Blood Coagulation and Fibrinolysis (BLOOD COAGUL FIBRIN)

Publications in this journal

• Article: Hypofibrinogenemia, dysfibrinogenemia or hypodysfibrinogenemia? : Comment on 'The dilemma of inherited dysfibrinogenemia during pregnancy'

  Oo TH
  Blood Coagulation and Fibrinolysis 03/2013; 24(3):353-4.
• Article: Cardioversion safety in patients with non-valvular atrial fibrillation: which patients can be spared transesophageal echocardiography?

  Rui Providência, Ana Faustino, Luís Paiva, Joana Trigo, Ana Botelho, José Nascimento, A.M. Leitão-Marques
  Blood Coagulation and Fibrinolysis 07/2012;
• Article: Reviewed diagnosis of primary and secondary immune thrombocytopenic purpura in 79 adult patients hospitalized in 2000–2002

  Lorenzo Cirasino, Anna M Robino, Marco Cattaneo, Pietro E Pioltelli, Enrico M Pogliani, Enrica Morra, Paola Colombo, Giancarlo A Palmieri
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  ABSTRACT: Despite the accepted distinction between primary and secondary immune thrombocytopenic purpura (ITP), a systematic analysis of the incidence of secondary ITP is not available. The present study was aimed at verifying the frequency and, consequently, the approximate rates of prevalence and incidence of secondary ITP and analysing its clinical and laboratory characteristics in patients needing ordinary hospital treatment for ITP. The study was based on 79 consecutive, adult ITP patients admitted to three Italian hospitals in 2000–2002. Using data collected in a previous study on the appropriateness of hospital management of ITP, we evaluated the frequency of secondary ITP, with the diagnosis formulated on the basis of new acquisitions, derived its rates of prevalence and incidence, and examined the available clinical and laboratory parameters. At our case review, a diagnosis of secondary ITP could be formulated in 38% of the 79 patients. This frequency was significantly higher than that determined at the time the patients were discharged from hospital (13.9%) (P = 0.000). The derived rates of prevalence and incidence of secondary ITP in the general population were, respectively, 2.3 and 1.23 per 100 000 inhabitants per year. In comparison with patients with primary ITP, those with a secondary form more frequently had spleen enlargement (P = 0.000), hepatomegaly (P = 0.001) and lower haemoglobin values (P = 0.005). The high frequency of secondary ITP must be mainly attributed to the currently available knowledge about the nature of some forms of ITP. Particular contributors to the high frequency were cases secondary to infections and those observed in patients who had undergone bone marrow or solid organ transplantation. Some clinical and laboratory alterations appear to be more frequent in secondary ITP than in primary ITP. However, the importance that the identification of particular forms of ITP, such as those secondary to Helicobacter pylori or hepatitis C virus infections, has on the choice of treatment suggests that these conditions must be ascertained independently of the presence or absence of clinical and laboratory alterations.
  Blood Coagulation and Fibrinolysis 12/2010; 22(1):1–6.
• Article: Anticoagulant and fibrinogenolytic properties of the venom of Polybia occidentalis social wasp

  Paula G Czaikoski, Danilo L Menaldo, Silvana Marcussi, Anne LC Baseggio, André L Fuly, Rafael C Paula, Andreza U Quadros, Pedro RT Romão, Maria LT Buschini, Fernando Q Cunha, Andreimar M Soares, Marta C Monteiro
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  ABSTRACT: Previous studies have shown that venoms of social wasps and bees exhibit strong anticoagulant activity. The present study describes the anticoagulant and fibrinogen-degrading pharmacological properties of the venom of Polybia occidentalis social wasp. The results demonstrated that this venom presented anticoagulant effect, inhibiting the coagulation at different steps of the clotting pathway (intrinsic, extrinsic and common pathway). The venom inhibited platelet aggregation and degraded plasma fibrinogen, possibly containing metal-dependent metalloproteases that specifically cleave the Bβ-chain of fibrinogen. In conclusion, fibrinogenolytic and anticoagulant properties of this wasp venom find a potential application in drug development for the treatment of thrombotic disorders. For that, further studies should be carried out in order to identify and isolate the active compounds responsible for these effects.
  Blood Coagulation and Fibrinolysis 09/2010; 21(7):653–659.
• Article: Discrepancy in factor VIII 1-stage/2-stage activity in a child with Arg531 -> His mutation

  Shriram V Nath, Vaughan K Williams, Adrian B Griffiths, Tamas Revesz
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  ABSTRACT: Routine screening of infants born to known hemophilia carriers includes a factor VIII (FVIII) level. In routine practice, mild FVIII deficiency variants may be missed by laboratories that exclusively use a one-stage activated partial thromboplastin time-based activity assay. This case illustrates such a possibility with a discrepancy between the one-stage and two-stage assays performed on a child who carries the Arg531 → His mutation.
  Blood Coagulation and Fibrinolysis 06/2010; 21(5):474–475.
• Article: Shortened activated partial thromboplastin time: causes and management

  Giuseppe Lippi, Gian Luca Salvagno, Luigi Ippolito, Massimo Franchini, Emmanuel J Favaloro
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  ABSTRACT: Throughout the long history of the hemostasis laboratory, and as an evaluation of the coagulation cascade, the results of the activated partial thromboplastin time (APTT) have primarily been considered as an index of loss-of-function and rarely as an index of gain-of-function. Nevertheless, there are now several clinical and technical reasons that no longer allow us to simply ignore or overlook shortened APTTs in laboratory practice. It has long been suspected that the leading cause of shortened APTTs are related to preanalytical problems, in which case it would be inappropriate for a laboratory to issue such a test result, which would expectedly not adequately mirror the patient's true condition. Should such artifactual results be reliably ruled out, that is by confirming short APTT values on subsequent samples, it would then be worth considering to troubleshoot potential causes, inasmuch as this phenomenon may reflect a variety of clinically meaningful conditions, including an increased risk of thromboembolic events, cancer, myocardial infarction, thyroid disorders, diabetes, and pregnancy. Although there are no univocal data supporting the origin of this singular phenomenon as yet, we strongly encourage the utility of postanalytical laboratory guidance, including a relevant short accompanying comment in the laboratory report linked to the APTT test result, for example, noting ‘Short APTT–potentially reflective of in-vitro activation of blood coagulation due to difficult collection. If the value is systematically confirmed in subsequent samples, please contact the laboratory to help assess the cause’.
  Blood Coagulation and Fibrinolysis 06/2010; 21(5):459–463.
• Article: Severe bleeding in a woman heterozygous for the fibrinogen [gamma]R275C mutation

  Chantelle M Rein, Brian L Anderson, Morgan M Ballard, Christopher M Domes, Joshua M Johnston, Russell Jared Jr Madsen, Kathryn KM Wolper, Andrew S Terker, John M Strother, Thomas G Deloughery, David H Farrell
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  ABSTRACT: The dysfibrinogen γR275C can be a clinically silent mutation, with only two out of 17 cases in the literature reporting a hemorrhagic presentation and four cases reporting a thrombotic presentation. We describe here a particularly severe presentation in 54-year-old female patient who required a hysterectomy at 47 years of age due to heavy menstrual bleeding. Coagulation studies revealed a prolonged prothrombin time and thrombin time, a normal fibrinogen antigen level, and a low fibrinogen activity level. Molecular analysis of the patient's DNA revealed a γ chain gene mutation resulting in an amino acid substitution at residue 275 (γR275C). Protein sequencing of the fibrinogen γ chain confirmed this mutation, which was named Fibrinogen Portland I. This case demonstrates that the γR275C mutation can lead to a severe hemorrhagic phenotype.
  Blood Coagulation and Fibrinolysis 06/2010; 21(5):494–497.
• Article: Recombinant-activated factor VII for control and prevention of hemorrhage in nonhemophilic pediatric patients

  Ampaiwan Chuansumrit, Sumate Teeraratkul, Suthep Wanichkul, Suporn Treepongkaruna, Nongnuch Sirachainan, Samart Pakakasama, Pracha Nuntnarumit, Suradej Hongeng, the rFVIIa Study Group
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  ABSTRACT: A total of 108 episodes among 103 nonhemophilic pediatric patients (nine newborns, 16 infants and 78 children) treated with recombinant factor-activated VII (rFVIIa) were evaluated retrospectively. These episodes were divided into two groups: group 1 included 86 occurrences for hemorrhagic control of ongoing massive bleeding due to thrombocytopenia and coagulopathy unresponsive to blood component therapy in patients with dengue hemorrhagic fever, life-threatening, intraoperative and postoperative bleeding; group 2 included 22 episodes for prevention of hemorrhage with invasive procedures in patients with chronic liver disease and associated coagulopathy, and patients without preexisting hemostatic disorder but at high risk due to their underlying diagnosis and required surgical intervention. The effective control of hemostasis response rate in group 1 was significantly lower than in group 2. The median total dose per kilogram of rFVIIa group 1 was twice that of group 2. The overall case-fatality rate related to bleeding or underlying conditions was 31.1% (32/103). Adverse events were observed in three patients (2.9%) receiving rFVIIa for control of intraoperative and postoperative bleeding in the setting of corrective cardiac surgery. These results support the safety and potential benefit of rFVIIa for control and prevention of hemorrhage in pediatric patients without congenital hemophilia.
  Blood Coagulation and Fibrinolysis 05/2010; 21(4):354–362.
• Article: Effects of acidosis, alkalosis, hyperthermia and hypothermia on haemostasis: results of point of care testing with the thromboelastography analyser

  Albert JDWR Ramaker, Peter Meyer, Jan van der Meer, Michel MRF Struys, Ton Lisman, Wim van Oeveren, Herman GD Hendriks
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  ABSTRACT: In this study we assessed the effects of changes in pH, temperature, and their combination in whole blood on thromboelastographic variables. Blood was collected from six healthy volunteers. Thromboelastograph (TEG series 5000; Haemoscope Corporation, Illinois, USA) channels were set at temperatures of 32, 37, and 39°C and each was filled with artificially acidified, alkalified, and neutral blood, respectively. Acidification (pH 6.95) significantly impairs thromboelastographic variables reaction time r (from 23.3 to 33.7 min; P = 0.0280), kinetic time k (from 8.7 to 16.1 min; P = 0.028), angle α (from 24.3° to 13.8°; P = 0.028), prothrombin time (from 11.4 to 12.1 s; P = 0.044), and activated partial thromboplastin time (from 29.3 to 45.0 s; P = 0.028). A temperature drop from 37 to 32°C in blood of neutral pH significantly impaired k (from 8.7 to 10.2 min; P = 0.028) and α (from 24.3° to 21.0°; P = 0.027), whereas maximum amplitude ma significantly increased (from 46.5 to 52.5 mm; P = 0.027). A temperature rise from 37 to 39°C at pH 7.37 did not affect any of the TEG variables. Artificial alkalization (pH 7.68) at a temperature of 37°C had no effect on any of the measured variables. Acidosis causes a significant impairment of clot formation and clot strength. Hypothermia had the same effects, but to a lesser extent. These findings emphasize the need for correction of acidosis and hypothermia to normalize haemostasis.
  Blood Coagulation and Fibrinolysis 08/2009; 20(6):436-439.
• Article: Erythrocyte folate and 5-methyltetrahydrofolate levels decline during 6 months of oral anticoagulation with warfarin

  Agata Sobczynska-Malefora, Dominic J Harrington, Miranda CE Lomer, Claire Pettitt, Sophie Hamilton, Savita Rangarajan, Martin J Shearer
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  ABSTRACT: Dietary fluctuations of vitamin K are detrimental to oral anticoagulant control. Attempts to improve control through the avoidance of vitamin K-rich foods (mainly green vegetables) may inadvertently compromise folate status, itself a risk factor for thromboembolism. We evaluated the effect of a 6-month period of warfarin therapy on folate status in 114 patients using measurements of red-cell folate and 5-methyltetrahydrofolate and plasma folate and total homocysteine. Circulatory levels of phylloquinone, vitamin B12 and methylmalonic acid were also determined. A subset of 45 patients completed 7-day food diaries at the beginning and end of their treatment. There was a significant decrease in total erythrocyte folate (P = 0.005) and 5-methyltetrahydrofolate (P = 0.002) during the study. A concurrent increase in plasma phylloquinone (P = 0.003) was attributed to warfarin-induced perturbation of vitamin K metabolism. No other longitudinal changes were observed. Folate and phylloquinone intakes correlated with each other at baseline (P = 0.024) and after treatment (P = 0.011). Based on robust measurements of erythrocyte folates, patients showed a significant impairment in folate status after 6-month therapy with warfarin. The majority of patients had intakes of folate and phylloquinone below the national average or UK guidelines. The study highlights the need for improved dietary management of patients taking oral anticoagulants.
  Blood Coagulation and Fibrinolysis 05/2009; 20(4):297-302.
• Article: Anaphylaxis in patients with congenital bleeding disorders and inhibitors

  Massimo Franchini, Giuseppe Lippi, Martina Montagnana, Giovanni Targher, Marco Zaffanello, Gian Luca Salvagno, Gianna Franca Rivolta, Caterina Di Perna, Annarita Tagliaferri
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  ABSTRACT: Anaphylactic reactions are rare emergencies observed in patients with inherited bleeding disorders. When these adverse events occur in patients with inhibitors, they further complicate the management of an already challenging clinical situation. Anaphylactoid inhibitors have been reported in patients with inhibitors associated with hemophilia A, hemophilia B, and type 3 von Willebrand disease. In this review, we summarize the current literature data on the occurrence of anaphylactoid reactions in patients with inherited bleeding disorders and alloantibodies. In particular, we focus on the pathophysiology of the inhibitor development and its management.
  Blood Coagulation and Fibrinolysis 05/2009; 20(4):225-229.
• Article: Epidemiological survey of haemophiliacs with inhibitors in France: orthopaedic status, quality of life and cost - the 'Statut Orthopedique des Patients Hemophiles' avec Inhibiteur study

  Natalie Stieltjes, Marie F Torchet, Laure Misrahi, Valérie Roussel-Robert, Thierry Lambert, Claude Guérois, Marie A Bertrand, Marie E Briquel, Annie Borel-Derlon, Gérard Dirat
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  ABSTRACT: The physical condition of severe haemophilia and the impact of advances in replacement therapy have been much studied, but little work has been done on patients who developed inhibitors. The 'Statut Orthopédique des Patients Hémophiles avec Inhibiteur' study was conducted in France in order to assess the orthopaedic status and quality of life of such patients, and the cost of their medical management. Fifty haemophiliacs aged 12-63 years with a history of high-responder inhibitors were included. Clinical assessment showed that only 12% of the patients had a nil pain score and 2% a nil clinical score, as per Gilbert scale. The mean clinical score was significantly higher in patients over 35 years of age than in younger ones. However, younger patients appeared to have a more impaired orthopaedic status than young haemophiliacs without inhibitors of similar age in previous published cohorts. Surprisingly, older haemophiliacs tended to have the best mental quality of life, contrasting with their highly impaired orthopaedic condition and physical quality of life. The mean cost of clinical resources consumed during the year preceding enrolment was €268 999, 99% of which was related to clotting factor. Marked between-patient differences in cost were noted. Our study suggests that the management of haemophiliacs with inhibitors should be improved in order to prevent haemophilic arthropathy to an extent similar to that of patients without inhibitors. Cost-benefit assessment of any therapeutic strategy should always be combined with quality-of-life evaluation.
  Blood Coagulation and Fibrinolysis 12/2008; 20(1):4-11.
• Article: Thrombotic thrombocytopenic purpura in a patient with very early pregnancy: clinical presentation and autopsy findings.

  Aman Sharma, Bishan Radotra, Ajay Wanchu, Pankaj Malhotra, Surjit Singh, Subhash Varma
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  ABSTRACT: Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy leading to microvascular occlusion resulting in ischemic dysfunction of various organs. Pregnancy has been thought to precipitate it during second and third trimester, but its reports in first trimester are extremely rare. We report the clinical protocol of a young lady with 5-week period of gestation, who presented with fever, seizures and altered sensorium, and succumbed to her illness during an episode of seizure. Complete autopsy findings are also presented in detail.
  Blood Coagulation and Fibrinolysis 11/2008; 19(7):727-30.
• Article: Extensive venous thrombosis following administration of high-dose glucocorticosteroids and tranexamic acid in relapsed Evans syndrome.

  Robert Escher
  Blood Coagulation and Fibrinolysis 11/2008; 19(7):741-2.
• Article: Structural homology of HIV-1 GP41 and human platelet glycoprotein GPIIIa.

  Viroj Wiwanitkit
  Blood Coagulation and Fibrinolysis 11/2008; 19(7):739-740.
• Article: Platelet GPIIb/IIIa receptor: how prone to mutation?

  Viroj Wiwanitkit
  Blood Coagulation and Fibrinolysis 11/2008; 19(7):740-741.
• Article: Vasopressin acts on platelets to generate procoagulant activity.

  Marian Tomasiak, Halina Stelmach, Tomasz Rusak, Michał Ciborowski, Piotr Radziwon
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  ABSTRACT: The aim of our study was to examine whether arginine vasopressin (AVP) is able to evoke in human platelets a procoagulant response due to activation of an Na+/H+ exchanger. It was found that treatment of platelets with AVP (20-100 nmol/l) results in generation of a weak calcium signal, activation of Na+/H+ exchanger, aggregation, and development of a procoagulant response. The AVP-evoked procoagulant response was dose and time dependent, weaker than that produced by collagen or monensin (mimics Na+/H+ exchanger), and less pronounced following the inhibition of Na+/H+ exchanger by 5-(N-ethyl-N-isopropyl) amiloride or genistein. Flow cytometry studies reveal that in-vitro platelet treatment with AVP results in an unimodal left shift in the forward and side scatter of the entire platelet population, indicating morphological changes on the plasma membrane. The shift was dose related, weaker than that evoked by collagen, similar to that produced by monensin and strongly reduced in the presence of 5-(N-ethyl-N-isopropyl) amiloride or genistein. Using flow cytometry, we demonstrated enhanced expression of phosphatidylserine on the AVP-treated platelets. AVP-evoked phosphatidylserine exposure was dose dependent, inhibited by 5-(N-ethyl-N-isopropyl) amiloride or genistein and weaker than that produced by collagen. AVP in a dose-dependent manner produced a rise in platelet volume. The swelling was inhibited by 5-(N-ethyl-N-isopropyl) amiloride, and its kinetics was similar to that observed in the presence of monensin. We conclude that prolonged treatment of platelets with AVP results in a procoagulant response, which may occur as a consequence of Na+ influx mediated by Na+/H+ exchanger.
  Blood Coagulation and Fibrinolysis 11/2008; 19(7):615-24.
• Article: Effect of platelet count on secretion capacity: formulization and use of the formulae for evaluation of platelet secretion in thrombocytopenic patients.

  Yahya Buyukasik, Hakan Goker, Naciye S Buyukasik, Nilgun Sayinalp, Ibrahim C Haznedaroglu, Osman I Ozcebe
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  ABSTRACT: The correlation between platelet count and bleeding time is nonlinear. The bleeding time prolongs more prominently as platelet count decreases toward 10 000 microl(-1); however, it becomes stable near 100 000 microl(-1). Clinical observations suggest that platelet functional capacity may also play a role in bleeding complications during thrombocytopenia. However, no routine method has been described for evaluation of platelet function during thrombocytopenia. To test if platelet functional capacity is affected by the cell count, as suggested by the platelet count-bleeding time correlation. To evaluate lumiaggregometry as a possible tool for studying platelet functions and prediction of bleeding in thrombocytopenic patients. Collagen-induced ATP release was studied in different dilutions of 22 healthy platelet-rich plasmas. The relationship between platelet count and ATP release was formulized. ATP release was also tested in 24 thrombocytopenic (10 000-50 000 microl(-1). ) patients, and the results were compared with expected levels derived from the formulae. ATP release increased in a cubic fashion as platelet count elevated. ATP secretion values were within normal limits or increased in patients with idiopathic thrombocytopenic purpura. However, some patients with megakaryocyte deficiency had a secretion defect. ATP secretion was decreased in four out of seven patients with bleeding symptoms compared with no persons without bleeding (P = 0.003). Platelet functional capacity is affected by the cell count. Lumiaggregometry is potentially useful in evaluating platelet functions during thrombocytopenia.
  Blood Coagulation and Fibrinolysis 11/2008; 19(7):633-7.
• Article: Practical approach to anticoagulation for cardiopulmonary bypass in the patient with congenital prolonged activated partial thromboplastin time.

  Lana Cankovic, Brad L Steenwyk, David C McGiffin, Vance G Nielsen
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  ABSTRACT: Patients with rare, congenital deficiencies of contact proteins (e.g., factor XII, prekallikrein, high-molecular-weight kininogen) present an important challenge with regard to safe anticoagulation during cardiopulmonary bypass. Specifically, activated coagulation time values are obtained with devices that utilize contact protein activators to generate thrombin and assess the efficacy of heparin-mediated antithrombin activation, with an activated coagulation time value of 480 s considered 'safe'. Patients with contact protein deficiencies will routinely have activated coagulation time values that exceed normal baseline values to an unpredictable extent, which, when coupled with heparin administration may well exceed 480 s but still potentially not reflect adequate antithrombin activation. We present the successful management of anticoagulation of a patient with either a prekallikrein or kininogen deficiency during cardiopulmonary bypass for coronary artery bypass graft surgery with Hepcon-based heparin concentration determinations. This approach, and the other alternatives previously mentioned, can be utilized to safely care for these rare patients in the setting of cardiac surgery.
  Blood Coagulation and Fibrinolysis 11/2008; 19(7):725-6.
• Article: Comparative gene expression profiling in three primary human cell lines after treatment with a novel inhibitor of Rho kinase or atorvastatin.

  Marjan Boerma, Qiang Fu, Junru Wang, David S Loose, Alessandra Bartolozzi, James L Ellis, Sharon McGonigle, Elsa Paradise, Paul Sweetnam, Louis M Fink, Marie-Catherine Vozenin-Brotons, Martin Hauer-Jensen
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  ABSTRACT: Inhibitors of Rho kinase (ROCK) are a relatively new class of drugs with potential benefits in oncology, neurology, and fibrotic and cardiovascular diseases. ROCK inhibitors modulate many cellular functions, some of which are similar to the pleiotropic effects of statins, suggesting additive or synergistic properties. Studies to date have used compounds that inhibit both isoforms of ROCK, ROCK1 and ROCK2. This study was designed to compare gene expression profiles of atorvastatin with the newly developed ROCK2 inhibitor SLx-2119 in primary cultures of normal human endothelial cells, smooth muscle cells, and fibroblasts. Cells were treated with each compound for 24 h, after which total RNA was isolated and genome-wide gene-expression profiles were obtained with Illumina arrays. Because of the known effect of statins on the actin cytoskeleton and on connective tissue growth factor, a prominent growth factor involved in tissue fibrosis, the effects of SLx-2119 and atorvastatin on the actin cytoskeleton and connective tissue growth factor mRNA were also examined in cultures of smooth muscle cells with a fibrotic phenotype, isolated from biopsies of human intestine with radiation-induced fibrosis. Although SLx-2119 and atorvastatin affected expression of genes belonging to the same biological processes, individual genes were mostly different, consistent with synergistic or additive properties. Both SLx-2119 and atorvastatin reduced connective tissue growth factor mRNA and remodeled the actin cytoskeleton in fibrosis-derived smooth muscle cells, suggesting that both compounds have antifibrotic properties. These results form the basis for further studies to assess the possible therapeutic benefit of combined treatments.
  Blood Coagulation and Fibrinolysis 11/2008; 19(7):709-18.