Thrombosis Journal (Thromb J)

Publications in this journal

• Article: Emphasis on the Role of PF4 in the Incidence, Pathophysiology and Treatment of Heparin Induced Thrombocytopenia.

  M Margaret Prechel, Jeanine M Walenga
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  ABSTRACT: Heparin Induced Thrombocytopenia (HIT) is caused by antibodies that recognize platelet factor 4 (PF4) associated with polyanionic glycosaminoglycan drugs or displayed on vascular cell membranes. These antibodies are elicited by multimolecular complexes that can occur when heparin is administered in clinical settings associated with abundant PF4. Heparin binding alters native PF4 and elicits immune recognition and response. While the presence of heparin is integral to immunogenesis, the HIT antibody binding site is within PF4. Thus HIT antibodies develop and function to cause thrombocytopenia and/or thrombosis only in the presence of PF4. Future emphasis on understanding the biology, turnover and regulation of PF4 may lead to insights into the prevention and treatment of HIT.
  Thrombosis Journal 04/2013; 11(1):7.
• Article: Giant left atrium associated with massive thrombus formation.

  Ahmad K Darwazah, Hamdy Sayed
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  ABSTRACT: Giant left atrium is a condition characterized by huge enlargement of the left atrium with a diameter exceeding 65mm. It is most commonly associated with long standing rheumatic mitral valve disease. We present a 45-year-old female patient with rheumatic mitral stenosis associated with giant left atrium occupied by an 11x10x5cm thrombus weighing 500gms. The patient underwent successful mitral valve replacement and thrombectomy through an inverted T-shaped biatrial incision.
  Thrombosis Journal 03/2013; 11(1):5.
• Article: Postpartum deep vein thrombosis and pulmonary embolism in twin pregnancy: undertaking of clinical symptoms leading to massive complications.

  Leslie Fiengo, Federico Bucci, Gregorio Patrizi, Domenico Giannotti, Adriano Redler
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  ABSTRACT: BACKGROUND: Deep Vein Thrombosis (DVT) is an important cause of morbidity and is the first cause of maternal death after delivery in Western Nations. The risk of venous thromboembolism is present throughout the pregnancy and is maximal during postpartum, especially after twin delivery. Many of the signs and symptoms of DVT overlap those of a normal pregnancy causing difficulty for diagnosis.Case report: We report the case of a 33 year-old woman transferred to our Department one week after caesarean section for twin delivery. She presented with severe abdominal pain, fever, abdominal distension and shortness of breath. She had no personal or family history of thromboembolism. Computerized Tomography Scan revealed right ovarian vein thrombosis, left renal vein thrombosis extending up to the Inferior Vena Cava and pulmonary embolism with bilateral pleural effusion. Caval filter was positioned and anticoagulation therapy associated with antibiotics was instituted. Pancreatitis showed up two days after and was promptly treated. Three months after discharge the caval filter was removed and oral anticoagulation was stopped. During a 12-months follow-up, she remained stable and symptom free. RESULTS: Ovarian vein thrombosis is rare but recognition of signs and symptoms is fundamental to start adequate therapy and avoid potential serious sequelae. The risk for maternal postpartum ovarian vein thrombosis is increased by caesarean section delivery of twins. Such patients should be closely monitored. We illustrated how an underestimated condition can lead to massive complications.
  Thrombosis Journal 02/2013; 11(1):4.
• Article: Recombinant human soluble thrombomodulin administration improves sepsis-induced disseminated intravascular coagulation and mortality: a retrospective cohort study.

  Takahiro Kato, Takamasa Sakai, Miki Kato, Mao Hagihara, Takaaki Hasegawa, Katsuhiko Matsuura, Takashi Nakagawa
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  ABSTRACT: BACKGROUND: Early treatment of disseminated intravascular coagulation (DIC) can be associated with improved patient outcomes. The Japanese Ministry of Health and Welfare (JMHW) and the International Society on Thrombosis and Haemostasis (ISTH) criteria are the most specific for diagnosis of septic DIC. The revised Japanese Association for Acute Medicine (JAAM) criteria are able to diagnose sepsis-induced DIC in the early stage. Recombinant human soluble thrombomodulin (rhTM) has recently been used for treating DIC. Previous studies have shown a benefit of using rhTM for DIC diagnosed by the JMHW or ISTH criteria, but not the JAAM criteria. The purpose of this study was to sequentially evaluate coagulation biomarkers and the DIC score after giving rhTM treatment to patients with sepsis-induced DIC diagnosed according to the JAAM criteria. METHODS: We performed a retrospective cohort study. Critically ill patients were included if diagnosed with sepsis-induced DIC according to the JAAM criteria. They were either treated without rhTM (control group) or with rhTM (treatment group). The primary outcome was the DIC score on day 7. The secondary outcome was 28-day mortality from the start of DIC treatment. Changes in the results of coagulation tests were assessed over time from the start of treatment to day 7. RESULTS: Twelve and 23 patients were assigned to the treatment and control groups, respectively. The DIC score on day 7 was significantly lower in the treatment group (3.3 +/- 1.4) than in the control group (4.9 +/- 1.8, p < 0.05). Estimated survival showed lower in treatment group than control group. There was significant difference between the control group and the treatment group (p < 0.05). The D-dimer level on day 7 was significantly lower in the treatment group (7.5 +/- 4.1 mug/mL) than in the control group (30.9 +/- 33.6 mug/mL, p < 0.05). Life-threatening bleeding did not occur. Our results indicated that rhTM improved sepsis-induced DIC and mortality. CONCLUSIONS: Recombinant human soluble thrombomodulin may improve sepsis-induced DIC diagnosed according to the JAAM criteria without an increased bleeding risk.
  Thrombosis Journal 02/2013; 11(1):3.
• Article: Purification and characterization of mutant miniPlasmin for thrombolytic therapy.

  Xiaotao Lin, Yan Wang, Yanwen Zhang, Bing Huang, James J Lin, Scott J Hallock, Hong Yu, Hongwei Shao, Jing Yan, Bo Huang, Xuejun C Zhang, Wei Cao, Xueming Xu, Xinli Lin
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  ABSTRACT: BACKGROUND: Previous animal studies by us and others have indicated that catheter-administered plasmin or its des-kringle derivatives may be more appropriate alternatives to plasminogen activators for treating thrombolytic diseases, since it has a very short serum half-life and therefore does not result in hemorrhaging. We have previously produced recombinant miniPlasmin (mPlasmin) that was proven suitable for treating peripheral arterial occlusion in animal models. However, our previous results showed that non-specific cleavage at position K698 of mPlasmin during activation hindered the further development of this promising therapeutic candidate. In order to minimize or eliminate the non-specific cleavage problem, we performed saturation mutagenesis at the K698 position to develop a mutant form of mPlasmin for thrombolytic therapy. METHODS: We changed K698 to 16 other amino acids, with preferred E. coli codons. Each of these mutants were expressed in E. coli as inclusion bodies and then refolded, purified, and subsequently characterized by detailed kinetic assays/experiments/studies which identified highly active mutants devoid of non-specific cleavage. RESULTS: Activation studies indicated that at those conditions in which the wild type enzyme is cut at the non-specific position K698, the active mutants can be activated without being cleaved at this position. CONCLUSIONS: From the above results, we selected two mutants, K698Q and K698N, as our lead candidates for further thrombolytic drug developments. The selected mutants are potentially better therapeutic candidates for thrombolytic therapy.
  Thrombosis Journal 01/2013; 11(1):2.
• Article: Prothrombotic markers in patients with acute myocardial infarction and left ventricular thrombus formation treated with pci and dual antiplatelet therapy.

  Svein Solheim, Ingebjørg Seljeflot, Ketil Lunde, Vibeke Bratseth, Svend Aakhus, Kolbjørn Forfang, Harald Arnesen
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  ABSTRACT: BACKGROUND: The aim of the present study was to compare circulating levels of selected prothrombotic markers in patients suffering acute myocardial infarction (AMI) with and without left ventricular (LV) thrombus. METHODS: One hundred patients with AMI treated with PCI on the LAD and dual antiplatelet therapy were included. LV thrombus formation was detected by echocardiography and/or MRI in 15 patients. Fasting blood samples were drawn 4--5 days (baseline), 6--7 days, 8--9 days, 2--3 weeks and 3 months after the AMI for determination of haemostatic markers. RESULTS: We found higher levels of soluble tissue factor (TF) and D-dimer in the LV thrombus group 4--5 days, 8--9 days and 3 months (only TF) after the AMI compared to the patients without thrombus formation (p<0.05). Patients with TF in the upper quartile at baseline had significantly higher risk for LV thrombus (OR 4.2; 95% CI 1.2 -14.5; p=0.02, adjusted for infarct size).The levels of prothrombin fragment 1+2 (F1+2) and endogenous thrombin potential (ETP) were significantly lower in the thrombus group after 8--9 days (only ETP), 2--3 weeks and 3 months. The levels of plasminogen activator inhibitor 1 activity and tissue plasminogen activator antigen did not differ between the groups. CONCLUSION: In the acute phase of AMI, we found higher levels of TF and D-dimer in the LV thrombus group, indicating hypercoagulability of possible importance for the generation of mural thrombus. Lower levels of F1+2, ETP and D-dimer in the thrombus group late during follow-up are probably induced by the initiated anticoagulation therapy.
  Thrombosis Journal 01/2013; 11(1):1.
• Article: Variability between laboratories performing coagulation tests with identical platforms: a nationwide evaluation study.

  Michael Nagler, Lucas M Bachmann, Lorenzo Alberio, Anne Angelillo-Scherrer, Lars M Asmis, Wolfgang Korte, Adriana Mendez, Guido Reber, Hans Stricker, Dimitrios A Tsakiris, Walter A Wuillemin
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  ABSTRACT: While the assessment of analytical precision within medical laboratories has received much attention in scientific enquiry, the degree of as well as the sources causing variation between them remains incompletely understood. In this study, we quantified the variance components when performing coagulation tests with identical analytical platforms in different laboratories and computed intraclass correlations coefficients (ICC) for each coagulation test. Data from eight laboratories measuring fibrinogen twice in twenty healthy subjects with one out of 3 different platforms and single measurements of prothrombin time (PT), and coagulation factors II, V, VII, VIII, IX, X, XI and XIII were analysed. By platform, the variance components of (i) the subjects, (ii) the laboratory and the technician and (iii) the total variance were obtained for fibrinogen as well as (i) and (iii) for the remaining factors using ANOVA. The variability for fibrinogen measurements within a laboratory ranged from 0.02 to 0.04, the variability between laboratories ranged from 0.006 to 0.097. The ICC for fibrinogen ranged from 0.37 to 0.66 and from 0.19 to 0.80 for PT between the platforms. For the remaining factors the ICC's ranged from 0.04 (FII) to 0.93 (FVIII). Variance components that could be attributed to technicians or laboratory procedures were substantial, led to disappointingly low intraclass correlation coefficients for several factors and were pronounced for some of the platforms. Our findings call for sustained efforts to raise the level of standardization of structures and procedures involved in the quantification of coagulation factors.
  Thrombosis Journal 01/2013; 11(1):6.
• Article: Diastolic Timed Vibro-Percussion At 50 Hz Delivered Across A Chest Wall Sized Meat Barrier Enhances Clot Dissolution And Remotely Administered Streptokinase Effectiveness In An In-Vitro Model Of Acute Coronary Thrombosis.

  Andrew Hoffmann, Harjit Gill
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  ABSTRACT: BACKGROUND: Low Frequency Vibro-Percussion (LFVP) assists clearance of thrombi in catheter systems and when applied to the heart and timed to diastole is known to enhance coronary flow. However LFVP on a clotted coronary like vessel given engagement over a chest wall sized barrier (to resemble non-invasive heart attack therapy) requires study. METHODS: One hour old clots (n=16) were dispensed within a flexible segment of Soft-Flo catheter (4 mm lumen), weighted, interfaced with Heparinized Saline (HS), secured atop a curved dampening base, and photographed. A ~4 cm meat slab was placed over the segment and randomized to receive intermittent LFVP (engaged, - disengaged at 1 second intervals), or no LFVP for 20 minutes. HS was pulsed (~120/80 mmHg), with the diastolic phase coordinated to match LFVP delivery. The segment was then re-photographed and aspirated of fluid to determine post clot weight. The trial was then repeated with 0.5 mls of Streptokinase (15,000 IU / 100 microlitre) delivered ~ 2 cm upstream from the clot. RESULTS: LFVP - HS only samples (vs. controls) showed; a) development of clot length fluid channels absent in the control group (p < 0.0002); b) enhanced dissolved clot mixing scores ( 5.0 vs. 0.8, p < 2.8 E -- 6); and c) increased percent clot dissolution (23.0% vs. 1.8% respectively, p < 8.5 E-6). LFVP - SK samples had a similar comparative clot disruptive profile, however fluid channels developed faster and percent clot dissolution more than doubled (51.0% vs. 3.0%, p< 9.8 E- 6). CONCLUSION: Diastolic timed LFVP (50 Hz) engaged across a chest wall sized barrier enhances clot disruptive effects to an underlying coronary like system.
  Thrombosis Journal 11/2012; 10(1):23.
• Article: Triple antithrombotic therapy in patients with atrial fibrillation undergoing coronary artery stenting: hovering among bleeding risk, thromboembolic events, and stent thrombosis.

  Mila Menozzi, Andrea Rubboli, Antonio Manari, Rossana Palma, Roberto Grilli
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  ABSTRACT: Dual antiplatelet treatment with aspirin and clopidogrel is the antithrombotic treatment recommended after an acute coronary syndrome and/or coronary artery stenting. The evidence for optimal antiplatelet therapy for patients, in whom long-term treatment oral anticoagulation is mandatory, is however scarce. To evaluate the safety and efficacy of the various antithrombotic strategies adopted in this population, we reviewed the available evidence on the management of patients receiving oral anticoagulation, such as a vitamin-k-antagonists, referred for coronary artery stenting.Atrial fibrillation is the most frequent indication for oral anticoagulation. The need of starting antiplatelet therapy in this clinical scenario raises concerns about the combination to choose: triple therapy with warfarin, aspirin, and a thienopyridine being the most frequent and advised. The safety of this regimen appeared suboptimal because of an increased risk in hemorrhagic complications. On the other hand, the combination of oral anticoagulation and an antiplatelet agent is suboptimal in preventing thromboembolic events and stent thrombosis; dual antiplatelet therapy may be considered only when a high hemorrhagic risk and low thromboembolic risk are perceived. Indeed, the need for prolonged multiple-drug antithrombotic therapy increases the bleeding risks when drug eluting stents are used.Since current evidence derives mainly from small, single-center and retrospective studies, large-scale prospective multicenter studies are urgently needed.
  Thrombosis Journal 10/2012; 10(1):22.
• Article: Acute ischemic stroke following Hump-nosed viper envenoming; first authenticated case.

  Vijayabala Jeevagan, Ariaranee Gnanathasan, Thashi Chang
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  ABSTRACT: Hump-nosed pit viper (Genus Hypnale) is a medically important venomous snake in Sri Lanka and Southwestern India which causes significant morbidity and mortality. Envenoming of this snake results in hemostastic dysfunction, thrombotic microangiopathy, acute kidney injury and death. This case describes an authenticated first case of ischemic stroke in a 65 year old male following envenoming by H.hypnale in Sri Lanka.
  Thrombosis Journal 09/2012; 10(1):21.
• Article: Venous thromboembolism risk and prophylaxis in the acute hospital care setting: report from the ENDORSE study in Egypt.

  Hadi A Goubran, Sherif Sholkamy, Alaa El-Haddad, Alaa Mahmoud, Mounir Rizkallah, George Sobhy
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  ABSTRACT: BACKGROUND: Venous thromboembolism (VTE) is a leading cause of hospital-related deaths worldwide. However, the proportion of patients at risk of VTE who receive appropriate prophylaxis in Egypt is unknown. The ENDORSE study in Egypt is part of a global initiative to uncover the incidence of high-risk surgical and medical patients and determine what proportion of these patients receive appropriate VTE prophylaxis. METHODS: Ten Egyptian hospitals participated in this observational study, enrolling all surgical and medical patients that met the study criteria. This resulted in a cohort of 1,008 patients in acute care facilities who underwent a retrospective chart review. Each patient's VTE risk status and the presence or absence of appropriate prophylactic care was assessed according to the American College of Chest Physicians (ACCP) guidelines 2004. RESULTS: Of the 1,008 patients enrolled, 395 (39.2%) were found to be at high-risk for VTE. Overall, 227 surgical patients were at high-risk, although only 80 (35.2%) received ACCP-recommended prophylaxis. Similarly, 55/268 (32.75%) of high-risk medical patients received appropriate VTE prophylaxis. Low molecular weight heparin was the most commonly used anticoagulant, while mechanical prophylactic use was quite low (1.5%) in high-risk patients. CONCLUSIONS: In Egypt, more than one-third of all patients hospitalized for surgery or acute medical conditions are at high risk for developing VTE. However, only a small fraction of these patients receive appropriate VTE prophylaxis. Corrective measures are necessary for preventing VTE morbidity and mortality in these high risk patients.
  Thrombosis Journal 09/2012; 10(1):20.
• Article: Postoperative thromboembolic prophylaxis in joint replacement surgery: Guidelines and daily practice.

  Arina J Ten Cate-Hoek, Karly Hamulyák
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  ABSTRACT: This is a commentary discussing the article published in Thrombosis Journal by Subramanian et al. [Thrombosis Journal 2012, 10:15].
  Thrombosis Journal 09/2012; 10(1):18.
• Article: Platelet function in the postprandial period.

  Helmut Sinzinger, Robert Berent
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  ABSTRACT: BACKGROUND: Postprandial hyperlipidemia and hyperglycemia have been related to cardiovascular events. Among different underlying mechanisms platelet activation seems to be responsible too. No comparable data between various tests in normo- vs. hyperlipidemics before and at different time intervals are available after a fat meal. We aimed to compare 9 of them within the same patients at several time points in postprandial hyperlipidemia. RESULTS: For some tests baseline values between the groups were significantly different (TXB2, platelet sensitivity, sedimentation and WU-test). However, hyperlipidemia revealed a variable influence on the tests examined. Some of the available tests apparently sensitive to show platelet activation reflect the increase in triglycerides (TG), such as the sedimentation index. ADP-induced platelet aggregatory activity in count adjusted washed isolated platelet samples during postprandial hyperlipidemia indicates mildly enhanced platelet activity, but does not seem to induce significant changes in aggregation. In patients with severe hypertriglyceridemia (> 400 mg/dl fasting) changes in platelet function are more pronounced due to delayed decay and may last up to 16 hours paralleling TG reaching the prevalue. The overwhelming majority of platelet function tests do not significantly respond to postprandial hyperlipidemia. The correlation between the tests applied is poor. For standardization purpose, platelet aggregation tests, aimed to examine proaggregatory capacity in atherosclerosis, should only be performed at the same time of the day after a fasting period > 6 hours. The great variation in preanalytical work-up on comparison of various tests, large number of platelet tests available and their respective potential value are discussed. CONCLUSIONS: At present, the suspicion that platelet function is significantly activated in the postprandial period cannot be supported by any of the tests used. The information provided is valuable to know for which test and group of patients a fasting period of which duration is recommendable.
  Thrombosis Journal 09/2012; 10(1):19.
• Article: Effects of computer-assisted oral anticoagulant therapy.

  Rune S Rasmussen, Pernille Corell, Poul Madsen, Karsten Overgaard
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  ABSTRACT: BACKGROUND: Computer-assistance and self-monitoring lower the cost and may improve the quality of anticoagulation therapy. The main purpose of this clinical investigation was to use computer-assisted oral anticoagulant therapy to improve the time to reach and the time spent within the therapeutic target range compared to traditional oral anticoagulant therapy by physicians. METHODS: 54 patients were randomized equally into 3 groups. Patients in two groups used CoaguChek® systems to measure international normalized ratio (INR) values and had dosages of anticoagulation treatment calculated in a computer system by an algorithm specific to each group. The third group received traditional anticoagulation treatment by physicians. The obtained INR values were compared regarding the time to reach, and the time spent within, the therapeutic target range, corresponding to INR values from 2 to 3. RESULTS: Patients randomized to computer-assisted anticoagulation and the CoaguChek® system reached the therapeutic target range after 8 days compared to 14 days by prescriptions from physicians (P = 0.04). Time spent in the therapeutic target range did not differ between groups. The median INR value measured throughout the study from all patients by CoaguChek® at 2.5 (2.42-2.62) was lower than measured by a hospital-based clinical and biochemical laboratory at 2.6 (2.45-2.76), (p = 0.02). CONCLUSIONS: The therapeutic target range was reached faster by the use of computer-assisted anticoagulation treatment than prescribed by physicians, and the total time spent within the therapeutic target range was similar. Thus computer-assisted oral anticoagulant therapy may reduce the cost of anticoagulation therapy without lowering the quality. INR values measured by CoaguChek® were reliable compared to measurements by a clinical and biochemical laboratory.
  Thrombosis Journal 08/2012; 10(1):17.
• Article: Circulating microRNA-126 in patients with coronary artery disease: correlation with LDL cholesterol.

  Xiao Sun, Man Zhang, Akimasa Sanagawa, Chieko Mori, Shiori Ito, Soichiro Iwaki, Hiroki Satoh, Satoshi Fujii
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  ABSTRACT: BACKGROUND: Coronary artery disease (CAD) is a major problem worldwide. Atherosclerosis and thrombosis underlying CAD involve multiple cell types. New and useful diagnostic markers are required. MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the gene expressions involved in various cellular processes. Endothelial dysfunction is implicated in early processes of athero-thrombosis. Thus, it was hypothesized that the level of vascular endothelium-enriched miRNAs would be altered in plasma samples of CAD patients. METHODS: Vascular endothelium-enriched miRNA (miR-126) level was analyzed in plasma from 31 patients with CAD and 36 patients without CAD (qRT-PCR analysis). RESULTS: MiR-126 was not significantly down-regulated or up-regulated in CAD patients. Interestingly, the level of miR-126 was significantly decreased in patients with CAD and high low-density lipoprotein (LDL) cholesterol level. In contrast, the level of miR-126 was significantly increased when LDL cholesterol was high in patients who had risk factors for CAD but did not have angiographically significant CAD. CONCLUSION: MiR-126 was not significantly down-regulated or up-regulated in CAD patients and was not suitable for discriminating CAD patients from patients without CAD. The oppositely-directed relationship between miR-126 and LDL cholesterol in patients with or without CAD may have significant implications for identifying a potential role of miR-126 in cholesterol metabolism.
  Thrombosis Journal 08/2012; 10(1):16.
• Article: Platelet-dependent thrombography gives a distinct pattern of in vitro thrombin generation after surgery with cardio-pulmonary bypass: potential implications.

  Rose Said, Véronique Regnault, Marie Hacquard, Jean-Pierre Carteaux, Thomas Lecompte
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  ABSTRACT: BACKGROUND: Bleeding remains a potentially lethal complication of cardio-pulmonary bypass (CPB) surgery. The purpose of this study was to obtain a better insight into in vitro thrombin generation in the context of CPB. METHODS: We used Calibrated Automated Thrombography to assess blood coagulation of 10 low-risk patients operated for valve replacement with CPB, under 2 experimental conditions, one implicating platelets as platelet dysfunction has been described to occur during CPB. RESULTS: Our main finding was that CPB-induced coagulopathy was differently appreciated depending on the presence or absence of platelets: the decrease in thrombin generation was much less pronounced in their presence (mean endogenous thrombin potential change values before and after CPB were -3.9% in the presence of platelets and -39.6% in their absence). CONCLUSION: Our results show that experimental conditions have a profound effect in the study of in vitro thrombin generation in the context of CPB.
  Thrombosis Journal 08/2012; 10(1):15.
• Article: 'A 12-month review of a modified protocol using low dose Dabigatran Etexilate in postoperative thromboembolic prophylaxis in joint replacement surgery'

  Padmanabhan Subramanian, Shanjitha Kantharuban, Sophie Shilston, Oliver J Pearce
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  ABSTRACT: BACKGROUND: Venous Thrombo-embolic disease is currently a hot topic especially in the UK. 25,000 patients per year die of Pulmonary Emboli (PE) in the United Kingdom (UK). Hip and knee arthroplasty surgery is associated with an increased rate of deep vein thrombosis (DVT) and pulmonary embolus (PE). The National Institute for Clinical Excellence (NICE) guidelines introduced in January 2010 recommended use of subcutaneous heparin or an oral anticoagulant (Dabigatran or Rivaroxiban) for 10-14 days post knee and 28-35 days post hip arthroplasty. In our unit we were keen on the advantages of an oral anticoagulant post arthroplasty in terms of patient compliance, and avoiding the need for self administered injection in the community. METHODS: We analysed all the notes, blood results and imaging of patients undergoing total hip or knee arthroplasty and present 1 year's data using a regime of subcutaneous Dalteparin whilst an inpatient, followed by discharge on oral Dabigatran at a low dose (150 mg once daily). RESULTS: There were 337 patients over 1 year with hip and knee arthroplasty, with a 1.19 % rate of DVT with no PEs and 1 death due to an unrelated cause. There was a transfusion rate of 11.57 % with 1.19 % patients taken back to theatre for evacuation of haematomas. There were no reported adverse effects of Dabigatran. CONCLUSION: Our treatment protocol is a novel practical approach for VTE prophylaxis in hip and knee replacement patients. This approach shows promising data but no definitive evidence to warrant wide-spread use of this new regime. This data can act as a foundation for larger randomised clinical trials.
  Thrombosis Journal 08/2012; 10(1):14.
• Article: Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population.

  Karthick Rajendran, Nalini Devarajan, Manohar Ganesan, Malathi Ragunathan
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  ABSTRACT: Obesity, characterised by increased fat mass and is currently regarded as a pro-inflammatory state and often associated with increased risk of cardiovascular diseases (CVD) including Myocardial infarction. There is an upregulation of inflammatory markers such as interleukin-6, interleukin-6 receptor and acute phase protein CRP in Acute Myocardial Infarction (AMI) patients but the exact mechanism linking obesity and inflammation is not known. It is of our interest to investigate if serum leptin (ob gene product) is associated with AMI and correlated with inflammatory proteins namely Interleukin-6 (IL-6) and high sensitivity - C reactive protein (hs-CRP). Serum leptin levels were significantly higher in AMI patients when compared to Non-CVD controls. IL-6 and hs-CRP were also elevated in the AMI group and leptin correlated positively with IL-6 and hs-CRP. Incidentally this is the first report from Chennai based population, India. The strong correlation between serum levels of leptin and IL-6 implicates an involvement of leptin in the upregulation of inflammatory cytokines during AMI. We hypothesise that the increase in values of IL-6, hs-CRP and their correlation to leptin in AMI patients could be due to participation of leptin in the signaling cascade after myocardial ischemia.
  Thrombosis Journal 08/2012; 10(1):13.
• Article: Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment.

  Vibeke Bratseth, Alf-Åge R Pettersen, Trine B Opstad, Harald Arnesen, Ingebjørg Seljeflot
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  ABSTRACT: BACKGROUND: Cardiovascular disease with disturbances in the haemostatic system, might lead to thrombotic complications with clinical manifestations like acute myocardial infarction (AMI) and stroke. Activation of the coagulation cascade with subsequent increased thrombin generation, characterizes a prothrombotic phenotype. In the present study we investigated whether prothrombotic markers were associated with risk factors and clinical subgroups in a cohort of patients with angiographically verified coronary artery disease (CAD). The patients were randomized to long-term treatment with the antiplatelet drugs aspirin or clopidogrel, and we further investigated the effect on hypercoagulability of such treatment for 1 year, of which limited data exists. METHODS: Venous blood samples were collected in fasting condition between 08:00 and 10:30 am, at baseline when all patients were on aspirin therapy (n = 1001) and in 276 patients after 1 year follow-up on aspirin or clopidogrel. In vivo thrombin generation was assessed by prothrombin fragment 1 + 2 (F1+2) and D-dimer, and the endogenous thrombin potentiale (ETP) in the calibrated automated thrombogram (CAT) assay, representing ex vivo thrombin generation. In addition soluble tissue factor (sTF) and free- and total tissue factor pathway inhibitor (TFPI) were measured. RESULTS: We found age to be significantly associated with F1+2 and D-dimer (beta = 0.229 and beta =0.417 respectively, p <0.001, both). Otherwise, only weak associations were found. F1+2 and D-dimer were higher in women compared to men (p <0.001 and p = 0.033, respectively). Smokers had elevated levels of ETP compared to non-smokers (p = 0.014). Additionally, patients on renin-angiotensin system (RAS) inhibition showed significantly higher levels of F1+2, compared to non-users (p = 0.013). Both aspirin and clopidogrel reduced levels of ETP after 12 months intervention (p = 0.003 and p <0.001, respectively) and the levels of F1+2 were significantly more reduced on aspirin compared to clopidogrel (p = 0.023). CONCLUSIONS: In the present population of stable CAD, we could demonstrate a more hypercoagulable profile among women, smokers and patients on RAS medication, assessed by the prothrombotic markers F1+2, D-dimer and ETP. Long-term antiplatelet treatment with aspirin alone seems to attenuate thrombin generation to a greater extent than with clopidogrel alone. The study is registered at www.clinicaltrials.gov: NCT00222261.
  Thrombosis Journal 08/2012; 10(1):12.