bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Fibronectin, Vitronectin, and Leptin Levels in Coronary Artery Disease: Impacts on Thrombosis and Thrombolysis
Authors: Ekmekci Hakan , Ekmekci Ozlem B. , Sonmez Huseyin , Ozturk Zeynep , Domanic Nergiz , Kokoglu Emine
Published: March 2006

In this study, the levels of fibronectin, vitronectin, leptin, tissue plasminogen activator (t-PA), and lipid parameters were investigated in patients with coronary artery disease (CAD) and control group. The average plasma fibronectin levels in CAD patients group were significantly higher compared with the control group (p=0.006). Moreover, in patients with triple-vessel disease, plasma fibronectin levels were found to be significantly higher than those in the control group (p<0.05). Plasma vitronectin levels in patients with CAD were found to be significantly higher than those in the control group (p=0.000). In addition, in patients with double vessel disease plasma vitronectin levels were significantly higher than no vessel disease and control group, triple vessel disease was significantly higher as compared with no vessel disease, single vessel disease, and control group (p<0.05). We could not find any significant differences in t-PA values between CAD patients and control group. On the other hand, the avarage leptin levels in the group of patients were higher than those in the control group but there were no statistically significant differences found between them (p>0.05) because of high SD values. There was strong (+) correlation between fibronectin, vitronectin, and severity of disease [vitronectin/severity of disease, r = 0.5074 (p = 0.000), fibronectin/severity of disease, r = 0.2971 (p = 0.007)]. In conclusion, we can say that fibronectin and vitronectin have become greatly important in pathogenesis of coronary artery disease. High leptin levels may be contribute to platelet aggregation in patients with coronary artery disease. But, elevated serum levels of leptin cannot be useful diagnostic and monitoring markers in patients with coronary artery disease.
Evaluation of New Japanese Diagnostic Criteria for Disseminated Intravascular Coagulation in Critically Ill Patients
Authors: Gando Satoshi , Wada Hideo , Asakura Hidesaku , Iba Toshiaki , Eguchi Yutaka , Okamoto Kohji , Ohtomo Yasuhiro , Kawasugi Kazuo , Koga Shin , Koseki Kazuhide , Tsuji Hajime , Mayumi Toshihiko , Murata Atsuo , Nakagawa Masao , Endo Shigeatu
Published: March 2006

New Japanese diagnostic criteria were prepared for disseminated intravascular coagulation (DIC) in critically ill patients and their usefulness was compared with the criteria of the International Society of Thrombosis and Haemostasis (ISTH) and those of the Japan Ministry of Health and Welfare (JMHW). In a retrospective study of patients with platelet counts of less than 150 × 103/mL, 52 cases (33.3%), 66 cases (42.3%), and 101 cases (64.7%) were diagnosed as DIC by the ISTH, JMHW, and new Japanese DIC criteria, respectively. The DIC state as diagnosed by the new Japanese DIC criteria included both DIC states as diagnosed by ISTH or JMHW criteria. Some DIC states diagnosed by the JMHW criteria included those diagnosed by ISHT criteria but this was not universal. The mortality of DIC as diagnosed by the ISTH or JMHW criteria was markedly high, compared to that for DIC diagnosed by the new Japanese criteria. The mortality of patients without DIC by ISTH was also high when they were diagnosed as DIC by the new Japanese criteria. The frequency of DIC by each set of diagnostic criteria was significantly higher in patients with infection than in those without infection. The mortality of DIC by each set of diagnostic criteria was significantly higher in patients with infection than in those without infection, and the mortality of overt-DIC by ISTH diagnostic criteria was also high in patients without infection.
Platelet Function and Fibrinolytic Activity in Patients with Bronchial Asthma
Authors: Tutluoglu Bülent , Gurel Cigdem Bayram , Ozdas Sule Beyhan , Musellim Benan , Erturan Serdar , Anakkaya A. Nihat , Kılınc Günseli , Ulutin Turgut
Published: March 2006

Platelets have the capacity to release mediators with potent inflammatory or anaphylactic properties. Platelet factor-4 (PF4) and beta-thromboglobulin (BTG) are two of these mediators. On the other hand, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) are two important mediators of fibrinolysis. Both mediators are secreted mainly by vascular endothelium. Plasma levels of PF4, BTG, PAI-1, and tPA may show changes in chronic inflammatory diseases such as asthma. This study examined the role of thrombocytes and the function of the endothelium ın asthmatic patients during an attack and during a stable phase. Eighteen patients with known allergic asthma who came to our emergency department with an asthma attack and 14 control subjects were included in the study. Blood samples were taken after starting therapy with salbutamol inhalation. Lung function tests were performed after receiving the first emergency therapy for asthma. Plasma levels of PF4, BTG, PAI-1, tPA were determined before starting steroid therapy and after receiving 1 week of steroid therapy. Plasma levels of PF4 among patients with an asthma attack were significantly higher than those of controls (150.5±8.92 IU/mL vs. 92.5±7.63 IU/mL, p<0.001). A further increase in plasma PF4 levels was detected after steroid therapy (163.5±9.16 IU/mL). Plasma BTG levels of patients on admission were not statistically different from those in the control group (140.4±6.34 IU/mL vs. 152.2±8.71 IU/mL). An increase was detected after therapy (171.6±7.27 IU/mL) and post-treatment plasma levels were statistically meaningful versus the controls. Plasma levels of tPA and PAI were statistically higher than those in controls in asthmatic patients on admission (6.01±2.72 vs. 5.4±2.3 ng/mL for tPA and 75.2±27.2 ng/mL vs. 32.7±14.3 ng/mL for PAI-1). Further increases were detected in two parameters after 1 week of therapy with steroids (tPA levels were 6.85±2.96 ng/mL and PAI-1 levels were 83.5±29.6 ng/mL). There seems to be an increased activity of platelets during an asthma attack. Elevated PAI-1 and tPA levels may also indicate the activated endothelium in asthma. Increases of plasma levels of PAI-1 and tPA after steroid therapy need further investigation because elevated PAI-1 levels enhance airway remodeling.
Polymorphonuclear Leukocyte Integrinsin Deep Venous Thrombosis
Authors: Caimi G. , Canino B. , Ferrara F. , Montana M. , Presti R. Lo
Published: March 2006

The polymorphonuclear leukocytes (PMN) have a role in the pathophysiology of deep venous thrombosis (DVT). We examined the phenotypical expression of PMN beta2-integrins (CD l l a, CDl l b, CD 11c) in a group of 19 subjects with leg DVT. PMN cells were incubated with fluorescent monoclonal antibodies against CD11a, CD11b, CD11c, and the evaluation was made by flow cytofluorimetry. The same integrins were determined after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA) and N-formylmethionyl-leucyl-phenylalanine (fMLP). In DVT subjects, at baseline, the phenotypical expression of CD11b was decreased and that of CD11c increased when compared with normal controls. In normal subjects PMN activation with PMA and fMLP led to a constant increase of all PMN adhesion molecules, while in DVT subjects the CDl l a did not show any change. These data might have therapeutical ap plications, especially with the aim of preventing post-thrombotic deterioration of vein function.
Argatroban Treatment for Patients with Intoleranceto Heparin and Hirudin
Authors: Kemkes-Matthes Bettina , Walenga Jeanine M. , Harenberg Job , Fareed Jawed
Published: March 2006

Argatroban is a synthetic thrombin inhibitor that acts independently of any cofactor. It inhibits free as well as fibrin- and clot-bound thrombin. The clinical history of two patients is presented, both with previous allergic reactions toward heparin and hirudin. In both patients, antibodies against hirudin were documented. Argatroban was successfully used in both patients without any side effects. We conclude argatroban to be the drug of choice in patients with intolerance to heparin and hirudin. Moreover, genetic variations affecting the hepatic catabolism of argatroban might exist, because very different dosages of argatroban were needed in the two patients.
Genetics of Platelet Glycoprotein Receptors: Risk of Thrombotic Events and Pharmacogenetic Implications
Authors: Mikkelsson Jussi , Perola Markus , Karhunen Pekka J.
Published: March 2006

Platelet aggregation and coronary thrombosis have a central role in the development of acute coronary syndromes and myocardial infarction (MI). Therapies aimed at inhibiting platelet aggregation have shown great benefit in individuals with coronary disease or with multiple risk factors for coronary disease. Genetic variation in platelet surface receptors mediating thrombus formation has been suggested to be associated with platelet hyperreactivity, with increased risk of MI and possibly with the benefit received from various antithrombotic drug treatments. This review focuses on discrepancies and their likely explanations in studies on platelet glycoprotein genetics. Current knowledge on important issues concerningcoronary event phenotypes and pharmacogenetics is analyzed. Possible future applicability of these data to patient treatment isalso discussed.
High-dose Intravenous Dalteparin Can be Monitored Effectively Using Standard Coagulation Times
Authors: Wilson James M. , Gilbert Jerry , Harlan Mary , Bracey Arthur , Allison Paul , Schooley Chad , Pinto Kathleen
Published: March 2006

The objective of this study was to examine the pharmacokinetics of intravenous dalteparin (Fragmin, Pharmacia-Upjohn, Peapack, NJ) and to assess the accuracy of standard coagulation-based monitoring techniques as an estimate of drug concentration with which to guide dosing. Knowledge of the kinetic behavior of low-molecular-weight heparins (LMWHs) and the possible utility of coagulation times for monitoring may aid in the development of safe and effective dosing algorithms for percutaneous coronary interventions. Twenty normal volunteers were treated at 2-week intervals with each of three intravenous dalteparin doses. Measurement of anti-IIa, anti-Xa, activated partial thromboplastin time (aPTT), activated clotting time (ACT), and low-range ACT was performed at baseline and at seven additional time points over 8 hours. The half-life of intravenous dalteparin is 77 minutes with slight dose-related variation. The aPTT, LR-ACT, and standard ACT are prolonged after dalteparin administration with the increase closely correlated to anti-Xa activity (aPTT, r = 0.85; LR-ACT, r = 0.79). Classification of anticoagulation intensity range using aPTT or LR-ACT in comparison to anti-Xa activity (0.5-0.99, 1.0-1.49, 1.5-2, >2) displays a level of agreement (kappa: aPTT = 0.69, LR-ACT = 0.59) that is comparable to values reported for coagulation time guidance of unfractionated heparin administration. Standard coagulation times are sensitive to the anticoagulant effect of dalteparin with a degree of correlation that suggests their utility for estimating drug concentration during high dose therapy. Trials establishing a relationship between monitoring and clinical efficacy, and the risk/reward of different treatment ranges alone or in combination with GPIIb/IIIa inhibitors and clopidogrel, are necessary.
Effect of Antihypertensive Treatment on PlasmaFibrinogen and Serum HDL Levelsin Patients with Essential Hypertension
Authors: Papadakis John A. , Mikhailidis Dimitri P. , Vrentzos George E. , Kalikaki Antonia , Kazakou Irene , Ganotakis Emmanuel S.
Published: March 2006

The influence of hypertension, and its treatment, on circulating lipid and fibrinogen (Fib) concentrations in patients with essential hypertension was investigated. The lipid profile and Fib levels were measured in 353 patients (131 men) with essential hypertension. Their median age was 60 years (range: 18-85 years). All patients had normal results from liver, renal, and thyroid function tests. There were 162 patients (45.9%) who were not receiving antihypertensive treatment. Of the remaining patients, 117 were taking ‘lipid-hostile’ (β-blockers, thiazide diuretics) antihypertensives and 74 were taking ‘lipid-neutral’ (angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin-II receptor blockers) agents. Patients who were taking ‘lipid-hostile’ antihypertensive drugs had significantly higher plasma Fib concentrations when compared with those taking ‘lipid-neutral’ antihypertensives or those not receiving antihypertensive treatment. These differences were not attributable to established factors that influence plasma Fib levels, since when smokers and patients with diabetes mellitus and/or vascular disease were excluded, the difference remained significant. In addition, in these more homogeneous groups, patients receiving ‘lipid-neutral’ treatment had significantly higher serum high-density lipoprotein (HDL) cholesterol levels when compared with both those taking ‘lipid-hostile’ antihypertensives and untreated ones. There were no significant differences in the other lipid variables, independently of the presence/absence or the type of antihypertensives. These results suggest that antihypertensive drugs have additional effects, beyond lowering blood pressure, on other vascular risk factors, like Fib and HDL. These effects may depend on the type of drug used.
A Protocol for the Use of Enoxaparin During Pregnancy: Results from 85 Pregnancies Including 13 Multiple Gestation Pregnancies
Authors: Huxtable Lindsay M. , Tafreshi Mohammad J. , Ondreyco Sharon M.
Published: March 2006

Many practitioners consider low-molecular-weight heparin (LMWH) an alternative to unfractionated heparin, although there are limited safety data regarding maternal and fetal outcomes in patients using an LMWH during pregnancy. A retrospective chart review was performed on 72 patients with thrombophilia exposed to the LMWH, enoxaparin, during pregnancy. Eighty-five pregnancies resulted in 93 of 99 potential live births. Eleven of 12 twin pregnancies and one triplet pregnancy were successful. One preterm live birth infant of 33 weeks’ gestation did not survive. Three patients with thrombophilia spontaneously aborted. A patient receiving injectable fertility treatment had spontaneously aborted one twin at 5 weeks’ gestation. One patient terminated the pregnancy after discovering the presence of Down’s syndrome. The mean maximum dose required to achieve a therapeutic anti-Xa level of 0.2-0.4 IU/mL at 5 to 6 hours following administration, was 38.1 mg every 12 hours (median 35 mg, range 30-75 mg every 12 hours). The mean anti-Xa level was 0.28 IU/mL (median 0.3, range 0.05-0.8 IU/mL). A total of nine patients experienced bleeding events, two requiring discontinuation of enoxaparin for the remainder of the pregnancy. Two patients experienced injection site reactions requiring discontinuation of enoxaparin. Three patients developed preeclampsia, two placenta abruptio, and one placenta previa. No thromboembolic complications or osteoporotic fractures had occurred. Enoxaparin was safe and effective for preventing thromboembolism and adverse obstetrical complications in our patients, including 12 of 13 multiple gestation pregnancies.
Prevalence of Thromboembolic Disease IncludingSuperior Vena Cava and Brachiocephalic Veins
Authors: Oymak Fatma Sema , Buyukoglan Hakan , Tokgoz Bulent , Ozkan Metin , Tasdemir Kutay , Mavili Ertugrul , Gulmez Inci , Demir Ramazan , Ozesmi Mustafa
Published: March 2006

Thrombosis of the brachiocephalic veins or superior vena cava (SVC) is rare. This study was conducted to determine the prevalence and characteristics of thrombosis of brachiocephalic veins and SVC, and its association with symptomatic pulmonary embolism (PE). The prevalence of thrombosis involving the brachiocephalic veins and SVC was evaluated retrospectively at a university hospital during the 3-year period. Patients were identified by hospital records and review of computer-generated lists of of all venograms, contrast-enhanced chest computed tomography, and magnetic resonance angiograms of the upper extremity and SVC. Thrombosis of the brachiocephalic veins and SVC was diagnosed in 33 (0.03%) of 100,942 patients of all ages [(32 of 70,751 adult patients≥ 20 years; 0.04%)]. Twenty-three (70%) patients initially had secondary thrombosis with multiple risk factors: associated with malignancy in 14 (42%) patients, chronic disorders in 13 (39%) patients, central venous lines (CVL) and peripheral venous lines (PVL) in 9 (27%) patients, and thrombophilia in 10 (38%) of 26 patients. Swelling of the arm, head, and neck was present in 32 (97%) patients. Symptomatic PE developed before thrombosis being treated in 12 (36%) patients. All patients except eight (three, thrombolytic; five, thrombectomy) received anticoagulant therapy. Thrombosis of the SVC and brachiocephalic veins is an uncommon but serious complication in patients with malignancy, chronic disorders, CVL, PVL, and thrombophilia. Because it is important clinical problem with frequent PE, the patients with appropriate clinical findings should be diagnosed early with imaging tests and treated with anticoagulant drugs.
Clinicohematologic Spectrum in Patientswith Lupus Anticoagulant
Authors: Bhattacharya M. , Biswas A. , Kannan M. , Mishra P. , Kumar A. , Choudhry V. P. , Saxena R.
Published: March 2006

A retrospective analysis of clinicohematologic parameters of 25 patients with lupus anticoagulant was carried out. The hematologic tests included dilute Russel viper venom test (dRVVT), kaolin clotting time (KCT), activated partial thromboplastin time, and prothrombin time. The diagnosis of lupus anticoagulants was based on the presence of prolonged KCT/dRVVT, its absence of correction with normal plasma and correction by phospholipids. Specific factor assays and platelet aggregation studies were performed wherever required. Ten patients (40%) had thrombosis, which was venous in 5 (50%) and arterial in 4 (40%). One patient (10%) had both arterial and venous thrombosis and presented with catastrophic antiphospholipid syndrome. Eighteen female patients conceived. Four (22%) of these had recurrent first trimester abortion. Five (20%) patients had bleeding manifestations. One (4%) of these had hypoprothrombinemia and was diagnosed to have hypoprothrombinemia lupus anticoagulant syndrome. However in two of these patients, no cause of bleeding could be identified other than the presence of lupus anticoagulants. It is concluded that patients with lupus anticoagulant have a varied spectrum of hemostatic disorders. Bleeding may sometimes occur in these patients due to associated thrombocytopenia or associated factor inhibitors. Rarely, it may occur due to presence of lupus anticoagulants alone.
The Plasma Levels of Prostanoids and Plasminogen Activator Inhibitor-1 in Primary and Secondary Thrombocytosis
Authors: Birdane A. , Haznedaroğlu I. C. , Bavbek N. , Koşar A. , Büyükaşık Y. , Özcebe O. , Dündar S. V. , Kirazlı Ş.
Published: March 2006

An elevated platelet count is a common finding in both hospitalized and ambulatory patients. Thrombosis and bleeding complications are more frequently observed in patients with clonal thrombocytosis than secondary thrombocytosis. The aim of this study was to investigate the behaviors of plasminogen activator inhibitor type 1 (PAI-1), the inhibitor of fibrinolysis; and thromboxane A2 and 6-keto-PGF1 α, the products of endoperoxides, in 16 patients affected with clonal thrombocytemia as compared with 16 patients with reactive thrombocytosis and 15 normal controls. In the clonal thrombocytemia group, plasma levels of PAI-1 antigen and activity were significantly higher than both reactive thrombocytosis and control group. Plasma levels of 6-keto-PGF1α were significantly higher in the clonal thrombocytemia group than the other two groups and also higher in the reactive thrombocytosis group than the control group, which was also significant. This study confirms that arachidonate metabolism is frequently deranged in patients with thrombocytosis and hypofibrinolysis due to increased PAI-1 plasma levels as shown in the clonal thrombocytosis group. This may explain the thrombotic tendency in myeloproliferative disorders.
The Role of Plasma Exchange in HELLP Syndrome
Authors: Eser Bulent , Guven Muhammet , Unal Ali , Coskun Ramazan , Altuntas Fevzi , Sungur Murat , Serin Ibrahim Serdar , Sari Ismail , Cetin Mustafa
Published: March 2006

Plasma exchange therapy has been successfully used in selected patients with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome who have organ failure or refractory to treatment. There is no prospective study regarding plasma exchange and its effect in HELLP syndrome. The aim of this study was to investigate the effects of early postpartum use of plasma exchange in patients with HELLP syndrome on outcomes. The mortality rate and the recovery times were compared in patients with HELLP syndrome treated with plasma exchange and historic control group of patients treated conservatively. During a 3-year period (between April 2000 and December 2003), 29 consecutive patients with HELLP syndrome were treated with single or multiple plasma exchange by using fresh-frozen plasma at post-partum period. The control group consist of 26 patients with HELLP syndrome treated between 1993 and 1999. Maternal mortality rate was 23.1% in the control group; there was no death in plasma exchange group; and the mortality rate was significantly higher in the control group (p=0.006). The length of stay at the intensive care unit was shorter in the plasma exchange group (p<0.0001). Rapid improvement of the platelet, aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels were observed in the plasma exchange group. This study showed that postpartum early plasma exchange therapy improves treatment outcomes in patients with severe HELLP syndrome.
Study on the Phylogenetic Treeof Human Platelet Glycoproteins
Authors: Wiwanitkit Viroj
Published: March 2006

Platelet glycoprotein is an important group of glycoporteins on platelets. Several types of platelet glycoproteins have been studied for their functions in the hemostasis system. A bioinformatic analysis was performed to find out how the platelet glycoproteins’ genes are related to each other. A multiple sequence alignment phylogenetic tree was performed to present the family tree of the human platelet glycoproteins recorded in the genomic database, ExPASY. These derived sequences from the database were processed by ClustalW and subsequently used for preparation of the distance matrix by Phylip protdist. The final generated phylogenetic tree of human platelet glycoproteins was presented and discussed.
β2 Glycoprotein 1 in Indian Patients with SLE
Authors: Bhattacharyya Maitreyee , Kannan M. , Biswas Arijit , Kumar Ashok , Saxena Renu
Published: March 2006

Forty-five patients with systemic lupus erythematosus (SLE) were investigated to evaluate the role of antiphospholipid antibodies in causation of thrombosis in Indians. The antiphospholipid antibodies studied included lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), and anti-β2-glycoprotein 1 (aβ2-GP1). Twenty-seven patients (60%) had clinical manifestations of antiphospholipid antibody syndrome. Nineteen patients (42.2%) had a history of thrombosis, and eight (17.7%) had a history of recurrent fetal loss. aβ2-GP1 was (IgG) was positive in 23 (51.1%), aCL in 13 (28.8%), and LAC in four (8.8%). Of 19 patients with thrombosis, 14 (73.6%) were positive for aβ2-GP1, eight (42.1%) for aCL, and none of them was positive for LAC. Of the eight patients with recurrent fetal loss, two (25%) patients were positive for β2-GP1, five (62.5%) for aCL, and one (12.5%) for LAC. Of 18 patients without any manifestations of antiphospholipid syndrome (APS), seven patients (38.8%) were positive for aβ2-GP1, and three (16.6%) for aCL and LAC each. It is concluded that presence of aβ2-GP1 increases the risk of thrombosis and therefore should be looked for in all cases of SLE to consider prophylactic antithrombotic therapy in these patients.
Global Fibrinolytic Capacity Increased Exponentially in Metastatic Colorectal Cancer
Authors: Kockar Cem , Kockar Olga , Ozturk Mustafa , Dagli Mehmet , Bavbek Nüket , Kosar Ali
Published: March 2006

Colorectal cancers are one of the most common malignancies associated with coagulation abnormalities ranging from asymptomatic laboratory changes to massive thromboembolism or hemorrhage. It was previously shown that global fibrinolytic was increased in non-metastatic colorectal cancer. In this study global fibrinolytic capacity was measured in patients with colorectal cancer and metastatic liver disease, which always more commonly displays various coagulation disorders. Nineteen patients with biopsy-proven colorectal cancer, 30 patients with metastatic colorectal cancer, and 20 healthy control subjects were involved into the study. Using standart silicated fibrin pellets and tissue plasminogen activator, fibrinolytic capacity of the plasmas was detected with the amount of D-dimer produced before the reaction was stopped by adding aprotinin to the medium. Mean global fibrinolytic capacity (GFC) was increased to higher levels in patients with metastatic disease compared to levels in non-metastatic disease (p<0.05). Fibrinogen/GFC ratio correlated to the increase of D-dimer levels. Global fibrinolytic capacity was much higher in metastatic disease, reflecting a progression to overt disseminated intravascular coagulation.
Diagnosis of Antiphospholipid Syndrome During the Diagnostic Workup of Second-Trimester Fetal Bradycardia
Authors: Seckin Neslihan Carda , Inegöl Ilknur , Turhan Nilgün Öztürk , Bavbek Nüket
Published: March 2006

Antiphospholipid syndrome (APS) is an autoimmune disorder associated with either arterial and/or venous thrombosis (1). Two cases of APS, which were diagnosed in the second trimester during the diagnostic workup of fetal bradycardia, are presented.
Efficiency of Systematic Thrombophilia Screening in Idiopathic Venous Thrombosis: A Prospective Study in Internal Medicine
Authors: Pottier P. , Cormier G. , Truchaud F. , Planchon B.
Published: March 2006

In case of unprovoked venous thromboembolism (VTE), the screening of thrombophilia is recommended whatever the age of the patient and the type of risk factors (RF). This prospective study was conducted in patients with unprovoked VTE to detect some predictive factors to have a higher risk of thrombophilia, focusing on age, history of venous thromboembolism, and the existence of a triggering event. From July 2000 to July 2002, in an Internal Medicine Department, unrelated patients with unprovoked VTE were included. Those unprovoked thromboembolic events were defined by the absence of association between permanent and transient RF. The primary outcome measure was the positivity of the thrombophilia screening for any type of abnormality detected (deficit of protein C, S, antithrombin, presence of a lupus anticoagulant, research of V and II mutations). Seventy-four patients were included. Eight died during the follow-up. A higher risk of thrombophilia was found in patients younger than 40 (p=0.03), or with a family but not personal history of VTE (p=0.01) or with transient RF (p=0.02). The most frequent abnormality of coagulation found in patients younger than 40 was the presence of a lupus anticoagulant. As a new strategy for the screening of thrombophilia, one could propose the following attitude: only patients with transient RF or family history of VTE could undergo a complete screening; for all the remaining patients who are younger than 40, a research of a lupus anticoagulant would be only performed. This strategy should now be balanced against the currently recommended systematic attitude in further studies.
Usefulness of Fully Automated Measurement of Reticulated Platelets Using Whole Blood
Authors: Abe Yasunori , Wada Hideo , Sakakura Miho , Nishioka Junji , Tomatsu Hiroaki , Hamaguchi Yukio , Oguni Shinichiro , Shiku Hiroshi , Nobori Tsutomu
Published: March 2006

Reticulated platelets (RP) were measured with an automated hematology analyzer (modified R-2000) in 287 healthy volunteers and in 212 patients with thrombocytopenia. In healthy volunteers, the RP was 0.48 ± 0.26% in men and 0.48 ± 0.32% in women. No significant difference in the RP values due to gender or age (21-60 years) was observed. Furthermore, the reverse correlation was observed between platelet counts and RP. The RP was high in patients with idiopathic thrombocytopenic purpura (ITP), those with high fibrinogen and fibrin degradation products (FDP), and those with high C-reactive protein (CRP), but low in patients after chemotherapy. The RP was highest in active phase of ITP, and relatively high in the partial remission phase of aplastic anemia. In patients after chemotherapy, the patients had a minimum phase of RP and then a maximum phase of RP before platelet counts increased. RP was significantly high in the maximum phase and significantly low in the minimum phase. The relationships between platelet count and RP were negatively correlated in patients with ITP, high FDP, or high CRP, but were not correlated in patients with aplastic anemia, liver disease, or after chemotherapy. These results show that RP reflects the pathology of thrombocytopenic disorders and the measurement of RP is useful for the differential diagnoses and analysis of platelet kinetics.
Abciximab Does Not Inhibit the Increase of Thrombin Generation Produced in Platelet-Rich Plasma In Vitro by Sodium Arachidonate or Tissue Factor
Authors: Altman Raul , Scazziota Alejandra , Santoro Silvina , Gonzalez Claudio
Published: March 2006

Aspirin and platelet membrane glycoprotein (GP) IIb/IIIa blockers are currently used for acute coronary events, and in percutaneous coronary intervention for preventing further coronary outcomes, because they inhibit platelet function. Aspirin also inhibits thrombin generation (TG) in platelet-rich plasma (PRP) activated by sodium arachidonate (AA). The effect of the platelet membrane GP IIb-IIIa (integrin αIIbβ3) blocker abciximab on thrombin generation was studied in vitro using PRP. Thirty healthy volunteers taking no medication, and 28 volunteers who had taken aspirin (160 mg/day for 3-4 days), were included in the protocol. Control or in vivo aspirinated PRP, stimulated or not by AA or tissue factor (TF), was investigated for the inhibitory effect of abciximab pre-incubated for 3 minutes. AA and TF added in vitro activated non-aspirinated PRP: lag-time (LT) and time to peak (TTP) were significantly shortened. Peak TG (PTG) and endogenous thrombin potential (ETG) were increased by AA but not TF; thus, AA seems to be more efficient than TF for TG in this system. Abciximab added in vitro to non-activated, non-aspirinated PRP had no effect on LT, TTP, or ETP, but caused a decrease in PTG that was not statistically significant. Abciximab (3 or 4 μg/mL) added in vitro to AA or TF-activated, non-aspirinated PRP produced no effect on TG, although in aspirinated platelets both LT and time to peak were prolonged. AA as well as TF added in vitro to PRP or in vivo aspirinated PRP increased TG, although AA seems to be more efficient in our assay system. Abciximab, which affects nonaspirinated, nonactivated PRP weakly, has no effect on AA or TF in activated control PRP or in vivo aspirinated PRP.
Transitioning from Argatroban to Warfarin Therapy in Patients with Heparin-induced Thrombocytopenia
Authors: Hursting Marcie J. , Lewis Bruce E. , Macfarlane Donald E.
Published: March 2006

Argatroban, a direct thrombin inhibitor used for thromboprophylaxis or treatment in heparin-induced thrombocytopenia (HIT), is routinely monitored using the activated partial thromboplastin time (aPTT) yet also prolongs the international normalized ratio (INR). Peritransitional INRs, aPTTs, anticoagulant dosing patterns, and outcomes were evaluated in 165 HIT patients who were transitioned, without guidelines, from argatroban to warfarin therapy. Argatroban (median doses: 1.5-2.0 mcg/kg/min) and warfarin (median dose: 5 mg initially with 3.8 mg/day thereafter) overlapped a median 4 days. Median (5-95th percentile) aPTTs (in seconds) and INRs, respectively, were 59.8 (38.8-82.9) and 3.2 (1.7-7.0) during argatroban monotherapy, 68.6 (44.5-104) and 5.3 (2.4-16) maximally during cotherapy, 59.9 (38.7-92.2) and 4.0 (2.2-11.6) immediately before argatroban cessation during cotherapy, and 36.0 (25.6-60.2) and 2.3 (1.3-7.3) within a median 10-12 hours after argatroban cessation. Major bleeding occurred in 1 (0.6%) patient pretransitionally and no patient during or after cotherapy. Eighteen (10.9%) patients experienced 19 peritransitional adverse outcomes (one death, two amputations, 16 new thromboses); these patients had more severe HIT than event-free patients (median baseline platelet count, 39 vs. 83 × 109/L). Of 108 patients with post-transitional INR data, 43 achieved a therapeutic INR (prospectively defined as 1.9-3.5), 34 were subtherapeutic, and 31 were supratherapeutic, with no across-group trend in new thrombosis. Hence in the absence of guidelines, physicians transfer patients from argatroban to warfarin therapy with acceptably low complication rates in HIT, without systematically over- or under-dosing warfarin. Furthermore, INRs greater than 5 commonly occur in HIT patients during argatroban monotherapy and argatroban/warfarin cotherapy, without major bleeding.
Prevention of Edema in Long Flights with Pycnogenol®
Authors: Cesarone M. R. , Belcaro G. , Rohdewald P. , Pellegrini L. , Ippolito E. , Scoccianti M. , Ricci A. , Dugall M. , Cacchio M. , Ruffini I. , Fano F. , Acerbi G. , Vinciguerra M. G. , Bavera P. , Di Renzo A. , Errichi B. M. , Mucci F.
Published: March 2006

The aim of this study was to evaluate the prevention of edema during long-haul flights with an oral, anti-edema and antithrombotic agent (Pycnogenol®, Horphag, Research Management SA, Geneva, Switzerland) in asymptomatic subjects. The assessment of edema was performed by evaluating an analogue scale, the rate of ankle swelling by strain-gauge derived rate of ankle swelling (RAS), and by assessing the ankle circumference variation. The study included 211 subjects; 169 completed the study (88 in the control group and 81 in the Pycnogenol® group). There were no important differences between the two groups (comparable for age, gender, weight, body mass index, and pattern distribution). The edema score, the RAS, and the circumference at inclusion were also comparable. After the flight in those treated with Pycnogenol®, the edema score was increased only by 17.9% (vs. an increase of 58.3% in the control group) (p<0.05). The RAS, evaluated in 22 subjects in the Pycnogenol® group (age 44.5; SD 8) and in 23 in the control group (age 45; SD 9) was increased on average by 91% in the control group and 36% in the Pycnogenol® group (p<0.05). The variation on circumference at the ankle was 6% in the Pycnogenol® group (11% in the control group; p<0.05). These results indicate a positive effect of Pycnogenol® on edema during long flights when considering subjective and objective data. No unwanted effects were observed.
Hemostatic Status and Fibrinolytic Response Potential at Different Phases of the Menstrual Cycle
Authors: Koh Stephen C.L. , Prasad R. N.V. , Fong Y. F.
Published: March 2006

Coagulation and fibrinolytic variables including platelet function and endogenous fibrinolytic response were determined in 30 normal healthy women volunteers not on any known medication during the period of study. They were between 18 years and 38 years old and had normal menstrual cycles of between 28 days and 30 days. Blood samples were obtained within one menstrual cycle and after having fasted overnight within days 1 to 3 (menstruation), 5 to 9 (follicular), 10 to 14 (mid-cycle), and 21 to 26 (luteal) of the menstrual cycle. Analysis of variance (ANOVA) showed no significant differences in the hemostatic parameters studied between the phases of the menstrual cycle except for a reduced D-dimer level at mid-cycle. Significant fibrinolytic response was seen after venous occlusion but they were not significantly different between the phases of the menstrual cycle. The women were then divided into either normal weight (n=22) or overweight (n=8) according to World Health Organization (WHO) classification and the data reanalyzed. Elevated tissue plasminogen activator antigen and plasminogen activator inhibitor-1 levels except at menstruation and total protein S except at follicular phase were observed in overweight women together with increased plasminogen level only at luteal phase. Significant endogenous fibrinolytic response seen during the menstrual cycle was not different between normal and overweight women. The study demonstrated that systemic coagulation, fibrinolysis, and platelet function were probably not influenced by natural hormonal changes occurring during the menstrual cycle except for an associated reduced fibrinolytic state at mid-cycle. The hemostatic system in this small group of healthy overweight women studied appeared to be physiologically compromised.
Functional Determination of Plasminogen Activatorin Arginine-stabilized Plasma
Authors: Stief T. W. , Richter A. , Bünder R. , Maisch B. , Renz H.
Published: March 2006

Reliable data on plasminogen activator (PA) activities in blood of patients receiving fibrinolytic treatment are lacking. This is due to the continuing in vitro action of PA after blood withdrawal. We have elaborated a new simple stabilization technique for plasma involving the addition of arginine in final concentrations greater than 500 m M. In this study, new assays for PA in stabilized plasma are developed. The assay was performed with substrate plasma, that is, pooled normal plasma, preoxidized with chloramine-T; oxidant amount and oxidation time were optimized. The chloramine consumption by plasma was assayed with a KJ-assay (absorbance increase at 405 nm by addition of 200 μL 4 M KJ to 25 μL oxidized plasma). The substrate plasma concentration in the PA assay and the PA acting time was optimized. The inhibition of PA by the cations Na+, K+, Mg2+, and Ca2+ was evaluated. The optimized PA assay consists of incubation of 10 μL arginine-stabilized plasma with 10 μL 1.5 M arginine, pH 8.7 and 10 μL 100 m M CT in PBS. After 30 minutes (37°C), 175 μL 15 m M CT oxidized EDTA plasma are added. After 40 minutes (37°C), 75 μL Stop-CS Reagent is added and ΔA at 405 nm was determined, giving PA + plasmin activity in plasma. A control value (basal plasmin activity) consists of the addition of Stop-CS Reagent before 175 μL oxidized EDTA plasma. To obtain plasmatic PA activity, the control value has to be subtracted from the PA main value. The assay is matrix-independent and linear up to 1250 IU/mL t-PA, 790 U/mL reteplase, or 199 IU/mL u-PA (37 n M). With arginine stabilization of plasma and the described determination of plasminogen activator activity in arginine-stabilized plasma, it is feasible to determine the activity of plasminogen activators in blood of patients receiving fibrinolytic treatment without artefactual in vitro changes of the samples.
Comparable Levels of Activity and Antigen in Factor XII Deficiency: A Study of 21 Homozygotes and 58 Heterozygotes
Authors: Girolami A. , Gavasso S. , Pacquola E. , Cabrio L. , Lombardi A. M. , Girolami B.
Published: March 2006

Results of coagulation studies on 21 homozygote patients with factor XII (FXII) deficiency revealed that all of them had no cross-reacting material (CRM) in their plasma. The 58 heterozygotes had in every instance an antigen level comparable to that of clotting activity namely, approximately 50% of normal. An analysis of all pertinent literature also showed that the presence of CRM is very rare in FXII deficiency. CRM is present in approximately 5% of homozygote patients. More precisely, seven of 145 patients. Only in one case, the antigen level was normal (FXII Washington). This prevalence appears lower than that observed for another contact phase factor (prekallikrein). The significance of blood abnormal forms of FXII has not been completely clarified yet. Their study appears useful in the attempt of clarifyng the structure-function relation of factor XII.
Roles of Methylenetetrahydrofolate Reductase C677T Polymorphism in Repeated Pregnancy Loss
Authors: Wiwanitkit Viroj
Published: March 2006

Congenital thrombophilia in repeated pregnancy lost (RPL) has been noted for years. Methylenetetrahydrofolate reductase (MTHFR) gene is an interesting gene, mentioned for its possible roles in RPL. There is considerable controversy regarding the clinical role of MTHFR C677T polymorphism as a risk factor of RPL. Here, a summative analysis is performed on the recent previous reports on the MTHFR C677T and its correlation to RPL. The metanalysis was performed to assess the correlation between the pattern of MTHFR C677T polymorphism and RPL. From available eight case-control studies, 752 patients and 625 controls are evaluated. The overall frequencies of 4G allele for the patients and controls are 31.5 and 33.5, respectively. According to this study, 53.1% of subjects with T allele have RLP while 55.3% of subjects without T allele have RLP. From overall risk estimation, the subjects with T alleles have 0.96 times lower risk to RLP. According to this analysis, the pattern of MTHFR C677T polymorphism might not represent a useful marker of increased risk for RPL. In addition, there was no association between pattern of MTHFR C677T polymorphism and ethnicity of the patients in this study.
Life-Threatening Hypercoagulable State Following Splenectomy in ITP: Successful Management with Aggressive Antithrombotic Therapy and Danazol
Authors: Tiede Maike P. , Ahn Eugene R. , Jy Wenche , Scagnelli Thomas , Bidot Carlos J. , Horstman Lawrence L. , Jimenez Joaquin J. , Ahn Yeon S.
Published: March 2006

A life-threatening hypercoagulable state (HCS) is reported that developed after splenectomy in idiopathic thrombocytopenic purpura (ITP). A 50-year-old active male was rejected for blood donation because of an incidental finding of low platelet counts, 40,000/uL. The diagnosis was ITP. Although asymptomatic, he underwent splenectomy because of poor response to steroids and intravenous (IV) gamma globulin. One month after splenectomy, he suffered pulmonary emboli without deep venous embolism (DVT), followed by bilateral DVT, threatening amputation of the legs. Emergency thrombolysis, insertion of stent, and IV heparin saved his legs. Extensive workup for HCS was negative. IV heparin was witheld for colonoscopy for possible gastrointestinal neoplasm, at which time DVT recurred, necessitating another thrombolysis and heparin infusion. He was discharged on enoxaparin, antiplatelet therapy, and danazol. Platelet hyperactivation, characterized by high platelet microparticles (PMP) and CD62P, was present throughout his course of active ITP, resolving when ITP went into remission with danazol therapy. ITP has remained in remission for 4 years after stopping enoxaparin and danazol. In vitro, his plasma in active ITP induced activation of normal platelets, generating PMP and inducing CD62p-positive platelets and platelet aggregates; his plasma from remission had no effect. This indicates the presence of a platelet activating factor, possibly anti-platelet antibodies. Splenectomy may have allowed procoagulant PMP to accumulate to high levels resulting in HCS. We advise awareness of thrombotic complications post-splenectomy in the subset of ITP patients who are largely asymptomatic and exhibit persisting platelet activation.
An Interesting Cause of Pulmonary Emboli: Acute Carbon Monoxide Poisoning
Authors: Sevinc Alper , Savli Haluk , Atmaca Hasan
Published: March 2006

Carbon monoxide poisoning, a public health problem of considerable significance, is a relatively frequent event today, resulting in thousands of hospitalizations annually. A 70-year-old lady was seen in the emergency department with a provisional diagnosis of carbon monoxide poisoning. The previous night, she slept in a tightly closed room heated with coal ember. She was found unconscious in the morning with poor ventilation. She had a rare presentation of popliteal vein thrombosis, pulmonary emboli, and possible tissue necrosis with carbon monoxide poisoning. Oxygen treatment with low-molecular-weight heparin (nadroparine) and warfarin therapy resulted in an improvement in both popliteal and pulmonary circulations. In conclusion, the presence of pulmonary emboli should be sought in patients with carbon monoxide poisoning.
Thrombosis in Hemophiliacs with Prothrombotic Molecular Defect
Authors: Iannaccaro Piergiorgio , Santoro Rita , Sottilotta Gianluca , Papaleo Giuseppina , Muleo Gaetano
Published: March 2006

Thrombosis in hemophiliacs is a very unusual event mostly reported in patients treated with concentrates containing large quantities of activated coagulation factors. A patient with hemophilia A is reported who had an acute myocardial infarction and in whom investigation for hereditary thrombophilia showed a prothrombotic molecular defect, the G20210A prothrombin mutation.
A Comparison of Lepirudin and Argatroban Outcomes
Authors: Smythe Maureen A. , Stephens Jennifer L. , Koerber John M. , Mattson Joan C.
Published: March 2006

Although both argatroban and lepirudin are used for the management of heparin-induced thrombocytopenia (HIT), data comparing these agents are lacking. The objective of this project was to compare the clinical outcomes of lepirudin vs argatroban therapy. Patients who received a direct thrombin inhibitor (DTI) from January 2000 to December 2001 were identified. Medical charts were retrospectively reviewed and relevant data extracted. The primary efficacy outcome was effective anticoagulation and the primary safety outcome was major bleeding. Data were analyzed using the t test and Fisher’s exact test. Sixty-one lepirudin patients and 29 argatroban patients received a DTI during the study period. A new diagnosis of HIT was the indication for DTI therapy in 44.8% of argatroban patients and 57.4% of lepirudin patients. Effective anticoagulation was achieved in 77.8% of argatroban patients and 69.5% of lepirudin patients (p = .61). Major bleeding occurred in 10.3% and 11.5% of argatroban and lepirudin patients, respectively (p = 1.0). Argatroban and lepirudin demonstrated comparable safety and efficacy outcomes.