Anticoagulation therapy for pulmonary embolism involving a myxoma mimicking, giant type C thrombus: A case report

Right heart thrombus(RHTh) with concurrent acute pulmonary embolism(PE) is rare and can seriously destabilize hemodynamics, leading to an emergency situation with high mortality. Diagnosis and treatment of RHTh with acute PE are not yet standardized. There are few reports of acute PE concurrent with RHTh and even less is known about patients with a right heart mural thrombus. For physicians, the diagnostic choice and treatment of these patients are particularly difficult due to the lack of knowledge. Here, we report a rare case of partial mural RHTh(type C RHTh) with acute PE. The mural mass in the right heart was initially diagnosed as atrial myxoma according to transthoracic echocardiography(TTE), and both pulmonary embolus and the mural mass were completely absorbed after administering Rivaroxiban. This case suggests that TTE alone is insufficient to identify and diagnoses a right heart mural mass such as this. However, novel oral anticoagulants may be effective at alleviating PE with type C RHTh.

Antithrombin Ⅲ deficiency in a patient with recurrent venous thromboembolism:A case report

BACKGROUND Antithrombin Ⅲ(AT3)deficiency,an autosomal dominant disease,increases the likelihood of an individual developing venous thromboembolism(VTE).Longterm anticoagulation treatment is required for those suffering from AT3 deficiency.CASE SUMMARY A man aged 23,who had a history of deep venous thrombosis(DVT),experienced recurrent pain and swelling in his right lower extremity for three days following withdrawal of Rivaroxaban.He was diagnosed with DVT and antithrombin Ⅲ deficiency as genetic testing revealed a single nucleotide variant in SERPINC1(c.667T>C,p.S223P).The patient was advised to accept long-term anticoagulant therapy.CONCLUSION Inherited AT3 deficiency due to SERPINC1 mutations results in recurrent VTE.Patients may benefit from long-term anticoagulant therapy.

Systemic right ventricle complications in levo-transposition of the great arteries: A case report and review of literature

BACKGROUND Congenitally corrected levo-transposition of the great arteries(L-TGA)is a congenital heart disease in which the ventricles and great arteries are transposed from their typical anatomy.In L-TGA,the double discordance,atrioventricular and ventriculoarterial,create an acyanotic milieu which allows patients to survive their early decades,however,progressive systemic right ventricle(sRV)dys-function creates complications later in life.sRV dysfunction and remodeling predisposes patients to intracardiac thrombus(ICT)formation.CASE SUMMARY A 40-year-old male with L-TGA presented with symptoms of acute decom-pensated heart failure.In childhood,he had surgical repair of a ventricular septal defect.In adulthood,he developed sRV dysfunction,systemic tricuspid valve(sTV)regurgitation,and left-bundle branch block for which he underwent cardiac resynchronization therapy.Transthoracic echocardiogram showed a sRV ejection fraction of 40%,severe sTV regurgitation,and a newly identified sRV ICT.ICT was confirmed by ultrasound-enhancing agents and transesophageal echocardio-graphy.Our patient was optimized with guideline-directed medical therapy and diuresis.Anticoagulation was achieved with a vitamin K antagonist(VKA)and he was later referred for evaluation by advanced heart failure and heart transplant services.CONCLUSION Anticoagulation with VKA is the mainstay of treatment in the absence of conclusive data supporting direct oral anticoagulant use in ICT in patients with congenital heart disease.This case illustrates the natural history of L-TGA and highlights the importance of surveillance and monitoring with dedicated cardiac imaging to identify complications.

Effectiveness and safety of apixaban and rivaroxaban vs warfarin in patients with atrial fibrillation and chronic kidney disease

BACKGROUND Randomized controlled trials(RCTs)of direct oral anticoagulants(DOACs)included a low proportion of atrial fibrillation(AF)patients with chronic kidney disease(CKD),and suggested that DOACs are safe and effective in patients with mild-to-moderate CKD.In a metanalysis of RCTs and observational studies,DOACs were associated with better efficacy(vs warfarin)in early CKD and had similar efficacy and safety profiles in patients with stages IV-V CKD.But few studies have provided data on the safety and effectiveness of each DOAC vs warfarin in patients with stage III CKD.The effectiveness and safety of DOACs in those patients are still subject to debate.AIM To assess and compare the effectiveness and safety of apixaban and rivaroxaban vs warfarin in this patient population.METHODS A cohort of patients with an inpatient or outpatient code for AF and stage III CKD who were newly prescribed apixaban and rivaroxaban was created using the administrative databases from the Quebec province of Canada between 2013 and 2017.The primary effectiveness outcome was a composite of ischemic stroke,systemic embolism,and death,whereas the primary safety outcome was a composite of major bleeding within a year of DOAC vs warfarin initiation.Treatment groups were compared in an under-treatment analysis using inverse probability of treatment weighting and Cox proportional hazards.RESULTS A total of 8899 included patients filled out a new oral anticoagulation therapy claim;3335 for warfarin and 5564 for DOACs.Compared with warfarin,15 mg and 20 mg rivaroxaban presented a similar effectiveness and safety composite risk.Apixaban 5.0 mg was associated with a lower effectiveness composite risk[Hazard ratio(HR)0.76;95%confidence interval(CI):0.65-0.88]and a similar safety risk(HR 0.94;95%CI:0.66-1.35).Apixaban 2.5 mg was associated with a similar effectiveness composite(HR 1.00;95%CI:0.79-1.26)and a lower safety risk(HR 0.65;95%CI:0.43-0.99.Although,apixaban 5.0 mg was associated with a better effectiveness(HR 0.76;95%CI:0.65-0.88),but a similar safety risk profile(HR 0.94;95%CI:0.66-1.35).The observed improvement in the effectiveness composite for apixaban 5.0 mg was driven by a reduction in mortality(HR 0.61;95%CI:0.43-0.88).CONCLUSION In comparison with warfarin,rivaroxaban and apixaban appear to be effective and safe in AF patients with stage III CKD.

Atrial Fibrillation: Epidemiological, Etiological and Hospital Management Aspects in Thies (Senegal)

Introduction: The objective of this work was to describe the epidemiological, etiological, clinical and therapeutic aspects of atrial fibrillation (AF) in Thies, Senegal. Materials and Methods: This was a retrospective, multicentre, descriptive study from February 1st, to May 28th, 2019 carried out in the 3 hospitals of the city of Thies that focused on patients with AF documented by an ECG. Valvular and non-valvular AF classification was used and the CHA2DS2-VASc score was used to assess thromboembolic risk. Results: We collected 67 patients with a female predominance (M/F sex ratio of 0.71). The prevalence of AF was 1.7%. The average age of patients was 66.67 ± 13.48 years. Forty-eight patients (71.64%) had palpitations and 32 patients (47.76%) had heart failure. Hypertension was the most common etiological factor found in 41 patients (61.19%) followed by rheumatic valvular disease in 25 patients (37.31%). The non-valvular AF was found in 42 patients (62.69%) of which 34 (80.95%) had a CHA2DS2-VASc score ≥ 2. Vitamin K antagonists (VKAs) were prescribed in 47 patients (79.66%) and aspirin alone in 12 patients (20.34%). Direct Oral Anticoagulants (DOACs) were not prescribed in any patient. Seven patients (10.44%) had a medical regulator treatment and no electrical cardioversion was performed. Conclusion: AF was a frequent rhythm disorder. Hypertension and rheumatic mitral valve disease were the most frequently associated etiological factors. The diagnosis was often late in the heart failure stage. Anticoagulant treatment was insufficiently prescribed and based exclusively on VKAs.

袋装血液保存液中易氧化物的GC-MS分析

A method was established for determination of the reducing substances released from plastic blood bags to anticoagulant.The samples were extracted with a solid-phase extraction procedure using dichloromethane as extract solvents.The extracts were measured with GC-MS.Several reducing substances,such as 1,2-benzenedicarboxylic acid,alkane and bis(2-ethylhexyl) phthalate,etc were found in anticoagulant.The method was simple and can be used for the quality control of plastic blood bags.

Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome: Pathogenesis, clinical manifestations, diagnosis,treatment, and outcomes

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.

Current practice of anticoagulant in the treatment of splanchnic vein thrombosis secondary to acute pancreatitis

Background:Severe acute pancreatitis is a common diagnosis in emergency general surgery and can be a cause of significant morbidity and mortality.A consequence of severe acute pancreatitis is thrombus in the splanchnic veins.These thrombi can potentially lead to bowel ischemia or hepatic failure.However,another complication of severe acute pancreatitis is retroperitoneal bleeding.At this time,it is unclear if treating patients for splanchnic vein thrombosis in the context of severe acute pancreatitis is associated with any outcome benefit.A systematic review might clarify this question.Data sources:A two-fold search strategy(one broad and one precise)looked at all published literature.The review was registered on PROSPERO(ID:CRD42018102705).MEDLINE,EMBASE,PubMed,Cochrane and Web of Science databases were searched and potentially relevant papers were reviewed indepen-dently by two researchers.Any disagreement was reviewed by a third independent researcher.Primary outcome was reestablishment of flow in the thrombosed vein versus bleeding complications.Results:Of 1462 papers assessed,a total of 16 papers were eligible for inclusion.There were no ran-domized controlled trials,2 were case series,5 retrospective single-center studies and 9 case reports.There were a total of 198 patients in these studies of whom 92(46.5%)received anticoagulation therapy.The rates of recanalization of veins in the treated and non-treated groups was 14%and 11%and bleeding complications were 16%and 5%,respectively.However,the included studies were too heterogeneous to undertake a meta-analysis.Conclusions:The systematic review highlights the lack evidence addressing this clinical question.There-fore a randomized controlled trial would be appropriate to undertake.

Portal vein thrombosis with protein C-S deficiency in a noncirrhotic patient

There are several conditions that can lead to portal vein thrombosis(PVT), including including infection, malignancies, and coagulation disorders. Anew condition of interest is protein C and S deficiencies, associated with hypercoagulation and recurrent venous thromboembolism. We report the case of a non-cirrhotic 63-year-old male diagnosed with acute superior mesenteric vein thrombosis and PVT and combined deficiencies in proteins C and S, recanalized by short-term low molecular heparin plus oral warfarin therapy.

Purification and characterization of a novel anti-coagulant from the leech Hirudinaria manillensis

Protease inhibitors have been reported rarely from the leech Hirudinaria manillensis.In this study,we purified a novel protease inhibitor(bdellin-HM-2)with anticoagulant properties from H.manillensis.With a molecular weight of 1.4x104,bdellin-HM-2 was also characterized with three intra?molecular disulfide bridges at the N-terminus and multiple HHXDD and HXDD motifs at theC-terminus.cDNAcloning revealed that the putative nucleotide-encoding protein of bdellin-HM-2 contained 132 ami no acids and was encoded by a 399 bp open reading frame(ORF).Sequence alignment showed that bdellin-HM-2 shared similarity with the“non-classical"Kazal-type serine protease inhibitors,but had no inhibitory effect on trypsin,elastase,chymotrypsin,kallikrein,factor Xlla(FXIIa),factor Xia(FXIa),factor Xa(FXa),thrombin,or plasmin.Bdellin-HM-2 showed anticoagulant effects by proIonging the activated partial thromboplastin time(aPTT),indicating a role in enabling H.manillensis to obtain a blood meal from its host.Our results suggest that bdellin-HM丒2 may play a crucial role in blood-sucking in this leech species and may be a pote ntial can didate for the development of clinical anti-thrombotic drugs.

Rate of anticoagulant use, and factors associated with not prescribing anticoagulant in older Thai adults with non-valvular atrial fibrillation: A multicenter registry

Objectives To investigate the rate of anticoagulant use,the reasons for not prescribing anticoagulant,and the factors associated with non-prescription of anticoagulant in older Thai adults with non-valvular atrial fibrillation.Methods A multicenter registry of patients with non-valvular atrial fibrillation was conducted during 2014 to 2017 in Thailand.Demographic,medical history,antithrombotic medication,non-antithrombotic medication,and laboratory data were collected and analyzed.Data were compared between the older adult (≥ 65 years) and younger adult (< 65 years) groups.The reasons why anticoagulant was not prescribed were collected,and predictive factors were identified.Results A total of 3218 patients (1873 males) with an average age of 67.3 ± 11.3 years were included.Almost two-thirds (61.0%) of patients were in the older adult group.Anticoagulant was prescribed in 2422 patients (75.3%): 81.4% in the older adult group and 65.7% in the younger adult group.The three main reasons for not prescribing anticoagulant were already taking antiplatelets,patient refusal,and bleeding risk.These reasons were more common in older adults as compared to younger adults.Multivariate analysis revealed current use of antiplatelets to be the most important factor that predict the non-prescription of anticoagulant in older population.Conclusions The prevalence of anticoagulant prescription among older Thai adults with atrial fibrillation is 81.4%.Taking antiplatelet drugs was found to be the strongest reason that predicts the non-prescription of anticoagulant in this patient population.A guideline should be developed to optimize the use of anticoagulant and antiplatelet in older adults.

In vitro and in silico analysis of dual-function peptides derived from casein hydrolysate

There is no study on food-derived peptide with both anticoagulant and angiotensin I-converting enzyme inhibitory (ACEI) activities yet. In this work, the anticoagulant and ACEI activities of the casein hydrolysates released by pepsin digestion were evaluated for the first time to the best of our knowledge. Results indicated that the casein hydrolysate exhibited potent anticoagulant activity by prolonging the thrombin time (TT) and the activated partial thromboplastin time (APTT). Compared with control samples, at 10 mg/mL, the TT and APTT of casein hydrolysate were 186.0 % ± 6.6 % and 163.5 % ± 7.4 %, respectively. The casein hydrolysate also showed a strong ACEI activity with an IC50 value of 1.775 mg/mL. The components of the bioactive casein hydrolysate were analyzed by nanoscale liquid chromatography quadrupole time-of-flight tandem mass spectrometry (NanoLC-Q-TOF-MS/MS). Total of 115 peptides were identified, among which 34, 9, 55 and 17 peptides were derived from α_(s1-), α_(s2-), β-, and κ-casein, respectively. The results of PeptideRanker and PepSite 2 analysis showed that 6 peptides (FRQFYQL, NENLLRF, NPWDQVKR, PVVVPPFLQ, PVRGPFPIIV, and ARHPHPHLSF) have both ACEI and anticoagulant activities by binding to the active sites of ACE and thrombin. This study indicated that casein is a potential functional food supplement that can be used for medical purposes.

Dabigatran,rivaroxaban,and apixaban are superior to warfarin in Asian patients with non-valvular atrial fibrillation:An updated metaanalysis

BACKGROUND Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation(AF)originated from western countries.AIM To systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran,rivaroxaban,and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF.METHODS Medline,Cochrane,and ClinicalTrial.gov databases were reviewed.A randomeffect model meta-analysis was used and I-square was utilized to assess the heterogeneity.The primary outcome was ischemic stroke.The secondary outcomes were all-cause mortality,major bleeding,intracranial hemorrhage,and gastrointestinal bleeding.RESULTS Twelve studies from East Asia or Southeast Asia and 441450 patients were included.Dabigatran,rivaroxaban,and apixaban were associated with a significant reduction in the incidence of ischemic stroke[hazard ratio(HR)=0.78,95%confidence interval(CI):0.65-0.94;HR=0.79,95%CI:0.74-0.85,HR=0.70,95%CI:0.62-0.78;respectively],all-cause mortality(HR=0.68,95%CI:0.56-0.83;HR=0.66,95%CI:0.52-0.84;HR=0.66,95%CI:0.49-0.90;respectively),and major bleeding(HR=0.61,95%CI:0.54-0.69;HR=0.70,95%CI:0.54-0.90;HR=0.58,95%CI:0.43-0.78;respectively)compared to warfarin.CONCLUSION Dabigatran,rivaroxaban,and apixaban appear to be superior to warfarin in both efficacy and safety in Asians with non-valvular AF.

Four 14(13→12)‑Abeolanostane Triterpenoids with 6/6/5/6‑Fused Ring System from the Roots of Kadsura coccinea

Four new rearranged 6/6/5/6-fused lanostane-type triterpenoids,kadcoccitanes A-D(1-4),were isolated from the roots of Kadsura coccinea,and their structures were mainly elucidated by comprehensive analysis of their spectroscopic data.Additionally,the structure of 1 was ambiguously verifed by single-crystal X-ray difraction,while the structure of 2,which features a novel 8,16-epoxy motif,was validated by quantum chemical calculation of NMR parameters and ECD spectrum.Moreover,1 and 4 were found to exhibited anticoagulant activity,while 3 and 4 were found to possess anti-platelet aggregation activity.

Thrombophilia Caused by Beta2-Glycoprotein I Deficiency： In Vitro Study of a Rare Mutation in APOH Gene

This study aimed to explore the mechanism of a novel mutation （p.Lys38Glu） in apolipoprotein H （APOH） gene causing hereditary beta2-glycoprotein I （β2GPI） deficiency and thrombosis in a proband with thrombophilia. The plasma level of β2GPI was measured by ELISA and Western blotting, and anti-β2GPI antibody by ELISA. Lupus anticoagulant （LA） was assayed using the dilute Russell viper venom time. Deficiency of the major natural anticoagulants including protein C （PC）, protein S （PS）, antithrombin （AT） and thrombomodulin （TM） was excluded from the proband. A mutation analysis was performed by amplification and sequencing of the APOH gene. Wild type and mutant （c.112A〉G） APOH expression plasmids were constructed and transfected into HEK293T cells. The results showed that the thrornbin generation capacity of the proband was higher than that of the other family members. Missense mutation p.Lys38Glu in APOH gene and LA coexisted in the proband. The mutation led to β2GPI deficiency and thrombosis by impairing the protein production and inhibiting the platelet aggregation. It was concluded that the recurrent thrombosis of the proband is associated with the coexistence ofp.Lys38Glu mutation in APOH gene and LA in plasma.

Hemorrhagic shock due to submucosal esophageal hematoma along with mallory-weiss syndrome:A case report

BACKGROUND Esophageal submucosal hematoma is a rare condition.Although the exact etiology remains uncertain,vessel fragility with external factors is believed to have led to submucosal bleeding and hematoma formation;the vessel was ruptured by a sudden increase in pressure due to nausea,and the hematoma was enlarged by antiplatelet or anticoagulant therapy.Serious conditions are rare,with a better prognosis.We present the first known case of submucosal esophageal hematoma-subsequent hemorrhagic shock due to Mallory-Weiss syndrome.CASE SUMMARY A 73-year-old female underwent endovascular treatment for an unruptured cerebral aneurysm.The patient received aspirin and clopidogrel before surgery and heparin during surgery,and was well during the surgery.Several hours after returning to the ICU,she complained of chest discomfort,vomited 500 m L of fresh blood,and entered hemorrhagic shock.Esophageal submucosal hematoma with Mallory-Weiss syndrome was diagnosed through an endoscopic examination and computed tomography.In addition to a massive fluid and erythrocyte transfusion,we performed a temporary compression for hemostasis with a Sengstaken-Blakemore(S-B)tube.Afterwards,she became hemodynamically stable.On postoperative day 1,we performed an upper gastrointestinal endoscopy and confirmed no expansion of the hematoma nor any recurring bleeding;therefore,we removed the S-B tube and clipped the gastric mucosal laceration at the esophagogastric junction.We started oral intake on postoperative day 10.The patient made steady progress,and was discharged on postoperative day 33.CONCLUSION We present the first known case of submucosal esophageal hematoma subsequent hemorrhagic shock due to Mallory-Weiss syndrome.

possible role of soluble fibrin monomer complex after gastroenterological surgery

AIM To examine the role of soluble fibrin monomer complex(SFMC) in the prediction of hypercoagulable state after gastroenterological surgery.METHODS We collected data on the clinical risk factors and fibrin-related makers from patients who underwent gastroenterological surgery at Hiroshima University Hospital between April 1, 2014 and March 31, 2015. We investigated the clinical significance of SFMC, which is known to reflect the early plasmatic activation of coagulation, in the view of these fibrin related markers.RESULTS A total of 123 patients were included in the present study. There were no patients with symptomatic VTE. Thirty-five(28%) patients received postoperative anticoagulant therapy. In the multivariate analysis, a high SFMC level on POD 1 was independently associated with D-dimer elevation on POD 7(OR = 4.31, 95%CI: 1.10-18.30, P = 0.03). The cutoff SFMC level was 3.8 μg/ml(AUC = 0.78, sensitivity, 63%, specificity, 89%). The D-dimer level on POD 7 was significantly reduced in high-SFMC patients who received anticoagulant therapy in comparison to highSFMC patients who did not.CONCLUSION The SFMC on POD 1 strongly predicted the hypercoagulable state after gastroenterological surgery than the clinical risk factors and the other fibrin related markers.

Design and fabrication of r-hirudin loaded dissolving microneedle patch for minimally invasive and long-term treatment of thromboembolic disease

Cardiovascular disease is the leading cause of global mortality,with anticoagulant therapy being the main prevention and treatment strategy.Recombinant hirudin(r-hirudin)is a direct thrombin inhibitor that can potentially prevent thrombosis via subcutaneous(SC)and intravenous(IV)administration,but there is a risk of haemorrhage via SC and IV.Thus,microneedle(MN)provides painless and sanitary alternatives to syringes and oral administration.However,the current technological process for the micro mould is complicated and expensive.The micro mould obtained via three-dimensional(3D)printing is expected to save time and cost,as well as provide a diverse range of MNs.Therefore,we explored a method for MNs array model production based on 3D printing and translate it to micro mould that can be used for fabrication of dissolving MNs patch.The results show that r-hirudin-loaded and hyaluronic acid(HA)-based MNs can achieve transdermal drug delivery and exhibit significant potential in the prevention of thromboembolic disease without bleeding in animal models.These results indicate that based on 3D printing technology,MNs combined with r-hirudin are expected to achieve diverse customizableMNs and thus realize personalized transdermal anticoagulant delivery for minimally invasive and long-term treatment of thrombotic disease.

Neolignans and Norlignans from Insect Medicine Polyphaga plancyi and Their Biological Activities

Ten neolignans or norlignans(1-10)including eight new compounds were isolated from the whole bodies of Polyphaga plancyi Bolivar.Their structures were identified by spectroscopic data.Compounds 3,4,8,and 9 are racemates indicated by chiral HPLC analysis.Chiral separation followed by ECD calculations allowed to clarify the absolute configurations of all the antipodes.All the new compounds were evaluated for their biological properties toward extracellular matrix in rat renal proximal tubular cells,human cancer cells(K562,A549,and Huh7),EV71,ROCK2,JAK3,DDR1,and coagulation.

Quantitation of bivalirudin,a novel anticoagulant peptide,in human plasma by LC-MS/MS:Method development,validation and application to pharmacokinetics

A rapid and sensitive method based on liquid chromatographtandem mass spectrometry （LC-MS/MS） for the determination of a novel anticoagulant peptide bivalirudin in human plasma has been developed and validated. Plasma samples were precipitated protein with acetonitrile and reextracted with dichloromethane, after which the analyte and triptorelin as an internal standard （IS） were separated on a 300SB-Cl8 column （150 mm x 4.6 mm i.d., 5 gm particle size） using 0.1% formic acid：methanol （45：55, v/v） as mobile phase. The triple-quadrupole mass spectrometer, equipped with electrospray ionization （ESI） interface, was operated in the positive ion mode, and the multiplereaction monitoring （MRM） transitions of bivalirudin and IS were at m/z 1091.0-650.4 and m/z656.5 - 249.3, respectively. The lower limit of quantification （LLOQ） was 1 ng/mL for 100 ng/mL plasma sample and the assay was linear over the concentration range 1 1000 ng/mL. The accuracy was within a range from -0.4% to 0.5% in terms of relative error （RE） and the intra- and inter-day precisions in terms of relative standard deviation （RSD） were 〈2.92 and 〈 3.36, respectively. The method was successfully applied to a pharmacokinetic study involving intravenous administration of bivalirudin （0.5 mg/kg） to Chinese volunteers.