Ml Of Thrombin Research Articles

Use of intrapulmonary administration of thrombin in hematological malignancy patients with alveolar haemorrhage: A case series.

Introduction:Alveolar hemorrhage (AH) is characterized by the acute onset of alveolar bleeding and hypoxemia and can be fatal. Thrombin has been widely used to achieve coagulation and hemostasis. However, the efficacy of thrombin in patients with AH is unclear. Thus, this study aimed to evaluate the efficacy of thrombin administration in patients with hematological malignancy and AH.Patient concerns and diagnoses:This retrospective study included 15 hematological malignancy patients (8 men and 7 women; mean age 47.7 ± 17.3 years) with AH who were administered intrapulmonary thrombin between March 2013 and July 2018.Interventions and outcomes:All patients received bovine-origin thrombin (1000 IU/ml, Reyon Pharmaceutical Co., Ltd., Seoul, Korea) via a fiberoptic bronchoscope. A maximum of 15 ml of thrombin was injected via the working channel to control bleeding. The ability of thrombin to control bleeding was assessed. Additionally, the change in the PaO2/FiO2 (PF) ratio after intrapulmonary thrombin administration was evaluated. Intrapulmonary thrombin was administered a minimum of 3 days after starting mechanical ventilation in all patients, and it immediately controlled the active bleeding in 13 of 15 patients (86.7%). However, AH relapse was noted in 3 of the 13 patients (23.1%). The PF ratio improved in 10 of 15 patients (66.6%), and the mean PF ratio was significantly higher after thrombin administration than before administration (P = .03). No adverse thromboembolic complications or systemic adverse events were observed.Conclusion:Thrombin administration was effective in controlling bleeding in hematological malignancy patients with AH. Intrapulmonary thrombin administration might be a good therapeutic option for treating AH.

Arthroscopic gel-type autologous chondrocyte implantation presents histologic evidence of regenerating hyaline-like cartilage in the knee with articular cartilage defect.

To investigate the clinical, radiological, and histological results of arthroscopic gel-type autologous chondrocyte implantation (GACI) in treating chondral defects of the knee. This study prospectively examined five males and five females with a mean age of 40.3 ± 10.3years who underwent arthroscopic GACI between March 2012 and February 2013. The gel comprised a mixture of 1ml of fibrinogen plus 0.1-0.2ml of thrombin. The mean size of chondral defect was 2.9 ± 1.2cm2 (range 1.2-5.4cm2). International knee documentation committee (IKDC) subjective score, knee injury and osteoarthritis outcome score (KOOS), knee society score, and visual analog scale (VAS) for pain were assessed preoperatively and during regular follow-up examinations performed for up to 5years postoperatively. Serial magnetic resonance imaging was performed for up to 2years after the surgery to observe healing, using the modified magnetic resonance observation of cartilage repair tissue (MOCART) score. In eight patients, second-look arthroscopy was performed at 1year after the implantation to assess the status of treated cartilage, and a portion of regenerated cartilage was harvested for histologic evaluation. The mean VAS score (p = 0.045), IKDC subjective score (p = 0.041), KOOS pain (p = 0.025), KOOS activities of daily living (p = 0.048), and KOOS quality of life (p = 0.029) showed significant improvement at 5years after the surgery. The modified MOCART evaluation showed that the scores were 59.5 ± 29.4 and 85.0 ± 8.0 at 12weeks and 2years after the operation, respectively. Histologic examination demonstrated a mean regenerated cartilage thickness of 3.5 ± 0.8mm and a mean Oswestry score of 8.2 ± 1.8. Immunohistochemistry analysis showed that the expression of collagen type II was more evident and more evenly distributed than collagen type I in regenerated cartilage. There was a significant correlation between Oswestry score and change in VAS scale from postoperative 2-5years. Arthroscopic GACI produces satisfactory clinical and radiologic outcomes, and histologic evaluation confirms sufficient regeneration of hyaline-like cartilage that correlates with improved symptoms. Therefore, it is an acceptable, minimally invasive, and technically simple option for the restoration of cartilage defects of the knee. IV.

Endoscopic ultrasound-guided coil embolization and thrombin injection of bleeding gastroduodenal artery pseudo-aneurysm

Background and Objectives:Gastroduodenal artery (GDA) aneurysms are rare but a potentially fatal condition if rupture occurs. The most common etiology is acute or chronic pancreatitis. The most common clinical presentation is gastrointestinal (GI) hemorrhage secondary to rupture of the aneurysm. Such a complication is not always related to the size of the aneurysm, and therefore, treatment should be planned as soon as a diagnosis is made. Surgical, endovascular, percutaneous, and endoscopic ultrasound (EUS)-guided interventions are used in the treatment of visceral artery pseudo-aneurysms.Methods:A 50-year-old male had an episode of alcohol induced acute moderate severe pancreatitis 1 month back. He presented with melena, requiring six units of blood transfusions for hemodynamic stabilization. After hemodynamic resuscitation, the patient underwent upper GI endoscopy to know the etiology of massive upper GI bleeding. Upper GI endoscopy showed a bulge with overlying ulceration in the second part of the duodenum. Side viewing endoscopy showed a pulsatile bulge with overlying large ulcer. Ultrasound abdomen showed pseudo-aneurysm of size 3.8 cm × 5.6 cm arising from GDA artery. Contrast-enhanced computed tomography abdomen with angiography showed a saccular pseudo-aneurysm of size 4 cm × 6 cm in relation to GDA. EUS from duodenal bulb showed a pseudo-aneurysm of size 4.1 cm × 5.8 cm arising from GDA. Radiological or EUS-guided interventions were considered. The advantages and disadvantages of both procedures were explained. The patient selected the option of EUS-guided coil embolization.Results:Under EUS and fluoroscopy guidance, five coils of 10 mm size were placed within pseudo-aneurysm through 19-gauge EUS needle. After coil embolization, contrast injection into the pseudo-aneurysm showed partial filling of pseudo-aneurysm. Review EUS 1 day after coil embolization showed high flow in the pseudo-aneurysm. Around 30% of pseudo-aneurysm was obliterated. On the 3rd day, 6 mL of human thrombin was (3000 IU) injected during second session of intervention in six boluses of 500 unit each. After thrombin injection, high-velocity flow was confined to the neck and periphery of pseudo-aneurysm. Further 2 mL of thrombin was injected. Immediately after thrombin injection, color Doppler EUS showed complete obliteration of pseudo-aneurysm. Two weeks later, repeat EUS showed completely obliterated pseudo-aneurysm with no flow.Conclusions:This case shows the practical problems of EUS-guided coil embolization of pseudo-aneurysms.

Human thrombin for the treatment of gastric and ectopic varices

To evaluate the efficacy of human thrombin in the treatment of bleeding gastric and ectopic varices. Retrospective observational study in a Tertiary Referral Centre. Between January 1999-October 2005, we identified 37 patients who were endoscopically treated with human thrombin injection therapy for bleeding gastric and ectopic varices. Patient details including age, gender and aetiology of liver disease/segmental portal hypertension were documented. The thrombin was obtained from the Scottish National Blood Transfusion Service and prepared to give a solution of 250 IU/mL which was injected via a standard injection needle. All patient case notes were reviewed and the total dose of thrombin given along with the number of endoscopy sessions was recorded. Initial haemostasis rates, rebleeding rates and mortality were catalogued along with the incidence of any immediate complications which could be attributable to the thrombin therapy. The duration of follow up was also listed. The study was conducted according to the United Kingdom research ethics guidelines. Thirty-seven patients were included. 33 patients (89%) had thrombin (250 U/mL) for gastric varices, 2 (5.4%) for duodenal varices, 1 for rectal varices and 1 for gastric and rectal varices. (1) Gastric varices, an average of 15.2 mL of thrombin was used per patient. Re-bleeding occurred in 4 patients (10.8%), managed in 2 by a transjugular intrahepatic portosystemic shunt (TIPSS) (one unsuccessfully who died) and in other 2 by a distal splenorenal shunt; (2) Duodenal varices (or type 2 isolated gastric varices), an average of 12.5 mL was used per patient over 2-3 endoscopy sessions. Re-bleeding occurred in one patient, which was treated by TIPSS; and (3) Rectal varices, an average of 18.3 mL was used per patient over 3 endoscopy sessions. No re-bleeding occurred in this group. Human thrombin is a safe, easy to use and effective therapeutic option to control haemorrhage from gastric and ectopic varices.

A sensitive and reliable detection of thrombin via enzyme-precipitate-coating-linked aptamer assay

Stable enzyme precipitate coatings (EPCs) with high enzyme loading were employed to develop a sensitive and reliable detection protocol, termed EPC-linked aptamer assay (EPC-LAA). EPC-LAA achieved the limit of detection to be 0.5 ng per mL of thrombin (13.5 pM), and maintained a reasonably stable detection signal even after storing all the reagents at 40 °C for 66 days.

Spray application of fibrin sealant with an angled spray tip device in laparoscopic inguinal hernia repair

BACKGROUND: The method of fibrin sealant (FS) application for hernia mesh fixation is essential to obtain its full benefits and advantages (i.e., the reduction of chronic pain). In several studies on hernioplasty, punctual mesh fixation with FS proved to be efficient in terms of fixation strength and elasticity and it was hypothesized that an angled tip laparoscopic spray system (LSS) would improve and facilitate the application of the sealant. The aim of the study was to examine the safety and handling of LSS as well as the one-year outcome. METHODS: After informed written consent was obtained, transabdominal preperitoneal hernioplasty (TAPP) was performed in 33 primary inguinal hernias in 27 non-selected consecutive patients by a single surgeon. A macroporous mesh (TI-Mesh ® , GfE, Germany) was fixed with 2 ml of FS composed of 1 ml of fibrinogen and 1 ml of thrombin (Tisseel ® = Tissucol ® ). The FS was applied using a newly developed angled spray catheter insertable through a 5 mm trocar and attached to a CO2 regulator device. Patients were followed up for one year. RESULTS: The angled tip allowed targeted distribution of FS by minimal movements of the device and was safe. The spray cone was always clearly visible during application. At 3 and 12 months no seromas were detectable. VAS score decreased corresponding to the absence of chronic pain and no recurrences occurred. Two milliliter FS for uni- and 4 ml for bilateral hernia meshes were sufficient. CONCLUSIONS: This new angled tip LSS provides excellent handling for an atraumatic broad fixation of mesh in the TAPP-hernioplasty, avoiding late seroma and recurrence despite a substantial reduction of the amount of FS required. It could therefore also help to save costs.

Ruptured hepatic artery aneurysm: A novel approach to distal control

We describe a unique method for obtaining distal control in a ruptured hepatic artery aneurysm. A 34-year-old man with Ehlers-Danlos syndrome type IV presented with a ruptured left hepatic artery aneurysm. The distal aneurysm was within the parenchyma of the liver. Proximal control was obtained with pledgeted sutures. The distal hepatic artery was difficult to control. Injection of 5 mL of thrombin into the distal left hepatic artery resulted in hemorrhage control. This technique should be considered in select patients in whom distal arterial control is challenging.

Therapuetic Use of Alum in Radiation Proctitis

Purpose: Lower gastrointestinal bleed resulting from radiation colitis is a challenging condition for the gastroenterologist. Radiation colitis is commonly seen after radiation treatment given for pelvic malignancies. There is no effective treatment available for radiation colitis. We propose to use Alum (Aluminum potassium sulfate) in the treatment of radiation induced bleeding from the rectum due to radiation injury. The mechanism of action of Alum is thought to be its astringent effect on the epithelium together with the induction of protein coagulation. There is some evidence about the anti-aggregation effect of Alum on the platelets which if true can be detrimental to our proposed study. Thus we first decided to study the effect of different concentrations of Alum on platelet aggregation in vitro. Methods: Use of 1% Alum on the platelet rich plasma PRP found to be causing precipitation which was later on tested on tyrodes buffer, serum as well as platelet poor plasma. Then we came up with three concentrations of Alum which did not cause any precipitation (1mM, 10 mM, and 25 mM). These concentrations were used to make stock solution. 50 cc of blood was obtained after consent from the medical residents. None of them was taking any aspirin or NSAIDS in past 10 days. Platelets were extracted after centrifuging whole blood at 1000 rpm for 20 minutes. Platelets were then washed three times with buffer containing inhibitors. We used optical aggregometer from (Chrono-log Corporation) to study the platelet aggregation. 450 ml of prp was taken in glass aliquots with a magnetic pallet. These were placed in the aggregometer at 1000 rpm and 10 ml of fibrinogen was added both in control and test aliquots. Different concentrations of Alum were used to incubate platelets for 3–5 minutes. After this 10 ml, 5ml, of TRAP, or 1ml,3ml of thrombin was added and effect was monitored graphically with the attached software (aggrolink). Results: Alum by itself does not cause any effect on platelet aggregation in any concentration. With 0.5 mM Alum there was 18% inhibition of TRAP induced aggregation, at 1 mM there was 14% inhibition, at 1.5 mM there was no. inhibition, at 2.5 mM there was 56% inhibtion of TRAP induced aggregation Conclusions: Alum is safe, cheap compound that should be used cautiously in the treatment of radiation induced bleeding as it can cause inhibition of platelet aggregation. This in vitro study will guide us to use Alum safely in vivo for possible treatment of radiation proctitis.

Percutaneous Injection of Thrombin for the Treatment of Pseudoaneurysms After Catheterization

The purpose of our study was to determine the efficacy of percutaneous thrombin treatment for iatrogenic pseudoaneurysms of the femoral artery in comparison with sonographically guided compression repair. Twenty-three pseudoaneurysms occurring after catheterization were treated percutaneously with an initial injection of 1.0 mL of thrombin solution via a 22-gauge spinal needle under continuous sonographic guidance. Four patients required the additional injection of 1.0-4.0 mL of thrombin for complete thrombosis. Repeated sonography was performed 24 hr after injection. Additionally, we compared our results with those of a control group by reviewing the imaging findings and medical records of 16 patients who underwent sonographically guided compression of iatrogenic pseudoaneurysms between January 1998 and July 1998. Twenty-two of 23 pseudoaneurysms occurring after catheterization were successfully treated with percutaneous thrombin injection. One recurrence was identified 24 hr after injection in a patient who experienced a significant complication. Procedure time was limited to 15 min with an overall success rate of 96%. Retrospectively, 18 iatrogenic pseudoaneurysms were identified in 16 patients. Six (60%) of 10 pseudoaneurysms were successfully compressed under sonographic guidance, with an average time to thrombosis of 32 min. Compression was unsuccessful for four pseudoaneurysms with an average compression time of 45 min. Compression could not be performed in seven patients (39%). The overall success rate of sonographically guided repair was 60%. Preliminary evidence suggests that sonographically guided percutaneous thrombin injection is a safe and effective method of treatment for iatrogenic pseudoaneurysms and offers significant advantages over conventional sonographically guided compression.

Effect of Fibrinogen and Thrombin Concentrations on Mastectomy Seroma Prevention

Seroma formation remains a significant clinical problem which increases morbidity and hospital costs in patients undergoing mastectomy operations. This study evaluated the effect of varying the concentrations of fibrinogen and thrombin in fibrin sealant on successfully preventing seroma formation in a rat model. After axillary dissection, control animals (Groups I and II) had 1 ml of either normal saline or thrombin (100 U/ml) applied to the axilla while treated animals (Groups III–VIII) had increasing concentrations of 0.5 ml of fibrinogen (25, 50, or 100 mg/ml) and 0.5 ml of thrombin (10 or 100 U/ml) applied. Seroma volumes (means ± standard deviation) were measured on Postoperative Day 5. They were largest in Group I (3.1 ± 1.9 ml,n= 13) and Group II (3.9 ± 2.7 ml,n= 15) and then decreased from a high in Group III (2.5 ± 2.4 ml,n= 15) using fibrinogen, 25 mg/ml, and thrombin, 10 mg/ml, to a low in Group VIII (0.8 ± 1.0 ml,n= 15) using fibrinogen, 100 mg/ml, and thrombin, 100 U/ml. Analysis of variance revealed a statistically significant difference in the mean seroma fluid volumes between the groups (P= 0.0021), while Scheffe's comparison showed a specific significant difference (P= 0.028) between the thrombin control (Group II) and the highest concentration fibrin sealant (Group VIII). The difference in seroma volumes for all control animals (Groups I and II), 3.5 ± 2.4 ml, and all treated animals (Groups III–VIII), 1.7 ± 2.1 ml, was highly significant by unpairedttest. (P< 0.0001). Thus, fibrin sealant was useful in reducing seroma formation in this rat model with the highest concentration of fibrinogen and thrombin appearing most effective. These data may be useful in guiding future clinical trials in humans.

Thrombin in the management of full thickness macular holes.

As thrombin is a known stimulator of retinal glial and pigment epithelial cells, we performed a pilot study to evaluate the use of thrombin as adjunctive mitogen therapy in vitreous surgery for full-thickness macular holes. Macular hole surgery was performed on 25 eyes of 24 consecutive patients with stage II, III, or IV macular holes. After removal of the posterior hyaloid, peeling of epiretinal membranes, and fluid-air exchange, 0.05 mL or 0.1 mL of thrombin (100 units/ mL) was placed over the macular hole. After infusion of a gas tamponade, the patient's head was kept in a supine position for 1 hour, and then was kept in a prone position for approximately 2 weeks. Closure of the macular hole with one procedure was achieved in 80% of the eyes. Sixty-five percent of the eyes with a closed macular hole achieved a visual acuity of 20/40 or better. Postoperative inflammation was present in all eyes, and a small hypopyon developed in 28% of the eyes. Thrombin therapy failed to markedly increase the success rate of macular hole surgery.

Controlled release of sisomicin from fibrin glue

It seems reasonable to incorporate antibiotics into fibrin glue (FG) used for the presealing of grafts in vascular surgery, to prevent graft infection. This study was conducted to investigate whether FG is appropriate as a biodegradable drug carrier for antibiotics by determining the release behavior of sisomicin (SISO) from FG. By adding 0.12 ml of thrombin (36 U) with 1.75 mg of SISO to a fibrinogen solution (0.12 ml: 9.6 mg), a fibrin glue containing SISO was prepared in a Teflon cast (1 cm in diameter). Then a Dacron ® sheet (1 cm in diameter) was placed on the FG (SISO-FG-Dacron disk; 2.7 mm in thickness). In vitro it was demonstrated that after 8 h and 21 h, 90% and 100% of SISO was released from the SISO-FG-Dacron disk. The SISO-FG-Dacron disk was implanted in an abdominal skin pocket of a rabbit. After 8 h approximately 90% of SISO was released from the FG. The release behavior of SISO in the animal experiment was compatible with temporal courses of serum and tissue SISO levels following implantation of SISO-FG-Dacron disks. One hundred percent SISO from the SISO-Dacron disk(control), prepared by soaking the Dacron sheet in SISO, was released at 1 h. FG is thus concluded to be usable not only as a tissue adhesive but as a drug carrier for controlled release. The in vitro experimental procedure of this study facilitated evaluation of the in vivo release of the drug from FG, as evident from the close agreement of the results of the in vitro experiment with those in the animal experiment.

Isolation and Properties of a Thrombin-sensitive Protein of Human Platelets

A glycoprotein of human platelets is released into the incubation medium upon treatment of the intact cells with 1 unit per ml of thrombin for 2 min. The cellular location and properties of this protein differ from those of other thrombin-labile platelet proteins such as fibrin-stabilizing factor, fibrinogen, and the contractile protein thrombosthenin. It occurs only in the particulate fraction and is released only from intact cells. Thrombin concentrations of 100 units per ml do not release this thrombin-sensitive protein from sonicated platelets. As isolated from the incubation supernatant of thrombin-treated platelets the thrombin-sensitive protein is excluded from Sephadex G-200; it has an apparent molecular weight of 190,000 in sodium dodecyl sulfate polyacrylamide gels, from which it has been purified and partially characterized. No smaller subunits have been found. It has limited solubility in the absence of detergent, and is highly sensitive to proteolytic degradation in whole platelets and after release from the cells. Membrane-bound and released forms of the thrombin-sensitive protein show no significant difference in molecular weight or amino acid and carbohydrate composition, suggesting that release does not involve proteolysis of the thrombin-sensitive protein itself by thrombin. This protein contains 3.9% sialic acid, 1.6% N-acetylglucosamine, and 25% each of acidic and nonpolar residues. Although it contains carbohydrate the thrombin-sensitive protein does not represent the major membrane glycoprotein of platelets, for it contains only 5% of the total platelet sialic acid. The thrombin-sensitive protein accounts for approximately 5% of the total protein in the particulate fraction of human platelets and represents about 20 to 30% of the protein found in the incubation supernatant after thrombin treatment.

An application of fibrinolytic preparations on clotting and dissolution of the blood in urine

In the urological field, the fibrin-clot included blood-clot in the urine is one of the important problems in a sense of obtaining good urine output through the urinary tract.Recently, as fibrinolytic preparations advanced, these have been administered to the treatment of vascular occlusive diseases such as thrombosis.In urine, there is a fibrinolytic enzyme i. e. urokinase (U. K.), and uropepsin, trypsin-inhibitory substance and a thromboplastin-like substance are pointed out as substances associated with this enzyme.This paper reviews my experience about clotting and dissolution of the blood in urine reacted with these preparations in vitro.1. The experiments of 1ml of these preparations to 10g of blood-clot in 30ml of urine:1) Urokinase: A solution of 5, 000 and 2, 500u/ml dissolved the blood-clot initially incompletely, but thereafter clotted total urine with blood, and then redissolved the urine and the blood-clot.The solution of 1, 250, 625 and 312.5u/ml did not clot it temporarily, but dissolved it completely. The solution of 625u/ml to the blood-clot in urine dissolved extremely.2) Plasmin: The dissolution of the solution of 62.5u/ml to the blood-clot in urine was extreme, also that of 31.25u/ml.The dissolution of the higher concentrated solutions was later and incomplete than that of 62.5u/ml.3) Streptokinase: The dissolved curve of the solutions ranging from 3, 125 to 50, 000u/ml to the hood-clot were almost parallel to the concentration of the solution, but that of 6, 250u/ml was most rapidly.2. The clotting and dissolution of 2.5ml of the venous blood and 0.5ml of U. K.—solutions in 7.5ml of urine:1) The clotting time; The clotting of the total urine with the blood was observed. The control without U. K. clotted after 46 minutes. When the U. K.—solution of 1, 350u/ml was added the sample added the purified U. K. and the commercial U. K. clotted after 51 and 61.5 minutes respectively.2) The dissolution: The dissolution of the clot added to purified U. K. was most rapidly up to 170 minutes, but equivalent dissolution of the clot added to purified U. K. and of the control was at 170 minutes.In general, the dissolution of the clot added to commercial U. K. was latest.3. The clotting and dissolution of 0.25ml of U. K.—Solution on 2.5ml of the fresh venous blood involved 0.5g of the same patient's fresh blood-clot. The concentration of U. K.—solution was 1, 350u/ml.1) The clotting time: The clotting time of the control without U. K., that added the purified U. K. and the commercial U. K. were 21 minutes and 5 seconds, 14 minutes and 30 seconds, and 20 seconds respectively.2) The clot added to purified U. K. and commercial U. K. dissolved much more rapidly than the control.4. The clotting time of 10ml of the urine with 2ml of the same patient's venous blood added 0.1ml of Trostin (Chugai)—solution and 0.1ml of Thrombokinase (Geigy)—solution was shorter than the control without these thromboplastin agents.Thereafter, the dissolution time of the U. K.—solution (1.0ml) ranged from 100 to 500u/ml to total clotting was from 180 to 900 minutes, but that of the control without U. K. could not be observed at 1, 800 minutes.The dissolution time of the PL-solution (1ml) of 250u/ml was 146 minutes, and 125u/ml 165 minrutes, 25u/ml ranged from 180 to 900 minutes.5. In series of 15ml of urine added to 0.5ml of U. K.—solution of 312.5u/ml, PL-Solution of 62.5u/ml, SK-solution of 3, 125u/ml respectively, the control without thromboplastin agent, and the sample added Trostin-solution, Thrombokinase-solution and Trostin-solution plus Thrombokinase-solution were prepared respectively.Thereafter, 5ml of banked blood, 0.1ml of CaCl2 and 0.1ml of thrombin were added to these samples.