Why anticoagulant studies on sepsis fail frequently --- start with SCARLET / 中华创伤杂志(英文版)

The Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin (SCARLET) trial has many defects, and thus cannot be the terminator of recombinant thrombomodulin (rTM). On the contrary, it provides sufficient evidence for further research. Based on analysis focusing on the failure of SCARLET and several previous anticoagulant studies, it is most important for new studies to grasp the following two points: (1) The enrolled cases should have sufficient disease severity and a clear standard for disseminated intravascular coagulation; (2) Heparin should not be used in combination with the investigated drugs. Multiple post-hoc analyses show that no combination of heparin will not increase the risk of thromboembolism. In fact, the combination of heparin can mask the true efficacy of the investigated drug. Due to the complexity of sepsis treatment and the limitations of clinical studies, the results of all treatment studies should be repeatedly verified, rather than be determined at one stroke. Some research conclusions contrary to disease physiology, pharmacology and clinical practice may be deceptive, and should be cautious rather than be simply accepted. On the other hand, the dissenting voices in the "consensus" scene are often well discussed by the authors and should be highly valued.

Evaluation of an anticoagulation management method based on mobile health technology and artificial intelligence / 中华健康管理学杂志

Objective:To evaluate an anticoagulation management method based on mobile health technology and artificial intelligence.Methods:The study was a single-center, prospective, randomized, controlled, non-inferiority clinical trial. From November 2017 to September 2018, 67 patients who received warfarin therapy after mechanical valve replacement were consecutively enrolled and randomized into two groups: 34 were randomized to intervention group and 33 to control group. The intervention group was managed via Anticlot Assistant and the control group was handled as routine care. Evaluations were performed at least 3 months after enrollment and ended on 30 September 2019. Non-inferiority was evaluated using one-sided tests with a non-inferiority margin set 11.0% for time in therapeutic range (TTR) and 10.0% for the percentage of international normalized ratio (INR) in the therapeutic range.Results:The mean TTR was (58.2±23.4)% in the intervention group and (54.8±23.6)% in the control (the difference: 3.4%; low limit of one-side 95% confidence interval for the difference: -6.4%; and P value for non-inferiority was 0.009). The percentage of INR in the therapeutic range was (55.4±21.9)% in the intervention group and (52.8±22.5)% in the control (the difference: 2.6%, low limit of one-side 95% confidence interval for the difference: -6.6%; and P value for non-inferiority was 0.012). Conclusion:The outcomes of patients managed via the anticoagulation management method base on mobile health technology and artificial intelligence are not inferior to those handled as routine care.

Anticoagulation in pulmonary TB induced deep vein thrombosis is it always warranted: a case report

India is a densely populated developing country and accounts for one quarter of the total tuberculosis cases reported worldwide. Deep vein thrombosis (DVT) has been associated with 1.5-3.4% cases of tuberculosis. A 14 year female presented with complaints of cough with progressive breathlessness (NYHA Grade III) since 15 days along with easy fatiguability and fever for 3 days. The patient was started on Anti-Tubercular Treatment (ATT) as per RNTCP guidelines after thorough investigations. One week after the patient was started on ATT, the patient developed edema of the right lower limb accompanied by pain. Color doppler was suggestive of thrombosis in the superficial and deep veins. Early immobilization and physiotherapy was started immediately. Over a period of 10 days, the swelling gradually decreased, and pain subsided. Tuberculosis is an independent risk factor for the development of venous thromboembolism irrespective of the presence of other risk factors. Emphasis is thus laid on high index of suspicion and early diagnosis to control and prevent further complications like pulmonary embolism. We can propose that in patients diagnosed with pulmonary tuberculosis, early immobilization and physiotherapy can prevent the development of DVT.

Subcutaneous Self-Injection Therapy of Heparin for a Case of Ebstein Disease with Artificial Valve and Warfarin-Induced Skin Ulcer / 日本心臓血管外科学会雑誌

We report a successful conversion of anti-coagulant therapy from warfarin to heparin for a case of mechanical heart valve and warfarin-induced skin ulcer. A 57-year-old female who was diagnosed with Ebstein disease and underwent mechanical valve replacement suffered from a recurring and resistant leg skin ulcer. Nine years after the induction of warfarin, her right leg skin ulcer occurred suddenly and worsened gradually. No dermatological treatment could cure it and three auto-skin transplantations were performed in the past four years. The definitive cause of the ulcer could not be diagnosed by any laboratory study or image inspection. Further, after every transplant surgery, the resumption of warfarin had made her ulcer recur and worsen. Therefore, we finally came to think of this disease as the warfarin-induced skin ulcer. To avoid warfarin, subcutaneous self-injection therapy of Heparin-Ca was applied as her anti-coagulation after the 4th transplant surgery. The patient was discharged from hospital on post-operative day 78 with a good condition of the transplanted skin graft and right leg. An adequate level of APTT could be maintained with injections of 10,000 units of Heparin-Ca twice a day and data on D Dimer and cardiac echography show no thromboembolism at the out-patient visits. The result of auto-skin transplantation is also a good course under this therapy. As we have very few reports concerning heparin self-injection therapy for artificial valves, it is very important that careful observation should be continued.

Study of anticoagulant protocols in patients undergoing non-cardiac surgery after percutaneous coronary intervention / 重庆医学

Objective To study the anticoagulant treatment protocols during perioperative period in the patients undergoing non-cardiac surgery after percutaneous coronary intervention(PCI).Methods Seventy-one patients undergoing non-cardiac surgery after PCI in this hospital from January 2014 to June 2016 were selected and given the low molecular weight heparin treatment before elective surgery.After surgery,the patients were divided into the anti-coagulation group and non-anticoagulation group.Then the occurrence situation of postoperative major adverse cardiac events was observed.Results The general indicators such as sex,age,complicating hypertension and diabetes and stent length and complication situation had no statistical differences between the two groups(P＞0.05).Within postoperative 7 d,there were 3 cases of unstable angina pectoris in the anti-coagulation group and 10 cases in the non-anticoagulation group,the difference between them was statistically significant(P＜0.05).The creatine phosphate kinase(CK) level at postoperative 24 h in the anti-coagulation group and non-anticoagulation group was significantly increased compared with pre-operation(P＜0.05),and the levels of CK-MB and cTnI had an increasing trend compared with before operation,but the difference was not statistically significant(P＞0.05).The preoperative and postoperative CK,CK-MB and cTnI levels had no statistical difference between the two groups(P0.05).Conclusion The anticoagulation therapy during perioperative priod in the patients undergoing non-cardiac surgery within 1 year after PCI can obviously reduce the occurrence of major adverse cardiac events.

Isolation and characterization of phospholipase A1 from Vespa tropica ducalis / 中草药

Objective: To find an effective method to isolated phospholipase from Vespa tropica ducalis and characterize its biological activities to support the pathogenic mechanism research and officinal value exploitation in the future. Methods: The component with phospholipase activity was isolated by successive gel filtration (Sephadex G-75, supferfine) and heparin affinity chromatography steps (Hitrap Heparin HP). The protein was identified by peptide mass fingerprinting, N-terminal amino acid determination and blast analysis, as well as phospholipase A1 (PLA1) activity monitor. Plasma recalification time test was employed to detect the effect of Vtp32 on coagulation. Results: A protein with phospholipase activity was orderly separated and purified from V. tropica ducalis venom using gel filtration and heparin affinity chromatography. The purified protein was homogenous on the SDS-PAGE gel with relative molecular mass of 32 000, so it was termed as Vtp32. Peptide mass fingerprinting assay and N-terminal amino acid sequence blast result revealed that Vtp32 showed high homologous with PLA1 from wasp of Vespa genus. In addition, Vtp32 hydrolyzed the sn-1 ester linkage of phospholipids. These results indicated that Vtp32 was PLA1 from V. tropica ducalis. Vtp32 hydrolyzed phosphatidylcholine, and the hydrolysis product can lyse human erythrocytes. Vtp32 delayed the recalification time of human plasma and hence had anti-coagulation activity. Conclusion: PLA1 is widely existed in the venom from V. tropica ducalis. Gel filtration followed by heparin affinity chromatography is an effective isolation strategy for the purification of PLA1. The results show that V. tropica ducalis PLA1 has hemolytic and anticoagulative activity.

Study on the Anti-coagulation Effect and Mechanism of Fibrinolytic Enzyme SNFE in Sipuculus Nudus / 中国药房

OBJECTIVE:To study the anti-coagulation effect and mechanism of fibrinolytic enzyme SNFE in sipuculus nudus, and provide reference for further development of SNFE. METHODS:40 mice were randomly divided into blank control group(nor-mal saline),Xueshuantong group(positive control,15 mg/kg)and SNFE low-dose,high-dose group(15,30 mg/kg),10 in each group. After intravenous injection in tail,tail bleeding time (BT) and clotting time (CT) were respectively determined to investi-gate the anti-coagulation effect of SNFE. After taking blood in abdominal aorta of rats,test was divided into blank control group, positive control group and SNFE low-mass concentration,medium-mass concentration,high-mass concentration groups (0.25, 0.50,1.00 mg/mL). Prothrombin time(PT),re-calcium time(PRT)(using orokinase as positive drug,100000 U/mL),and max-mum platelet aggregation rate (PAG) in 5 min under adenosine diphosphate (ADP) inducer (using asprin as positive drug,0.50 mg/mL) were respectively determined,and anti-coagulation effect mechanism of SNFE was analyzed. RESULTS:Compared with blank control group,BT,CT of mice in each group were prolonged,with statistical significance in Xueshuantong group and SNFE high-dose group (P<0.05 or P<0.01). Plasma PT of rats in positive control group,SNFE medium-dose,high-dose groups and PRT in each administration group were significantly prolonged(P<0.05 or P<0.01);and PAG in administration group was signifi-cantly reduced(P<0.01). CONCLUSIONS:The fibrinolytic enzyme SNFE in sipuculus nudus can play its anti-coagulant effect by inhibiting the activity of coagulation factors in internal and external sources and ADP-induced platelet aggregation.

Study on the Anti-coagulation Effect and Mechanism of Fibrinolytic Enzyme SNFE in Sipuculus Nudus / 中国药房

OBJECTIVE:To study the anti-coagulation effect and mechanism of fibrinolytic enzyme SNFE in sipuculus nudus, and provide reference for further development of SNFE. METHODS:40 mice were randomly divided into blank control group(nor-mal saline),Xueshuantong group(positive control,15 mg/kg)and SNFE low-dose,high-dose group(15,30 mg/kg),10 in each group. After intravenous injection in tail,tail bleeding time (BT) and clotting time (CT) were respectively determined to investi-gate the anti-coagulation effect of SNFE. After taking blood in abdominal aorta of rats,test was divided into blank control group, positive control group and SNFE low-mass concentration,medium-mass concentration,high-mass concentration groups (0.25, 0.50,1.00 mg/mL). Prothrombin time(PT),re-calcium time(PRT)(using orokinase as positive drug,100000 U/mL),and max-mum platelet aggregation rate (PAG) in 5 min under adenosine diphosphate (ADP) inducer (using asprin as positive drug,0.50 mg/mL) were respectively determined,and anti-coagulation effect mechanism of SNFE was analyzed. RESULTS:Compared with blank control group,BT,CT of mice in each group were prolonged,with statistical significance in Xueshuantong group and SNFE high-dose group (P<0.05 or P<0.01). Plasma PT of rats in positive control group,SNFE medium-dose,high-dose groups and PRT in each administration group were significantly prolonged(P<0.05 or P<0.01);and PAG in administration group was signifi-cantly reduced(P<0.01). CONCLUSIONS:The fibrinolytic enzyme SNFE in sipuculus nudus can play its anti-coagulant effect by inhibiting the activity of coagulation factors in internal and external sources and ADP-induced platelet aggregation.

Variation of prothrombotic state markers in patients with type 2 diabetes mellitus who have microvascular complication / 中国医师进修杂志

Objective To investigate the variation of coagulation parameters in type 2 diabetes mellitus(T2DM)patients with microvascular complication. Methods Coagulation and fibrinolysis parameters were measured in 40 healthy controls (control group) and 80 T2DM patients (T2DM group) with (47 patients) and without (33 patients) microvasular complications. Results Compared with those in control group, the serum levels of fibrinogenand D-D dimmersin in T2DM group were found to be increased significantly:(4.29±1.70) mg/L vs. (3.12±0.49) mg/L, 0.395 (0.265-0.910) mg/L vs. 0.215 (0.163-0.300) mg/L, P<0.05;while the activity of antithrombin III and protein S levels were significantly decreased in T2DM group:(94.11±25.04)%vs. (103.90±12.48)%,(70.23±23.22)%vs. (90.35±17.35)%, P<0.05. Amongst the T2DM patients, the serum levels of APTT, fibrinogen,D-D dimmers, and the activity of protein S in patients with microvascular complication were found to be significantly higher than those in patients without microvascular complication:(38.09±5.73) s vs. (34.53±4.13) s,(4.60±1.93) mg/L vs.(3.86±1.21) mg/L, 0.630(0.320-1.200) mg/L vs 0.310(0.240-0.405) mg/L, (79.4± 22.16)%vs. (57.15±18.05)%, P<0.05. Conclusion Hypercoagulable state and decreased anti-coagulation ability may contribute to the risk of development of microvascular complication in T2DM patients.

The Anti-platelet/Anti-coagulation strategy and Prognosis in Coronary Artery Disease Patients Combining With Atrial Fibrillation After Percutaneous Coronary Intervention / 中国循环杂志

Objective: To explore the correlation between antithrombotic strategy and its prognostic value in coronary artery disease (CAD) patients combining with atrial ifbrillation (AF) after percutaneous coronary intervention (PCI). Methods: A total of 570 CAD patients with AF received PCI in our hospital from 2012-01 to 2013-12 were retrospectively analyzed by CHADS2 and HAS-BLED Score system. According to CHADS2 Results: Compared with Low risk of stroke group, the patients in High risk of stroke group had the worse prognosis and higher rate of MACCE occurrence,P0.05. The major bleeding events in patients with warfarin were a little higher than those without warfarin,P>0.05. The minor bleeding events were increased in both Low risk stroke group asP Conclusion: Warfarin medication may obviously decrease the occurrence rates of MACCE and ischemic events in high risk of stroke patients, while in low risk patients, warfarin could not further decrease the occurrence of MACCE and ischemic events. Warfarin could increase the risk for minor bleeding in both low risk and high risk of stroke in CAD patients combining with AF after PCI.

Evaluation of Thrombolytic Effect of Seven Different Bangladeshi Plants.

Aim: From time past till date, proper documentation of the use of medicinal plants are helpful in drug development and research. The objective of this study is to evaluate several plant extracts of Bangladesh for their thrombolytic activity. Study Design: There are seven different plants from unlike families were studied in this primary research work. They were collected between August-September (2012) and the thrombolytic effect of their extractions was investigated. Streptokinase was used as standard to compare with and evaluate the significance of each result. Result: Among all studied plants Gardenia coronaria showed most promising result of 49.61±0.866% of lysis, whereas streptokinase exhibited a lysis of 75.36±0.964%. The extracts of Hedychium thyrsiforme and Artocarpus chaplasha showed also promising activity with 48.39±1.813% and 43.69±0.906% of thrombolytic effect, respectively. Conclusion: All the plants used in this study showed promising thrombolytic activity compared to standard. Proper phytochemical characterization and isolation of the constituent compounds responsible for this activity may be further investigated and could be a future source of lead thrombolytic compounds.

Control perioperatorio de la anticoagulación en el paciente con prótesis valvular para cirugía no cardiaca / Preoperative control of anti coagulation in patients with valvular prosthesis for non cardiac surgery

Introducción: las terapias de anticoagulación y antiagregación son frecuentemente utilizadas en pacientes cardiópatas. La conducción anestésica de estos pacientes tiene peculiaridades que de no cumplirlas puede llevar a complicaciones severas o a la muerte del paciente. Objetivo: revisar la conducta anestésica ante un paciente cardiópata anticoagulado para cirugía no cardiaca electiva y de urgencia. Método: se hizo una revisión de las características del paciente cardiópata anticoagulado, se analizaron las causas de la anticoagulación y se valoró la interrupción o no del tratamiento anticoagulante ante procederes mayores, menores, electivos y urgentes. Se detalla la monitorización intraoperatoria y la reiniciación del tratamiento anticoagulante post-cirugía. Conclusiones: el éxito de la cirugía no cardiaca del paciente cardiópata anticoagulado, sólo es posible gracias al conocimiento y cumplimiento de las particularidades de estos pacientes. No es posible improvisar ante estos casos, que implican una gran responsabilidad médica y legal para el anestesiólogo.

Introduction: therapies of anti coagulation and anti aggregation are frequently used in cardiopath patients. The anesthetic conduction of these patients has some peculiarities which in case they are not fulfilled they may lead to severe complications or even the death of the patient. Objective: to revise the anesthetic conduct in front of cardiopath patients and is anti coagulated for elective or emergent non cardiac surgery. Method: a revision of the characteristics of this patient was carried out, the causes of anti coagulation were analyzed , the causes of anti coagulation were analyzed as well as the causes of anti coagulation and the interruption or not of the anti coagulant treatment ante main, minor, elective or urgent procedures. The intra operative monitoring is detailed and the reinitiating of post surgery anti coagulant treatment. Conclusion: the success of the non cardiac surgery of the cardiopath patient and takes an anti coagulant treatment is only possible thanks to the knowledge and fulfillment of particularities of this patient. It is not possible to improvise with these cases which explain a great medical legal responsibility for the anesthesiologist.

Anticoagulation Therapy, Thrombolytic Therapy, and Use of Blood Products in Neonates

Neonatal coagulation disorders and thromboembolism require timely management. Failure to treat these conditions at the appropriate time may lead to death or the development of significant long-term sequelae. However, most current guidelines for managing neonatal coagulation disorders and thromboembolism are empiric and not based on randomized clinical trials. Thus, it is not easy to choose an appropriate management strategy for these conditions in clinical settings. In this review, therapeutic guidelines currently utilized in clinics and novel therapeutic options still under investigation are presented and reviewed.

A stent thrombosis that developed due to altered preoperative anticoagulation therapy in a patient with a drug eluting stent (DES): A case report

A 73 year-old man was admitted to our hospital because of septic shock. He had undergone drug eluting stent (DES) insertion 40 days before this admission. After about 50 days in the hospital, a coccyx sore required a flap operation. The anticoagulation therapy (aspirin and clopidogrel) was then changed to LMWH. Eleven days after this change, he developed very severe chest pain. The emergency coronary angiography showed occlusion of the left anterior descending artery, left circumflex artery, and right coronary artery due to thrombosis. During the angiography procedure, his heart collapsed. We performed cardio-pulmonary resuscitation (CPR), but were unsuccessful. Patients in very high risk groups need special attention during peri-operative periods. Doctors must have full knowledge about the different anticoagulation strategies, and cooperation among the different clinical departments is needed to properly treat these high risk patients.

Delay in onset of metabolic alkalosis during regional citrate anti-coagulation in continous renal replacement therapy with calcium-free replacement solution.

Regional citrate anti-coagulation for continuous renal replacement therapy chelates calcium to produce the anti- coagulation effect. We hypothesise that a calcium-free replacement solution will require less citrate and produce fewer metabolic side effects. Fifty patients, in a Medical Intensive Care Unit of a tertiary teaching hospital (25 in each group), received continuous venovenous hemofiltration using either calcium-containing or calcium-free replacement solutions. Both groups had no significant differences in filter life, metabolic alkalosis, hypernatremia, hypocalcemia, and hypercalcemia. However, patients using calcium-containing solution developed metabolic alkalosis earlier, compared to patients using calcium-free solution (mean 24.6 hours,CI 0.8-48.4 vs. 37.2 hours, CI 9.4-65, P = 0.020). When calcium-containing replacement solution was used, more citrate was required (mean 280ml/h, CI 227.2-332.8 vs. 265ml/h, CI 203.4-326.6, P = 0.069), but less calcium was infused (mean 21.2 ml/h, CI 1.2-21.2 vs 51.6ml/h, CI 26.8-76.4, P ≤ 0.0001).

Effect of Processing on Pharmacological Actions of Dipsacus Asperoides and Its Different Processed Products / 中成药

Objective:To study the effect of processing on pharmacological actions Dipsacus asperoides and its different processed products.Methods:The analgestic effect of Dipsacus asperoides in mice was observed in hot plate and acetic acid-induced writhing test. The anti-inflammatory action was studied in mouse ear swelling test and capillary permeability test and anti-coagulation action in mice was also observed by mouse blood coagulation time test.Results:The experimental results show that all processed Products of Dipsacus asperoides can inhibit the pain and has the actions of auti-inflammation and auti-coagulation. Conclusion: The actions of its processed products with wine is the most powerful.