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Objective:To study the predictive value of peripheral blood cathepsin (Cat) level on arteriovenous fistula stenosis and therapeutic effect of urokinase combined with argatroban in patients with maintenance hemodialysis (MHD).Methods:The clinical data of 120 patients with MHD from January 2017 to January 2021 in the First Affiliated Hospital of Hebei North University were retrospectively analyzed. Among them, 72 patients had arteriovenous fistula stenosis (stenosis group), and 48 patients had not arteriovenous fistula stenosis (non-stenosis group). The patients in stenosis group were treated with urokinase combined with argatroban, and the therapeutic effect was evaluated; the stenosis degree of arteriovenous fistula stenosis was evaluated by digital subtraction angiography (DSA). The levels of Cat K and S in peripheral blood were detected by enzyme linked immunosorbent assay. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of Cat K and S in peripheral blood on arteriovenous fistula stenosis in patients with MHD. The independent risk factor of arteriovenous fistula stenosis in patients with MHD was analyzed by multivariate Logistic regression analysis.Results:The levels of Cat K and S in peripheral blood in stenosis group were significantly higher than those in non-stenosis group: (404.34 ± 12.43) μg/L vs. (344.22 ± 12.09) μg/L and (124.55 ± 13.43) μg/L vs. (84.60 ± 12.45) μg/L, and there were statistical differences ( t = 26.39 and 16.68, P<0.01). The result of DSA showed that mild stenosis of arteriovenous fistula stenosis was in 33 cases, moderate stenosis in 23 cases, and severe stenosis in 16 cases. The levels of Cat K and S in peripheral blood in patients with moderate stenosis and severe stenosis were significantly higher than those in patients with mild stenosis: (399.83 ± 11.79) and (476.27 ± 12.24) μg/L vs. (372.61 ± 12.88) μg/L, (125.77 ± 12.75) and (151.69 ± 11.86) μg/L vs. (110.54 ± 12.07) μg/L, the indexes in patients with severe stenosis were significantly higher than those in patients with moderate stenosis, and there were statistical differences ( P<0.01). After treatment, excellent was in 40 cases, effective in 23 cases, and ineffective in 9 cases. The levels of Cat K and S in peripheral blood in patients with effective and ineffective were significantly higher than those in patients with excellent: (404.78 ± 10.96) and (491.30 ± 10.26) μg/L vs. (384.52 ± 10.36) μg/L, (121.85 ± 10.99) and (232.65 ± 10.61) μg/L vs. (101.78 ± 10.61) μg/L, the indexes in patients with ineffective were significantly higher than those in patients with effective, and there were statistical differences ( P<0.01). The ROC curve analysis result showed that the area under the curve of Cat K combined with Cat S in peripheral blood in forecasting arteriovenous fistula stenosis in patients with MHD was larger than that of Cat K and S alone (0.699 vs. 0.635 and 0.611), and the accuracy and specificity were also significantly higher (80.83% vs. 48.33% and 60.00%, 89.58% vs. 76.25% and 81.33%), the optimum cut-off values of Cat K and S in peripheral blood were 401.23 and 123.65 μg/L. Multivariate Logistic regression analysis result showed that the levels of Cat K and S in peripheral blood were the independent risk factor of arteriovenous fistula stenosis in patients with MHD ( OR = 1.02 and 1.63, 95% CI 0.90 to 1.93 and 1.33 to 2.32, P<0.01). Conclusions:The levels of Cat K and S in peripheral blood can predict the occurrence and extent of arteriovenous fistula stenosis in patients with MHD, and could also predict the therapeutic effect of urokinase combined with agatroban.
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Objective:To evaluate the safety and efficacy of argatroban applied as alternative anticoagulant in critical illness patients underwent extracorporeal membrane oxygenation (ECMO) with contraindications of unfractionated heparin (UFH), and to further explore the effective dose of argatroban.Methods:From July 1, 2013 to February 28, 2022, there were 14 patients who admitted in the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital received ECMO and used argatroban for anticoagulation (argatroban group). Two of them received argatroban as the initial anticoagulant. The remaining 12 patients used UFH at first, and then switched to argatroban. UFH group included 28 patients who received UFH for anticoagulation after matching the demographic characteristics. Primary endpoint was the prevalence of ECMO-related thrombotic events. Secondary endpoints included the type of thrombotic events, prevalence of ECMO-related major bleeding events, bleeding sites, ICU mortality, mortality during ECMO, liver and kidney function, thrombelastogram, blood transfusion, dosage of argatroban, the dynamic changes of coagulation variables 4 days before and 7 days after argatroban treatment.Results:In argatroban group, there were 8 patients received veno-venous ECMO (VV-ECMO), 2 patients with veno-arterial ECMO (VA-ECMO), and 4 patients with veno-arterio-venous ECMO (VAV-ECMO). In UFH group, VV-ECMO was applied in 23 patients, VA-ECMO and VAV ECMO was established in 3 patients and 2 patients, respectively. In endpoint events, the incidence of ECMO related thrombotic events in argatroban group was slightly higher than that in UFH group (28.6% vs. 21.4%). The ECMO running time in argatroban group was slightly longer than that in UFH group [days: 16 (7, 21) vs. 13 (8, 17)]. The incidence of ECMO-related bleeding events (28.6% vs. 32.1%) and mortality during ECMO (35.7% vs. 46.4%) in argatroban group were slightly lower than those in UFH group. However, the differences were not statistically significant (all P < 0.05). The platelet transfusion in argatroban group was significantly higher than that in UFH group [U: 7.7 (0, 10.0) vs. 0.8 (0, 1.0)]. The coagulation reaction time (R value) in thrombelastography in argatroban group was significantly longer than that in UFH group [minutes: 9.3 (7.2, 10.8) vs. 8.8 (6.3, 9.7)]. The maximum width value [MA value, mm: 48.4 (40.7, 57.9) vs. 52.6 (45.4, 61.5)] and blood clot generation rate [α-Angle (deg): 54.1 (45.4, 62.0) vs. 57.9 (50.2, 69.0)] in the argatroban group were significantly lower than those in the UFH group (all P < 0.05). The activated partial thromboplastin time (APTT) was prolonged after changing from UFH to argatroban in the argatroban group [seconds: 63.5 (58.4, 70.6) vs. 56.7 (53.1, 60.9)]. The PLT level showed a decreasing trend during UFH anticoagulation therapy, and gradually increased after changing to argatroban. D-dimer level was 19.1 (7.0, 28.7) mg/L after switching to argatroban, and then no longer showed an increasing trend. The level of fibrinogen (FIB) showed a decreasing trend during the anticoagulant therapy of UFH (the lowest was 23.6 g/L), and fluctuated between 16.8 and 26.2 g/L after changing to argatroban. The median initial dose of argatroban was 0.049 (0.029, 0.103) μg·kg -1·min -1, which the highest dose was in VV-ECMO patients of [0.092 (0.049, 0.165) μg·kg -1·min -1]. The initial dose of VAV-ECMO was the lowest [0.026 (0.013, 0.041) μg·kg -1·min -1], but without significant difference ( P > 0.05). The maintenance dose of argatroban was 0.033 (0.014, 0.090) μg·kg -1·min -1, VV-ECMO patients was significantly higher than those in VA-ECMO and VAV-ECMO patients [μg·kg -1·min -1: 0.102 (0.059, 0.127) vs. 0.036 (0.026, 0.060), 0.013 (0.004, 0.022), both P < 0.05]. Conclusion:Argatroban appears to be a feasible, effective and safety alternative anticoagulant for patients with contraindications to UFH who undergoing ECMO support.
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Objective:To investigate the efficacy and safety of sequential treatment with tirofiban and argatroban in acute isolated pontine infarction (AIPI) caused by branch atheromatous disease (BAD).Methods:Consecutive patients with AIPI caused by BAD within 48 h of onset and admitted to Zhengzhou Central Hospital from April 2021 to April 2022 were enrolled retrospectively. The patients were divided into sequential treatment group and tirofiban group according to their therapeutic modalities. In the tirofiban group, tirofiban was pumped intravenously within 48 h after admission, and dual antiplatelet therapy with aspirin and clopidogrel was added 4 h before tirofiban was discontinued. On the basis of tirofiban treatment, the sequential treatment group was followed by argatroban for 5 days when tirofiban is discontinued. The main outcome measure was the modified Rankin Scale (mRS) score at 3 months after the onset . A score of <2 was defined as a good outcome. The secondary outcome measure was all the adverse events during the treatment and follow-up. Multivariate logistic regression analysis was used to determine the independent factors of the outcomes. Results:A total of 64 patients with AIPI caused by BAD were enrolled, including 32 in the sequential treatment group and 32 in the tirofiban group. There was no statistical difference in baseline data between the two groups, but the rate of good outcomes at 3 months after onset in the sequential treatment group was significantly higher than that in the tirofiban group (78.1% vs. 50.0%; χ2=5.497, P=0.019). Multivariate logistic regression analysis showed that after adjusting for low-density lipoprotein cholesterol, the higher baseline National Institutes of Health Stroke Scale score was independently associated with the poor outcomes (odds ratio 2.067, 95% confidence interval 1.343-3.182; P=0.001), while the sequential treatment was independently associated with the good outcomes (odds ratio 0.248, 95% confidence interval 0.064-0.957; P=0.043). Conclusion:Early application of sequential treatment with tirofiban and argatroban in AIPI caused by BAD may effectively improve the outcomes of patients, and the safety is good.
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Objective To investigate the effect of argatroban in repair of spinal cord injury in rats.Methods A total of 54 female Wistar rats were selected and divided into three groups according to the random number table:sham group,injury group and Argatroban group,with 18 rats in each group.The sham group only took the T101amina;the injury group used the spinal cord injury device to make the rat spinal cord injury model;the Argatroban group received Argatroban treatment after spinal cord injury.The recovery of hindlimb motor function was evaluated by BBB score and clined plate test before injury and 7,14,21,28,35 and 42 days after injury.The sensory evoked potentials (SEP) and motor evoked potentials (MEP) were detected 42 days after operation.HE staining was used to compare the size of the cavity in the local region 42 days after injury.Results At day 7 after injury,the BBB score was (3.7 ±0.5) points and the inclined plane test was (28.0 ± 2.6) ° in the Argatroban group,which were better than those in the injury group [(3.3 ± 0.5) points,(24.3 ± 1.9) °] (p ＜ 0.05).At day 42 after injury,the BBB score was (13.0 ± 0.8) points and inclined plane test was (50.7 ± 2.7) ° in the Argatroban group,which were significantly better than those in the injury group [(9.7 ± 1.3) points,(40.5 ± 2.7)°] (p ＜0.05).But all the above values in the Argatroban group were significantly lower than those in the sham group [(21.0 ± 0.0) points,(60.0 ± 0.0) °] (P ＜ 0.05).At day 42 after operation,the SEP latency [(25.0 ± 0.9)ms] in the Argatroban group was significantly shorter than that in the injury group [(31.5 ± 1.9) ms];the amplitude [(2.1 ± 0.1) μV] in the Argatroban group was lower than that in the injury group [(0.5 ± 0.1) μV] (P ＜ 0.05).The MEP latency [(11.5 ± 1.0) ms]in the Argatroban group was significantly shorter than that in the injury group [(17.5 ± 1.1) ms],and the amplitude [(4.8 ± 0.8) μV] in the Argatroban group was lower than that in the injury group [(2.8 ± 0.7) μV] (P ＜ 0.05).And the SEP or MEP latency and amplitude in the Argatroban group showed significant differences compared to the sham group [(7.5 ± 1.0) ms,(7.5 ± 1.0) μV] (P ＜0.05) . HE staining showed that the central area of the lesion in the Argatroban group [(0.35 ± 0.04) mm2]was significantly smaller than that in the injury group [(0.71 ± 0.05)mm2].Conclusion After spinal cord injury,argatroban can protect the spinal cord tissue effectively in the injured area and promote recovery of sensory and motor function in the hind limbs of rats.
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Objective@#To investigate the effect of argatroban in repair of spinal cord injury in rats.@*Methods@#A total of 54 female Wistar rats were selected and divided into three groups according to the random number table: sham group, injury group and Argatroban group, with 18 rats in each group. The sham group only took the T10lamina; the injury group used the spinal cord injury device to make the rat spinal cord injury model; the Argatroban group received Argatroban treatment after spinal cord injury. The recovery of hindlimb motor function was evaluated by BBB score and clined plate test before injury and 7, 14, 21, 28, 35 and 42 days after injury. The sensory evoked potentials (SEP) and motor evoked potentials (MEP) were detected 42 days after operation. HE staining was used to compare the size of the cavity in the local region 42 days after injury.@*Results@#At day 7 after injury, the BBB score was (3.7±0.5)points and the inclined plane test was (28.0±2.6)° in the Argatroban group, which were better than those in the injury group [(3.3±0.5)points, (24.3±1.9)°] (P<0.05). At day 42 after injury, the BBB score was (13.0±0.8)points and inclined plane test was (50.7±2.7)° in the Argatroban group, which were significantly better than those in the injury group [(9.7±1.3) points, (40.5±2.7)°] (P<0.05). But all the above values in the Argatroban group were significantly lower than those in the sham group [(21.0±0.0)points, (60.0±0.0)°](P<0.05). At day 42 after operation, the SEP latency [(25.0±0.9)ms] in the Argatroban group was significantly shorter than that in the injury group [(31.5±1.9) ms]; the amplitude [(2.1±0.1)μV] in the Argatroban group was lower than that in the injury group [(0.5±0.1)μV] (P<0.05). The MEP latency [(11.5±1.0)ms] in the Argatroban group was significantly shorter than that in the injury group [(17.5±1.1)ms], and the amplitude [(4.8±0.8)μV] in the Argatroban group was lower than that in the injury group [(2.8±0.7)μV] (P<0.05). And the SEP or MEP latency and amplitude in the Argatroban group showed significant differences compared to the sham group [(7.5±1.0)ms, (7.5±1.0)μV](P<0.05). HE staining showed that the central area of the lesion in the Argatroban group [(0.35±0.04)mm2] was significantly smaller than that in the injury group [(0.71±0.05)mm2].@*Conclusion@#After spinal cord injury, argatroban can protect the spinal cord tissue effectively in the injured area and promote recovery of sensory and motor function in the hind limbs of rats.
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Objective To investigate the safety of argatroban in vertebral artery stenting and its effect on postoperative restenosis.Methods From January 2013 to September 2017,patients undergoing vertebral artery stenting in the Department of Neurology,Jinling Hospital were enrolled prospectively.They were divided into agatraban group and heparin group by random number table method.The argatroban group received argatroban anticoagulation during the procedure,and was continuously used for 5 d after procedure;while the heparin group underwent heparin anticoagulation during the procedure,and used saline as placebo after procedure.Clinical follow-up was performed at 1,3,and 6 months after procedure.Digital subtraction angiography,CT angiography,or magnetic resonance angiography were performed at 6 months to evaluate the restenosis of the treated blood vessels.The primary endpoints included intraoperative safety,in-stent restenosis after procedure,and any clinical events that occurred during the follow-up period,including stroke,cardiovascular events,and death.Major safety events included bleeding from various organs,allergic reactions,liver dysfunction,and embolism events.Kaplan-Meier survival curve was used to evaluate the incidence of vascular events during the follow-up period.Results A total of 105 patients were enrolled in the analysis,including 53 in the argatroban group and 52 in the heparin group.During the periprocedural period,no hemorrhagic events,allergic reactions,liver dysfunction or embolism events occurred in both groups.There were no significant differences in preoperative vertebral artery stenosis degree,postoperative residual stenosis degree,and stenosis degree at 6 months after procedure between the two groups,but the increase of stent stenosis at 6 months after procedure in the agatroban group was significantly lower than that in the heparin group (13.56％ ±26.41％ vs.4.25％ ± 15.76％;P =0.031).There was no significant difference in the incidence of stroke recurrence (P =1.000) and clinical events (P=0.739) between the two groups during the long-term follow-up period.Conclusions It is safe to use agatraban anticoagulant therapy in the vertebral artery stenting.Continuous use of agatraban anticoagulation after procedure may effectively reduce the increase of stent stenosis at 6 months after procedure.
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Objective@#To investigate the safety of argatroban in vertebral artery stenting and its effect on postoperative restenosis.@*Methods@#From January 2013 to September 2017, patients undergoing vertebral artery stenting in the Department of Neurology, Jinling Hospital were enrolled prospectively. They were divided into agatraban group and heparin group by random number table method. The argatroban group received argatroban anticoagulation during the procedure, and was continuously used for 5 d after procedure; while the heparin group underwent heparin anticoagulation during the procedure, and used saline as placebo after procedure. Clinical follow-up was performed at 1, 3, and 6 months after procedure. Digital subtraction angiography, CT angiography, or magnetic resonance angiography were performed at 6 months to evaluate the restenosis of the treated blood vessels. The primary endpoints included intraoperative safety, in-stent restenosis after procedure, and any clinical events that occurred during the follow-up period, including stroke, cardiovascular events, and death. Major safety events included bleeding from various organs, allergic reactions, liver dysfunction, and embolism events. Kaplan-Meier survival curve was used to evaluate the incidence of vascular events during the follow-up period.@*Results@#A total of 105 patients were enrolled in the analysis, including 53 in the argatroban group and 52 in the heparin group. During the periprocedural period, no hemorrhagic events, allergic reactions, liver dysfunction or embolism events occurred in both groups. There were no significant differences in preoperative vertebral artery stenosis degree, postoperative residual stenosis degree, and stenosis degree at 6 months after procedure between the two groups, but the increase of stent stenosis at 6 months after procedure in the agatroban group was significantly lower than that in the heparin group (13.56%±26.41% vs. 4.25%±15.76%; P=0.031). There was no significant difference in the incidence of stroke recurrence (P=1.000) and clinical events (P=0.739) between the two groups during the long-term follow-up period.@*Conclusions@#It is safe to use agatraban anticoagulant therapy in the vertebral artery stenting. Continuous use of agatraban anticoagulation after procedure may effectively reduce the increase of stent stenosis at 6 months after procedure.
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Some 50% of patients who undergo cardiac surgery will have heparin-induced thrombocytopenia (HIT) antibodies, only 1% will develop typical clinical HIT. Especially delayed-onset HIT is not well-known and extremely rare. A 83-year-old man underwent aortic valve replacement (AVR) with a bioprosthetic valve (Mitroflow 21 mm) and pulmonary vein isolation (PVI). Intravenous unfractionated heparin (8,000 I.U./day) was administered for 5 days after surgery. He had a good recovery and was discharged to home with a platelet count of 100,600/μl on POD 15 on warfarin. On POD 18, he was readmitted to our hospital due to cerebral infarction with hemiparesis. As MRI revealed a multiple left hemispheric infarction, the presence of cardiogenic cerebral infarction was suspected. Continuous intravenous administration of unfractionated heparin (15,000 I.U./day) was started. On POD 24, the platelet count fell to 27,000/μl, and a contrast CT scan revealed a giant thrombus in the aortic arch. He was found to have HIT antibodies, supporting a diagnosis of HIT. After cessation of heparin therapy and administration of vitamin K antagonist, argatroban was administered. He recovered neurologically and was discharged on POD 58. He remains well at 3 years follow up. If a patient has an unexplained and severe thrombocytopenia after cardiovascular surgery, delayed-onset HIT should be taken into consideration.
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A 67-year-old man with dilated cardiomyopathy was admitted to our hospital for treatment of cardiac failure. After using heparin because cerebral infarction developed during hospitalization, in acknowledgment of thrombocytopenia, we reach the diagnosis of HIT. We judged surgery to be necessary because heart failure had difficulty with catecholamine secession and the left ventricular dilation progressed rapidly, and performed left ventriculoplasty, mitral valve plasty. There were no complications such as the thrombosis during cardiopulmonary bypass, and the postoperative course was good without leading to re-thoracotomy due to bleeding. He passes without a heart failure symptom by the follow of one year 6 months after surgery at home.
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Forced degradation study of argatroban under conditions of hydrolysis (neutral, acidic and alkaline), oxidation, photolysis and thermal stress, as suggested in the ICH Q1A (R2), was accomplished. The drug showed sig-nificant degradation under hydrolysis (acidic, alkaline) and oxidation (peroxide stress) conditions. The drug remained stable under thermal and photolytic stress conditions. In total, seven novel degradation products (DP-1 to DP-7) were found under diverse conditions, which were not reported earlier. The chemical structures of these degradation products were characterized by 1H NMR, 13C NMR, 2D NMR, Q-TOF-MSn and IR spectral analysis and the proposed degradation products structures were further confirmed by the individual synthesis.
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Objective :To explore influence of argatroban on cerebral blood flow ,levels of CXC chemokine ligand 16 (CX-CL16) and high sensitive C reactive protein (hsCRP) in patients with acute cerebral infarction (ACI).Methods :A total of 100 ACI patients were selected ,randomly and equally divided into routine treatment group and argatroban group (received argatroban based on routine treatment ) ,both groups were treated for 10d.Score of United States national institutes of health stroke score (NIHSS) ,cerebral blood flow and levels of CXCL16 and hsCRP were compared between two groups be-fore and after treatment .Results :Compared with before treatment ,after treatment ,there were significant reductions in NIHSS score ,levels of endothelin (ET)-1 ,CXCL16 and hsCRP ,and significant rise in mean blood flow velocities of mid-dle cerebral artery (MCA) and anterior cerebral artery (ACA) and nitric oxide (NO) level in two groups (P＝0.001 all) ;compared with routine treatment group after treatment ,there were significant reductions in NIHSS [ (9.78 ± 3.59) scores vs.(7.02 ± 3.67) scores] ,levels of ET-1 [(75.75 ± 10.67) pg/ml vs.(62.56 ± 9.45) pg/ml] ,CXCL16 [(2.01 ± 0.84) ng/ml vs.(1.67 ± 0.75) ng/ml] and hsCRP [(4.42 ± 1.66) mg/L vs.(3.89 ± 1.37) mg/L] ,and significant rise in mean blood flow velocities of MCA [ (48.87 ± 5.23) cm/s vs.(55.35 ± 6.35) cm/s] and ACA [ (41.25 ± 4.89) cm/s vs. (47.88 ± 5.47) cm/s] and NO level [ (55.77 ± 6.36) μmol/L vs.(65.76 ± 6.86) μmol/L] in argatroban group , P＜0.05 or ＜0.01.There was no significant difference in incidence rate of hemorrhage events between two groups (P＝0.315). Conclusion : Argatroban based on routine treatment can more effectively improve cerebral blood flow and vascular endothe-lial function ,reduce levels of CXCL 16 and hsCRP ,and improve clinical therapeutic effect .
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Objective To observe the anticoagulant efficacy and safety of argatroban and unfractionated heparin (UFH) in continuous blood purification (CBP) treatment and provide the theoretical basis for optimizing the anticoagulant mode of CBP treatment in critically ill patients. Methods Sixty patients treated with CBP in Binhai Hospital of General Hospital of Tianjin Medical University from September 2015 to October 2016 were enrolled, and they were divided into two groups by random number table method, each group 30 cases. Before CBP therapy, the patients in argatroban group were treated with argatroban for anti-coagulation, the first dose was 250 μg/kg, the additional dose was 1 μg·kg-1·min-1 continuously infused before sustained filtration, and 20-30 minutes before the end of the CBP treatment, the dose added was stopped; the patients in UFH group were treated with UFH before CBP treatment, the first dose was 0.3-0.5 mg/kg, the additional dose was 5-10 mg/h, and 30 minutes before the end of CBP treatment the dose added was stopped. The changes of activated partial thromboplastin time (APTT) were monitored, before and after the end of CBP treatment, the coagulation of blood in the CBP filter/circuit and bleeding tendency of patients in two groups were observed, and the differences in platelet (PLT) counts were compared between the two groups before and after CBP treatment. Results The APTT of the two groups were significantly longer at 3 hours after treatment and before the end of treatment than those before treatment [UFH group (s): 64.96±7.35, 64.33±6.27 vs. 37.77±5.23; argatroban group (s):70.19±6.18, 72.03±6.39 vs. 40.10±5.11], and at 1 hour after the end of treatment, APTT basically returned to baseline level in argatroban group (s: 39.6±5.06), while in the UFH group APTT was still higher than that before treatment (s: 64.17±6.59). There were no statistical significant differences in the blood coagulation score of the CBP filter/circuit and bleeding score and gradation of patients between the two groups (both P > 0.05). After treatment the PLT levels of the two groups were significantly lower than those before treatment, but the level of PLT in the argatroban group was significantly higher than that in the UFH group (×109/L: 192.20±50.05 vs. 160.00±57.12, P < 0.05). Conclusion In comparison, argatroban has a better anticoagulant effect in CBP treatment for critically ill patients, argatroban is superior to UFH in controllability, so that using the former one can lower the incidence of thrombocytopenia and risk of bleeding.
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Objective To observe the anticoagulant efficacy and safety of argatroban and unfractionated heparin (UFH) in continuous blood purification (CBP) treatment and provide the theoretical basis for optimizing the anticoagulant mode of CBP treatment in critically ill patients. Methods Sixty patients treated with CBP in Binhai Hospital of General Hospital of Tianjin Medical University from September 2015 to October 2016 were enrolled, and they were divided into two groups by random number table method, each group 30 cases. Before CBP therapy, the patients in argatroban group were treated with argatroban for anti-coagulation, the first dose was 250 μg/kg, the additional dose was 1 μg·kg-1·min-1 continuously infused before sustained filtration, and 20-30 minutes before the end of the CBP treatment, the dose added was stopped; the patients in UFH group were treated with UFH before CBP treatment, the first dose was 0.3-0.5 mg/kg, the additional dose was 5-10 mg/h, and 30 minutes before the end of CBP treatment the dose added was stopped. The changes of activated partial thromboplastin time (APTT) were monitored, before and after the end of CBP treatment, the coagulation of blood in the CBP filter/circuit and bleeding tendency of patients in two groups were observed, and the differences in platelet (PLT) counts were compared between the two groups before and after CBP treatment. Results The APTT of the two groups were significantly longer at 3 hours after treatment and before the end of treatment than those before treatment [UFH group (s): 64.96±7.35, 64.33±6.27 vs. 37.77±5.23; argatroban group (s):70.19±6.18, 72.03±6.39 vs. 40.10±5.11], and at 1 hour after the end of treatment, APTT basically returned to baseline level in argatroban group (s: 39.6±5.06), while in the UFH group APTT was still higher than that before treatment (s: 64.17±6.59). There were no statistical significant differences in the blood coagulation score of the CBP filter/circuit and bleeding score and gradation of patients between the two groups (both P > 0.05). After treatment the PLT levels of the two groups were significantly lower than those before treatment, but the level of PLT in the argatroban group was significantly higher than that in the UFH group (×109/L: 192.20±50.05 vs. 160.00±57.12, P < 0.05). Conclusion In comparison, argatroban has a better anticoagulant effect in CBP treatment for critically ill patients, argatroban is superior to UFH in controllability, so that using the former one can lower the incidence of thrombocytopenia and risk of bleeding.
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OBJECTIVE:To study clinical effect of argatroban for progressive stroke patients of different cerebral ischemic ranges. METHODS:A total of 116 progressive stroke patients selected from neurology department of our hospital during Feb. 2015-May 2016 were divided into anterior circulation (ischemia) group (n=60),posterior circulation (ischemia) group (n=50) and lacunar(cerebral infarction)group(n=6)according to cerebral ischemic ranges. They all received routine treatment combined with argatroban,and given continuous intravenous infusion of argatroban 60 mg/d on the day and 2nd day of disease aggravation, and then continuous intravenous infusion of argatroban 5th day after relieving,3 h/time,bid,7 d as a treatment course. NIHSS scores,modified RANKIN (mRS) scores,APTT and ADR were compared among 3 groups. RESULTS:Forteen days after treat-ment,NIHSS scores and mRS scores of 3 groups were decreased significantly compared to before treatment,with statistical signifi-cance (P0.05). No obvious ADR was found in 3 groups. CONCLUSIONS:Argatroban shows significant therapeutic efficacy for progressive stroke of different ischemic ranges with good safety;especially for the patients with anterior circulation ischemics stroke,the effect is quick and anticoagulant effect is significant.
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<p>A 66-year-old man with an unknown medical history developed chest pain and a diagnosis of acute myocardial infarction (AMI) was given by his physician. Percutaneous coronary intervention was performed in the left anterior descending artery. Echocardiography revealed ventricular septal perforation (VSP) ; therefore, the patient was transferred to our hospital. After admission, his platelet count dropped rapidly during heparin administration, and left ventricular thrombosis and deep vein thrombosis were noted, raising a suspicion of heparin-induced thrombocytopenia (HIT). To establish cardiopulmonary bypass, argatroban alone was insufficient to prolong the Powered by Editorial Manager<sup>®</sup> and ProduXion Manager<sup>®</sup> from the Aries Systems Corporation activated clotting time (ACT) ; thus, nafamostat mesilate was also used for coronary artery bypass grafting and surgical repair of VSP. It took many hours to normalize the ACT, requiring re-exploration for excessive bleeding. On the 37th postoperative day, the patient was transferred to another hospital. We performed cardiac surgical procedures using argatroban in a patient who developed HIT during the course of VSP following AMI ; however, we had difficulty in controlling the ACT. Since, to the best of our knowledge, there are no previous studies reporting surgical case of VSP complicated by HIT, we present this case with a review of the relevant literature.</p>
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Objective:To explore the effect of argatroban combined with Kallikrein on progressive cerebral infarction.Methods: One hundred and fifty two progressive cerebral infarction patients were randomized into groups observation (n=76) and control (n=76). Observation group were given treatment ofargatroban and Kallikrein, control only Kallikrein. NIHSS scores, Barthel index, Modified Rankin Scales(MRS) were used to evaluate the efficacy in two groups.Results: The difference of the effect was significant in two groups(x2=11.463,P>0.05).In both of the two groups, NIHSS scores were decreased, there was significant difference between the two groups (t=1.501,t=1.844,t=1.341;P<0.05). The Barthel index in argatroban combined Kallikrein group was higher than Kallikrein group, Modified Rankin Scales was lower than Kallikrein group, and there was significant difference between the two groups (t=2.121,t=2.332,t=2.219;P<0.05). The observation group and the control group patients don''t have bleeding gums,subcutaneous bleeding, gastrointestinal bleeding and other adverse reactions.Conclusion: Argatroban combined with Kallikrein, improve the neurologic impairment symptoms, clinical effect, improve the life quality of the patients, of a relatively good effect in treatment of progressive cerebral infarction, can improve obviously the cognitive ability and neural function and patients, activities of daily living. Moreover, its security and tolerability are good.
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OBJECTIVE:To explore the role of clinical evidence-based pharmacy in anticoagulant treatment strategies during continuous renal replacement therapy (CRRT). METHODS:Taking a thrombocytopenia patient of anticoagulant treatment during CRRT for instance,clinical pharmacists analyzed the evidence of taken argatroban anticoagulant therapy during CRRT for high risk blooding and thrombocytopenia patients based on evidence-based pharmacy combined with clinical data,monitored the efficacy and safety and evaluated the treatment process. RESULTS:Totally five literature about anticoagulant treatment strategies during CRRT for high risk blooding and thrombocytopenia patients were obtained,including one systematic review,one RCT and three cohort studies. Based on the above evidences,good results were achieved in the clinical practice of this patient,no thrombotic or hemor-rhagic complications occurred in this patient,platelet count and coagulation indicators of patients also improved. CONCLUSIONS:Evidence-based pharmacy plays an important role in anticoagulant treatment strategies during CRRT.
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OBJECTIVE:To explore the pharmacoeconomic effect of Ginkgo dipyidamolum,argatroban or sodium ozagerl combined with edaravone in the treatment of acute cerebral infarction(ACI). METHODS:In retrospective study,64 ACI patients were divided into group A(Ginkgo dipyidamolum+edaravone,22 cases),group B(argatroban+edaravone,19 cases)and group C (sodium ozagerl+edaravone,23 cases). Therapeutic efficacies were observed after 7-14 days of treatment;therapy cost was calculat-ed,and cost-minimization analysis was used to evaluate pharmacoeconomics. RESULTS:There was no statistical significance in to-tal effective rate among 3 groups(P>0.05);the costs of group A,group B and group C were 8 746.36 yuan,10 770.64 yuan and 8 264.67 yuan. Results of sensitivity analysis were in line with those of cost-minimization analysis. CONCLUSIONS:Therapy plan of sodium ozagerl+edaravone is the economical regime in the treatment of ACI .
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<p>A 53-year-old man was urgently hospitalized with chronic renal failure, congestive heart failure, pulmonary edema, and pneumonia. He received respiratory support and dialysis after hospitalization in the intensive care unit. Coronary arteriography revealed an old myocardial infarction and unstable angina (triple vessel disease). Surgery was planned. However, after dialysis under heparin administration, clot formation was noted in the dialyzer. Serological tests confirmed the presence of antibodies to heparin-platelet factor 4 complex ; accordingly, heparin-induced thrombocytopenia (HIT) was diagnosed. Coronary artery bypass surgery should preferably be performed early in the case of coronary artery disease. However, surgery during the acute phase of HIT when antibodies to heparin-platelet factor 4 complex (HIT antibodies) are present is associated with a very high risk of developing thromboembolism. There is no criterion regarding the optimal timing for surgery when HIT antibodies are present. Therefore, clinicians are often confused about this. In cases where the platelet count, D-dimer level, fibrinogen degradation product (FDP) level, and fibrinogen level improve, thrombin production due to HIT antibodies is thought to decrease. We considered that the improvement in these values suggests that the number of HIT antibodies decreases and thus HIT antibody activity would be reduced. We evaluated the platelet count, D-dimer level, FDP level, and fibrinogen level over time and accordingly determined the optimal timing for surgery. In the present case, argatroban administration was started after HIT developed, and the platelet counts increased gradually ; the D-dimer and FDP levels decreased, whereas there were no significant changes in the fibrinogen levels. Although HIT antibodies were still present, we performed off-pump coronary artery bypass grafting under the administration of argatroban when the platelet count, D-dimer, and FDP values improved. The patency of coronary bypass grafts was confirmed postoperatively ; the patient did not develop thromboembolism during the perioperative period and was discharged without complications. When HIT antibodies are present, an improvement in platelet count, D-dimer, and FDP values is thought to be useful in determining the optimal timing of surgery.</p>
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Objective To evaluate the effect of heparin and argatroban on the coagulating function and the vascular thrombosis in the early period after pediatric living related liver transplantation (LRLT).Method Eighty-four congenital biliary atresia pediatric patients who had performed LRLT were involved in this study.According to the method of anticoagulation,the patients were divided into two groups (heparin group and argatroban group).Antithrombin Ⅲ (AT-Ⅲ) activity,activated partial thromboplastin time (APTT) and international normalized ratio (INR) of two groups were measured in the first 5 days after LRLT.In order to determine whether vascular thrombosis existed,Doppler ultrasound was performed daily.Result There were no significant differences in gender,age,body weight,graft-recipient weight ratio and whether to accept Kassi procedure between two groups.The AT-Ⅲ activity of two groups was low and increased gradually after operation.There was no significant difference between two groups.There were no significant differences in APTT and INR between two groups immediate and at first day after operation.After anticoagulation,the differences in APTT and INR between two groups were significant.The incidence of vascular thrombosis was 4.76％ (3/63) and 0(0/21) respectively in heparin and argatroban groups.There was no significant difference between two groups.During treatment,there were no severe complications in two groups,such as active hemorrhage and allergy.Conclusion Argatroban is a direct anticoagulant.It is independent on the level of AT-Ⅲ activity.It may play an important role for preventing vascular thrombosis after pediatric LRLT.