bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelium-Independent Relaxation of Vascular Smooth Muscle by 17β-Estradiol
Authors: Gonzales Rayna J. , Kanagy Nancy L.
Published: November 2007

Background: Estrogens directly dilate arteries, and this acute relaxation of vascular smooth muscle (VSM) may contribute to the cardioprotective effect of this important hormone. However, the mechanism by which estrogens relax VSM is not clear.

Methods and Results: Based on observations in isolated smooth muscle cells, we hypothe sized that 17β-estradiol (E 2) causes dilation through receptor-mediated activation of K+ channels in VSM cells. To test this hypothesis, E2-relaxation was studied in arteries from male Sprague-Dawley rats. We observed that the estrogen receptor antagonist, tamoxifen (3 μmol) attenuated E2 relaxation, suggesting that at least a portion of the relaxation depends on activation of E2 receptors. The nitric oxide synthase inhibitor, Nω-nitro-L-arginine (100 μmol) did not affect E2 relaxation in either denuded or endothelium-intact arterial strips. Furthermore, inhibition of guanylyl cyclase with LY83583 (10 μmol) had no effect on the relaxation, suggesting that nitric oxide does not contribute to this relaxation. Vascular seg ments contracted with 90 mmol KCl to disrupt the K+ gradient had a similar E2 relaxation to segments contracted with phenylephrine (10 -6 mol/L) indicating that E2 relaxation does not require K+-channel activation. Finally, E2 pretreatment inhibited contraction of arterial segments depleted of intracellular calcium but in the presence of extracellular calcium. However, E2 did not affect contraction of strips in calcium-free solution.

Conclusions: These final experiments suggest that E2 inhibits Ca2+ influx but not intracellu lar calcium release. Together, these studies establish that E2 causes receptor-mediated relax ation of peripheral resistance arteries through inhibition of calcium entry independent of nitric oxide production, guanylyl cyclase stimulation, and K+-channel activation.
Primary Hyperparathyroidism and Polymorphic Ventricular Tachycardia
Authors: Speakman Mark T. , Ostrzega Enrique
Published: November 2007

Background: Primary hyperparathyroidism is a rare but important cause of ventricular arrhythmias.

Methods and Results: The medical records of a patient with primary hyperparathyroidism and polymorphic ventricular tachycardia was reviewed. The patient was serially interviewed and examined before and after parathyroidectomy. A literature search was performed. The association of primary hyperparathyroidism and polymorphic ventricular tachycardia is rare. Hypokalemia and hypomagnesemia occur infrequently in primary hyperparathyroidism.

Conclusions: The potential for malignant ventricular arrhythmias in the setting of primary hyperparathyroidism must be recognized.
State-of-the-Art-Review : Exclusion and Diagnosis of Pulmonary Embolism by a Rapid ELISA D-dimer Test and Noninvasive Imaging Techniques within the Context of a Clinical Model
Authors: Jacques Michiels Jan , Pattynama Peter M. T.
Published: November 2007

A negative rapid ELISA D-dimer test alone in out patients with a low to moderate clinical probability (CP) on pulmonary embolism (PE) is predicted to safely exclude pul monary embolism. The combination of a negative rapid ELISA D-dimer test and a low to moderate CP on PE followed by compression ultrasonography (CUS) for the detection of deep vein thrombosis (DVT) is safe and cost-effective as it reduces the need for noninvasive imaging techniques to about 50% to 60% of outpatients with suspected PE. A high probability ven tilation-perfusion (VP) scan or a positive spiral CT consistent with PE and the detection of DVT by CUS are currently con sidered to be clear indications for anticoagulant treatment. Sub sequent pulmonary angiography (PA) is the gold standard di agnostic strategy to exclude or diagnose PE in suspected out patients with a negative CUS. a positive rapid ELISA D-dimer test, and a nondiagnostic VP scan or negative spiral CT to prevent overtreatment with anticoagulants. However, the will ingness of clinicians and the availability of resources to per form PA is restricted, a fact that has provided an impetus for clinical investigators to search for alternative noninvasive strat egies to exclude or detect venous thromboembolism (VTE). Serial CUS testing for the detection of DVT in patients with a low to moderate CP on PE and a nondiagnostic VP scan or negative spiral CT is predicted to be safe and will reduce the need for PA to less than 10% or even less than 5%. This noninvasive serial CUS strategy restricts the need for invasive PA to a minor group of patients (<5%) with the combination of a low CP on PE and high probability VP scan or the combi nation of a nondiagnostic VP scan or negative spiral CT and a high CP on PE. Prospective evaluations are warranted to imple ment and to validate the advantages and the disadvantages of the various combinations of nonivasive strategies and to com pare serial CUS testing versus PA in randomized clinical man agement studies of outpatients with suspected pulmonary em bolism.
Value of Prothrombin Fragment 1.2 (F 1.2) in the Diagnosis of Stroke in Young Patients With Antiphospholipid Antibodies
Authors: Ellis Martin H. , Kesler Anat , Friedman Ziva , Drucker Ilana , Radnai Yehudit , Kott Edna
Published: November 2007

The presence in the serum of antiphospholipid an tibodies (aPL) is associated with venous and arterial thrombo sis. This observation has led to the search for these antibodies in young patients with ischemic neurologic syndromes. How ever, 1% to 5% of healthy people may be found to have cir culating aPL without necessarily being at increased risk of thromboembolism. Thus, the finding of APLA in a patient with cerebral ischemia does not necessarily provide an explanation for the etiology of the clinical syndrome. The aim of this study was to determine whether the presence of aPL in young patients with stroke or transient ischemic attacks represents a possible cause of hypercoagulability as defined by ongoing thrombin formation with resultant elevation of prothrombin fragment 1.2 (F1.2) levels.

This was a retrospective, case-control study involving 57 subjects. Twenty-seven patients had a recent cerebrovascular ischemic event—either TIA or a stroke. Fifteen were positive for aPL, and 12 were aPL-negative.

Thirty subjects, matched for age and sex with no history of cerebrovascular disease, served as controls. Of this group, 20 were aPL-positive and 10 were aPL-negative. Causes of hy percoagulability other than aPL were excluded by laboratory testing. A positive test for aPL was repeated after a 6-week interval and two positive tests were required for a patient to be regarded as being aPL-positive. Levels of F1.2 were measured by an ELISA technique.

There was a significant difference ( p < 0.05) in the mean F1.2 levels between the aPL-positive group with a history of cerebrovascular disease (mean F1.2 = 2.3733) and each of the other study groups. There was no statistically significant dif ference between any of the other study groups.

Our findings suggest that F1.2 levels are elevated in young patients with cerebrovascular syndromes who have aPL and in whom other causes of hypercoagulability and atherosclerotic vascular disease are absent. Elevated F1.2 in these patients may be a potential marker of the hypercoagulable state associated with aPL.
Rapid ELISA D-Dimer Testing in the Exclusion of Venous Thromboembolism in Hospitalized Patients
Authors: Freyburger Geneviève , Trillaud Hervé , Labrouche Sylvie , Gauthier Pascal , Javorschi Sandrine , Grenier Nicolas
Published: November 2007

The clinical diagnosis of deep-vein thrombosis (DVT) and pulmonary embolism (PE) is known to be unreli able. Until now, no biological marker has been found to con firm thrombosis, but help can be gained from a biological marker ruling out the diagnosis of DVT or PE, i.e., the sensitive measurement of D-dimer (DD) species. This article summa rizes our experience in introducing a rapid D-dimer test (ELISA VIDAS D-dimères test, bioMérieux) in a collaborative strategy for thrombosis diagnosis during 9 consecutive months involving 1,131 measurements. The efficacy of the DD test was very different according the type of patient, and departments where the DD test provides a real diagnostic benefit were iden tified. High clinical probability for thrombosis was encountered in 32 patients and radiology was carried out, although D-dimer was negative: none of these patients was found to have a throm bosis after radiologic examination. However, extensive prog ress must be made in test prescription to reduce the excessive rate of positive D-dimer tests (78%) and positive measurements that are not followed up by radiology (42%).
Risk of Thrombosis in Patients Homozygous and Heterozygous for Factor V Leiden in the East Bohemian Region
Authors: Dulíček Petr , Maly J. , Šafářová M.
Published: November 2007

A retrospective investigation on the frequency of thrombotic events in 227 heterozygous and 16 homozygous carriers for the factor V R506Q mutation (factor V Leiden) from 102 unrelated families in the East Bohemian region is reported. A majority of 130 of the 227 (57%) heterozygous and a minority of 5 of 16 (31 %) homozygous carriers for the factor V R506Q mutation remained asymptomatic. Deep venous thrombosis without pulmonary embolism in a minority was the main and the most frequent clinical manifestation in 97 of 243 carriers for the factor V R506Q mutation. Deep venous throm bosis occurred in 92 of 227 (41%) heterozygous and in 11 of 16 (69%) homozygous carriers of the factor V R506Q. Spontane ous thrombosis prevailed in symptomatic men. Thrombosis in women usually occurs during risk situations well known to elicit venous thrombosis. Oral contraceptives and pregnancy were significantly the most frequent risk factors in female car riers of the factor V R506Q mutation, which in fact can readily explain the lower average age for the first thrombotic event of 30.6 years in women compared to 37.1 years in men.
State-of-the-Art Review : Review and Management of Patients With the Prothrombin G20210A Polymorphism
Authors: Nguyen Adrian
Published: November 2007

A single mutation in the 3'-untranslated region of the prothrombin gene, resulting in a G to A substitution, was recently reported. This finding added to the growing list of genetic disorders thought to be responsible for familial throm bophilia. Although most studies are in general agreement about the elevated risk of venous thrombosis in individuals carrying this mutation, its role in the first event of venous thromboem bolism and recurrent events is unclear. Even less clear is the role that this mutation plays in the formation of arterial throm bosis (including coronary artery disease and cerebral ischemia), as studies show contradicting results. Because of this, it is not recommended as part of the routine screening of patients with venous thromboembolism. However, there are certain sub groups of patients who should undergo testing. The discovery of this prothrombin mutation has important clinical implica tions because it is the second most common cause of genetic thrombophilia, second only to the factor V Leiden. Moreover, its discovery likely will augment the clinician's ability to sys tematically risk-stratify an individual's likelihood of develop ing spontaneous thrombosis.
Prevalence of Genetic Mutations That Predispose to Thrombophilia in a Greek Cypriot Population
Authors: Angelopoulou Katerina , Nicolaides Andrew , Constantinou Deltas C.
Published: November 2007

Several hereditary disorders, particularly those af fecting the physiological anticoagulation systems, have been well established as risk factors for venous thromboembolism. In the present study, we investigated the prevalence of the following thrombogenic mutations in a Greek-Cypriot popula tion : the G1691 factor V Leiden mutation, the G20210A mu tation in the prothrombin gene, and the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR). All three vari ants have been documented to be significant risk factors for various cardiovascular conditions. Ninety unrelated subjects were screened. For the Leiden mutation, 11 subjects (12.2%) were heterozygous and one (1.1%) was homozygous. Seven subjects (7.8%) were heterozygous for the G20210A variant in prothrombin; no homozygotes were identified. The C677T mu tation in MTHFR was found in 40 individuals in the heterozy gous state (44.4%), and in 16 individuals in the homozygous state (17.8%). These data demonstrate that Greek-Cypriots have an increased frequency of thrombogenic mutations, and suggest that screening for these mutations should be seriously considered, especially when surgery or pregnancy is planned. This is the first study for the frequency of mutations in risk factors that predispose to thrombophilia on the island of Cyprus.
State-of-the-Art Review : Effect of Sarpogrelate Hydrochloride on Platelet-Derived Microparticles and Various Soluble Adhesion Molecules in Diabetes Mellitus
Authors: Shouzu Akira , Nomura Shosaku , Hayakawa Takashi , Omoto Seitaro , Shimizu Hidekazu , Miyake Yutaka , Yonemoto Toshinaga , Fukuhara Shiro , Iwasaka Toshiji , Nishikawa Mitsushige , Inada Mitsuo
Published: November 2007

We measured platelet-derived microparticles, ac tivated platelets, and various adhesion molecules in 48 patients with diabetes mellitus. We also performed a comparative study of these parameters before and after administration of sarpo grelate hydrochloride. The numbers of platelet-derived micro particles and activated platelets were increased significantly in diabetic patients, and CD63-positive platelets were increased in patients with diabetic complications and poorly controlled blood glucose. Soluble adhesion molecules and thrombomodu lin were also increased significantly. After administration of sarpogrelate hydrochloride, not only CD62p- and CD63- positive platelets, but also platelet-derived microparticles were decreased significantly. Soluble adhesion molecules and throm bomodulin were also significantly decreased after the treat ment. These data suggest that (a) in patients with diabetes, antiplatelet therapy with sarpogrelate hydrochloride is a useful antithrombin therapy because it suppresses the production of intrinsic coagulants by activated platelets; and (b) sarpogrelate hydrochloride decreases endothelial cell damage via adhesion molecules.
Severity of Illness, Outcomes, and Resource Use in Elderly Cancer Patients with Deep Venous Thrombosis
Authors: Escalante Carmen P. , Kurtin Danna , Rivera Edgardo , Elting Linda S.
Published: November 2007

Low-molecular-weight heparins provide new op tions for outpatient management of deep venous thrombosis. Because elderly patients with cancer are at increased risk of developing deep venous thrombosis, outpatient therapy for treatment of deep venous thrombosis may be important in this population. We compared the severity of illness, outcomes, and cost of deep venous thrombosis in elderly patients with cancer to those seen in younger patients with cancer. We examined all 766 episodes of deep venous thrombosis treated at the Univer sity of Texas M.D. Anderson Cancer Center between January 1, 1994 and December 31, 1996. Severity of illness level and predicted risks of mortality and readmission were obtained from a commercially available disease staging system (Inforum System). Observed outcomes and cost were based on data col lected from the 766 episodes of deep venous thrombosis at our institution. One hundred nineteen (16%) episodes of deep ve nous thrombosis occurred in patients 70 years of age or older. The severity of illness scale (1-5, least-most severe) were iden tical (3.7) in the 3 groups studied (< 70 years, 70-79, years and ≥80 years). The predicted risk of death during hospitalization (6%, 9%, 8%, respectively, by group, P = 0.12) and readmis sion in 30 days (5%, 4%, 3%, respectively, P = 0.04) were similar among the groups. The observed death rates during hospitalization were 5%, 6%, and 6%, respectively ( P = 0.91), and the rates of hospitalization for deep venous thrombosis recurrence were 22%, 16%, and 28%, respectively ( P = 0.27). The similarities in outcomes and resource use between elderly and younger patients suggest that elderly patients with cancer are not at greater risk of serious clinical outcomes or a pro longed clinical course. There is significant potential for outpa tient management of these patients.
Portal Vein Thrombosis Associated to Prothrombin G20210A Mutation and Protein C Deficiency
Authors: Mira Yolanda , del Castillo Gloria García , Estellés Amparo , Villa Piedad , Vayá Amparo , Ortuño Carmen , Aznar Justo
Published: November 2007

We describe a patient with left branch portal vein thrombosis involving two thrombophilic alterations, the pro thrombin G20210A mutation and protein C deficiency. In spite of not being under anticoagulant treatment, the thrombus in the portal vein underwent complete and spontaneous lysis. No other risk factors were detected and no family history related to thrombosis was found.
Thromboelastograph Assay for Measuring the Mechanical Strength of Fibrin Sealant Clots
Authors: Glidden Paul F. , Malaska Christine , Herring Steven W.
Published: November 2007

In order to provide sustained hemostasis or tissue sealing, fibrin sealants must generate adhesive clots with me chanical properties capable of resisting forces, such as shear, that might break or tear the clot. Commercial preparations of fibrin sealants should generate clots of adequate and consistent mechanical strength. The mechanical strength of fibrin sealants is often measured as bonding strength in in vivo or ex vivo animal wound models. These tests can be useful predictors of clinical efficacy. However, these, as well as many in vitro tensile strength tests for fibrin sealant, tend to be laboratory specific and require extensive reagent preparation time and analyst training. The thromboelastograph has historically been used to screen for plasma protein and platelet disorders that lead to defective clot formation. The authors have developed a simple in vitro test, using a standard thromboelastograph that can provide reliable, reproducible information on the rheology of clots generated by fibrin sealant preparations. Using this method, the shear strength of fibrin sealant clots was measured and shown to correlate with the fibrinogen, but not the throm bin, concentration in the sealant. Shear strength was also shown to correlate with the sealant concentration of the fibrin cross- linking proenzyme, factor XIII. Sealants containing lysine, which can act as an alternate substrate for factor XIII enzyme and prevent efficient fibrin chain cross-linking, were shown by this method to generate clots of substantially reduced shear strength. The method distinguished between thrombin- catalyzed clot formation and other fibrinogen clotting mecha nisms as evidenced by the significantly lower shear strength associated with batroxobin-generated fibrin clots.
Global Anticoagulant Effects of a Novel Sulfated Pentomanan Oligosaccharide Mixture
Authors: Piccolo Pietro , Iqbal Omer , Demir Muzaffer , Qing Ma  , Gerbutavicius Rolandas , Fareed Jawed
Published: November 2007

PI-88 is a potent antiproliferative agent, which is developed for various indications in cancer. This agent is obtained from yeast fermentation and is primarily composed of pentamannose and tetramannose oligosacchafide units. PI-88 is capable of prcaclucang anticoagulant effects, which are mediated by heparin cofactor II. The purpose of this study was to determine the anticoagulant properties of PI-88 in native whole blood, freshly drawn from human volunteers, supplemented with PI-88 at various concentrations (0-100 μg/mL). Whole blood activated clotting time (ACT) was measured using Hemochron instruments. PI-88 produced a strong anticoagulant effect at 100 μg/mL (479.0 ± 59.5 see). This anticoagulant effect was comparable to that observed in interventional cardiology and open-heart surgery. At the lower level, PI-88 produced concentration-dependent effects on ACT. Using thromboelastographic techniques (TEG), the effect of PI-88 was measured in terms of various parameters. PI-88 produced potent anticoagulant effects in the TEG studies. At the concentration of 25 μg/mL, it produced a complete anticoagutant effect in whole blood. Whole blood samples supplemented with PI-88 showed a concentration-dependent decrease in the generation of various markers of clotting activation. These results clearly suggest that PI-88 exerts an anticoagulant effect in whole blood. Because of the low-molecular-weight nature and a novel mechanism of action, this new drug may be considered for further development, particularly in cancer patients.
Venous Thromboembolism in Young Patients From Western India: A Study
Authors: Ghosh K. , Shetty S. , Madkaikar M. , Pawar A. , Nair S. , Khare A. , Pathare A. , Jijina F. , Mohanty D.
Published: November 2007

The goal of this article is to study the association of known markers of thrombophilia with venous thrombosis in young patients (< 45 years) from the Western part of India. A prospective study of 432 patients (252 males and 180 females, age 1-45 years) was conducted between 1994 and 2000 (6 years). The diagnosis was confirmed in all the patients by ultrasound with Doppler or by a computed tomograph (CT) scan of the brain with or without contrast depending on the case. Detailed clinical examination, and family history was taken to establish recurrent thrombosis and familial occurrence of thrombosis. The markers studied were protein C, protein S, antithrombin (AT) III, factor V Leiden mutation, prothrombin gene G20210A polymorphism, and the thermolabile MTHFR variant C677T polymorphism, using appropriate techniques. Lupus inhibitor was tested in the first 72 patients using Dilute Russel Viper Venom Time (DRVVT) test, and anticardiolipin antibodies were tested by enzyme-linked immunosorbent assay. Protein C, protein S, and AT III deficiency was detected in 9.5%, 6.5%, and 2.6%, respectively, among the patients. Anticardiolipin antibody was present in 9.9% of the patients, whereas lupus anticoagulant was present in 8.3% of patients; factor V Leiden mutation was detected in 3% of patients; thermolabile variant of MTHFR C677T polymorphism was present in 14.9% of patients with 1.2% homozygotes. Prothrombin G20210A polymorphism was not detected in any sample in this population. One hundred and four patients of 432 (24.9%) had recurrent attacks of thrombosis without any proximate precipitating cause, whereas 7.5 % of the patients had another close member of the family with a history of deep venous thrombosis. Eighty-six members from 28 families (out of 32 families giving family history of thrombosis) were investigated and found to have protein C and protein S deficiency in seven each; factor V Leiden was present in 6, and MTHFR C677T polymorphism was present in 5 cases. Hence, 25 of 86 members (28%) from the family of patients with familial history deep venous thrombosis had positive markers for thrombophilia. Thus, we could show that in young patients presenting with thrombosis, at least 34% of them had a demonstrable cause for thrombophilia. Prothrombin gene polymorphism G20210A seems to be nonexistent in our population and AT III deficiency also appears to be low compared to other markers of thrombophilia. There is a high prevalence of variant MTHFR C677T in our series, but the incidence of MTHFR C677T in our general population is also high. Hence, the significance of this finding in our cases of deep venous thrombosis remains to be seen, but we did not see any homozygotes when we tested 70 randomly selected asymptomatic persons, whereas in the present series, 1.8% of the patients had homozygosity for the MTHFR C677T polymorphism.
State-of-the-Art Review: The Oral Anticoagulant Saga: Past, Present, and Future
Authors: Duxbury B. McD. , Poller Leon
Published: November 2007

Oral anticoagulation originated with the discovery of the harmful agent causing "sweet clover disease" in cattle in North America in the 1920s. The causative agent dicoumarol was isolated in Link's laboratory in 1940. A range of related compounds was then synthesized, the most popular of which proved to be warfarin. Oral anticoagulant administration posed problems of individual variation in response to these drugs and the need for regular laboratory monitoring by prothrombin time (PT). Monitoring problems arose from the introduction in the 1950s of some poorly responsive commercial tissue extracts for use as tissue extract thromboplastin reagent in the PT. More oral anticoagulant drug was then needed to prolong the test to the required therapeutic targets, with a resultant increase in bleeding. It was not until 1983 that the problem was resolved and it was shown that the less intense UK-type regimen was just as effective as the higher North American type dosage in the prevention of venous thrombosis but caused much less bleeding. This study led to the widespread adoption of the "low-dose warfarin" regimen that, combined with the World Health Organization PT standardization scheme using the international normalized ratio (INR), has led to improved effectiveness and safety of oral anticoagulation. This has permitted increased administration of warfarin in a widening spectrum of clinical disorders. The last remaining problem is the limited success of doctors in achieving the therapeutic INR targets, which may be improved by computer-assisted dosage.
State-of-the-Art Review: Endothelial Dysfunction in the Pathogenesis of Atherosclerosis
Authors: Poredoš Pavel
Published: November 2007

Healthy endothelium plays a central role in cardiovascular control. Therefore, endothelial dysfunction (ED), which is characterized by an imbalance between relaxing and contracting factors, procoagulant and anticoagulant substances, and between proinflammatory and antiinflammatory mediators, may play a particularly significant role in the pathogenesis of atherosclerosis. Endothelial dysfunction is closely related to different risk factors of atherosclerosis, and to their intensity and duration. The involvement of risk factors in ED is also supported by results of interventions studies that showed regression of ED with treatment of risk factors. Because risk factors are commonly accompanied by decreased bioavailability of nitric oxide, the common denominator whereby different risk factors cause ED is most probably increased oxidative stress. Endothelial dysfunction may promote atherogenesis through different mechanisms such as increased adherence of monocytes, macrophages, and enhanced permeability of the endothelial layer. Further, ED probably plays an important role in the growth of atherosclerotic lesions and in the development of thrombotic complications in late stages of the disease. Because ED is a key underlying factor in the atherosclerotic process, markers of endothelial abnormalities have been sought. Detection of ED is based on tests of endothelium-dependent vasomotion (dilation capability of peripheral and coronary arteries) and on circulating markers of endothelial function (endothelin-1, von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor, and adhesion molecules). Using these tests it is possible to follow the dose response of harmful effects of risk factors, and the effects of preventive procedures on vessel wall function.
Spontaneous Platelet Aggregation With Congenital Giant Platelet Containing Large Granules and Thick Membrane
Authors: Zhaoyue Wang  , Jumei Shi  , Yue Han  , Yingchun Wang  , Changgeng Ruan
Published: November 2007

Inherited giant platelet disorders are a heterogeneous group of disorders. In the current study, a patient was reported with moderate bleeding tendency, giant platelets, and spontaneous platelet aggregation, which were not affected by the administration of aspirin or ticlopidine. The electron microscopy of platelets showed a black and thick plasma membrane with crystal-like fine hairs in the exterior coat and more large and variously shaped granules in the cytoplasm. The expression of glycoprotein (GP) Ib, GP IIb, and GP IIIa on platelet surface was normal, and no mutations in genes for GP Ibα, GP Ibβ, and GP IX were detected. These phenomena are so distinguishable from those of Mondreal platelet syndrome and other hereditary giant platelet disorders, that we propose that this patient probably has a novel platelet disorder, which has not yet been reported.
Low-Molecular-Weight Heparins: Weeks or Months Instead of Days of Treatment
Authors: Kher A. , Samama M.M.
Published: November 2007

Low-molecular-weight heparins (LMWHs) have been used for more than a decade in the prophylaxis and treatment of venous thromboembolism and recently in coronary artery disease. During the past few years, the duration of treatment has been increased in several pathologic conditions. A number of clinical studies provided evidence that the duration of prophylaxis after hip replacement should be prolonged up to 35 days after surgery. Several clinical trials concluded that LMWHs provide an effective and safe alternative to oral anticoagulants in the secondary prevention of deep vein thrombosis. A recent trial showed that extended dalteparin treatment is useful for protection against further complications while patients are waiting for invasive procedures. Finally, LMWHs seem to be safe during pregnancy.
Hemostasis in Children With Dysbacteriosis in Chronic Constipation
Authors: Kirgizov I.V. , Sukhorukov A.M. , Dudarev V.A. , Istomin A.A.
Published: November 2007

The purpose of the study was to investigate hemostasis in children with dysbacteriosis disturbance in chronic constipation. The disturbance of factors in the inner mechanism of blood coagulation (VII, IX, XI, XII) in compensated chronic constipation was defined based on the reduction in colon bacillus levels. We observed hypocoagulation caused by the reduced activity of the prothrombin complex factors, disaggregate thrombocytopathy, and endotheliosis with fibrinolysis inhibition in subcompensated chronic colostasis with continuous reduction of colon bacillus levels and pathogenic microflora appearance. In decompensated colostasis there was an increase in pathogenic microorganisms and a continuous reduction of colon bacillus levels. In hemostasis there was a factor deficiency in inner (XII, XI, IX, VIII) and outer (II, V, VII, X) blood coagulation mechanisms. Fibrinolysis inhibition, endotheliosis development with thrombocyte aggregation, and microthrombosis formation were determined. Thus, in children with chronic constipation, there was a marked reduction in the amount of colon bacillus, which led to the reproduction of pathogenic bacteria. We also observed chronometric hypocoagulation with the inner (XII, XI, IX. VIII) and outer (II, V, VII, X) mechanisms of blood coagulation, at the base of which there is the deficiency of vitamin K-dependent factors (II, VII, IX, X) and a slightly marked disturbance in the final stage of coagulation. In thrombocyte vascular hemostasis, thrombocytopathy was observed with increased adenosine-5-diphosphate aggregation and the inhibition of the inner mechanism with fibrinolysis and endotheliosis.
Day-Night Variations in Blood Levels of Nitric Oxide, T-TFPI, and E-Selectin
Authors: Kanabrocki Eugene L. , George Magdalena , Hermida Ramon C. , Messmore Harry L. , Ryan May D. , Ayala Diana E. , Hoppensteadt Debbie A. , Fareed Jawed , Bremner Fraser W. , Third Jane L. H. C. , Shirazi Parvez , Nemchausky Bernard A.
Published: November 2007

Circadian (8/24 hours) variations in serum nitric oxide (NO), total tissue factor pathway inhibitor (T-TFPI), and E-selectin levels were studied in healthy adults and in subjects with type II diabetes. We postulated a possibility a functional relationship between them because vascular endothelium is the primary site of their synthesis and functions. NO is released by the action of eNO synthase isoform and modulates physiologic responses (e.g., vascular dilation, relaxation, increasing blood flow, inhibition of platelet and white blood cell adhesion); T-TFPI, a coagulation inhibitor, is also released from endothelial cells, and is bound to plasma lipoproteins and to glycosaminoglycans; E-selectin is expressed on endothelial cells after activation by inflammatory cytokines (interleukin-1β and tumor necrosis factor-α) and elevated levels have been reported in a variety of pathologic conditions, including diabetes. We found that obese diabetic subjects had greater mean concentrations of NO and E-selectin than healthy men, 39.25 versus 12.71 μM and 81.51 versus 26.03 ng/mL, respectively. The T-TFPI levels were essentially similar in both groups of men, 47.10 versus 48.76 ng/mL. We observed that the time of peak concentrations of T-TFPI and E-selectin was similar to the timing of NO trough levels, suggesting a possible functional relationship. It may be hypothesized, therefore, that the higher concentrations of NO, unbalanced by increases in T-TFPI and E-selectin, may result in increased vascular wall uptake of lipoproteins in diabetic subjects, who are at greater risk than healthy men for developing diffuse atherosclerosis.
New Anticoagulants for the Cardiovascular Patient
Authors: Walenga Jeanine M. , Fareed Jawed , Bick Rodger L. , Pifarré Roque
Published: November 2007

Manuscript received May 9, 1994; accepted July 7, 1994. Address correspondence and reprint requests to Dr. Jeanine M. Walenga, Department of Pathology, Loyola University Med ical Center, 2160 South First Avenue, Maywood, IL 60153, U.S.A. Summary: Invasive cardiac procedures and cardiac sur gery, which have become a significant component of health care, provide a particular case scenario where there are special considerations given to control bleeding and to have available alternative anticoagulants for pa tients unable to tolerate heparin (e.g., heparin-induced thrombocytopenia). We describe a comprehensive proto col for blood preservation in cardiac surgery incorporat ing the patient's medical history, autologous transfusions, and intraoperative techniques of heparin and protamine titration and dosing. Furthermore, various new anticoag ulants under clinical development are discussed, particu larly hirudin, hirulog, iloprost, ancrod, Lomoparan, low- molecular-weight heparins, 1-deamino-8-D-arginine- vasopressin (DDAVP), and aprotinin. These approaches should benefit the patient with difficult to control periop erative bleeding, heparin-induced thrombocytopenia, al lergic reactions to protamine, platelet dysfunction, and poor response to heparin (e.g., due to antithrombin III deficiency).
Ten Years' Experience with the "Sticky Platelet Syndrome"
Authors: Mammen Eberhard F.
Published: November 2007

We describe a 10-year experience with a con genital platelet abnormality characterized by hyperaggre gability with ADP and/or epinephrine. The syndrome has so far been identified in >200 patients and their families. Clinical symptoms are transient or permanent arterial oc clusions, thrombotic in nature, affecting especially the coronary and cerebral vasculature, including ophthalmic vessels. The patients have no identifiable risk factors and are usually young (5-45 years), and other hypercoagula ble states are excluded. In many cases the vascular acci dent is precipitated by severe stressful events. Occasion ally the syndrome is found in patients with recurrent ve nous thromboembolism while they are on optimal oral anticoagulant therapy. In the laboratory the patients' platelets are hyperaggregable with decreasing ADP and/ or epinephrine concentrations added to platelet-rich plasma. Two forms are identified: Type I is marked by hyperaggregability with ADP and epinephrine, while Type II evidences hyperaggregability only with epineph rine. No abnormalities are found when other aggregation stimulators are used. By electron microscopy the plate lets are more readily activated by surface contact, with a greater tendency toward aggregate formation. Plasma lev els of platelet release proteins, platelet factor 4, and β-thromboglobulin are not elevated. The syndrome is treated with low-dose aspirin, which reverses the hyper aggregability and improves clinical symptoms. We hy pothesize that in vivo adrenaline release leads to in creased platelet clumping, which can transiently or per manently occlude small vessels. It is conceivable that altered surface receptors on the platelets might be respon sible for this congenital problem.
Intracerebral Hemorrhage Remote from a Radiosurgically Obliterated Arteriovenous Malformation
Authors: Hudgins W. Robert , Kilgore Bassett B. , Simpson Charles W. , Hood Terry W. , Barker Jerry L.
Published: November 2007

Follow-up angiography that no longer shows a cerebral arteriovenous malformation (AVM) after radio surgery is thought to indicate obliteration and protection from risk of hemorrhage. However, angiographically oc cult vascular malformations can bleed, so one might ques tion the degree of protection provided by radiosurgery. The patient reported here was anticoagulated for deep vein thrombosis after a cerebellar AVM had been "oblit erated" by treatment with a gamma knife. He subse quently suffered a fatal supratentorial hemorrhage. At au topsy, no bleeding was seen in the region of the throm bosed AVM. This case is presented as further evidence of the efficacy of radiosurgery in the treatment of cerebral AVMs.
Impaires Anticoagulant Activity of Protein C and Activation of Neutrophils in Extensive Lung Cancer
Authors: Scitz Rainer , Rappe Nicole , Wolf Martin , Heidtmann Hans-Heinrich , Maasberg Michael , Immel Anette , Kraus Michael , Egbring Rudolf , Pfab Rüdiger , Havemann Klaus
Published: November 2007

Lung cancer is associated with an increased incidence of thrombosis. An activation of coagulation is demonstrable in lung cancer patients by sensitive activation markers, as well as a stimulation of neutrophil granulocytes, which are known to interfere with hemostasis, e.g., by degrading inhibitory proteins. We assessed antigen level, amidolytic activity, and clotting activity of the plasma anticoagulant protein C and the activation markers thrombin-antithrobin complex (TAT) and neutrophil elastase-α1-antitrypsin complex (EAT) in 67 lung cancer patients before antineoplastic treatment was begun. The protein C clotting activity was lower (p = 0.010) in the patients with extensive than in those with limited disease. However, the median levels remained within the normal range in both groups (91 vs. 108% of normal). The median amidolytic activity levels (110 vs. 117% of normal ; NS) were higher than the protein C antigen levels (82 vs. 77% of normal; NS) in- both groups. There was no significant correlation of protein C measurements with TAT levels, but there were significant negative correlations between EAT and protein C clotting activity and antigen level. The data suggest that in patients with lung cancer, there may be an alteration of the protein C molecule, which reduces antigen level and impairs clotting activity without affecting amidolytic activity. The negative correlation with EAT levels might point to limited degradation of protein C by neutrophil enzymes, leading to partial loss of epitopes detected by the immunologic determination and of structures necessary for the biologic effect of protein C upon clotting time. Further studies should clarify whether such a modification of protein C could contribute to the increased incidence of thrombosis in lung cancer patients. Key Words: Lung cancer-Neutrophil elastase-Protein C.
Failure to Generate Comparable International Normalized Ratio Values Using Five Different Thromboplastin Reagents in Parallel Studies of Patients Receiving Warfarin
Authors: Schmitz Laura L. , Olson Sandra L. , Shapiro Robert S. , McCormick Stanley R. , Kubic Virginia L.
Published: November 2007

Warfarin therapy has traditionally been monitored using the prothrombin time (PT). A significant problem with this assay is the variable sensitivity of commercially available thromboplastin reagents to reduction of vitamin K-dependent coagulation factors. The International Normalized Ratio (INR) was developed as a means of standardizing PT values between laboratories that use different thromboplastins and types of instrumentation. Parallel testing of samples from 63 patients stabilized on oral anticoagulation with five different thromboplastins was undertaken. Forty-eight percent of all samples had INR values that were not identical but showed good correlation. Fifty-two percent of the samples had clinically significant discrepancies of their INR values. In this group, patients in the therapeutic range with one thromboplastin appeared over- or underanticoagulated based on the INR using a different thromboplastin. In order to determine whether use of a low-ISI thromboplastin reagent could provide more reproducible INR results, concurrent testing of specimens from 36 patients on stable oral anticoagulation was undertaken between our hospital laboratory and another, nonaffiliated institution. Both hospitals used similar instrumentation and thromboplastin reagents. Under these conditions, the INR values generated between laboratories correlated highly. The inability to generate consistent INR values in parallel testing using different thromboplastins with identical samples and instrumentation raises concern about the reliability of the INR, and suggests that further analysis is necessary to identify the source of these discrepancies. In the interim, our data show use of a recombinant thromboplastin with a low-ISI value substantially improves interlaboratory variation in INR value. Key Words: International Normalized Ratio—Prothrombin time—Thromboplastin—Anticoagulation monitoring.
Significance of the PAP Complex in Thermal Injury
Authors: Kowal-Vern A. , Walenga J.M. , Levi M. , Sharp-Pucci M.M. , Gamelli R.L.
Published: November 2007

Plasmin-antiplasmin complex (PAP) has been reported previously as elevated in sepsis syndrome and infection. To assess the value of PAP complex and the thrombin-antithrombin (TAT)/PAP ratio in thermal injury, sixty patients were studied within the first 36 h, at 5-7 days following injury, and at time of infection. The patient population was categorized by percent burn (2° + 3°): <20%, n = 22; 20-40%, n = 18; >40%, n = 20. PAP increased significantly between days 1 and 5 in the <20% and 20-40% burn groups ( p < 0.01) and in the >40% group ( p < 0.002). The TAT/PAP ratio was elevated on day 1 in the 20-40% group ( p < 0.04) and the >40% group ( p < 0.001), and decreased to near normal limits on day 5 in both groups. These data revealed a proportionately greater incidence of coagulation activation than fibrinolysis on day 1. Of 16 episodes of sepsis syndrome or severe infection, PAP was elevated, average 14.6 nM (normal < 8 n M), in 10 (63%) patients. PAP was significantly elevated on day 5 during the clinically stabilized phase regardless of percent burn ( p = 0.01). In individuals who had a burn wound surface area of >40%, the PAP values were significantly higher for those who did not survive ( p < 0.03). PAP did not appear to correlate with the type of burn or with inhalation. Although PAP complex levels were elevated in thermal injury patients with sepsis syndrome or severe infection, they were not a specific predictor of infection. In conclusion, PAP complex and the TAT/PAP ratio provided useful information as to the fibrinolytic status of thermally injured patients with correlation to survival, but without correlation to sepsis and infection.
Thorotrast-Induced Angiosarcoma Complicated by Disseminated Intravascular Coagulation and Microangiopathic Hemolytic Anemia: Case Report and Review
Authors: Baker William , Bick Rodger L. , Schale David P. , Swinyer Bruce P.
Published: November 2007

Thorium dioxide was first used for radiographic imaging studies as early as 1915. Carcinogenesis was clearly established by the 1940s, such that by 1956 worldwide usage had ceased. Malignancies were noted to appear from 15 to 45 years after injection. A case of thorotrast-induced hepatic angiosarcoma is presented, which was complicated by disseminated intravascular coagulation and microangiopathic hemolytic anemia. Since multiple medical conditions existed, it was unclear which was primarily responsible for these complications. This is the first reported association between thorotrast-induced malignancy and disseminated intravascular coagulation. The world literature is reviewed.
Patients with APC Resistance Compared with Those with Other Clotting Inhibitor Deficiencies Show Later Onset of Venous Thrombosis During Oral Contraception
Authors: Girolami Antonio , Simioni Paolo , Zanardi Sandra , Scarano Luigi , Girolami Bruno
Published: November 2007

The prevalence of deep vein thrombosis in female patients with antithrombin III (AT III), protein C, or protein S deficiency who are on oral contraception has been compared with that of patients with activated protein C (APC) resistance. In the latter case the prevalence was lower (36.4%) than in the AT III deficiency group (71.4%) but similar to that seen in the protein C and protein S group (25%).' Furthermore, venous thrombosis occurred with APC resistance much later than with AT III, protein C, or protein S defects. The time lag between onset of oral contraception and thrombosis (~16 cycles) was not statistically different from that seen in a group of women who were known to have no antithrombin III, protein C, or protein S defects. It appears that as far as the interaction with oral contraception is concerned APC resistance is a much less severe condition compared with other clotting inhibitor defects. Key Words: Oral contraceptive—Activated protein C resistance—Deep vein thrombosis.
Validity of International Normalized Ratio in Expressing Prothrombin Times in Anticoagulated and Nonanticoagulated Patients
Authors: Alshameeri Rasheed , Mammen Eberhard F. , Paisley Christa , Perry Christine
Published: November 2007

We investigated the effect of four thrombo plastins with different International Sensitivity Index (ISI) values on prothrombin times (PTs), expressed as International Normalized Ratios (INRs), of 30 normal plasmas, 30 patients on stable oral anticoagulant (OA) therapy, and 30 patients with prolonged PTs for reasons other than OA therapy. Normal ranges became signifi cantly longer when three thromboplastins of rabbit brain origin were used—the lower the ISI, the wider the normal range. The human placenta-derived thromboplastin had a range similar to the values obtained with the most insen sitive rabbit reagent. Significantly different INR values were noted when normal plasmas and plasmas of patients with prolonged PTs not due to OA therapy were tested. This was not the case when specimens from patients on OAs were tested. When PT values from 212 consecutive ly selected patients were tested with the least sensitive rabbit reagent (ISI 2.477) and the most sensitive human placenta reagent (ISI 1.06), significantly more "abnor mal" PTs were identified with the high-sensitivity throm boplastin. The data indicate that special attention has to be paid to "normal" ranges when thromboplastins with low ISI replace less sensitive reagents, that INR should not be used to express PT in patients not on stable OA therapy, and that with the routine use of highly sensitive reagents (low ISI) more abnormal patients are identified.