Low Molecular Heparin Research Articles

GW24-e1133 Effect of Yindan Xinnaotong capsule on serum IL-6 of patients suffering from unstable angina pectoris

ObjectivesUnstable angina pectoris (UAP) is a kind of common clinical type of coronary artery atherosclerosis heart disease. Due to the serious condition and great harm, the heart disease severely affects...

GW24-e3563 Clinical application of min-diameter atria stleel-wire in modified percutaneous ballon mitral valvuloplasty

ObjectivesTo evaluate the feasibility, safety and efficacy of the min- diameter half and two convolutionsatria steel-wire that is used in improving percutaneous balloon mitralvalvuloplasy (PBMV)MethodsAll patients received warfarin tabella every...

PMMA embolization to the left dorsal foot artery during percutaneous vertebroplasty for spinal metastases

Distal arterial embolization to the foot with PMMA during vertebral augmentation has not been previously reported. We report a rare case of distal PMMA embolization to the dorsal foot artery during ipsilateral percutaneous lumbar vertebral augmentation in a patient with spinal osteolytic metastases. A 68-year-old woman was admitted because of severe disabling low back pain. Plain roentgenograms, MRI and CT-scan revealed osteolysis in the L4 and L5 vertebral bodies with prevertebral soft tissue involvement. Percutaneous vertebroplasty with PMMA was performed in L2 to L5 vertebrae under general anesthesia. Intraoperatively, leakage into the segmental vessels L3 and L5 was observed. Four hours after the procedure the clinical diagnosis of acute ischemia and drop foot on the left was made. CT-angiography justified linear cement leakage in the course of the left third lumbar vein and fifth lumbar artery, and to the ipsilateral common iliac artery. The patient was treated with low molecular heparin and the ischemia resolved without further sequelae 1 week postoperatively. PMMA leakage is a complication associated with vertebroplasty and kyphoplasty. Although the outcome of the PMMA embolization to the vessels resolved without sequelae, in our case spine surgeons and interventional radiologists should be aware on this rare complication in patients with osteolytic vertebral metastases even when contemporary cement containment techniques are used.

Acute Cerebral Infarction Caused by Cerebral Vasospasm Due to High-Voltage Electrical Injury

Acute Cerebral Infarction Caused by Cerebral Vasospasm Due to High-Voltage Electrical Injury

Effects of hemocoagulase on perioperative blood loss and coagulation in patients with low molecular heparin anticoagulation undergoing total hip replacement

Objective Objective to investigate the effects of hemocoagulase on perioperative blood loss and coagulation in patients with low molecular heparin (LMWH) anticoagulation undergoing total hip replacement (THR).Methods Forty ASA Ⅰ or Ⅱpatients aged 60 y～75 y scheduled for total hip replacement were randomly divided into two groups (n=20).The forty patients received LMWH for 4 000 IU im 1 d preoperatively.10 min before incision,Group H received hemocoagulase for 2 IU iv and group C received Normal Saline for 5 ml iv.The intraoperative and postoperative 24 h bleeding volume was measured respectively;meanwhile,the coagulation parameters were measured immediately,24 h after operation respectively.We examined the deep vein thrombosis through CDFI 5 d after operation.Results The intraoperative and postoperative 24 h bleeding volume were (629±97) ml and (273±87) ml in Group C,and they were (312±79) ml and (213±74) ml,respectively.The intraoperative and postoperative 24 h bleeding volume in Group H were less than Group C (P＜0.05).In both groups,Hb,RBC,Hct immediately and 24 h after operation were significantly lower than preoperation (P＜0.05).In both groups,APTT,PT,Fib immediately and 24 h after operation were same to preoperation (P＞0.05).The rate of deep venous thrombosis were 13％ and 7％ in two groups,and there was no difference (P＞0.05).Conclusions Perioperative bleeding volume can be reduced by intravenous injecting hemocoagulase preoperatively,and the coagulation can not be influenced. Key words: Batroxobin; Blood coagulation tests; Intraoperative complications,postoperative complications; Arthroplasty, replacement, hip; Heparin, low-molecular-weight

Suppurative cystadenoma of ovary with left ventricular thrombus: a case report

4. Ozkan B, Emel M. Ozdemir M, et al. M-mode, 2-D and Doppler echocardiographic study in 65 patients with Behcet’s syndrome. Eur Heart J. 1992;13:638-41. Left ventricular thrombus (LVT) is a frequent complication observed after myocardial infarction, in a patient with congestive heart failure (CHF) and dilated cardiomyopathy. LVT is usually associated with severe wall motion abnormality, severe hypokinesis, akinesis, dyskinesis or aneurysmal dilatation. LVT rarely forms with normal wall motion and systolic function of left ventricule, for example in patients with inflammatory bowel diseases or malignancy. The process of clot formation is explained by a hypercoagulable state due to increased concentrations of prothrombotic factors. We report a case of a 57-year old woman, who was admitted to our hospital with a few months history of progressive anemia, abdominal pain, fever, weight loss and erythema nodosum. Her past medical history included hypothyroidism, chronic obstructive pulmonary disease and nicotinism. Radiological examination revealed tumefaction in the area of terminal ileum. Immunological and tumor markers were normal. Echocardiography showed normal left ventricular size and systolic function. There was an abnormal mass, size 15x8 mm, attached to the apical third of interventricular septum which was protruding into the cavity of left ventricule (differential diagnosis — thrombus versus tumor). Since the patient had very high serum levels of inflammatory factors, prophylactic dose of low molecular heparin was added to the therapy. Due to the clinical presentation associated with ileus and suspected intra-abdominal abscess, and need for emergent surgical evaluation, the patient was transferred to Cancer Clinic. The patient underwent surgical resection of the terminal ileum and ovariectomy. Pathohistology showed suppurative cystaednoma of ovary. Warfarin therapy continued. Follow up echocardiography showed complete resolution of previously existed cardiac mass in the left ventricule. A complete patient’s recovery was noted.

Intramural hematoma of the esophagus in a woman with chronic renal failure and prophylactic heparin therapy

CASE REPORT An 86 year-old woman experienced chest pain, dyspnea, and dysphagia two days following orthopaedic surgery for a bimalleolus fracture of the right ankle. The patient was on prophylactic low weight molecular heparin and was affected by chronic renal failure. The chest computed tomography (CT) ruled out a pulmonary embolism but showed an intramural esophageal mass involving the entire esophagus. The lesion exhibited a blood like CT attenuation content that did not enhance after contrast administration. The esophagogram with gastrografin did not reveal filling defects nor communications between lumen and mucosa. Magnetic resonance confirmed CT results and excluded an aortic dissection. All radiological findings were suggestive of intramural hematoma of the esophagus. DISCUSSION AND CONCLUSIONS Intramural hematoma of the esophagus (IHE) is part of the spectrum of esophageal injuries that includes Mallory-Weiss tear and Boerhaave’s syndrome. IHE is the result of a hemorrhage within the submucosal layer. Predisposing conditions are abnormal hemostasis, traumatic events, aortic diseases. It can also occur spontaneously (idiopathic). Treatment should be conservative and includes risk factors withdrawal. The hematoma usually resolves in 1 to 3 weeks.

Mobile left ventricular thrombus in left ventricular dysfunction: case report and review of literature

Left ventricular (LV) thrombi carry a high risk of embolization. Therapeutic recommendations like treatment with low molecular heparin and intravenous unfractionated heparin (UFH), thrombolysis or surgical thrombectomy have failed to reach a consensus. A 56-year-old female patient presented in cardiogenic shock to the emergency department. Echocardiography demonstrated a dilated LV with a severely depressed global systolic function and a large LV apical thrombus. Treatment with UFH was initiated as well as a treatment with catecholamines for stabilizing the patient's hemodynamic situation. On the follow-up echocardiographic examination, extensive free-floating parts of the thrombus could be documented. Given the high risk of embolization in a now hemodynamically stable situation, emergency surgical embolectomy was performed. A conservative procedure might be useful for bridging till surgical treatment is available and/or the risk due to surgery is acceptable. In absence of evidence-based guidelines for the treatment of LV thrombi, individualized management options concerning surgical, embolization and bleeding risk must be taken into account.

First-in-man evaluation of the transapical APICA ASC access and closure device: the initial 10 patients

The aim of this study was to evaluate the initial and short-term results of a new apical access and closure device to facilitate and standardize the transapical (TA) approach to transcatheter aortic valve implantation (TAVI). The apical access, stabilization and closure (ASC™) device consists of three components: an introducer system, a left ventricular low-profile titanium coil and a closure cap. The ASC™ introducer system is anchored and rotated into the myocardium almost like a corkscrew, using the titanium coil. Following the TA-AVI procedure, the closure cap is introduced and delivered through the system into the titanium coil for final sealing. A total of 11 high-risk elderly patients (EuroSCORE I: 27.8 ± 16.7; EuroSCORE II: 6.6 ± 5.0 and The Society of Thoracic Surgeons (STS) score: 5.9 ± 2.7%) were evaluated for TA-AVI by our interdisciplinary Heart Team and subsequently included in the trial after informed consent was obtained. One patient was excluded due to the presence of deep epicardial fat tissue. In all other cases, the titanium coil provided sufficient sealing throughout the procedure without the presence of perisheath bleeding. After delivery of the closure cap, no relevant bleeding was observed in any patient. Pericardial drainages were removed early in all patients. One patient suffered from non-device-related pericardial effusion requiring surgical decompression on postoperative day 6. Two patients suffered from delayed minor strokes, most likely due to arrhythmia. All patients received aspirin, clopidogrel and low molecular heparin after the procedure. Discharge echocardiography revealed no changes in left ventricular function when compared with baseline and no new onset wall motion abnormalities. All 10 patients were alive at 30 days. TA access and closure are both feasible and safe using the APICA ASC™ device. The system facilitates and standardizes TA access and closure by providing a sufficient and secure sealing during and after the TA-AVI procedure.

Ефективність і безпека застосування низькомолекулярних гепаринів для лікування та профілактики гострого коронарного синдрому

Ефективність і безпека застосування низькомолекулярних гепаринів для лікування та профілактики гострого коронарного синдрому

Heparin Oligosaccharides Inhibit Chemokine (CXC Motif) Ligand 12 (CXCL12) Cardioprotection by Binding Orthogonal to the Dimerization Interface, Promoting Oligomerization, and Competing with the Chemokine (CXC Motif) Receptor 4 (CXCR4) N Terminus

The ability to interact with cell surface glycosaminoglycans (GAGs) is essential to the cell migration properties of chemokines, but association with soluble GAGs induces the oligomerization of most chemokines including CXCL12. Monomeric CXCL12, but not dimeric CXCL12, is cardioprotective in a number of experimental models of cardiac ischemia. We found that co-administration of heparin, a common treatment for myocardial infarction, abrogated the protective effect of CXCL12 in an ex vivo rat heart model for myocardial infarction. The interaction between CXCL12 and heparin oligosaccharides has previously been analyzed through mutagenesis, in vitro binding assays, and molecular modeling. However, complications from heparin-induced CXCL12 oligomerization and studies using very short oligosaccharides have led to inconsistent conclusions as to the residues involved, the orientation of the binding site, and whether it overlaps with the CXCR4 N-terminal site. We used a constitutively dimeric variant to simplify the NMR analysis of CXCL12-binding heparin oligosaccharides of varying length. Biophysical and mutagenic analyses reveal a CXCL12/heparin interaction surface that lies perpendicular to the dimer interface, does not involve the chemokine N terminus, and partially overlaps with the CXCR4-binding site. We further demonstrate that heparin-mediated enzymatic protection results from the promotion of dimerization rather than direct heparin binding to the CXCL12 N terminus. These results clarify the structural basis for GAG recognition by CXCL12 and lend insight into the development of CXCL12-based therapeutics.

An effect of anticoagulants on the FTIR spectral profile of mice plasma

BACKGROUND: Although, it is well known that various types of anticoagulant influence on plasma biochemistry in clinical chemistry analysis, the evaluation of such an effect on IR spectrum of plasma has not been reported so far. OBJECTIVE: In this study, we compare FTIR spectra of plasma films from healthy mice C57Bl/6J, which were collected by application of various types of anti-clotting agents such as low molecular heparin, trisodium citrate, EDTA and aspisol. METHODS: FTIR spectra were recorded using Fourier Transform Infrared imaging and evaluated with a support of Principal Component Analysis (PCA). RESULTS: We found significant changes in spectral profile of plasma among three groups of anticoagulants: (1) nadroparine administrated intraperitoneally and blood collected by using aspisol, (2) citrate, and (3) EDTA, heparin and EDTA/aspisol. The spectral variation is mainly found in the regions associated with proteins and lipids. CONCLUSIONS: Spectral features found in this study indicate the alternation in structure of plasma proteins as well as lipids/fatty acids. This suggests a careful choice of the anticoagulant in clinical/pharmacological studies on plasma with the use of FTIR spectroscopy.

Successful outcome from empirical use of heparin and aspirin in unexplained pregnancy loss

Abstract Success in pregnancy of a 42-years old woman with a history of unexplained recurrent miscarriages is described. She had a sub-septate uterus with free spillage bilaterally, based on hysterosalpingogram, and it was corrected by hysteroscopy in October 2009, which was followed by transcervical septal resection (TCRS). Clomiphene citrate was given ovulation. She was treated with folic acid supplementation, aspirin 75 mg, micronized progesterone 400 mg/d, and low molecular heparin 2500 IU/d, from the diagnosis of pregnancy at 5 weeks, until the delivery. However, at 28 weeks glucose tolerance test with 100 g glucose revealed mild derangement in first (159 mg/dL) and second (164 mg/dL) hour values; metformin was given for the control of sugar. Heparin injections were given to the patient continuously during the antenatal period. No major bleeding episode was noted during pregnancy or delivery. A male child weighing 3.2 kg with a good APGAR score was delivered at the end of the term. Both anatomical abnormality and advanced maternal age had determinative role in pregnancy loss, but TCRS and antithrombotic heparin and aspirin treatment had the blithesome effect.

Thalidomide (THAL) and Lenalidomide (LEN)-Associated Venous Thromboembolism (VTE): Optimal Prophylaxis Strategies Remain Elusive

AbstractAbstract 4692 Background:Thalidomide (THAL) and lenalidomide (LEN) are established treatments for multiple myeloma (MM), often in combination with other drugs. Venous thromboembolism (VTE) is a common feature of therapy as evidenced by a Boxed warning to package inserts for both drugs when administered to MM patients. Oncologists are encouraged to consider VTE prophylaxis even though optimal strategies for prophylaxis remain mostly elusive. We sought to (1) determine the prevalence of VTE events among in-patients receiving THAL or LEN at a tertiary academic medical center and (2) to determine whether patients receiving concomitant VTE prophylaxis therapies (aspirin, heparin, low molecular heparin or other oral anticoagulants) have lower rates of VTE events. After obtaining Institutional Review Board approval we completed an extensive retrospective chart review. Methods:We abstracted data from de-identified pharmacy records connected to charts of in-patients with MM who were treated with THAL or LEN (N=102) by every hematologist on staff; we excluded redundant charts (N=11), analyzing the remaining charts (N=91). A syndrome specific case report form developed by the Principal Investigator was used to collect data. General Demographic information, adverse drug events (ADE), response to ADE, treating physicians' assessment, disease and general ADE outcomes, and causality were recorded. Data were analyzed statistically using Chi square and comparison of demographic variables was done using the Fisher's exact t-test. Kaplan-Meier curve was applied to survival data. Results:Total time on THAL (N=69; median=12 days, range=0–1098 days); total time on LEN (N=40; median=14.5 days, range=0–731 days); VTE rate for THAL was 25%; LEN was 26.67%; both were 41.67%, p=0.30. All pts received heparin; 1 received LMWH. For Epo alpha, VTE rate was 30.00% in those who did not receive EPO and 35.48% in those who did; p=0.64. For Coumadin, 25.71% who did not receive coumadin suffered VTE while 52.38% on Coumadin did not, p=0.032. For ASA, 33.33% pt who did take ASA experienced a PE while 26.32% of those on ASA did not; p=0.78. For lovenox VTE occurred in 33.33% of patients not on lovenox while 29.41% of those on lovenox had no VTE, p=0.82. Overall, 22 patients experienced VTE (8 on LEN and 14 on THAL). If there was an adverse event, the drug was discontinued. Follow-up time was a median of 11.2 months (range.07 – 115months). Kaplan-Meier curve for overall survival (OS) revealed that 31/91 persons died; 1 year OS was 70%, 2 year OS was 62%, and 5 year OS 50%; Kaplan-Meier curve for VTE-free survival revealed 25/87 persons with VTE, 1 year VTE-free survival was 73%, 2 year VTE-free survival was 64%, 5 year VTE-free survival was 64%. Conclusion:VTE rates were high in our study and mirrors rates reported in other studies. Optimal VTE prophylaxis strategies for MM patients who receive LEN or THAL remain elusive. Providers are encouraged to use at least one of the standard oral or subcutaneous anti-coagulants. A formal randomized trial of alternative VTE strategies is needed. Disclosures:No relevant conflicts of interest to declare.

Early SAPIEN transcatheter heart valve dysfunction due to tissue ingrowth in an octogenarian

A high-risk 83-year-old woman (Euroscore: 29 %, STSscore: 7 %) presented with severe aortic stenosis New York Heart Association class III. The interdisciplinary heart team considered her to be high-risk due to severe peripheral occlusive disease, which required several previous interventions, chronic renal insufficiency, diabetes mellitus and frailty. The patient thus received an Edwards SAPIEN XT prosthesis by transapical implantation using the 24F Ascendra-II sheath, in July 2011. The procedure went uneventfully and the patient was discharged 10 days after surgery. On discharge the patient received aspirin, clopidogrel (3 months) and low molecular heparin until full mobilization as antithrombotic therapy. ECG revealed good left ventricular and aortic valve prosthesis function with a small paravalvular leakage at that time (Fig. 1). Six months later her ambulatory follow-up visit was unremarkable, as well with persistently good aortic valve function (Fig. 1). After 1 year, the patient was readmitted to our hospital due to recurrent cardiac decompensations. She had to undergo leg amputation due to ulcus cruris caused by severe peripheral occlusive disease which was treated several times interventionally as well as surgically, prior to readmission. Her post-operative course after that procedure had been uneventful without any signs of wound healing problems. Several wound swabs and pathological examinations of the amputated limb could exclude any bacterial infection. At admission to our hospital, the patient showed no typical signs of infection. Initial blood chemistry before aortic replacement revealed a slightly raised CRP, but normal WBC count (Table 1). Transesophageal echocardiography revealed severe transvalvular aortic valve regurgitation and presence of one immobile leaflet at this time. Even though there were no direct clinical signs of endocarditis according to DUKE criteria, neither vegetations nor any positive blood cultures, the patient was evaluated for conventional redo procedure to definitively exclude an infectious event. Intraoperatively, the aortic valve prosthesis was in a stable intra-annular position. There were neither any macroscopic vegetations nor any paravalvular leak or dehiscence. The noncoronary leaflet occurred to be retracted (Fig. 2). The SAPIEN XT prosthesis was explanted and sent for further histological examination (Fig. 3). The native calcified aortic valve leaflets were then resected and a 25 mm Medtronic Hancock prosthesis was successfully implanted. Tricuspid valve repair was performed in addition. In total, cross clamp time was 75 min and bypass time 110 min. The post-operative course was uneventful, the patient was extubated the same day and had a good further recovery, despite the need for some temporary renal support. Discharge echocardiography showed sufficient aortic valve prosthesis with a mean gradient of 6 mmHg and a sufficient tricuspid valve repair with a mean gradient of 3 mmHg. J. Blumenstein (&) A. Van Linden W. K. Kim W. Skwara M. Schoenburg M. Arsalan J. Kempfert T. Walther Department of Cardiac Surgery, Kerckhoff-Klinik Heartcenter, Benekestrasse 2-8, 61231 Bad Nauheim, Germany e-mail: j.blumenstein@kerckhoff-klinik.de

THE VALUE OF CLOPIDOGREL TO ACUTE NON-ST ELEVATION MYOCARDIAL INFARCTION

ObjectivesTo observe and evaluate the clinical efficacy and safety of clopidogrel on acute non-ST elevation myocardial infarction (NSTEMI) .Methods30 patients with acute NSTEMI in the control group were treated with...

CLINICAL RESEARCH OF FONDAPARINUX IN TREATING UNSTABL ANGINA

ObjectivesTo observe the immediate effect and security of fondaparinux in treating unstable angina.Methods232 patients with unstable angina were selected and randomly divided into Group A (116 cases) and Group B...

CLINICAL APPLICATION OF MIN-DIAMETER ATRIA STEEL-WIRE IN MODIFIED PERCUTANEOUS BALLOON MITRAL VALVULOPLASTY

ObjectivesTo evaluate the efficacy, feasibility and safety of the min-diameter half and two convolutions atria steel-wire used in modified percutaneous balloon mitral valvuloplasty (PBMV).MethodsTotally 63 patients with moderate and severe...

Top-Down Approach for the Direct Characterization of Low Molecular Weight Heparins Using LC-FT-MS

Low molecular heparins (LMWHs) are structurally complex, heterogeneous, polydisperse, and highly negatively charged mixtures of polysaccharides. The direct characterization of LMWH is a major challenge for currently available analytical technologies. Electrospray ionization (ESI) liquid chromatography-mass spectrometry (LC-MS) is a powerful tool for the characterization complex biological samples in the fields of proteomics, metabolomics, and glycomics. LC-MS has been applied to the analysis of heparin oligosaccharides, separated by size exclusion, reversed phase ion-pairing chromatography, and chip-based amide hydrophilic interaction chromatography (HILIC). However, there have been limited applications of ESI-LC-MS for the direct characterization of intact LMWHs (top-down analysis) due to their structural complexity, low ionization efficiency, and sulfate loss. Here we present a simple and reliable HILIC-Fourier transform (FT)-ESI-MS platform to characterize and compare two currently marketed LMWH products using the top-down approach requiring no special sample preparation steps. This HILIC system relies on cross-linked diol rather than amide chemistry, affording highly resolved chromatographic separations using a relatively high percentage of acetonitrile in the mobile phase, resulting in stable and high efficiency ionization. Bioinformatics software (GlycReSoft 1.0) was used to automatically assign structures within 5-ppm mass accuracy.

Primary Budd-Chiari syndrome - a single center experience.

Budd-Chiari syndrome (BCS) is recognized as a clinical manifestation of various prothrombotic conditions which may be lethal within 3 years of the onset of symptoms if untreated. This study is a retrospective analysis of patients with BCS managed between 2004 and 2011. The diagnosis was confirmed with contrast CT-angiography and/or Doppler ultrasound. BCS was diagnosed in 20 patients (11 females and 9 males), median age 38 years (ranging from 18 to 56). Twelve patients were referred as acute BCS for the liver transplant (LTx) assessment. Thrombosis of the hepatic veins was caused by myeloproliferative disorders (n=8), end-stage liver disease (n=4), protein C deficiency (n=3), paroxysmal nocturnal hemoglobinuria (PNH) (n=1), antiphospholipid syndrome (n=1) and secondary poliglobulia (n=1). In two patients the origin of BCS could not be established despite appropriate screening. Median follow-up was 29 months. Low molecular heparin with subsequent conversion to vitamin K antagonists was routinely applied in all patients. Two patients underwent TIPS procedure with good long term outcome and 10 subjects received LTx; 1 patient was lost to follow-up and 1 died of chest infection 9 years since the diagnosis of BCS was made; 14 patients, including those who received LTx, were alive and well at least one year after BCS diagnosis. All survivors remain stable and are followed-up on a regular basis. Strict adherence to the diagnostic and therapeutic guidelines plays a crucial role in the management of BCS patients. Our results confirm the efficacy of anticoagulation as well as TIPS and/or OLT in treatment of this rare condition.