bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of Thrombophilia, Hypofibrinolysis, and Retinal Vein Occlusion
Authors: Glueck Charles J. , Wang Ping , Bell Howard , Rangaraj Venkat , Goldenberg Naila
Published: March 2006

We prospectively assessed whether thrombophilia and hypofibrinolysis, amplified by thrombophilic hormone replacement therapy (HRT), were associated with retinal vein occlusion (RVO). We studied 44 cases (18 men, 26 women), ≥ 3 months after RVO, 42 with central RVO, 2 with branch RVO, in the consecutive order of their referral by 2 community-based ophthalmologists. PCR and serologic coagulation assays were compared to 83 and 40 healthy adult normal controls, respectively. The 4G allele frequency of the plasminogen activator inhibitor-1 (PAI-1) gene, associated with hypofibrinolysis, was 56 of 88 (64%) in cases vs 79 of 166 (48%) in controls, X2 = 5.95, p = .015. The PAI-1 gene product, plasminogen activator inhibitor activity (PAI-Fx), was higher in cases than controls (age-race-sex-adjusted mean 12.2 U/mL vs 6.3, p = .013). By stepwise logistic regression, the PAI-1 gene 4G allele was associated with RVO, odds ratio 1.94, 95% CI 1.12-3.34, p = .018. Thrombophilic resistance to activated protein C (RAPC) was present in 6 of 32 (19%) of cases vs 0 of 40 (0%) controls, Fisher’s p [pf] = .006. Thrombophilic high factor VIII (>150%) was present in 3 of 30 (10%) cases vs 0 of 40 (0%) controls, p = .041, pf = .07. Comparing 23 RVO cases ≤ age 55 and controls ≤ age 55 (n = 44 for PCR, n = 40 for serologic measures), RAPC was present in 17% of cases vs 0% controls (pf = .026), high Factor VIII in 17% vs 0% (pf = .026), heterozygosity for the G1691A Factor V Leiden mutation in 13% vs 2% (pf = 0.11), and the 4G allele frequency of the PAI-1 gene 74% vs 39% (p = .0001). PAIFx was higher in cases than controls (age-race-sex adjusted mean 12.7 U/mL vs 6.7, p = .016). The case-control odds ratio for the PAI-1 4G allele was 5.54, 95% CI = 1.86-16.7, p = .002. Of the 26 women, 9 (35%) took HRT; 4 of the 9 had PAI-1 gene 4G4G homozygosity, 2 had thrombophilic high anticardiolipin antibody (IgG), 1 was heterozygous for the G1691A Factor V Leiden mutation, and 2 were heterozygous for the thrombophilic PL A1/A2 mutation of the platelet glycoprotein IIb/IIIa gene. Associations between heritable coagulation disorders and RVO, most marked in cases ≤ age 55, and often amplified in women by thrombophilic HRT, are, speculatively, causal.
Control of Bleeding Caused by Thrombocytopenia Associated With Hematologic Malignancy: An Audit of the Clinical Use of Recombinant Activated Factor VII
Authors: Brenner Benjamin , Hoffman Ron , Balashov Dmitriy , Shutluko Elena , Čulić Srđana , Nizamoutdinova Elena
Published: March 2006

This paper presents an analysis of 24 cases in which recombinant factor VIIa (rFVIIa) was used in the management of hemorrhage in patients with thrombocytopenia associated with hematologic malignancies. This is the largest case aggregation to date and focuses on preliminary experience in the off-label use of this hemostatic agent. Data were extracted from the international, Internet-based registry, www.haemostasis.com, accessed in September 2003. The search results were manually cross-checked against monthly summary reports. The physicians providing the cases were contacted individually to approve the use of their cases, supply any information missing from the database, and validate the data already held. Patients with acute myeloid leukemia, acute lymphoblastic leukemia, Hodgkin’s disease, non-Hodgkin’s lymphoma, Burkitt’s lymphoma, B-cell or T-cell lymphoma, or aplastic anemia received rFVIIa at total doses of between 18 and 1040 μg/kg body weight. Bleeding stopped in 11 of 24 (46%) patients, markedly decreased in 8 of 24 (33%) patients, and decreased in 4 of 24 (17%) patients. In most patients, the response was achieved within 2.5 hours of administration of rFVIIa. The use of rFVIIa was generally well tolerated—1 case of ischemic stroke was considered to be possibly related to rFVIIa administration, but this has yet to be confirmed. A review of these 24 cases submitted to the www.haemostasis.com database suggests that rFVIIa is beneficial in the management of hemorrhage in patients with thrombocytopenia and hematologic malignancies. This warrants further investigation in rigorously controlled clinical trials.
Different Effect of Statins on Platelet Oxidized-LDLReceptor (CD36 and LOX-1) Expressionin Hypercholesterolemic Subjects
Authors: Bruni Fulvio , Pasqui Anna Laura , Pastorelli Marcello , Bova Giovanni , Cercignani Michela , Palazzuoli Alberto , Sawamura Tatsuya , Auteri Alberto , Puccetti Luca
Published: March 2006

Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular mortality by decreasing cholesterol as well as by non-lipid-related actions. Oxidized low-density lipoproteins (ox-LDL) are pro-atherogenic molecules and potent platelet agonists. CD36 and lectin-like ox-LDL receptor-1 (LOX-1) are specific ox-LDL receptors also expressed in platelets. This study was planned to address whether treatment with atorvastatin 10 mg/day, pravastatin 40 mg/day or simvastatin 20 mg/day could affect platelet CD36 and LOX-1 expression. Twenty-four patients for each treatment were evaluated after 3, 6, and 9 days and at 6 weeks for complete lipid profile (chromogenic), ox-LDL (ELISA), platelet P-selectin (P-sel), CD36, LOX-1 (FACS), and intracellular citrullin recovery (iCit) (HPLC). Data show hyperactivated platelets (P-sel absolute values, percent variation in activated cells, all p < 0.001), and CD36 and LOX-1 overexpression (all p < 0.001) in patients at baseline. P-sel, CD36, and LOX-1 were significantly decreased by atorvastatin and simvastatin (all p < 0.01) and related with iCit increase (r = 0.58,p < 0.001) and platelet-associated ox-LDL (r = 0.51, p < 0.01) at 9 days. Pravastatin reduced LOX-1 and P-sel (p < 0.05) at 6 weeks in relation with decreased LDL and ox-LDL (r = 0.39, p < 0.01 and r = 0.37, p < 0.01, respectively). These data suggest that atorvastatin and simvastatin reduce platelet activity by exposure of CD36 and LOX-1 before significant LDL reduction, whereas pravastatin action is detected later and in relation with LDL and ox-LDL lowering. Rapid and consistent reduction of CD36 and LOX-1 could be considered a direct anti-atherothrombotic mechanism related to the role of ox-LDL in platelet activation, platelet-endothelium interactions, and NO synthase activity.
Gefitinib Affects Functions of Platelets and Blood Vesselsvia Changes in Prostanoids Balance
Authors: Kanazawa Shigenori , Yamaguchi Kazuyuki , Kinoshita Yoshimi , Muramatsu Mikiko , Komiyama Yutaka , Nomura Shosaku
Published: March 2006

Prostaglandins (PGs) and thromboxane (TX) produced by cyclooxygenase (COX) have a great influence on vascular systems and platelet functions. The serum levels of epidermal growth factor (EGF) and PGs were measured in patients with lung cancer treated with gefitinib, and the influence of EGF on platelet aggregation was investigated. Twenty patients were investigated. The serum level of TXB2 increased significantly in all patients who received gefitinib for 2 weeks (before vs. after = 94.1 ± 47.3 vs. 190.9 ± 54.3, p<0.01). TXB2 also increased significantly in responders without concurrent chemotherapy (before vs. after = 79.3 ± 35.5 vs. 194.5 ± 58.1, p<0.05), but not in non-responders (before vs. after = 106. 5 ± 65.8 vs. 162. 2 ± 52.8, N.S.). PG 6-keto F1α and PGE2 did not exhibit significant changes. Furthermore, EGF showed no significant change (after vs. before = 234 ± 35 vs. 276 ± 72, N.S.). Although there was no correlation between the levels of EGF and TXB2 (N.S.), the PG 6-keto F2α/TXB2 ratio decreased significantly (before vs. after = 0.054 ± 0.018 vs 0.033 ± 0.015, p<0.05). The secondary platelet aggregation observed after high-dose adenosine diphosphate stimulation was inhibited after a 1-minute preincubation with EGF. Platelet aggregation in patients after gefitinib administration tended to accelerate and secondary aggregation was observed after low-dose adenosine diphosphate stimulation. We conclude that careful observation is needed for patients with chronic obstructive pulmonary disease, pulmonary fibrosis, and thromboembolic diseases receiving gefitinib. Furthermore, measurement of prostanoids may be a good predictor of the beneficial and adverse effects. Moreover, the combination of gefitinib with a COX inhibitor that regulates TXA2/PGI2 balance should be evaluated.
Endothelial Cell Activity in Chronic Obstructive Pulmonary Disease Without Severe Pulmonary Hypertension
Authors: Cella Giuseppe , Saetta Marina , Baraldo Simonetta , Turato Graziella , Papi Alberto , Casoni Gianluca , Rigno Manuela
Published: March 2006

Pulmonary hypertension is common in patients with chronic obstructive pulmonary disease (COPD), but the precise mechanism of vascular impairment in these patients is unknown. We, therefore, decided to investigate whether endothelial cell dysfunction is present in patients with COPD with a wide range of chronic airflow obstruction before the development of severe pulmonary hypertension. Selected plasma markers of endothelial cell activity were studied: nitrate+nitrite (NO-2/NO-3), thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), soluble selectins (endothelium sES, leukocyte sLS, platelet sPS), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1). Twenty-five patients with COPD (forced expiratory volume in one second/vital capacity [FEV1/VC] < 88% predicted) and 29 healthy control subjects were recruited to the study. Among patients nine had a pulmonary artery systolic pressure (PASP) between 15 and 30 mmHg, 13 between 32 and 38 mmHg, 2 had a PASP of 41 and 42 mmHg, respectively. One patient had severe pulmonary hypertension with a PASP of 70 mmHg. The average FEV1 of patients with COPD was 46 ± 4% predicted. As compared to control subjects, patients with COPD showed a significant increase in plasma levels of TM and TFPI, indicating that their endothelial cells are still able to produce potent coagulation inhibitors. Levels of NO-2/NO-3were similar in the two groups of subjects examined, further suggesting preserved endothelial function in patients with COPD. In regard to adhesion molecules, patients with COPD showed a reduction in sLS, sPS, and sPECAM-1, and an increase in sICAM-1. This study shows that endothelial cell activity is largely preserved in patients with COPD without severe pulmonary hypertension, suggesting that these patients, despite quite severe airway obstruction, retain reasonably normal endothelial function until they develop severe pulmonary hypertension.
Idiopathic Intracranial Hypertension: Associations with Thrombophilia and Hypofibrinolysis in Men
Authors: Glueck Charles J. , Goldenberg Naila , Golnik Karl , Sieve Luann , Wang Ping
Published: March 2006

The existence of an association between idiopathic intracranial hypertension (IIH) and coagulation disorders in men was assessed prospectively. Microthrombi, associated with thrombophilia-hypofibrinolysis, occlude arachnoid sinus villi, thus reducing resorption of cerebrospinal fluid, leading to IIH. Ten consecutively referred men with IIH, nine whites, one African American, median age 36 years, were 2 to 1 matched by age and race by healthy male controls. Polymerase chain reaction assays were done for four thrombophilic and one hypofibrinolytic gene mutations: G1691A factor V Leiden, G20210A prothrombin, C677T MTHFR, platelet glycoprotein IIb/IIIa (PL A1/A2), and 4G/5G polymorphism of the plasminogen activator inhibitor (PAI-1) gene promoter. Coagulation measures in plasma included dilute Russel’s viper venom time (dRVVT), activated partial thromboplastin time (aPTT), the lupus anticoagulant, factor VIII, factor XI, plasminogen activator inhibitor activity (PAI-Fx), protein C antigenic, protein S total (antigenic), protein S free (antigenic), antithrombin III (functional), and resistance to activated protein C (RAPC). Tests performed on serum included anticardiolipin antibodies, homocysteine, and Lp(a). The body mass index was 40 kg/m2 or greater (extremely obese) in two men, 30 to 40 kg/m2(obese) in three, and was 25 to 30 kg/m2 in five (overweight). Cases differed from controls for inherited 4G4G homozygosity of the PAI-1 gene, four of 10 (40%) vs. one of 20 (5%), Fisher’s p [pf]= .031, and for high levels (>21.1 U/mL) of the hypofibrinolytic PAI-1 gene product, PAI-Fx, 5 of 10 (50%) vs. one of 18 (6%), pf = .013. Thrombophilic factor VIII was high (≥ 150%) in three of 10 (30%) cases vs. zero of 16 (0%) controls, pf=. 046. The thrombophilic lupus anticoagulant was present in two of 10 (20%) cases vs. zero of 32 (0%) controls, pf = .052. Heritable hypofibrinolysis and heritable and acquired thrombophilia appear, speculatively, to be treatable etiologies of IIH in men. Understanding contributions of hypofibrinolysis and thrombophilia to the development of IIH should facilitate development of novel new approaches to treat this often-disabling neurologic disorder.
Plasma Levels of Thrombin-Activatable Fibrinolysis Inhibitor in Primary and Secondary Thrombocytosis
Authors: Kaftan O. , Balcik O. S. , Cipil H. , Ozet G. , Bavbek N. , Koşar A. , Dagdas S.
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 thrombin-activatable fibrinolysis inhibitor (TAFI) activity, the inhibitor of fibrinolysis, and also prothrombin time (PT), active partial thromboplastin time, and D-dimer and fibrinogen levels in 21 patients affected with clonal thrombocytemia as compared with 21 patients with reactive thrombocytosis and 21 healthy controls. In the clonal thrombocytemia group, plasma levels of TAFI activity were significantly higher than in both the reactive thrombocytosis and the control group. Plasma levels of leukocyte and platelet counts were significantly higher in the clonal thrombocytemia group than in the other two groups and also higher in the reactive thrombocytosis group than in the control group, which was also significant. Fibrinogen and D-dimer levels were higher in patients than in the control group but showed no significant difference between the clonal and secondary thrombocytosis groups. Plasma levels of PT and aPTT were higher in secondary thrombocytosis group than the clonal thrombocytosis group. The results of this study showed for the first time that TAFI activity is increased in patients with clonal thrombocytosis. These increased levels in clonal thrombocytosis can be considered a factor to explain the thrombotic tendency in myeloproliferative disorders.
Effects of Percutaneous Coronary Thrombectomywith the X-Sizer Catheter on Epicardial Flow and Microvascular Function in Acute Coronary Syndromes
Authors: Bilge Ahmet Kaya , Nisanci Yilmaz , Yilmaz Ercument , Ozben Beste , Oncul Aytac , Mercanoglu Fehmi , Meric Mehmet
Published: March 2006

During percutaneous coronary intervention, slow coronary flow and distal embolization are still important problems, especially in cases with intracoronary thrombus. The aim of this study was to learn the effectiveness and early term results of thrombectomy with the X-SIZER catheter system in acute coronary syndrome. Twenty-nine patients (22 [76%] men; 55.9 ± 11.1 years) with acute coronary syndrome and intracoronary thrombus detected in coronary angiography were included into the study. X-sizer thrombectomy was applied to 14 of the patients, and conventional percutaneous transluminal coronary angioplasty (PTCA) was applied to the others. Baseline characteristics were similar in both groups. Mean thrombolysis in myocardial infarction (TIMI) flow increased from 0.8 ± 0.9 to 2.4 ± 0.6 in X-sizer-treated patients (p<0.001) and TIMI 3 flow was maintained in 71.4% of the patients. Similary, mean TIMI flow increased from 0.36 ± 0.81 to 2.73 ± 0.47 in conventional PTCA-treated patients (p<0.001) and TIMI 3 flow was maintained in 73% of the patients (NS). Mean myocardial blush grade (MBG) increased from 0.7 ± 0.7 to 2.6 ± 0.6 in X-sizer-treated patients (p<0.001) and from 0.27 ± 0.65 to 2.36 ± 0.67 in the conventional PTCA-treated patients (p<0.001). Postprocedural MBG 3 was obtained in 64.3% of X-Sizer-treated patients and in 45% of controls. Although microvascular function in the thrombectomy-applied patients was found better, there was no significant difference between the two groups. Furthermore it was detected that the use of tirofiban yielded no additional improvement in epicardial and microvascular flow. In acute coronary syndromes, use of X-sizer in addition to primary percutaneous coronary interventions is a safe and relatively effective method in the prevention of distal embolization.
Clinico-Hematologic Profile of Factor XIII-Deficient Patients
Authors: Bhattacharya M. , Biswas A. , Ahmed R. P.H. , Kannan M. , Gupta M. , Mahapatra M. , Choudhry V. P. , Saxena R.
Published: March 2006

A retrospective analysis of clinico-hematologic parameters of 18 factor XIII-deficient patients was carried out. The hematologic tests included activated partial thromboplastin time (APTT), prothrombin time (PT), and clot solubility. Laboratory diagnosis of FXIII deficiency was made where bleeding time, PT, APTT, and thrombin time were normal and the clot solubility test result with 5M urea was positive. Factor XIII level with family screening was performed using commercially available kits. History of prolonged bleeding from the umbilical stump was present in four (22.2%) patients. The most common site of bleeding was the skin (11 of 18 patients). Three patients were given prophylaxis (FFP in two, factor XIII in one). A high prevalence of recurrent abortion in female pa tients with FXIII deficiency (two of the three patients in this study) was observed.
eNOS Gene Affects Red Cell Deformability: Role of T-786C, G894T, and 4a/4b Polymorphisms
Authors: Fatini Cinzia , Mannini Lucia , Sticchi Elena , Cecchi Emanuele , Bruschettini Alessia , Leprini Emanuela , Pagnini Paolo , Gensini Gian Franco , Prisco Domenico , Abbate Rosanna
Published: March 2006

Plasma viscosity and erythrocyte deformability play a key role in maintaining and regulating microcirculation. In vitro and in vivo studies suggested a role for nitric oxide (NO) in modulating flow-mediated vasodilatation and red blood cell deformability. Impaired NO availability due to mutations in eNOS gene might contribute to the altered haemorheologic state. The aim of this study was to investigate the role of eNOS T-786C, G894T, and 4a/4b polymorphisms in modulating the haemorheologic state in a clinical condition characterized by a microcirculatory disorder. Eighty patients with idiopathic sudden sensorineural hearing loss (ISSHL) and 80 healthy subjects were studied. By using a dominant model of inheritance, we found a significant association between eNOS 894T rare variant and ISSHL (odds ratio [OR] 894TT+GT = 2.08, p = 0.03) after adjustment with traditional vascular risk factors. A higher percentage of altered red cell deformability both in patients and in controls carrying the eNOS rare variants was found in comparison to subjects carrying the wild type. Apart from the disease, eNOS T-786C and G894T polymorphisms independently affected the deformability index (OR,-786CC+TC = 2.81, p = 0.01 and OR, 894TT+GT = 2.5, p = 0.02, respectively), in particular in subjects in whom the contemporary presence of the two rare alleles was observed (OR,-786CC+TC and 894TT+GT combined genotype = 6.9, p<0.0001). Our study documented that eNOS gene affects the red blood cell deformability, so possibly contributing to ISSHL, which may represent a suitable model of microcirculatory disorder.
Effects of High-Dose Methylprednisolone Therapy on Coagulation Factors in Patients with Acute Immune Thrombocytopenic Purpura
Authors: Oner Ahmet Faik , Bay Ali , Kuru Mehmet , Uner Abdurrahman , Arslan Sukru , Caksen Hüseyin
Published: March 2006

Autoimmune thrombocytopenic purpura (ITP) is a disease that presents with skin and mucous membrane bleeding due to thrombocytopenia. In the literature, there are a few studies about the effect of high-dose steroid therapy on coagulation tests in different diseases, but their results are still controversial. In this study, coagulation parameters were investigated that might have a role in hemostatic compensation in childhood acute ITP before and after high-dose methylprednisolone (HDMP) treatment. The study includes 21 children age 1.5 to 14 years with acute ITP and 21 healthy age-matched control subjects. All patients with acute ITP received HDMP for 7 days. Before and after HDMP treatment (0 and 8 days) prothrombin time, partial thromboplastin time, fibrinogen, Protein C, Protein S, antithrombin III, and the levels of factor II (FII), FV, FVII, FVIII, FIX, FX, FXI, and FXII were studied in all subjects. The results were compared with those of the control group. Pre-treatment Protein C and Protein S levels in the patient group were significantly lower than those in the control groups (p<0.05). Protein S and Protein C levels were significantly improved after HDMP treatment in patient group. There were lower FV, FVII, FX values in the patient group compared to the control groups on admission. There was no difference in AT III and fibrinogen levels before and after treatment. As a result, some changes in the coagulation system associated with thrombocytopenia were observed in patients with acute ITP. These changes may be accepted as compensatory mechanisms to maintain hemostasis.
Confirmation of the Value of a Modified Long-distance Polymerase Chain Reaction in the Detection of Inversion Intron 22 in Severe Hemophilia A: A Technical Note
Authors: Lombardi Anna Maria , Cabrio Laura , Zanon Ezio , Pellati Donatella , Vettore Silvia , Girolami Antonio
Published: March 2006

Hemophilia A is one of the most common bleeding disorders in man. Approximately half the families with a severe disease have an inversion of the factor VIII gene. The inversion may be detected with a long polymerase chain reaction. This is a simple and reproducible method that may yield satisfactory results in approximately 24 hours. The long-distance polymerase chain reaction amplify three very large amplicons with a very GC-rich region of several kilobases, and is detected with a Expand Long Template DNA polymerase (Roche, Mannheim, Germany). Recently this polymerase has been changed with a new chemical composition. The object of the present method is to standardize the technique using the new Expand Long polymerase. For the new protocol, the cycling conditions, the concentration of nucleotide primers, and the buffer are changed. The need for a rapid response is determined in the case of hemophilia A patients, not only by the desire to reach a proper classification, but also by the urgency to inform the carrier status of the mother or of a female relative.
The Effect of Anthracycline-Based (Epirubicin) Adjuvant Chemotherapy on Plasma TAFI and PAI-1 Levels in Operable Breast Cancer
Authors: Demirkan Binnaz , Özcan Mehmet Ali , Alacacıoğlu Ahmet , Yüksel Faize , Ündar Bülent , Alakavuklar Mehmet
Published: March 2006

An increased incidence of thromboembolic events has been described in women receiving systemic chemotherapy for breast cancer. The effect of anthracycline-based adjuvant chemotherapy regimens on fibrinolytic system markers of plasminogen activator inhibitor-1 (PAI-1) and thrombin activitable fibrinolysis inhibitor (TAFI) was investigated in patients with operable breast cancer. Twenty-four patients with operable breast cancer (median age, 54.5 years; range, 37-72 years) enrolled in our study. Stage I-II and stage IIIA cases received EC (Epirubicin 90 mg/m2/d1, I.V. and cyclophosphamide 600 mg/m2/d1, I.V.) and FEC (5-fluorouracil 500 mg/m2/d1, I.V., epirubicin 100 mg/m2/d1, I.V., and cyclophosphamide 500 mg/m2/d1, I.V.) as an adjuvant chemotherapy regimen, respectively. Each group consisted of 12 patients. Blood samples were obtained at baseline and just before the third cycle of EC and fourth cycle of FEC chemotherapy regimens. Plasma TAFI antigen and PAI-1 levels did not disclose any statistical difference between basal and postchemotherapy levels within each group and between two groups. Although postchemotherapy D-dimer levels were statistically higher in the FEC group than in the EC group, results in both groups were within normal ranges. More studies concerning the role of fibrinolytic system in breast cancer patients receiving chemotherapy, probably including cases with advanced stage and with different chemotherapy regimens and dose intensities, are needed.
Hypercoagulopathy in Stroke Patients with Nonvalvular Atrial Fibrillation: Hematologic and Cardiologic Investigations
Authors: Turgut Nilda , Akdemir Osman , Turgut Burhan , Demir Muzaffer , Ekuklu Galip , Vural Özden , Özbay Gültaç , Utku Ufuk
Published: March 2006

The coagulation system is activated and coagulation activation markers are elevated in acute ischemic stroke with nonvalvular atrial fibrillation (NVAF). The etiology, severity, and prognosis of the ischemic stroke might be estimated with the level of the activation of the coagulation system. In this study, prothrombin F1+2 (F1+2), D-dimer, and fibrinogen levels were measured in patients with acute ischemic stroke with and without NVAF, and stroke severity was compared with these hemostatic parameters. Of 55 patients, 29 had sinus rhythm (group I), 26 had NVAF (group II); 20 healthy subjects (group III) were included in the study. Subtypes of cerebral infarction were classified. The patients underwent stroke severity, electrocardiography, echocardiography, cranial computed tomography, cervical duplex ultrasonography, and hemostatic parameter studies. In group II, F1+2 level (2.83±0.89) was significantly higher than in group I (2.33±0.80) and III (1.94±0.64) (p values: group I-II, 0.036; groups II-III, 0.001; groups I-III, 0.104). In group III, fibrinogen level (251.64±60.96) was significantly lower than that in groups I (347.97±111.49) and II (364.04±86.20) (p=0.001). D-dimer was not significantly different between groups. In group I, lacunar syndrome (LACS), and in group II, partial and total anterior circulation syndrome (PACS+TACS) were more common (p=0.013, p=0.001, respectively). In group II, Scandinavian Stroke Scale scores were lower than those in group I (group I=45.2±14, group II=35.4±18.9, p=0.02). In conclusion, activation of coagulation, demonstrated by increment F1+2, is more abundant in the stroke patients with NVAF than in the stroke patients with sinus rhythm. Our results also showed that activation of the hemostatic system might be related to stroke subtype and stroke severity. It is suggested that the oral anticoagulation treatment as prophylaxis is important in the prevention of stroke in patients with NVAF.
In vitro Simulation of Therapeutic Thrombolysis With Microtiter Plate Clot-Lysis Assay
Authors: Stief Thomas W.
Published: March 2006

Only limited comparable data are available on the clot lysis power of the clinically used plasminogen activators (PA). Here the PA were used at different clinically relevant concentrations, and the lysis of the microclots was determined. A microclot lysis assay was used to study thrombolysis by urokinase, tissue-PA (t-PA), streptokinase, plasminogen-streptokinase activator complex (PSAC), reteplase, or tenecteplase. The clot turbidity served as a tool to determine clot mass: 100 μL fresh microclots were incubated with 25 μL PA in 6% bovine serum albumin (BSA)-phosphate-buffered saline (PBS) and 100 μL BSA-PBS or pooled normal human plasma; that is, the PA were in the liquid supernatant of a plasma clot and were not entrapped in the clot, an assay system comparable to normal physiology. The turbidity was determined after 0 to 5 hours (37°C) by a microtiter plate reader. The lysable clot turbidity (clot mass) was expressed in percent of 100% lysable clot control. The clot lysis activity is 100% minus the clot mass in percent. The effective doses at 50% (ED50) of lysis of fresh clots after 4 hours (37°C) with 6% BSA or pooled normal human plasma in the clot-supernatant were urokinase 128 or 180 IU/mL; t-PA 0.3 or 0.2 μg/mL; streptokinase 215 or 1371 IU/mL; PSAC 60 or 91 U/mL; reteplase 664 or 996 U/mL; tenecteplase 0.2 or 0.2 μg/mL. The presence of a plasma thrombus with plasma supernatant increases the activity of t-PA approximately 20-fold and that of tenecteplase approximately 400-fold after 4 hours (37°C), when compared to urokinase; in contrast, the lytic activity induced by reteplase decreases; i.e., the plasmin generated by reteplase is hampered on its lytic action against a thrombus. When comparing the clot lysability of microclots of 29 different donors, the only correlation (r > 0.6) was that between u-PA and t-PA. The lysability of individual clots by PA can be measured with the present routine-suited technique. It is suggested that different thrombolytic agents or concentrations thereof would have a different clinical outcome in different individuals.
Third Trimester Maternal Plasma Total Fibronectin Levels in Pregnancy-Induced Hypertension: Results of a Tertiary Center
Authors: Aydin Tahsin , Varol Füsun G. , Sayin Niyazi Cenk
Published: March 2006

The aim of this study was to evaluate maternal plasma total fibronectin values in pregnancy-associated hypertension in women in the third trimester of pregnancy. A total of 125 pregnant women at the 24th week of gestation participated in this study. Nonpregnant normotensive women were included as control group (n = 30). Plasma samples for fibronectin were obtained at the 24th, 28th, and 32nd weeks of gestation from all pregnant patients. From this cohort, 10 patients met the criteria for the diagnosis of gestational hypertension and 15 women met the stringent requirements of preeclampsia, whereas 100 patients were normotensive later in gestation. Plasma total fibronectin levels were determined by radial immunodiffusion technique. Data were analyzed using the SPSS program. The mean plasma fibronectin levels of the pregnant women in whom gestational hypertension and preeclampsia developed were significantly higher at the 24th, 28th, and 32nd weeks in comparison to normotensive pregnant women (p < 0.001). However, throughout the period from the 24th to 32nd weeks of pregnancy, plasma total fibronectin levels did not exhibit a significant change in normotensive pregnant patients or in patients with preeclampsia and gestational hypertension. There was also no correlation between plasma fibronectin levels and gestational age, mean arterial pressure, birth weight, and 5-minute Apgar scores in all groups (p < 0.05). The elevated maternal plasma fibronectin level over 40 mg/dL is capable of predicting preeclampsia with a sensitivity of 73% and a specificity of 92%. These results suggest that serial plasma fibronectin measurements before 24 weeks’ of gestation may be helpful in the early detection of preeclampsia in normotensive gravid women who are destined to become clinically preeclamptic.
Antiphospholipid-Mediated Thrombosis: Interplay Between Anticardiolipin Antibodies and Vascular Cells
Authors: López-Pedrera Chary , Buendía Paula , Barbarroja Nuria , Siendones Emilio , Velasco Francisco , Cuadrado Maria José
Published: March 2006

The antiphospholipid syndrome (APS) is characterized by thrombosis or pregnancy morbidity in the presence of antiphospholipid autoantibodies (aPL). aPL are a heterogeneous family of autoantibodies with diverse cross-reactivities whose origin and role have not been fully elucidated. Many of the autoantibodies associated with APS are directed against phospholipid-binding plasma proteins, such as β2-GPI and prothrombin, or phospholipid-protein complexes. The mechanisms by which aPL cause thrombosis are not completely understood. There is no unique mechanism able to explain all symptoms associated with the presence of aPL. Different theories have been proposed, including the effect of aPL on endothelial cells, monocytes, and platelets. aPL are able to recognize, injure, or activate cultured vascular endothelial cells. Cultured endothelial cells incubated with aPL express increased levels of cell adhesion molecules and tissue factor (TF), an effect mediated by β2-GPI, and may promote inflammation and thrombosis. Overexpression of TF has been also shown in monocytes in vitro and ex vivo. TF is the major initiator of coagulation in vivo; thus, its dysregulation may be one of the most important contributors to thrombosis. Effects of aPL upon platelets are not completely elucidated. aPL bind anionic phospholipid but they are normally in the inner side of cell membranes. When platelets are activated by different agonists, anionic phospholipids are exposed. There is some evidence showing that activated platelets are present in aPL-positive patients. Increased levels of β-thrombomodulin, and microvesicle formation seem to support this hypothesis. Activated platelets may contribute to thrombosis by persistent exposure of a procoagulant surface.
The Effects of Rosiglitazone Treatment on the Fibrinolytic System in Patients with Type 2 Diabetes Mellitus
Authors: Guldiken Sibel , Turgut Burhan , Demir Muzaffer , Arikan Ender , Kara Mujdat , Vural Ozden , Tugrul Armagan , Fareed Jawed
Published: March 2006

Patients with type 2 diabetes mellitus (DM) are at risk for the development of cardiovascular diseases, which can in part be explained by disturbances in the hemostatic and fibrinolytic systems. The effects of rosiglitazone treatment on the fibrinolytic system and insulin sensitivity in patients with type 2 DM were assessed. Twenty-four patients with type 2 DM and 28 healthy subjects were enrolled in the study. Plasma global fibrinolytic capacity (GFC), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) levels were measured. Insulin resistance was calculated by hoemostasis model assessment. Patients with type 2 DM then were placed on rosiglitazone (4 mg/day, for 12 weeks) in addition coexistent medication, and baseline tests were repeated. There was no difference between mean t-PA levels of the two groups. PAI-1 levels were higher in diabetic patients than control subjects (p < 0.01). Diabetic patients had lower GFC and t-PA/PAI-1 levels than control subjects (p < 0.05, p < 0.05). PAI-1 levels were positively correlated with waist circumference in diabetic group (r = 0.4, p < 0.05). After rosiglitazone treatment, there was no difference in mean plasma levels of GFC, t-PA, PAI-1 and t-PA/PAI-1 in diabetics. Insulin sensitivity significantly improved after the addition of rosiglitazone treatment in diabetic patients (p < 0.01). The short-term and low-dose treatment with rosiglitazone in type 2 diabetic patients has no effects on the fibrinolytic system, although it improves insulin sensitivity.
The Increase of Blood Anticardiolipin Antibody Depends on the Underlying Etiology in Cerebral Ischemia
Authors: Chen Wei Hsi , Kao Yi-Fen , Lan Min-Yu , Chang Yung-Yee , Chen Shun-Sheng , Liu Jia-Shou
Published: March 2006

Although anticardiolipin antibody (aCL) has been suggested to be a potent risk factor for thrombosis and atherosclerosis in multiple arterial beds, conflicting results exist between aCL and cerebral ischemia in the general stroke population. To elucidate if this discrepancy relates to the heterogeneity of underlying etiologies, the blood beta2-glycoprotein I dependent-aCL in 432 Taiwanese adults was examined. The associated cerebral ischemia in these patients was classified into five subtypes according to the cause of cerebral ischemia. The results were compared with those in 100 healthy controls. A definite increase of aCL-IgG isotype was found in 41 patients (9.35%) and four controls (4.0%). The relative risk was 2.52. The frequency of increased aCL-IgG was 12.2%, 12.8%, 8.8%, 3.9%, and 3.5% in patients with large-artery atherosclerotic disease, stroke of unknown etiology, small-artery occlusive disease, cardioembolism, and stroke of other known etiology, respectively. Only patients with large-artery atherosclerotic disease (p<0.025) and stroke of unknown etiology (p<0.05) had higher frequencies of increased aCL than those in control subjects. The frequencies of abnormal results of activated partial thromboplastin time, antinuclear factor, Coombs’ test, and venereal disease research laboratory were 2.84%, 1.22%, 1.02%, and 1.34% in these 41 patients, respectively. Accordingly, aCL-IgG selectively increases in patients with large-artery atherosclerosis and stroke of unknown etiology, reflecting selective activation of humoral immunity for aCL in the pathogenesis of cerebral ischemia.
Difficulties in the Mutation Analysis of Plasminogen Gene: A Study in Two Patients with Ligneous Conjunctivitis
Authors: Sartori Maria Teresa , Saggiorato Graziella , Pellati Donatella , Dal Bello Federico , Lombardi Anna Maria , Opocher Giuseppe , Spiezia Luca , Girolami Antonio
Published: March 2006

The absence or very low levels of plasminogen cause a rare disabling disease called ligneous conjunctivitis, characterized by the growth of fibrin-rich pseudomembranes in the conjunctiva and on other mucosal surfaces. Several mutations have been detected in the plasminogen gene of patients affected with ligneous conjunctivitis. The human plasminogen gene, located on chromosome 6, has a marked homology with the genes belonging to the plasminogenapo(a) family, and with a number of pseudogenes and plasminogen-like genes located on chromosome 2. This work describes a series of nucleotide variations related to genes other than the plasminogen one, found during the genetic characterization of plasminogen defect in two unrelated patients with ligneous conjunctivitis. The results of automated sequences of each exon and intron-exon boundaries were compared with those of the human plasminogen gene from the NCBI gene bank. In particular, a co-amplified gene on chromosome 2 mimicking a 14 bp deletion in exon 5 of the plasminogen gene was identified by sequencing two different bands obtained from a long run of the PCR exon 5 product in NuSieve agarose gel, and by PstI restriction enzyme analysis of the same amplicons. Moreover, 21 single nucleotide exchanges due to plasminogen-like genes co-amplification were observed, namely one in exon 1, two in exon 4, three in exons 3, 5 and 16, four in exon 13, and five in exon 17. In conclusion, these data confirm the difficulty of plasminogen genetic analysis and may help researchers to better identify the true plasminogen gene mutations causing molecular defects.
Spontaneous Renal Subcapsular Hematomain an Anticoagulated Patient
Authors: Ferrando Fernando , Budía Alberto , Mira Yolanda , Vayá Amparo , Aznar Justo
Published: March 2006

This is a case report of spontaneous subcapsular renal hematoma in an anticoagulated patient who was without excessive hypocoagulability and who was hemodynamically stable. Active bleeding was ruled out and a conservative treatment of discontinuing anticoagulant therapy was chosen. The patient was observed expectantly with serial abdominal computed tomography and abdominal ultrasound during her stay in the hospital. When diminution of the hematoma was detected, oral anticoagulation was resumed.
Warfarin-Induced Skin Necrosis: A Case Report
Authors: Abdul-Jabar Hani Basil , Geroulakos George , Philpott Nicola , Fareed Jawed
Published: March 2006

Warfarin-induced skin necrosis is an unusual complication of anticoagulation therapy associated with high morbidity. A patient is presented who had protein C deficiency and in whom this complication developed twice within a short time as a result of delayed diagnosis. Early recognition of this syndrome has important implications in the treatment of such patients and may reduce the severity of complications.
Myocardial Infarction and Deep Venous Thrombosis in a Young Patient with Behçet Disease
Authors: Çalgüneri Meral , Aydemir Kudret , Öztürk M. Akif , Haznedaroğlu Ibrahim C. , Kiraz Sedat , Ertenli Ihsan
Published: March 2006

Behçet disease (BD) is a chronic relapsing systemic vasculitic disorder affecting the arteries, veins, and vessels of any size. Vascular lesions in BD usually represent an occlusive nature suggesting a hypercoagulable/prothrombotic state. Coronary arteries are rarely involved in BD. In this report, a 27-year-old male patient in whom myocardial infarction developed secondary to coronary arterial thrombosis together with deep venous thrombosis was presented. This is a review of the pathologic hemostasis and the prothrombotic state of BD.
Middle Cerebral Arterial Thrombosis in a Patient with Hypofibrinogenemia, 5 Days After rFVIIa and FFP Infusion
Authors: Patiroglu Turkan , Karakukcu Musa
Published: March 2006

A 13-year-old female patient is presented who had hypofibrinogenemia diagnosed as von Willebrand disease at 5 years of age at another hospital. She was admitted to the department of pediatric hematology with a severe headache, vomiting, and progressive right flaccid hemiplegia and lethargy. Contrast-enhanced computed tomography scan showed subdural hematoma in posterior parietal region of the brain and impending cerebellar herniation. She was given fresh-frozen plasma (FFP) and then activated factor VII (rFVIIa), 80 μg/kg was infused for replacement of von Willebrand factor. The subdural hematoma was emergently drained. The results of coagulation tests before infusion of FFP and rFVIIa revealed hypofibrinogenemia, and FFP was given every 48 hours. The patient recovered dramatically in a few days. Five days after rFVIIa infusion, a magnetic resonance angiography-proven right middle cerebral arterial thrombosis developed. It is an interesting point of discussion whether the middle cerebral arterial thrombosis was provoked as a consequence of rFVIIa and FFP infusion.
Recombinant Activated Factor VII Combined with Desmopressin in Preventing Bleeding from Dental Extraction in a Patient with Glanzmann’s Thrombasthenia
Authors: Lombardo Vincenzo Trapani , Sottilotta Gianluca
Published: March 2006

The case of a 41-year-old woman with Glanzmann’s thrombasthenia who underwent double dental extraction is presented. In the past, treatments with desmopressin (DDAVP) and tranexamic acid had often unsuccessful efficacy to stop or decrease bleeding. After ineffective DDAVP administration, the removal was performed successfully with recombinant activated factor VII (rFVIIa) infusion. rFVIIa infusion after DDAVP administration could be useful in patients with Glanzmann’s thrombasthenia in which DDAVP and tranexamic acid weren’t always effective.
Prescribing Amplification for Children: Adult-Equivalent Hearing Loss, Real-Ear Aided Gain, and NAL-NL1
Authors: Ching Teresa YC , Dillon Harvey
Published: March 2006

This paper focuses on how the acoustical differences between the ear canals of adults and children affect amplification requirements and describes efficient strategies to allow for these differences when prescribing and verifying amplification. We will first summarize the problem for hearing assessment and then describe how adult-equivalent hearing loss can be calculated to circumvent this problem. Example cases demonstrate manual calculation and automatic derivation by using the NAL-NL1 software. The advantage of using real-ear aided gain prescriptions rather than real-ear insertion gain prescriptions for young children is explained. The practical benefit of deriving coupler gain targets to achieve the required real-ear aided gain by using individually measured real-ear-to-coupler differences is emphasized, together with a discussion on the practical issues relating to calibration and probe tube placement in measuring real-ear-to-coupler differences. Finally, an illustrative case exemplifies the derivation of individualized coupler gain targets by using the NAL-NL1 software system to achieve the required real-ear aided gain for a young child.
Ensuring Accuracy of the Pediatric Hearing Aid Fitting
Authors: Marcoux André , Hansen Martin
Published: March 2006

Considerable effort has recently been dedicated towards early detection of hearing loss in infants. The goal is to subsequently fit hearing aids to hearing-impaired infants so that they can develop speech and language as early and as well as possible. The responsibility of the audiologist is to provide the child with the optimal amplification from the hearing aid. This paper gives an overview of aspects involved in correctly assessing the hearing loss and optimally fitting and verifying the performance of the child's hearing aids. Special emphasis is directed towards differences that exist between children and adults, and how these differences can be considered during a pediatric fitting. We suggest a stringent terminology that can help avoid ambiguous terms and connotations in the child's domain which are derived from those that have become established in adult audiometry and hearing aid fittings. The quantification of hearing thresholds and their appropriate representation is reviewed. An appropriate threshold-based prescription of gain or output of the hearing aid is described. Issues of verification and the actual programming of the hearing aid are discussed.
An Approach for Ensuring Accuracy in Pediatric Hearing Instrument Fitting
Authors: Seewald Richard C. , Scollie Susan D.
Published: March 2006

Hearing instrument fitting with infants and young children differs in several important ways relative to the fitting process with adults. In developing the Desired Sensation Level method, we have attempted to account for those factors that are uniquely associated with pediatric hearing instrument fitting. Within this article we describe how the external ear acoustics of infants and young children have been systematically accounted for in developing the Desired Sensation Level method. Specific evidence-based procedures that can be applied with infants and young children for the purposes of audiometric assessment, electroacoustic selection, and verification of hearing instrument performance are described.