervention group and 97.44% in the control group. The hemostatic efficacy and safety of CollaStat were found to be noninferior to those of Floseal since the higher limit (11.09%) of the confidence interval (CI) for the difference with Floseal was greater than the prespecified noninferiority margin of -13%. There were no statistically significant differences at the 5% level in hemostasis time, number of hemostatic agents used, hospitalization period, and amount of drainage between the 2 groups. Also, there was no incidence of medical device-related serious adverse events or adverse events in both groups. CONCLUSIONS: The hemostatic efficacy and safety of CollaStat were found to be noninferior to those of Floseal. Therefore CollaStat can be safely and effectively used in spinal surgery.

Thrombin Generation and Cirrhosis: State of the Art and Perspectives.

Epidemiological and laboratory studies performed in the last decades have changed our understanding of coagulopathy in cirrhosis, from a condition at increased risk of hemorrhagic events to one at higher thrombotic risk. However, it is not clear whether the decrease in factors that promote (except factor [F] VIII) versus inhibit coagulation in patients with cirrhosis results in a rebalanced state or in a hypercoagulable phenotype. This issue can be partially addressed using thrombin generation assays (TGA), which unlike routine clotting tests (prothrombin time or activated partial thromboplastin time) are sensitive to both procoagulant factors and coagulation inhibitors. However, many preanalytical issues and variable analytical methodologies used in TGAs complicate data analysis and interlaboratory comparisons. The introduction of TGAs in which activators of the protein C pathway (particularly soluble forms of thrombomodulin [TM]) are added has allowed detection of a reduced anticoagulant effect of TM or even a hypercoagulable phenotype as judged by endogenous thrombin potential. However, inter- and intra-assay variability may be greater with this TGA variant compared with "standard" TGAs. TGAs also allowed identifying main determinants of the hypercoagulability phenotype in the presence of TM: acquired antithrombin and protein C deficiencies, and elevated FVIII levels. The aim of this narrative review is to summarize the preanalytical and methodological variables of TGAs and also the findings of the main studies that have evaluated TGAs in patients with cirrhosis. The review also provides some propositions for future studies and outlines some perspectives on the potential implementation of this promising tool in clinical practice for the study of coagulation in patients with cirrhosis.

Fibrin and Thrombin Sealants in Vascular and Cardiac Surgery: A Systematic Review and Meta-analysis.

OBJECTIVE: In vascular and cardiac surgery, the ability to maintain haemostasis and seal haemorrhagic tissues is key. Fibrin and thrombin based sealants were introduced as a means to prevent or halt bleeding during surgery. Whether fibrin and thrombin sealants affect surgical outcomes is poorly established. A systematic review and meta-analysis was performed to examine the impact of fibrin or thrombin sealants on patient outcomes in vascular and cardiac surgery. DATA SOURCES: Cochrane CENTRAL, Embase, and MEDLINE, as well as trial registries, conference abstracts, and reference lists of included articles were searched from inception to December 2019. REVIEW METHODS: Studies comparing the use of fibrin or thrombin sealant with either an active (other haemostatic methods) or standard surgical haemostatic control in vascular and cardiac surgery were searched for. The Cochrane risk of bias tool and the ROBINS-I tool (Risk Of Bias In Non-randomised Studies - of Interventions) were used to assess the risk of bias of the included randomised and non-randomised studies; quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two reviewers screened studies, assessed risk of bias, and extracted data independently and in duplicate. Data from included trials were pooled using a random effects model. RESULTS: Twenty-one studies (n = 7 622 patients) were included: 13 randomised controlled trials (RCTs), five retrospective, and three prospective cohort studies. Meta-analysis of the RCTs showed a statistically significant decrease in the volume of blood lost (mean difference 120.7 mL, in favour of sealant use [95% confidence interval {CI} -150.6 - -90.7; p < .001], moderate quality). Time to haemostasis was also shown to be reduced in patients receiving sealant (mean difference -2.5 minutes [95% CI -4.0 - -1.1; p < .001], low quality). Post-operative blood transfusions, re-operation due to bleeding, and 30 day mortality were not significantly different for either RCTs or observational data. CONCLUSION: The use of fibrin and thrombin sealants confers a statistically significant but clinically small reduction in blood loss and time to haemostasis; it does not reduce blood transfusion. These Results may support selective rather than routine use of fibrin and thrombin sealants in vascular and cardiac surgery.

Ultrasound-guided thrombin injections for arterial pseudoaneurysms: a 14-year study conducted at King Khalid University Hospital Vascular Lab.

BACKGROUND: Arterial pseudoaneurysms are a well-known complication resulting from procedures requiring arterial wall puncture. Previously, surgical repair was the definitive treatment option for arterial pseudoaneurysms despite being relatively invasive and time-consuming. Ultrasound-guided thrombin injection (UGTI) has become the standard of care since its initial description back in 1997. We aimed to evaluate the safety and efficacy of UGTI for the treatment of arterial pseudoaneurysms at the King Khalid University Hospital Vascular Lab. METHODS: A retrospective analysis of prospectively maintained data was conducted on all patients diagnosed with arterial pseudoaneurysms by Doppler ultrasound between 2006 and 2019. Patients with large arterial pseudoaneurysms (>1.5 cm) qualified for thrombin injections. Individuals with a known hypersensitive to thrombin were excluded. All included patients were treated with UGTI until resolution and were followed at postoperative days 7 and 30. RESULTS: In all, 35 patients qualified for thrombin injections. The mean age of the included patient population was 56.5 (range, 24-81) years. The majority of them were hypertensive (N.=26, 74.3%), and a quarter of them were on anticoagulant treatment (N.=9, 25%). The mean thrombin injection dose was 1000 U (range, 500-1500 U). In 34 of 35 (97.1%) patients, a thrombin injection resulted in complete thrombosis of the pseudoaneurysm lumen within a few seconds. There were no complications or recurrence of pseudoaneurysm after UGTI during the follow-up period. CONCLUSIONS: Throughout the study period of 14 years, we did not encounter any procedural complications or arterial pseudoaneurysm recurrence. This is attributed to a safe procedural technique and proper patient selection. UGTI for arterial pseudoaneurysms is a safe, successful, and convenient treatment for both patients and surgeons.

Comparison of the Efficacy and Safety of Two Dosing Protocols for Ultrasound Guided Thrombin Injection in Patients with Iatrogenic Femoral Pseudoaneurysms.

OBJECTIVE: Ultrasound guided thrombin injection (UGTI) is a minimally invasive method of treatment for iatrogenic post-catheterisation femoral pseudoaneurysms (psAs). The optimal dosing protocol for UGTI has not been established. The aim of the study was to compare the success and complication rates between two different dosing protocols (the most commonly used "standard dose protocol" and the "low dose protocol," which is the fractionated administration of smaller thrombin doses of up to 40 IU every 15 s) in patients with a psA with sac volume of ≥1 mL. METHODS: This was a retrospective cohort study, and the analysis was performed using a case matching approach based on propensity score. From June 2004 to August 2018, 384 patients who underwent femoral puncture for transcatheter procedures were diagnosed with femoral psA with a sac volume of ≥1 mL and qualified for UGTI. The patients' mean age was 68 (±10.6) years and there were 217 (56.5%) women. To compare protocols, 124 patients treated according to the low dose protocol were nearest neighbour matched according to their propensity score to 124 patients treated according to the standard dose protocol. RESULTS: The overall success rate (99.2% vs. 98.4%; p = 1) and success rate of the first UGTI attempt (87.1% vs. 86.3%; p = .85) did not differ between the low dose and standard dose groups. Complications were less common in the low dose group (7.3% vs. 16.1%; p = .03) and the median total amount of thrombin used for procedures was smaller in the low dose group (120 IU vs. 195 IU; p = .01). CONCLUSIONS: In patients with femoral psA with sac volume of ≥1 mL, the use of the low dose protocol seemed to be equally effective as the standard dose protocol and was associated with a lower complication rate and reduced thrombin dose.

A Possible Allergic Reaction Case to Thrombin Injected into Pseudoaneurysm After Radiofrequency Ablation.

BACKGROUND Radiofrequency ablation is a minimally invasive treatment for arrhythmias, including frequent ventricular premature. As a complication of radiofrequency ablation, pseudoaneurysm can be treated conservatively or by ultrasound-guided thrombin injection. CASE REPORT We report a case that a possible allergic reaction to thrombin injected into pseudoaneurysm after radiofrequency ablation. CONCLUSIONS We hope that the report of successful management of the allergic reaction in this case may be of help to other doctors; we also emphasize the importance of checking the patient's history of allergies to thrombin when considering treating pseudoaneurysm with thrombin injection.

Curdione inhibits thrombin-induced platelet aggregation via regulating the AMP-activated protein kinase-vinculin/talin-integrin αIIbß3 sign pathway.

BACKGROUND: Curdione, a sesquiterpene compound isolated from the essential oil of Curcuma aromatica Salisb. inhibits platelet aggregation, suggesting its significant anticoagulant and antithrombotic effects. However, the mechanisms have not been fully elucidated. HYPOTHESIS: We hypothesized that curdione inhibits thrombin-induced platelet aggregation via regulating the AMP-activated protein kinase-vinculin/talin-integrin αIIbß3 signaling pathway. STUDY DESIGN: We performed in vitro assays to evaluate the effect of curdione on thrombin-induced expression levels of the AMPK signaling molecule and integrin αIIbß3 signaling pathway components. METHODS: Platelet proteins were extracted from washed human platelets, and the effects of curdione on thrombin-induced platelet aggregation were evaluated. The expression levels of the AMPK signaling molecule and integrin αIIbß3 signaling pathway-related proteins were examined using western blot and RT-PCR. The binding of vinculin and talin were studied using immunoprecipitation, double immunofluorescence staining and microscale thermophoresis. RESULTS: Platelet aggregation analysis showed that 0.02 U/ml thrombin significantly induces platelet aggregation. Western blot and RT-PCR analysis revealed that AMPK inhibits the vinculin/talin-mediated integrin αIIbß3 signaling pathway, and curdione downregulates the thrombin-induced expression of phosphorylated AMPK (P-AMPK) and P-integrin at both the protein and mRNA levels and downregulates vinculin and talin at the protein level. Furthermore, microscale thermophoresis experiments showed that curdione inhibits the binding of vinculin and talin. The results from the immunoprecipitation and double immunofluorescence staining were consistent with the results of the microscale thermophoresis experiments. CONCLUSION: Curdione inhibits thrombin-induced platelet aggregation via regulating the AMP-activated protein kinase-vinculin/talin-integrin αIIbß3 signaling pathway, which suggests its therapeutic potential in ethnomedicinal applications as an anti-platelet and anti-thrombotic compound to prevent thrombotic diseases.

Evaluation of Morphological and Clinical Factors Related to Failure of Percutaneous Treatment with Thrombin Injection of Femoral Pseudoaneurysms from Cardiac Catheterization.

BACKGROUND: Ultrasound-guided thrombin injection (UGTI) has become the method of choice in the treatment of pseudoaneurysm caused by endovascular procedures because it is minimally invasive, costs less, and effective, with short hospitalization time. The objective was identify the morphological aspects of femoral pseudoaneurysms and clinical aspects of patients that may lead to the failure of UGTI in femoral pseudoaneurysms after cardiac catheterization. POPULATION AND METHOD: From December 2012 to December 2016, 60 patients with pseudoaneurysms caused by cardiac catheterization were referred to the interventional radiology unit to be treated with UGTI. Medical charts were retrospectively reviewed for comorbidities, use of antiplatelet agents, anticoagulation, indication of cardiac catheterization, and so forth. Morphological aspects of the pseudoaneurysms such as volume, diameter (anteroposterior, laterolateral, and longitudinal), length, and diameter of the neck were analyzed. RESULTS: Technical success of UGTI was achieved in 100%. No clinical aspects of the patients were statistically significant for UGTI failure in occlusion of the pseudoaneurysms. For morphological aspects of pseudoaneurysm: anteroposterior (P = 0.029), longitudinal (P = 0.020), and neck diameters (P = 0.004) were statistically significant for UGTI failure. Logistic regression analysis for longitudinal diameter showed that for each centimeter, there was a 2.66 chance of failure of pseudoaneurysm thrombosis in a single thrombin injection session (95% confidence interval: 1.33-5.30). For longitudinal and neck diameters greater than 1.8 cm and 0.55 cm, respectively, there is a greater probability of needing more than one UGTI session for complete thrombosis. CONCLUSIONS: Among variables, the longitudinal dimension was more significant, and in a larger diameter, the treatment with thrombin injection presented greater complexity.

Influence of hypertriglyceridemia, hyperbilirubinemia and hemolysis on thrombin generation in human plasma.

Background Although accumulating evidence suggests that the hemostatic balance is impaired in patients with hypertriglyceridemia, hyperbilirubinemia or hemolytic anemias, little is known on the underlying biological mechanisms. This experimental study was aimed at exploring whether increasing values of triglycerides, bilirubin or cell-free hemoglobin promote thrombin generation in plasma. Methods Three different pools were prepared from three different sets of 20 normal routine plasma citrate samples. The native pools were spiked with increasing amounts of exogenous triglycerides (up to 8.8 mmol/L), bilirubin (up to 350 µmol/L) or autologous hemolyzed blood (up to 3.5 g/L cell-free hemoglobin). Using the fully-automated thrombin generation analyzer ST Genesia, we measured the following parameters: lag time (LT), time to peak (TP), peak height (PH) and endogenous thrombin potential (ETP). Results A sustained increase of PH and ETP was found in parallel with increasing triglyceride concentrations, peaking in the aliquot with 8.8 mmol/L. Conversely, LT and TP displayed an opposite trend, reaching a maximum decrease in the 8.8 mmol/L aliquot. Increasing bilirubin concentrations promoted remarkable increases of PH and ETP and decreases of TP and LT, up to 211 µmol/L. After this threshold, all parameters tended to return towards baseline values. A constant increase of PH and ETP was also noted in hemolyzed samples, peaking in the 3.5 g/L cell-free hemoglobin aliquot, whereas the TP and LT remained unchanged in all hemolyzed aliquots. Conclusions Our findings suggest that hypertriglyceridemia, hyperbilirubinemia and hemolysis may promote a hypercoagulable state in human plasma.

Hemostatic Thrombin-Gelatin Matrix-Related Intracranial Cyst Formation.

BACKGROUND: Local hemostatic agents have been used in the neurosurgical field for many years; it is safe and efficient with no fatal complication reported in the literature. We routinely used a gelatin-thrombin hemostatic agent (FloSeal Hemostatic Matrix) for hemostasis in minimally invasive endoscopic-assisted surgery for more than 500 patients with intracerebral hemorrhage. However, 2 cases with sterile cyst formation were encountered. CASE DESCRIPTION: We reported 2 cases with sterile cyst formation after the use of a gelatin-thrombin hemostatic agent. Both of them had intracerebral hemorrhage. One received endoscopic hematoma evacuation, and the other had traditional craniotomy. They all received drainage of the cyst due to progressive enlargement and the mass effect they exert. CONCLUSIONS: These sterile cysts were very close to the ventricle wall on images. We hypothesized that cyst wall may be formed not only by hemostatic agent-related fibrosis and inflammation according to the previous literature review but also by the presence of the check valve mechanism between the cyst and the ventricle, which caused further dilation of the cyst.

Results of TachoSil® associated with fibrin glue as dural sealant in a series of patients with spinal intradural tumors surgery. Technical note with a review of the literature.

A major problem of surgery for intradural spinal tumors (IST) is the occurrence in the post-operative period of a cerebrospinal fluid (CSF) leak. To the best of our knowledge, here we report on the largest series of IST patients in whom the TachoSil® associated to fibrin glue was used as dural sealant in this kind of surgery. Moreover, we extensively reviewed the literature reporting the results of TachoSil® in spine surgery. The data of 35 consecutive surgically treated IST patients were reviewed. In all cases TachoSil® associated with fibrin glue was used as dural sealant. Mean age was 58.14 ±â€¯15.56 years and mean follow-up (FU) was 23.20 ±â€¯9.76 months. The Modified McCormick Scale (MMS) was used to assess the functional status of patients pre-operatively and at latest FU. All article dealing with the use of TachoSil® in spine surgery were included in the literature review. A CSF collection (treated conservatively with needle aspiration and bed rest with no consequence) was observed only in 1 out of 35 cases. No wound infection nor adverse reaction to the TachoSil® occurred during the FU. At latest FU we observed an improvement of MMS grade in 23 patients (65.71%) and a stable functional status in 12 cases (34.28%). According to our experience and the literature review using the TachoSil® after dural closure is safe and effective in IST surgery. Better standardized studies are needed to establish the usefulness of TachoSil® for incidental dural tear in degenerative spine surgery.