bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Fibrinogen After rt-PA Administration
Authors: Meehan Carr Justine , Bovill Edwin G. , Tracy Russell P. , Mankowski Martin , Mann Kenneth G. , McDonagh Jan
Published: November 2007

Among patients participating in the TIMI-II protocol, there was a variability in the fibrinolytic re sponse to recombinant tissue plasminogen activator (rt- PA). A cohort of 20 TIMI-II patients was selected for detailed study because their responses to rt-PA varied widely in the degree of fibrin(ogen)olysis. Patient plasmas were analyzed by immunoblotting for changes in fibrino gen and plasminogen. Measurements of fibrinogen, fibrin ogen degradation product (FDP), D-dimer, Bβ 1-42, plas minogen, and t-PA were also correlated. Three patterns of response to rt-PA were identified: Group A ( n = 4) had fibrinogenolysis without fibrinolysis; Group B ( n = 11) had fibrinolysis and mild fibrinogenolysis; and Group C ( n = 5) had fibrinolysis with intense fibrinogenolysis. Group C patients also demonstrated qualitative changes in high- molecular-weight (HMW) and low-molecular-weight (LMW) fibrinogens, whereas Group A and B patients demonstrated only mild alterations in fibrinogen compo sition. Plasmin-inhibitor complexes were identified in all three groups. All patients had both plasmin-α2-anti plasmin and plasmin-α2-macroglobulin complexes at the 50-min time point. The concentration of pretreatment plasminogen correlated with the degree of fibrinogenoly sis.
Coronary Angioplasty in Patients with Unstable Angina, with Special Reference to Preceding Treatment with Antithrombin III and Heparin
Authors: Grip Lars , Hellekant Christer , Herzfeld Istvan , Malmberg Klas , Svane Bertil , Szamosi Alfred , Velander Mats , Ryden Lars
Published: November 2007

Seventy-nine patients undergoing percutane ous transluminal coronary angioplasty (PTCA) for unsta ble angina were analyzed with respect to preceding an tithrombin treatment; group I comprised patients (n = 26) without antecedent antithrombin therapy; group II, pa tients (n = 30) with heparin infusion for ≥24 h, and group III patients (n = 23) with ongoing heparin infusion and given antithrombin III concentrate immediately before the procedure because of plasma antithrombin III <85%. Immediate results were 89% (70 of 79) angiographic suc cess, five (6%) subacute occlusions (two subsequent non-Q wave infarctions), no emergency coronary artery bypass grafting (CABG), and no immediate mortality. There were no differences between the groups. From dis charge to 4 months, one patient died, one had a nonfatal infarction, and 24 (30%) had repeated PTCA or CABG. The cumulative 4-month event rate was 11 of 26 (42%) in group I, 10 of 30 (33%) in group II, and 7 of 23 (30%) in group III (NS). During PTCA, heparin bolus administra tion was guided by activated clotting time (ACT), aiming at>300 s. Baseline ACT was significantly less in patients not treated with heparin (129 ± 34 s in group I vs. 179 ± 38 and 162 ± 29 s in groups II and III, respectively; p < 0.05), but during the procedure, patients from all groups required the same amount of heparin (13,900 ± 4,800, 13,000 ± 6,800, and 13,000 ± 5,700 IU, respectively; NS) to reach similar maximum ACT levels (334 ± 36, 312 ± 32, and 319 ± 44 s, respectively; NS). Patients receiving warfarin ( n = 8) responded with a higher ACT (456 ± 110 s; p < 0.05) on lower doses of heparin (10,000 ± 3,800 IU). In conclusion, patients with unstable angina receiv ing individualized antithrombotic therapy can be success fully treated with PTCA, with an acute complication rate and long-term results comparable with those expected in patients undergoing elective procedures. The value of an tithrombin III substitution must be evaluated in random ized trials. Preprocedural heparin infusion does not re duce the need of extra heparin during the procedure. Key Words: Antithrombin III—Heparin—PTCA (percutane ous transluminal coronary angioplasty)—Unstable angina pectoris.
Anticoagulant Glycosaminoglycans Activate Respiratory Burst in Neutrophils and Monocytes
Authors: Johann Sabine , Zoller Christine , Haas Sylvia , Blümel Günther , Förster Reinhold
Published: November 2007

Using four different glycosaminoglycans (un fractionated heparin, low-molecular-weight heparin, pen tosan polysulfate, lactobionic acid) and the polypeptide hirudin, we investigated the influence of these anticoag ulant substances on both polymorphonuclear neutrophils and monocytes respiratory burst in vitro. Using real-time analysis, we demonstrated that both unfractionated and low-molecular-weight heparins, as well as pentosan polysulfate, trigger the respiratory burst in neutrophils and monocytes within 3 to 5 s at clinically relevant con centrations. These effects could be antagonized by pre- incubating the anticoagulant drugs with protamine. Scan ning electron microscopy confirmed an activated neutro phil phenotype after exposure to the anticoagulant compounds. Furthermore, we demonstrated that neither increased intracellular Ca2+ levels nor tyrosine phos phorylation of proteins, both mechanisms commonly in volved in the signal transduction in neutrophils, partici pate in the glycosaminoglycan-mediated activation of the respiratory burst. Our results indicate that defined anti coagulant substances can trigger the respiratory burst in vitro, which might also have clinical implications in cer tain diseases. Key Words: Glycosaminoglycans— Hirudin—Polymorphonuclear leukocytes—Monocytes— Respiratory burst—Flow cytometry.
Venous Thromboembolism and Malignant Brain Tumors: A Review
Authors: Jubelirer Steven J.
Published: November 2007

The incidence of venous thromboembolism (VTE) in patients with primary brain tumors varies be tween 1 and 60%. This variability in incidence is due to study differences in (a) methods of diagnosis of VTE— i.e., diagnosis at autopsy or clinical diagnosis; (b) amount of time from surgery to VTE diagnosis; (c) proportion of patients receiving deep venous thrombosis (DVT) pro phylaxis ; (d) clinical risk factors associated with VTE, such as paresis, prior thrombotic disease, and chemother apy; and (e) tumor location and histology. The etiology of VTE in patients with primary brain tumors is unknown. The preoperative hemostatic abnormalities noted in clin ical studies have been most consistent with compensated disseminated intravascular coagulation (DIC). These ab normalities, however, appear to be of little predictive value for the subsequent development of VTE. Studies involving brain tumor tissue or cell cultures have impli cated factors released by the tumor or surrounding neural tissue that activate the coagulation system or inhibit fi brinolysis. Recommendations for VTE prophylaxis in clude (a) earliest possible ambulation; (b) intermittent pneumatic compression in all nonambulatory patients preoperatively and postoperatively; and (c) s.c. heparin in high-risk patients. The role of low-molecular-weight heparin in VTE prophylaxis has not been established. Patients with malignant brain tumors can be safely anti coagulated with heparin and warfarin if these agents are carefully monitored. Of 197 patients in seven series who received anticoagulants, only 5 (2.5%) had intracranial bleeding. Vena caval filters and thrombectomy are rarely required. Thrombolytic therapy is contraindicated. Key Words: Venous thromboembolism—Deep venous throm bosis—Malignant brain tumors.
Normal Sialophorine (CD43) Expression in a Thrombocytopenic and Immunodeficient Woman Carrier of Wiskott—Aldrich Syndrome
Authors: Lewandowski Krzysztof , Zozulińska Maria , Szczepanik Adam , Dworacki Grzegorz , Tilgner Hanna , Zawilska Krystyna
Published: November 2007

We report on a 24-year-old thrombocytopenic woman with a history of recurrent infections, skin and mucosal bleeding, and a member of a family with the Wiskott—Aldrich syndrome. Hemorrhagic complications occurred at age 20, when mild peripheral thrombocyto penia (38-52 g/L) was confirmed. Four male family mem bers died of infectious complications at ages ranging from 6 months to 3 years. At the time of the study, she was free of infection. Physical examination exhibited ecchymoses of skin of the legs only, and her laboratory investigations demonstrated a lack of secondary waves of platelet ag gregation with adenosine diphosphate (ADP) and prolon gation of the lag phase after collagen stimulation. Inten sities of aggregation induced by ADP, collagen, and thrombin were decreased. Patient's plasma aggregating activity was diminished. Abnormal intraplatelet malo nylodialdehyde formation was also found. Assessment of the platelet volume distribution demonstrated the pres ence of normal-size population. Examination of isolated platelets by electron microscope showed a reduced num ber of dense bodies. The content of mepacrine-labeled platelet bodies in the fluorescent microscopy study was also diminished. Immunological investigations revealed a slight decrease in immunoglobulin G (IgG) serum concen tration and a low isohemagglutinin titer. Additionally, di minished percentages of T activated and total B cells were detected. Moreover, a slight increase of natural killer cells was revealed. Lymphocyte surface sialophorin (CD43) expression was normal. Polymorphonuclear cell (PMN) phagocytosis, chemotaxis, spontaneous migra tion, intravascular polymorphonuclear granulocyte aggre gate number, and Fc IgG receptor expression study all showed no abnormalities. However, a reduced bacteri cidal capacity of the PMN, reduced adhesion to albumin- covered plastic surfaces, and diminished resting super oxide/hydrogen peroxide production were found. Key Words: Wiskott-Aldrich syndrome carrier—Thrombo cytopenia—Immunodeficiency.
Modulation of Endothelium by Heparin and Related Polyelectrolytes
Authors: Fareed Jawed , Jeske Walter , Callas Demetra , Hoppensteadt Debra , Walenga Jeanine
Published: November 2007

The vascular endothelium is an important me diator of the hemostatic balance. In addition to shielding subendothelial tissue factor from flowing blood, endothe lial cells produce a number of substances which favor an antithrombotic state including TFPI and tPA. The ability of polyelectrolytes such as heparin and defibrotide to modulate endothelial function is examined using animal models and human studies. Like heparin, defibrotide is observed to increase plasma TFPI antigen levels. Addi tionally, defibrotide administration is observed to in crease plasma tPa antigen levels and to decrease PAI, TF and endothelin levels. Modulation of endothelial function by defibrotide may account for its beneficial effect in PAOD.
Characterization of an In Vitro Platelet Function Analyzer, PFA-100™
Authors: Kundu Sourav K. , Heilmann Eric J. , Sio Reynaldo , Garcia Carmen , Ostgaard Roy A.
Published: November 2007

A new in vitro system for the evaluation of platelet function, PFA-100 (currently under evaluation) is characterized. The system monitors platelet aggrega tion on a collagen-epinephrine-coated membrane as whole blood sample is aspirated under controlled flow conditions through a microscopic aperture cut into the membrane. The time required for the platelet plug to oc clude the aperture (closure time) is indicative of the plate let function in the sample. Incubation of normal blood samples with antibodies to glycoprotein (GP) Ib, GPIIb- IIIa, von Willebrand factor, or with the peptide Arg-Gly- Asp-Ser, resulted in a concentration-dependent prolonga tion in closure time. An anti-fibrinogen antibody did not impact the closure time. Closure time was also prolonged when the hematocrit or the platelet count was lowered to pathological values. The study indicates that PFA-100 could detect defects in platelet adhesion or aggregation. The simplicity of the test makes PFA-100 unique for rapid screening of a variety of platelet dysfunction.
Plasma Proteins of Hemostasis in the Hepatointestinal Form of Schistosomiasis Mansoni
Authors: Camacho-Lobato Luciana , Borges Durval Rosa
Published: November 2007

The hepatosplenic form of schistosomiasis mansoni is associated with impairment of blood coagula tion, a result of reduced synthesis of clotting factors and inhibitors, enhanced fibrinolytic activity, or "consump tion" of plasma clotting proteins. The pathogenesis of the latter mechanism has not been elucidated. Schistosoma mansoni (Sm) has a long lifespan as an intravascular fluke, probably a consequence of its ability to evade host immunologic defense mechanisms. In order to determine if the parasite is able to disturb hemostasis in vivo, we studied 21 non-alcoholics with normal body mass index, and HBsAg, anti-HBc, and anti-HCV negative adult males, who were not using drugs. Eleven had the hepa tointestinal form of the disease, with viable Sm ova in stools, and 10 were healthy volunteers (control group). Blood specimens were drawn by a two-syringe technique for both the performance of liver tests and determination of hemostasis proteins (prothrombin, antithrombin III, protein C, protein S, high-molecular-weight kininogen, and plasminogen). The latter proteins were assayed im munologically in plasma using specific antibodies. Statis tical analysis of the results failed to demonstrate any sig nificant difference between the two groups. We may therefore conclude that there is no derangement of he patic protein synthesis in the mild form of the disease and that Sm probably escapes host defense mechanisms in vivo, and does not contribute to the consumption coagu lopathy described in the hepatosplenic form of the dis ease.
State-of-the-Art Review: Factor Xa Versus Factor IIa Inhibitors
Authors: Kaiser Brigitte
Published: November 2007

The development of specific inhibitors of blood coagulation enzymes has led to a number of new anticoagulant/antithrombotic agents that could be useful for prophylaxis and/or treatment of thromboembolic disorders. Because thrombin is the central bioregulatory enzyme in hemostasis, blocking of the active site of the enzyme by a fast reaction with an inhibitor may effectively prevent intravascular coagulation as well as other important biological effects of thrombin. For the direct inactivation of thrombin, several classes of compounds have been developed and characterized in vitro and in vivo as potential antithrombotic agents including naturally occurring as well as synthetic thrombin inhibitors such as hirudin, hirulog, arginine (argatroban), and benzamidine (NAPAP) derivatives as well as tripeptide-type inhibitors (efegatran, D-Phe-Pro-Arg-CH2Cl, boroarginine derivatives). Experimental findings suggest that directly acting thrombin inhibitors may be effective in a wide range of arterial and venous thrombotic events. The important role of factor Xa in the coagulation cascade at the stage of the conversion of extrinsic and intrinsic pathways and the amplification of its procoagulant action by prothrombinase complex formation makes factor Xa a promising target also for antithrombotic drugs. Experimental studies on highly effective and selective factor Xa inhibitors (antistasin, tick anticoagulant peptide, yagin, DX-9065a) showed that inhibition of coagulation at a relatively early stage is a very effective way for the prevention of thrombotic processes. Furthermore, it is assumed that factor Xa inhibitors selectively inhibit thrombus formation without compromising hemostasis. In conclusion, both thrombin and factor Xa inhibitors are promising drugs for the management of thrombotic disorders. However, besides the strong inhibitory potency against the target enzyme, other pharmacological aspects such as pharmacodynamics, pharmacokinetics, and toxic side effects must be included in the evaluation of the potential usefulness of thrombin and factor Xa inhibitors for clinical indications. Key Words: Anticoagulants—Antithrombotics—Factor Xa inhibitors—Thrombin inhibitors.
Prevalence of Anemia and Occult Blood Losses in the Long-Term Follow-Up of Cardiac Mechanic Valve Patients Treated with a Combination of Low-Dose Aspirin Plus Low-Intensity Acenocoumarin
Authors: Fondevila Carlos G. , Meschengieser Susana S. , Santarelli Maria T. , Aixala Monica T. F. , Lazzari Maria A.
Published: November 2007

Mechanic replacement of cardiac prostheses requires lifelong and high-intensity oral anticoagulant treatment. The addition of aspirin to coumarin treatment has resulted in more effective thromboembolic prevention, though it also led to increased (digestive) bleeding. Aspiriri enhanced the risk of apparent or occult gastrointestinal bleeding in a dose-dependent fashion. The combined use of low-dose aspirin/low-intensity coumarins might offer a safer approach. We prospectively evaluated the prevalence of anemia markers in 127 prosthesic valve patients, receiving two treatment modalities: Group A comprised 62 patients who received 100 mg acetylsalicylic acid (ASA) added to acenocoumarin [international normatized ratio (INR) 2.5-3.5]. Group B comprised 65 patients receiving acenocoumarin alone (INR, 3.5-4.5). We found no significant differences in the mean values for the blood markers of anemia or for the presence of blood losses in urine and feces. The addition of low-dose ASA to less intense chronic anticoagulation does not increase the risk of developing anemia. Key Words: Anticoagulants—Aspirin—Coumarins—Gastrointestinal hemorrhage—Heart valve prosthesis.
Piyavit from the Medicinal Leech Is a New Orally Active Anticoagulating and Antithrombotic Drug
Authors: Baskova Isolda P. , Korostelev Alexander N. , Chirkova Lidiya D. , Zavalova Ludmila L. , Basanova Angelica V. , Doutremepuich Christian
Published: November 2007

Piyavit, a novel pharmacological preparation allowed in Russia as an oral antithrombotic drug for clinical use, contains medicinal leech saliva as the main source of biologically active substances that inhibit platelet-vascular and plasmic hemostasis and provide thrombolysis. It is shown that piyavit administered orally or subcutaneously to animals inhibits arterial thrombus formation. In 22 patients with acquired heart valvular disease after implantation of a cardiac artificial valve who received oral piyavit capsules and phenilin 2-3 days after the operation, blood hypercoagulability was reduced in comparison to that of 20 patients after the same type of operation who received only phenilin. An antiinflammatory effect and decreased blood hypercoagulability were observed in 38 patients with thrombophlebitis of the greater saphenous vein who received the same piyavit capsules orally. The results confirm that piyavit as an oral anticoagulant and antithrombotic drug may be an alternative to known antithrombotic preparations. Key Words: Anticoagulation—Antithrombotic drug—Leech saliva— Medicinal leech-Piyavit.
Lack of In Vitro Cross-Reactivity Predicts Safety of Low-Molecular Weight Heparins in Heparin-Induced Thrombocytopenia
Authors: Farag Sherif S. , Savoia Heten , O'Malley Cindy J. , McGrath Katherine M.
Published: November 2007

Alternative anticoagulation in patients with heparin-induced thrombocytopenia (HIT) is often problematic. The relatively high cross-reactivity rate reported for the low-molecular-weight heparins (LMWH) has discouraged their use in this setting. This study has investigated the safety of using the LMWH Fragmin, based on a negative heparin-dependent platelet aggregation test using the latter, in patients with proven HIT. Fifty-three evaluable patients with clinical and laboratory evidence of HIT were evaluated for cross-reactivity with Fragmin using a Fragmin-dependent platelet aggregation test. In 20 of 38 patients who showed no in vitro cross-reactivity. Fragmin was substituted for unfractionated heparin. The outcome of these 20 patients was evaluated and compared to that of the remaining 33 patients, in whom anticoagulates were ceased or warfarin or Orgaran was used. Eighteen of 20 patients treated with Fragmin increased their platelet count by ≥50 x 109/l from a mean nadir of 57.9 ± 4.7 x 109/l within 2.8 ± 0.29 days following substitution of Fragmin for unfractionated heparin. Twenty-eight of the 33 remaining patients who did not receive Fragmin increased their platelet count by ≥50 x 109/l from a mean nadir of 53.0 ± 4.8 x 109/l within 3.0 ± 0.29 days. In seven patients (two treated with Fragmin), response could not be evaluated due to death within 36 h of cessation of heparin or discharge from hospital. The results indicate that in vitro cross-reactivity testing employing a heparin-dependent platelet aggregation assay can be safely used to select patients with HIT for further anticoagulation with LMWH. Key Words: Fragmin—Crossreactivity—Heparin-induced thrombocytopenia.
Temporal Changes in the Activated Protein C Resistance Ratio in a Heterozygote for Factor V Leiden Are Abolished by Dilution in Factor V-Deficient Plasma
Authors: Meyer Todd , Garcia Maria , Helms Elizabeth , Francis Deborah A. , Francis John L.
Published: November 2007

Activated protein C resistance (APCR) is the single most common cause of hereditary thrombophilia and is caused by a mutation in the factor V molecule (FV Leiden). Screening for this defect has become a standard part of the laboratory evaluation of thrombophilia. However, the original APTT-based screening test does not discriminate completely between normal individuals and heterozygotes for FV Leiden. Diluting the patient's plasma in factor V-deficient plasma greatly improves the predictive ability of this test for the FV Leiden mutation. In this report we show that a heterozygote for FV Leiden (confirmed by DNA analysis) showed marked temporal variation in APCR ratio when tested by the original coagulation-based technique. Specifically, this individual tested normal in five of seven occasions tested (APCR ratio range 1.98-2.53; normal >2.0). Using the modified method, although some temporal variation remained, the diagnosis of APCR would have been made on every occasion (APCR ratio 1.85-2.12; normal >2.3). These findings constitute a further reason to use the modified procedure for APCR screening. Key Words: Thrombosis-Activated protein C resistance— Laboratory evaluation.
Laboratory Assessment of von Willebrand Factor: Altered Interpretation of Laboratory Data, and Altered Diagnosis of von Willebrand's Disease
Authors: Favaloro Emmanuel J. , Mehrabani Pirooz A. , Koutts Jerry
Published: November 2007

Three laboratory assays for von Willebrand Factor (vWF), namely, (i) a standard "antigen" [antisera-enzyme-linked immunosorbent assay (ELISA)-based] (vWF :Ag), (ii) a standard ristocetin-dependent platelet agglutination procedure (vWF:RCof), and (iii) a newly developed ELISA-based functional vWF collagen binding assay (vWF:CBA), were coevaluated. We (a) assessed their ability to detect vWF under different assay conditions and (b) reevaluated normal vWF reference ranges using citrated plasma from >200 normal individuals. The following effective normal reference ranges were derived: vWF-Ag (40-200%), vWF:CBA (50-400%), and vWF:RCof (45-200%). Based on other laboratory data, caution is indicated in the interpretation of "borderline" or "equivocal" test results (e.g., 35-55%), since these may derive from normal individuals or from vWD patients. In addition, our study shows that selection of different assay conditions, different test plasma dilutions, or different test sample processing methods can also lead to differences in the "apparent" levels of detected vWF. For example, using plasma from 100 normal individuals processed as "test samples," we determined that higher sample dilutions tended to provide lower (dilution factor adjusted) assay results in the case of the vWF:Ag and vWF:CBA, and higher assay results in the case of the vWF.RCof, with greater differences noted in test samples containing higher levels of vWF. The explanation for these findings relate to the assay design. Thus, in the diagnostic laboratory, the standard vWF:Ag, vWF:CBA, and vWF:RCof assays procedures are designed to provide calibration curves that are "upward linear" in the (vWD) clinically important region of 0-50% of normal, with a plateau tending at higher vWF levels. Using these standard methodologies, and standard plasma dilutions, high-vWF level test samples will tend to fall on or near the plateau, and results will be unreliable, with a tendency to be exaggerated the higher the vWF. These findings have particular relevance to research studies measuring vWF in patients suffering various clinical conditions (e.g., thrombotic thrombocytopenic purpura, diabetes, renal failure) where higher than normal levels of vWF may be anticipated. In these cases, laboratory-derived vWF levels could be "misrepresented" if the study design did not take into account the need to revise the vWF testing procedure. Key Words: von Willebrand factor-von Willebrand's disease—Laboratory assessment-Normal ranges—Reference ranges—Diagnosis.
Platelet Procoagulant Activity During,Peripheral Blood Stem Cell Harvest
Authors: Katsura Kaoruko , Nomura Shosaku , Gui Lan Xie  , Ohtani Tetsuji , Ishida Tomoko , Kagawa Hideo , Kitada Chikaho , Yamanaka Yoshitaka , Kitajima Hiroyuki , Fukuhara Shirou
Published: November 2007

We used flow cytometry to measure platelet-derived microparticle levels in plasma obtained from 16 patients during peripheral blood stem cell harvest (PBSC) and in platelet concentrates prepared by apheresis from 10 normal controls. We also studied the binding of an anti-P-selectin antibody and annexin-V to platelets. When all 60 harvests were assessed, we noted a significant difference in microparticle levels between patients with a platelet count >10 x 104/μl and those with a platelet count <10 X 10 4/μl (12.3 ± 4.4 vs. 75 ± 3.9%). In both the first and total harvests, the percentage of platelets and microparticles positive for anti-P-selectin and annexin-V were significantly higher than the normal control levels. These results suggest that patients undergoing mobilization by granulocyte colony-stimulating factor (G-CSF) who have a platelet count >10 X 10 4/μl are at risk of increased procoagulant activity after retransfusion following PBSC harvest. Key Words: Platelet-derived microparticle— Peripheral blood stem cell harvest—Granulocyte colony-stimulating factor.
Prevalence of Factor V Leiden Is Not Increased in Women with Recurrent Miscarriage
Authors: Metz Jack , Kloss Michael , O'Malley Cindy J. , Rockman Steven P. , DeRosa Lidia , Doig Rowan G. , McGrath Kathefine M.
Published: November 2007

The purpose of this study was to determine if there is an increased prevalence of the thrombophilic genetic mutant factor V Leiden in patients with recurrent miscarriage. Functional assays were conducted for activated protein C resistance and genetic detection of factor V Leiden in 100 women with recurrent miscarriage compared with a control group. The prevalence of factor V Leiden in patients was 6/100 (6%) compared with 3/85 (3.5%) in controls. The difference was not statistically significant. Antithrombotic prophylaxis with heparin and/ or aspirin in a subsequent pregnancy in five of the six patients with factor V Leiden was associated with maintenance of pregnancy and delivery of a live, healthy, full-term infant in four. We have been unable to demonstrate a statistically significant increased prevalence of factor V Leiden in women with recurrent miscarriage. If antithrombotic prophylaxis in pregnancy can be shown by controlled therapeutic trial to prevent miscarriage in these patients, identification of this subgroup would be important. Key Words: Recurrent miscarriage—Factor V Leiden—Activated protein C resistance.
Identification of Potential Predisposition to Clinical Atherosclerosis: A Clinical Concept Based on Integration of Significant Blood Parameters with Platelet Aggregation Scores
Authors: Kaplan Alexander , Kaplan Svetlana , Marcoe Karen F. , Sauvage Lester R. , Hammond William P.
Published: November 2007

We sought to develop a predictive method, based on the integration of blood parameters found to be significantly associated with thrombosis and progression of atherosclerosis, that would be more accurate than primary reliance on elevation of separate risk factors. The study involved 1,034 male subjects. Lipid profiles and fibrinogen levels were determined for 123 men with documented clinical atherosclerosis and 123 apparently healthy volunteers. There were significant differences between these groups for fibrinogen, triglycerides, and HDL cholesterol. An algebraic expression was then developed which combined normalized values of fibrinogen, HDL cholesterol, and triglycerides with platelet count and aggregation data to yield a numerical value, the clinical atheroscterosis predisposition (CAP) factor. We then tested this CAP factor with a validation group of 788 men, 372 of whom were patients with documented clinical atherosclerosis; the rest were apparently healthy. A 3-year prospective evaluation was done for 72 of the 123 apparently healthy volunteers. The CAP factor was 90% indicative of patient status for the 372 men with documented complications of atherosclerosis and appeared to predict severe coronary disease in the 3-year prospective evaluation. This initial study suggests that integrated analysis of thrombotic factors in white males. provides a useful estimate of an individual's risk for subsequent development of clinical atherosclerosis. Key Words: Atherosclerosis-Prevention and control-Blood-Platelets-Cholesterol-Triglycerides--Fibrinogen.
Rarity of Deep Vein Thrombosis and Ankylosing Spondylitis
Authors: Keung Yi-Kong , Yung Christianne
Published: November 2007

Deep vein thrombosis is rarely seen in patients with ankylosing spondylitis. Only two cases have been reported in the medical literature. We describe a case of idiopathic deep vein thrombosis associated with ankylosing spondylitis and discuss the reason why thrombosis in ankylosing spondylitis is rare. Key Words: Ankylosing spondylitis-Deep vein thrombosis.
Intra-Atrial Thrombosis and Homozygous Factor V Leiden Mutation
Authors: Simioni Paolo , Scalia Domenico , Tormene Daniela , Bongiovi Stefano , Sardella Corrado , Girolami Antonio
Published: November 2007

A 55-year-old woman with a previous history of thrombotic manifestations developed large left atrial thrombosis. Coagulative screening demonstrated the presence of severe activated protein C resistance due to homozygous factor V Leiden mutation that could explain the thrombophilic state in this patient. No other associated coagulation defects predisposing to thrombosis were identified. At the time of diagnosis of intra-atrial thrombosis, the patient presented with a moderate mitral valve stenosis and atrial fibrillation of recent onset. Both these conditions may account for the presence of left atrial thrombosis but it is suggested that inherited thrombophilia due to homozygous factor V Leiden mutation might have represented an additional predisposing factor for the development of the thrombotic phenomenon. The role of coagulation defects predisposing to thrombosis in the pathogenesis of intracardial thrombosis in patients with or without valvular diseases is still unknown and proper studies are required. Key Words: Thrombophilia-Factor V Leiden-Atrial thrombosis.
Efficacy of Danazol with Autoimmune Thrombocytopenia
Authors: Kim Steven W. , Rice Lawrence , McCarthy John J.
Published: November 2007

Seventy-nine cases of autoimmune thrombocytopenia seen by the Baylor Hematology section of The Methodist Hospital between 1991 and 1996 were retrospectively reviewed to assess the effectiveness of danazol in the treatment of autoimmune thrombocytopenia. Among the 42 patients who received danazol, the mean initial platelet count prior to treatment was 24.3 ± 17.4 (SD) × 109/L with a mean duration of disease of 53 months. Most cases were idiopathic, but some patients had underlying secondary disorders (rheumatoid arthritis, systemic lupus erythematosus, HIV, and/or Evans' syndrome). Overall 57% of the patients treated with danazol had an excellent or a good response with three patients who had unmaintained remission for >11 months. Minimal side effects were noted. Fifty percent of the patients with associated secondary disorders achieved an excellent or good response. The hemolytic component of all three Evans' syndrome cases was well controlled with danazol. In two cases, danazol was effective where a variety of other treatment regimens were not. An excellent or a good response was found in 58%, 62%, and 53% in patients >65 years old, between 45 and 65 years old, and <45 years old, respectively. Response rates were similar in males and females, Seventy percent of the nonsplenectomized patients had an excellent or a good response compared to 33% in postsplenectomy patients. Overall in view of its favorable side-effect profile, it is rational early on to attempt to abrogate the need for splenectomy, it may salvage splenectomy failures, and there is a reasonable response rate in those refractory to multiple prior therapies. Key Words: Autoimmune thrombocytopenia—Idiopathic thrombocytopenic purpura—Danazol— Systemic lupus erythematosus—HIV—Evans' syndrome.
The Antiphospholipid Thrombosis Syndromes: A Common Multidisciplinary Medical Problem
Authors: Bick Rodger L.
Published: November 2007

Antiphospholipid antibodies are increasingly being identified as a cause of arterial and venous thrombosis as well as fetal wastage syndrome via placental vascular thrombosis. The antiphospholipid thrombosis syndromes should be considered and searched for when suggestive clinical findings are present or when unexplained arterial or venous thrombosis occurs. Noting the presence and type of antiphospholipid antibody thrombosis syndrome assumes major importance with respect to not only making an accurate diagnosis of cause of thrombosis but also in selecting effective antithrombotic therapy. The antiphospholipid thrombosis syndromes and the thrombotic and other clinical manifestations span almost all medical specialities and should be construed as a truly multidisciptinary medical problem. Key Words: Thrombosis-Anticardiolipin antibody—Lupus anticoagulant.
Efficacy of Antithrombin Concentrates in Treatment for Asthmatic Symptoms Complicated in Antithrombin Abnormality with No Heparin Binding Activity
Authors: Yoshida Yoshimasa , Niiya Kenji , Maruyama Muneharu , Oosaki Rokuo , Fujishita Takashi , Kobayashi Masashi , Sakuragawa Nobuo
Published: November 2007

It is well-known that pulmonary embolism sometimes accompanies a bronchoconstrictive symptom, but the precise mechanism is not clearly understood. We report a unique case of antithrombin (AT) abnormality with no heparin-binding activity accompanied by pulmonary thromboembolism and asthmatic symptoms. Keeping AT activity >60% by infusion of AT concentrates, we successfully treated the asthmatic symptom, which did not respond to ordinary treatment for bronchial asthma and the anticoagulant therapy by warfarin potassium for pulmonary thromboembolism. Key Words: Antithrombin concentrates—Bronchial asthmatic symptom—Pulmonary thromboembolism—Antithrombin abnormality with no heparin binding activity
Fatal Cerebral Hemorrhage Complicating Thromboembolic Stroke in a Patient with Prosthetic Mitral Valve Thrombosis Treated with Thrombolytic Therapy
Authors: Barbero Fabio , Pengo Vittorio , Fasoli Giuseppe
Published: November 2007

We report the case of a 66-year-old male with a history of mitral valve replacement with a Sorin tilting-disk prosthesis and a subsequent operation for severe constrictive pericarditis. After 5 years of stable anticoagulant treatment, he suffered an intracerebral hemorrhage that required temporary withdrawal of warfarin. Thrombosis of the prosthesis, presenting as acute heart failure, was then determined. Due to high-operative and hemorrhagic risk, the patient was treated with low-dose thrombolytic therapy administered as two boluses of recombinant tissue plasminogen activator (r-tPA). The patient's hemodynamics improved strikingly. However, a few hours after the second dose, a devastating cerebral hemorrhagic infarction resulted in death. Autopsy showed the primarily ischemic nature of both strokes. The schemes of thrombolytic therapy in prosthetic heart valve thrombosis and the importance of a correct interpretation of pathogenesis of stroke in anticoagulated patients are discussed. Key Words: Heart valve thrombosis— Thrombolysis—Stroke—Warfarin.
Controversies in Antithrombotic Therapy in Cardiovascular Diseases
Authors: Altman Raul
Published: November 2007

Antithrombotic treatment became an important point in human medical treatment. Dicoumarols, heparin, aspi rin, and more recently, direct antithrombins and platelet glyco protein IIb/IIIa receptor blockers are the most frequent medi cations used as antithrombotics. The role of these drugs in the treatment of cardiovascular diseases remains controversial. Low-dose aspirin (80-100 mg/day) should be used for second ary prevention in patients with a history of coronary disease. Primary prevention in patients with no risk factors is not rec ommended. Studies using oral anticoagulant therapy indicated that long-term therapy achieves substantial benefit in arterial complications in patient survivors of myocardial infarction. Combined therapy of aspirin and a higher dose of oral antico agulant than that used in the CARS trial seem necessary after myocardial infarction, and further studies should be under taken. In the treatment of unstable angina, the combined use of aspirin and unfractioned heparin (UFH) is widely accepted. Low molecular weight heparin (LMWH) was also proposed for the treatment of these patients, but the beneficial effect of LMWH over UFH is a matter of discussion, and more prospec tive studies with different LMWHs should be undertaken be fore reaching a definitive answer. The use of hirudin needs additional studies because its superiority over heparin is un- proved. The initial clinical experience with blockers/inhibitors of platelet glycoprotein IIb/IIIa receptors has been promising, although some increase of bleeding was reported. According to published trials on the use of antiplatelet drugs and antithrom botic therapy in the prevention of acute closure after PTCA or after stent implantation, antithrombotic therapy decreased the incidence of abrupt closure or reocclusion at 30 days postan gioplasty, but neither antiplatelet agents nor other pharmaco logical agents have been shown to reduce significantly the rate of restenosis. Finally, oral anticoagulant in a target INR of 2.0 to 3.0 together with aspirin 100 mg/day provide good protec tion from thromboembolism and diminish the rate of minor bleeding complications in patients with cardiac valve replace ment.
Sticky Platelet Syndrome: A Common Cause of Unexplained Arterial and Venous Thrombosis
Authors: Bick Rodger L.
Published: November 2007

Sticky platelet syndrome (SPS) was first described in 1983. However, not until 1995 did the prevalence of SPS receive significant recognition in the medical literature. In 1995 we began to routinely add an SPS evaluation to patients re ferred for assessment for causation of arterial and venous thromboses to a large thrombosis hemostasis referral center. The results of our first 2-year experience suggest SPS to be a common cause of arterial and venous thromboses. With respect to otherwise unexplained venous thrombosis, the prevalence of SPS approximates that of activated protein C resistance (APC- R). During the past 24 months, we have evaluated 153 patients referred for evaluation of unexplained arterial or venous events. An evaluation for common and uncommon blood coagulation protein defects and SPS has been applied to these patients. It has been found that SPS accounted for about 21 % of otherwise unexplained arterial events (acute myocardial infarction, cere brovascular thrombosis, transient cerebral ischemic attacks, retinal thrombosis, and peripheral arterial thrombosis) and ac counted for about 13.2% of otherwise unexplained venous events (deep vein thrombosis, with or without pulmonary em bolus). These findings strongly suggest SPS to be a common cause of arterial and venous thromboses and a workup for SPS should be considered a routine assay in the workup of indi viduals with otherwise unexplained arterial or venous throm botic events. Because treatment with heparin or warfarin will not alleviate the thrombotic tendency of SPS, but simple aspirin therapy almost always will correct the defect and protect the individual from second events, it is particularly important to define the presence of this defect. Key Words: Thrombosis— Platelet defects—DVT—Coronary thrombosis—Cerebral thrombosis—Recurrent miscarriage.
Coronary and Peripheral Thrombolysis: Current Status and Recommendations
Authors: Gensini Gian Franco , Comeglio Marco , Colella Andrea
Published: November 2007

Thrombolytics are mainly indicated in acute myo cardial infarction (AMI), with limited evidence of usefulness in stroke and acute peripheral arterial occlusion (PAO). Throm bolytics can successfully dissolve thrombi in any vessel, but clinical benefit varies according to the involved vascular bed. The anticipated clinical benefit of thrombolytics in treating AMI, stroke, and PAO must be carefully balanced against the risk of bleeding (especially intracranial hemorrhage). In AMI, fibrinolytic agents reduce mortality rates by as much as 30% when started within 6 h of symptom onset and by as much as 50% if given within 1 to 2 h. Therefore, the timing of fibrino lytic therapy largely determines the magnitude of reduction in mortality after AMI. Streptokinase is a well-documented treat ment for AMI, with r-TPA plus IV heparin enabling better results, specially in anterior MI and in the elderly. Reteplase was not superior to alteplase in GUSTO-III and TNK-TPA is in the early phase of investigation. However their ease of admin istration and potential for more potent and specific clot lysis may prove advantageous. In acute stroke, the most recently reported phase III trials of streptokinase and recombinant tissue plasminogen activator (r-TPA) have stressed the importance of the clinical benefit/hemorrhage risk balance. These studies sup ported the viewpoint that the use of fibrinolytic agents for stroke must be limited to r-TPA in well-characterized patients and with a narrow time window. Finally, local administration of thrombolytic agents in acute arterial thrombosis, mainly in the limbs, is commonly used by interventional radiologists. Goods results have been reported in terms of safety and effec tiveness in the treatment of acute lower extremity ischemia. The preliminary results of the Thrombolysis or Peripheral Ar terial Surgery (TOPAS) trial suggest that recombinant uroki nase therapy (4,000 IU/min) is associated with limb salvage and patient survival rates similar to those achieved with sur gery, concurrent with a reduced need for complex surgery after thrombolytic intervention.

In summary, AMI represents the most important indication for thrombolysis, with large amounts of data supporting its use. In acute stroke, there is less evidence of efficacy and it is limited to a few well-characterized patients, whereas local ad ministration in patients with acute PAO may favorably affect patient outcome despite of the absence of evidence of improved limb salvage. Key Words: Thrombolysis—Myocardial infarc tion—Stroke—Acute peripheral arterial occlusion.
Antithrombin-III Activity and the Efficacy of Heparin in Progressing Ischemic Stroke
Authors: Rödén-Jüllig Åsa , Britton Mona , Svensson Jan
Published: November 2007

Heparin is often used in progressing ischemic stroke. However, a substantial part of the patients continue to progress while on treatment. The purpose of this study was to evaluate if antithrombin (AT) III activity before treatment could predict patients at risk for continued progression or if heparin-induced reduction in AT-III activity during treatment is related to continued progression. The study included 42 acute stroke patients with heaprin treatment for progression of isch emic stroke. The patients were continuously supervised for progression. Intravenous heparin therapy was started as soon as possible after the progression was noticed. Antithrombin-III activity was assessed before initiation of treatment and daily during the treatment period. Nine (21 %) of the 42 patients continued to progress while on treatment. There was no statis tically significant difference in AT III activity before treatment between patients who continued to progress and those where the progression ceased when treatment was initiated. Nor were there any differences in the mean AT III activity levels during treatment for patients with more or less favorable clinical course. The individual changes (Δ AT III) were similar in both patient groups as was the proportion of patients with their low est AT III activity in the thrombogenic range (continued: 22% vs. ceased: 27%). No clinically relevant influence of AT III activity on heparin efficacy in progressing ischemic stroke was found. Key Words: Stroke progression—Heparin treatment— Antithrombin activity.
Early Preoperative Thromboprophylaxis with Klexane® in Hip Fracture Surgery: A Placebo-Controlled Study
Authors: Jørgensen Per Seest , Strandberg Charlotte , Wille-Jørgensen Peer , Tørholm Carsten , Neergaard Kirsten , Paaske Birgit P. , Rasmussen Søren W. , Christensen Steen W. , Mantoni Margit , Thamsen Hanne
Published: November 2007

The aim of this study was to evaluate any possible benefits of early thromboprophylactic treatment in the preven tion of deep vein thrombosis (DVT) in high-risk hip fracture patients. Within 30 months, 239 patients were included in a double-blind placebo-controlled study. With the diagnosis of hip fracture confirmed, patients received either 40-mg Enoxa parin s.c. or placebo once daily until operation. Postoperatively, all patients received 40-mg Enoxaparin s.c. once daily until phlebography. Phlebography was first performed on the oper ated leg, and with no thrombosis detected, the other leg was investigated as well. The two groups did not differ demograph ically. Eighty-five patients were excluded. Eight patients died during the study period. The remaining 146 patients had as cending phlebography performed and 24 patients (16.4%) de veloped DVT. Nine (12%) of 75 patients in the Klexane® and 15 (21 %) of 72 patients in the placebo group developed DVT. The risk ratio was 0.58 (95% confidence limits 0.27-1.25) and p = .15 (X2 test). There was no difference in perioperative bleeding or transfusion requirements. We conclude that Klex ane® is an effective and safe thromboprophylactic agent in hip fracture patients. Key Words: Hip fracture—Thrombopro phylaxis—Low—molecular heparin.
Factor V Antigen Is Decreased in Both Types of Combined Factor V and Factor VIII Congenital Defects
Authors: Girolami Antonio , Zanon Ezio , Gavasso Sabrina , Girolami Bruno , Zerbinati Patricia
Published: November 2007

Factor V antigen was evaluated in four patients with combined factor V and factor VIII deficiency. Two of these patients belonged to type I combined defect (pure asso ciation between factor V deficiency and hemophilia A). The other two belonged to type II (common defect of factor V and VIII). Factor V antigen was low in all patients and compared well with factor V activity levels.

Factor VIIIc coagulant was low in all patients. On the con trary Von Willebrand factor (vWF) was normal in all patients.

The presence of low factor V antigen in type I combined factor V and factor VIII disease had never been described be fore even though it could have been anticipated on theoretical grounds. Heterozygous for true factor V deficiency are known in fact to have a parallel decrease of activity and antigen level.