Angioplasty, Balloon, Coronary ; Heart Injuries ; drug therapy ; etiology ; Humans ; Thrombin ; administration & dosage

Dabigatran is the first oral direct thrombin inhibitor approved by the US Food and Drug Administration (FDA) for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Because dabigatran is excreted mainly by the kidneys, serum levels of dabigatran can be elevated to a supratherapeutic range in patients with renal failure, predisposing to emergent bleeding. We describe the case of a 66-year-old man taking dabigatran 150 mg twice daily for atrial fibrillation and cerebral infarction who presented with hematochezia and disseminated intravascular coagulation. Laboratory evaluation showed a hemoglobin level of 6.3 g/dL, platelets of 138,000/mm3, activated partial thromboplastin time (aPTT) of 10?s, and an international normalized ratio (INR) of 8.17. Colonoscopy showed a bleeding anal fissure. Hemostasis was provided by hemoclips and packed red blood cells and fresh frozen plasma were transfused. Since then, there was no further hematochezia, however, bleeding including oral mucosal bleeding, hematuria, and intravenous site bleeding persisted. At presentation, his serum creatinine was 4.96 mg/dL (baseline creatinine, 0.9 mg/dL). Dabigatran toxicity secondary to acute kidney injury was presumed. Because acute kidney injury of unknown cause was progressing after admission, he was treated with hemodialysis. Fresh frozen plasma transfusion was provided with hemodialysis. At 15 days from admission, there was no further bleeding, and laboratory values, including hemoglobin, partial thromboplastin time, and prothrombin time were normalized. He was discharged without bleeding. After 2 months, he undergoes dialysis three times per week and no recurrence of bleeding has been observed.
Acute Kidney Injury* ; Aged ; Atrial Fibrillation ; Cerebral Infarction ; Colonoscopy ; Creatinine ; Dabigatran ; Dialysis ; Disseminated Intravascular Coagulation ; Embolism ; Erythrocytes ; Fissure in Ano ; Gastrointestinal Hemorrhage ; Hematuria ; Hemorrhage ; Hemostasis ; Humans ; International Normalized Ratio ; Kidney ; Partial Thromboplastin Time ; Plasma ; Prothrombin Time ; Recurrence ; Renal Dialysis ; Renal Insufficiency ; Stroke ; Thrombin ; United States Food and Drug Administration

Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.
Animals ; Area Under Curve ; Batroxobin ; administration & dosage ; blood ; pharmacokinetics ; pharmacology ; Dogs ; Enzyme-Linked Immunosorbent Assay ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Fibrinolytic Agents ; administration & dosage ; blood ; pharmacokinetics ; pharmacology ; Infusions, Intravenous ; Male ; Partial Thromboplastin Time ; Prothrombin Time ; Thrombin Time

Carotid Artery Diseases ; drug therapy ; Carotid Artery, Internal ; Child ; Female ; Humans ; Injections ; Leukemia, Promyelocytic, Acute ; complications ; Rupture, Spontaneous ; Thrombin ; administration & dosage ; Ultrasonography, Interventional

BACKGROUND: Bivalirudin is a direct thrombin inhibitor for patients with unstable angina undergoing percutaneous coronary intervention. METHODS: A sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of bivalirudin, in human plasma using nafarelin as internal standard (IS). Chromatographic separation was performed using a Shiseido MG3 mm column (2.0 x 50 mm) with a gradient mobile phase consisting of water and acetonitrile containing 0.1 % formic acid at a flow rate of 0.4 mL/min, and total run time was within 5 min. Detection and quantification was performed by the mass spectrometer using a multiple reaction-monitoring mode at m/z 1091.0 --> 650.3 for bivalirudin, and m/z 662.1 --> 249.3 for IS. RESULTS: The assay was linear over a concentration range of 10 - 10000 ng/mL with a lower limit of quantification of 10 ng/mL in human plasma. CONCLUSION: This method was successfully applied for pharmacokinetics study after intravenous administration of bivalirudin to healthy Korean male volunteers.
Administration, Intravenous ; Angina, Unstable ; Chromatography, Liquid ; Humans* ; Male ; Mass Spectrometry ; Methods ; Nafarelin ; Percutaneous Coronary Intervention ; Pharmacokinetics ; Plasma* ; Thrombin ; Water

During the past decade, many studies using platelet-rich plasma (PRP) or adipose-derived stem cells (ASCs) have been conducted in various medical fields, from cardiovascular research to applications for corneal diseases. Nonetheless, there are several limitations of practical applications of PRP and ASCs. Most reports of PRP are anecdotal and few include controls to determine the specific role of PRP. There is little consensus regarding PRP production and characterization. Some have reported the development of an antibody to bovine thrombin, which was the initiator of platelet activation. In the case of ASCs, good manufacturing practices are needed for the production of clinical-grade human stem cells, and in vitro expansion of ASCs requires approval of the Korea Food and Drug Administration, such that considerable expense and time are required. Additionally, some have reported that ASCs could have a potential risk of transformation to malignant cells. Therefore, the authors tried to investigate the latest research on the efficacy and safety of PRP and ASCs and report on the current state and regulation of these stem cell-based therapies.
Consensus ; Corneal Diseases ; Humans ; Korea ; Mesenchymal Stromal Cells ; Platelet Activation ; Platelet-Rich Plasma ; Stem Cells ; Thrombin ; Treatment Outcome ; United States Food and Drug Administration

Major vascular complications related to pancreatitis can cause life-threatening hemorrhage and have to be dealt with as an emergency, utilizing a multidisciplinary approach of angiography, endoscopy or surgery. These may occur secondary to direct vascular injuries, which result in the formation of splanchnic pseudoaneurysms, gastrointestinal etiologies such as peptic ulcer disease and gastroesophageal varices, and post-operative bleeding related to pancreatic surgery. In this review article, we discuss the pathophysiologic mechanisms, diagnostic modalities, and treatment of pancreatic vascular complications, with a focus on the role of minimally-invasive interventional therapies such as angioembolization, endovascular stenting, and ultrasound-guided percutaneous thrombin injection in their management.
Diagnostic Imaging ; Embolization, Therapeutic/methods ; Hemostasis, Endoscopic ; Hemostatics/administration & dosage ; Humans ; Pancreatitis/*complications ; Stents ; Thrombin/administration & dosage ; Ultrasonography, Interventional ; Vascular Diseases/diagnosis/*etiology/physiopathology/*therapy ; Vascular Surgical Procedures/*methods

OBJECTIVETo investigate the effects of Salvia Miltiorrhiza Liguspyragine Hydrochloride and Glucose Injection (, SLGI) on the expression of platelet membrane receptors proteinase-activated receptor-1 (PAR1) and proteinase-activated receptor-4 (PAR4) in end-stage renal disease (ESRD) patients on chronic haemodialysis (HD).

METHODSEighty-six ESRD patients on HD (treated group) were treated with SLGI, 7 days as one therapeutic course, for two successive courses. The previous therapies were unchanged. Flow cytometry was used to assess the expression of platelet PAR1 and PAR4 in the patients, and turbidity method was used to determine the platelet maximum aggregation rate (MAR). Meanwhile, renal function was measured. The final data were compared with those before treatment and with those in the normal control group (54 healthy subjects).

RESULTSCompared with the normal control group, the expressions of PAR1 and PAR4 and platelet MAR in ESRD patients on HD was significantly higher before treatment (P=0.001, P=0.006, and P=0.008); after treatment with SLGI, the above indices in patients were remarkably decreased (P=0.036 and P=0.046), except PAR4 (P=0.067), but still higher than those in the normal control group, however, it was not statistically significant.

CONCLUSIONS(1) The overexpression of PAR1 and PAR4 might lead to increased platelet aggregation and this could be one of the reasons for the thrombotic events in ESRD patients on HD. (2) SLGI was able to down-regulate the expression of PAR1 in ESRD patients on HD, improve platelet function, and regulate platelet activation.

Blood Platelets ; drug effects ; metabolism ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Female ; Glucose ; administration & dosage ; pharmacology ; Humans ; Kidney Function Tests ; Male ; Middle Aged ; Platelet Aggregation ; drug effects ; Receptors, Thrombin ; metabolism ; Renal Dialysis ; Salvia miltiorrhiza ; chemistry

BACKGROUNDThe non-operation treatment of intra-abdominal trauma guided contrast enhanced ultrasound (CEUS) is one of the hottest research topic. Gelatin/thrombin/calcium (GTC) was developed as a novel haemostatic agent for non-operable intra-abdominal trauma. We hypothesized that GTC can achieve haemostasis (without the use of pressure) within a short time in a large wound model by percutaneous injection under CEUS guidance.

METHODSForty Wister rats received large liver injuries by haemostatic clamp and were randomly divided into four groups, according to the haemostatic agent used. These included normal saline (NS) group A, lyophilising thrombin powder (LTP) group B, GTC group C, and absorbable α-cyanoacrylate (ACNA) group D. Each injury site was treated with one of the above materials and total bleeding time was recorded. All liver wounds were evaluated using CEUS at three periods: pre-injury, injury and post-treatment. The liver wounds were also evaluated by histology 3, 6, and 9 days after injury and the extents of abdominal adhesions were recorded.

RESULTSThe sensitivity of CEUS (100%) in detecting blunt traumatic liver lesions was significantly higher than conventional ultrasound (42.5%). Bleeding times at the injury site in the GTC group C ((129.3 ± 14.0) seconds) and ACNA group D ((5.2 ± 1.0) seconds) were significantly shorter than those in the NS group A ((369.5 ± 48.8) seconds, P < 0.01) and LTP group B ((324.7 ± 52.22) seconds, P < 0.01). The LTP group B showed no significant difference compared with the NS group A. Gross examination of liver tissue revealed that there were fewer intra-abdominal adhesions in the GTC group C (10%) than in the ACNA group D (100%). Histopathologic examination showed that GTC was completely absorbed after nine days.

CONCLUSIONSGTC, delivered by percutaneous injection under CEUS, may achieve haemostasis (without the use of pressure) within a short time in a large wound model. GTC is absorbable and may prevent intra-abdominal adhesions. Therefore, it may be the optimal choice for first aid treatment of large abdominal wounds in the setting of blunt trauma.

Animals ; Calcium ; administration & dosage ; therapeutic use ; Gelatin ; administration & dosage ; therapeutic use ; Hemorrhage ; diagnostic imaging ; drug therapy ; Hemostatics ; administration & dosage ; therapeutic use ; Injections ; Liver ; diagnostic imaging ; injuries ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Thrombin ; administration & dosage ; therapeutic use ; Ultrasonography

OBJECTIVETo observe the effects of multiwall carbon nano-onions (MWCNOs) on platelet aggregation and hemostatic function.

METHODSThe platelet aggregation was determined with Born's method at different concentration of MWCNOs (0, 0.2, 2.0, 20.0 microg/ml) in vitro. Twenty male SD rats were randomly divided into 4 groups which were exposed to 0, 2, 4 and 8 mg/kg MWCNOs, respectively. Then platelet count, platelet aggregation, activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), bleeding time (BT) and platelet count (PC) were measured at 12 h after receiving tail intravenous injection of MWCNOs. The effects of MWCNOs (4 mg/kg) on platelet aggregation and platelet count at different time points were observed.

RESULTSIn vitro, MWCNOs exhibited the potent inhibitory effects on rat platelet aggregation caused by ADP in a concentration-dependent manner. The platelet aggregation in the highest dosage of 20.0 microg/ml group was 50.0% +/- 6.9% which was significantly lower than that (73.2% +/- 4.3%) in control group (P<0.01). In vivo, the highest inhibitory was up to 20.4%, but there was no significant difference, as compared with control group. MWCNOs did not affect the APTT, PT, TT, BT and PC.

CONCLUSIONUnder this experimental condition, MWCNOs might inhibit platelet aggregation but not affect hemostatic function.

Animals ; Bleeding Time ; Blood Coagulation ; drug effects ; Carbon ; administration & dosage ; pharmacology ; Hemostasis ; drug effects ; Male ; Nanostructures ; Partial Thromboplastin Time ; Platelet Aggregation ; drug effects ; Platelet Count ; Prothrombin Time ; Rats ; Rats, Sprague-Dawley ; Thrombin Time