bluuebunny/crossref_metadata_2025 huggingface dataset:
State-of-the-Art-Review : Combined Heterozygous Plasminogen Deficiency and Factor V Leiden Defect in the Same Kindred
Authors: Sartori Maria Teresa , Simioni Paolo , Patrassi Giovanni Maurizio , Theodoridis Panagiotis , Tormene Daniela , Girolami Antonio
Published: November 2007

Combined plasminogen deficiency and resistance to activated protein C defect (factor V Leiden) have been de scribed in a few families and associated with a variable occur rence of thrombotic events. Here we describe a new family with thrombophilia and the presence of hypoplasminogenemia and factor V Leiden mutation. In addition, a brief review of the literature is presented. Nine patients belonging to this kindred underwent coagulation study for hereditary thrombophilia, which included plasminogen antigen and activity assays, an activated protein C resistance test, and genetic analysis for factor V Leiden mutation and for prothrombin variant 20210A. The proposita, a 40-year-old asymptomatic female with a fam ily history of thrombotic diathesis, was affected by heterozy gous plasminogen deficiency. Hypoplasminogenemia was found also in her two sisters, in one instance associated with factor V Leiden mutation. The mother was the putative carrier of hypoplasminogenemia, but she refused to be studied. The symptomatic father was heterozygous for factor V Leiden mu tation, but presented with normal plasminogen levels. Among the available siblings investigated from the paternal side, resis tance to activated protein C due to factor V Leiden mutation was found in three patients, one of whom experienced venous thromboembolism. Another uncle with a history of thrombotic disease showed no coagulation abnormalities. These findings together with the data from literature confirm the role of factor V Leiden as an independent risk factor for venous thromboem bolism, whereas isolated hypoplasminogenemia does not seem to increase the risk for thrombosis. There is no clear evidence that the coinheritance of these two defects may be associated with an additional risk for thrombosis compared with the pres ence of factor V Leiden mutation alone.
Defibrotide in Recurrent Thrombotic Thrombocytopenic Purpura
Authors: Pogliani Enrico Maria , Perseghin Paolo , Parma Matteo , Pioltelli Pietro , Corneo Gianmarco
Published: November 2007

Thrombotic thrombocytopenic purpura (TTP) is a common illness characterized by platelet thrombi within the microvascularization. In its natural course, this disease has had a mortality rate of 90%. Plasma infusion or exchange achieved a survival rate of 70% to 90%. However, 10% to 30% of patients surviving the initial TTP episode relapse at regular intervals. The treatment of recurrent forms of the disease re mains a challenge; several approaches have been shown to induce medium to long term remissions. We describe a patient with recurrent TTP whose disease remitted after administration of defibrotide.
Hemostatic Abnormalities in Patients With Thrombotic Complications on Maintenance Hemodialysis
Authors: Inoue Akiko , Wada Hideo , Takagi Mikio , Yamamuro Miho , Mukai Kenji , Nakasaki Takahiro , Shimura Minori , Hiyoyama Kazuyo , Deguchi Hiroshi , Gabazza Esteban C. , Mori Yoshitaka , Nishikawa Masakatsu , Deguchi Katsumi , Shiku Hiroshi
Published: November 2007

Before hemodialysis (HD), plasma levels of tissue factor (TF), free-TF pathway inhibitor (TFPI) and thrombo modulin (TM) were significantly higher in patients with HD than in healthy volunteers. Plasma levels of (T-F) TFPI and plasmin plasmin inhibitor complex (PPIC) were significantly higher in patients with HD than in healthy volunteers. During HD, plasma levels of TF and (T-F) TFPI were not significantly increased, but plasma levels of total TFPI and free TFPI at 1 hour after and at the end of HD were significantly increased, compared with levels before start of HD. Plasma level of PPIC 1 hour after start of HD was significantly higher than before start of HD, and plasma levels of thrombin antithrombin com plex (TAT). PPIC. D-dimer. TM, and protein C (PC) at the end of HD were significantly higher than before start of HD. In patients with thrombosis complications, plasma TF levels were significantly higher than in patients without thrombotic com plications during HD. Plasma levels of PC were significantly lower in patients with thrombotic complications than in patients without thrombotic complications. There was no significant difference between both groups during HD in hemostatic pa rameters, with the exception of TF and PC. Hemostatic abnormalities existed in patients with HD; espe cially, increased TF and decreased PC might cause thrombotic complications.
Atypical Variant of Acquired von Willebrand Syndrome in Wilms Tumor: Is Hyaluronic Acid Secreted by Nephroblastoma Cells the Cause?
Authors: Michiels Jan Jacques , Schroyens Wilfried , Bememan Zwi , van der Planken Marc
Published: November 2007

Acquired von Willebrand syndrome (AvWS) has been reported in eight children with Wilms tumor (nephroblastoma in four boys and four girls) at a mean age of 3.3 years (range, 0.33-9 years). Only three of eight patients with AvWS in Wilms tumor presented with mild mucocutaneous bleeding symptoms. The AVWS in seven children with Wilms tumor featured either undetectable or very low von Willebrand factor antigen (vWF.Ag) levels (mean, 3%) and decreased values for vWF ristoectin cofactor (RCF) activity (mean, 20%) and factor VIII coagulant (VIIIc) activity (mean, 16%). The response to 1-desamino-8-argi nine vasopressin (DDAVP) was good in two and poor in one patient. Multimeric analysis of the vWF showed a normal pattern of type I von Willebrand disease (vWD) in three patients and an absence of multimers consistent with type In v WD in two patients. The higher functional levels, as compared with antigen levels, with increased ratios for factor VIIIc/vWFAg (mean, 5.3) and vWF.RCF/vWF.Ag (mean, 6.6) in seven patients with Wilms tumor are unexplained physiologically and are not consistent with type I vWF deficiency. The absence of vWD in the patient's family, and the return of factor VIII-VWF parameters to normal after chemotherapy or surgical removal of the Wilms tumor, support the diagnosis of AvWS causally related to the Wilms tumor. The causative agent is thought to be hyaluronic acid secreted by nephroblastoma cells of the Wilms tumor. Prospective studies to determine the nature of AvWS in children with Wilms tumor are warranted.
Cytokines, Endothelium, and Adhesive Molecules in Pathologic Thrombopoiesis
Authors: Cobankara Veli , Oran Betul , Ozatli Duzgun , Haznedaroglu Ibrahim Celalettin , Kosar Ali , Buyukasik Yahya , Ozcebe Osman , Dundar Semra , Kirazli Serafettin
Published: November 2007

Clonal thrombocytosis (CT) associated with myeloproliferative disorders (MPD) is believed to be secondary to autonomous unregulated platelet production. Secondary or reactive thrombocytosis (RT) can be observed in a number of clinical circumstances and may be related to persistent production of some thrombopoietic factors acting on megakaryocytes (MK). The goal of this study is to assess the serum concentrations of these cytokines in control subjects and patients with MPD associated with thrombocythemia, RT, and autoimmune thrombocytopenic purpura (ATP). Eleven patients with MPD, five with chronic myeloid leukemia (CML), three with polycythemia vera (PCV), two with essential thrombocythemia (ET), one with myelofibrosis, 15 with RT, eight with ATP, and 12 healthy volunteers were enrolled in the study. Serum interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF), fibronectin, intracellular adhesion molecule-1 (ICAM-1), and thrombomodulin (TM) were measured in these groups. Interleukin-1β, IL-6, and TNF levels were high in patients with RT and ATP, suggesting that these cytokines act on early uncommitted progenitors, promoting commitment along the MK lineage and leading to thrombocytosis or compensation for thrombocytopenia. TM was significantly increased in patients with MPD compared to all other groups, probably indicating the presence of subclinical endothelial damage. Fibronectin levels were high in MPD and RT patients. This finding can be secondary to high platelet turnover in these patients. We found that ICAM-1 levels were high in patients with clonal thrombocytosis. ICAM-1 can be one of the factors initiating the events ultimately leading to clonal thrombocytosis. Thrombocythemia associated with MPD is an autonomous phenomenon not regulated by cytokines.
Low Tissue Plasminogen Activator Relative to Plasminogen Activator Inhibitor-1 as a Marker of Cardiac Complication in Children With Kawasaki Disease
Authors: Sakai Michio , Asayama Kohtaro , Otabe Hiroyuki , Kohri Takeo , Shirahata Akira
Published: November 2007

To determine whether the fibrinolytic system is related to the occurrence of cardiac complication in Kawasaki disease, we measured tissue plasminogen activator, plasminogen activator inhibitor-1, and related factors in the plasma of children with Kawasaki disease. Patients (mean age, 1.8 years) were classified into patients with cardiac complication (n = 9) and no complication (n = 14) groups echocardiographically. They underwent single, high-dose, intravenous γ-globulin infusion therapy. Blood was drawn just before and the day after the single high-dose intravenous γ-globulin infusion therapy (acute phase), and at early and late convalescent phases. Leukocytosis was normalized immediately after the single, high-dose, intravenous γ-globulin infusion therapy. C-reactive protein and fibrinogen were increased in the acute phase and normalized by convalescent phases. D-dimer fraction of fibrin degradation products changed in a similar manner. Tissue plasminogen activator and plasminogen activator inhibitor-1 were increased in acute phase. The tissue plasminogen activator/plasminogen activator inhibitor-1 ratio was lower in the complication group than in the no complication group throughout the observation period (0.095 versus 0.208 after single, high-dose, intravenous γ-globulin infusion therapy, p = 0.006; 0.094 versus 0.183 at late convalescent phase, p = 0.024). A low tissue plasminogen activator/plasminogen activator inhibitor-1 ratio can predict the propensity for cardiac complication, and can help the physician to decide whether additional therapies are necessary in acute phase Kawasaki disease.
The Influence of Antiphospholipid Antibodies on the Pregnancy Outcome of Patients With Recurrent Spontaneous Abortion
Authors: Heilmann L. , Tempelhoff G.-F. v. , Kuse S.
Published: November 2007

Several therapeutic regimens have been proposed for women with recurrent spontaneous abortion (RSA) and antiphospholipid antibodies (APA). Conflicting results have been reported about women with history of RSA, positive APA, and failure of standard therapy. To evaluate the use of intravenous immunoglobulin in RSA patients with APA and history of treatment failure, we initiated a study with standard therapy (aspirin and low-molecular- weight heparin) and intravenous immunoglobulin. We used an enzyme-linked immunosorbent assay (ELISA)test to screen IgG and IgM anticardiolipin antibodies, and a diluted Russel viper venom time assay for the lupus anticoagulant activity. Altogether. 66 pregnant women with positive APAs at the first visit could be included. Patients with hereditable thrainbaghilic factors were excluded. After confirmation of the pregnancy, women received a basis immunization of 0.3 g/kg immunoglobulin in a 4-week cycle until the 28th to 32nd week of gestation. All patients received 100 mg/d aspirin and 3,000 anti-Xa U/d certoparin. Among the 66 pregnant women, 17 were persistently autoantibody positive (25.8%), of whom 11 (16.7%) were ACA positive alone, 2 (3%) were lupus anticoagulant positive, and 4 (6.4%) had both antibody types. A total of 49 patients had positive APAs at the initial test, but were negative for ACA and lupus anticoagulant at the second test administered approximately 5 weeks after the start of therapy. We described this group in our following observation as "antibody negative." Sixteen of the 17 autoantibody-positive patients (94.1 %) were delivered of live infants compared with 40 patients (81.6%) in the antibody-negative group (odds ratio [OR]: 1.2; 95% CI: 0.98 to 1.4). The overall miscarriage rate was 12.1% and the fetal loss rate was 15.2%. Four patients (25%) in the antibody-positive group developed symptoms of preeclampsia and fetal growth retardation compared with four patients (9.8%) in the antibody-negative group. In conclusion. we see a reduction of the fetal loss rate in patients with RSA and positive APA (5.8%) compared with APAnegative (18.4%) women with the same therapy (OR: 0.3; 95% CI: 0.04 to 2.3).
Idiopathic Deep Vein Thrombosis and Subsequent Cancer: Suggestions for a Patient-Oriented and Practical Approach
Authors: Girolami Antonio
Published: November 2007

The relationship between an idiopathic deep vein thrombosis and a cancer is well established. It is not clear yet whether all patients with an idiopathic deep vein thrombosis should be thoroughly investigated for an occult cancer or only some. As a matter of fact, once a physician is faced with a patient who has an idiopathic deep vein thrombosis, three approaches are possible, mainly: 1) a wait and see approach; 2) a limited investigation; and 3) an extensive or invasive investigation. No sure criteria for the selection of the patients who should be extensively investigated are available. Suggestions have been made in this regard. Negative family or personal history for thrombosis, advanced age, deep vein thrombosis of upper limbs, existence of silent deep vein thrombosis in contralateral leg, tendency to relapse and/or to migrate, constitutional symptoms, or smoking may represent important clues that may justify an extensive study. This patient-oriented approach is mainly based on the experience of the caring physician.
Postoperative Reduction of Fibrinolysis as a Prognostic Factor of Fatal Outcome
Authors: Lotz Johannes , Walgenbach Stephan , Peetz Dirk , Dutkowski Peter , Junginger Theo , Prellwitz Winfried , Hafner Gerd
Published: November 2007

For the resection of an esophagus carcinoma a mortality rate of 2 to 30% was described, It is still unclear whether an abdominothoracic or transhiatal intervention is superior regarding the outcome. To investigate the prognostic value of fibrinolytic markers, plasmin-α2-antiplasmin (PAP) and D-dimer (DD) values were determined daily in the early postoperative period for 11days. In addition, the course of PAP and DD concentrations was compared with the method of esophagectomy. Of the 28 patients enclosed in the study, 5 died between day 10 and day 34 owing to adult respiratory distress syndrome and septicemia. The PAP and DD concentrations increased in survivors after surgery until day 5 and day 7, respectively. The concentrations were twofold and 10-fold higher than the upper reference level. In contrast, four of five nonsurvivors showed an inadequate increase in PAP concentrations within the reference range, whereas the course of DD was inconspicuous. The sensitivity and specificity of PAP and DD in respect to a fatal outcome was calculated by receiver operating characteristic analysis based on all results: sensitivity 76% (PAP-cut off value 760 μg/L) and 49% (DD 6 mg/L), specificity 77% and 72%, respectively. The biochemical markers showed no significant differences between the abdominothoracic and transhiatal esophagectomy. In the abdominothoracic intervention, lower PAP and higher DD concentrations were observed. The results showed that the PAP concentrations could detect a fatal outcome within the first 5 days after surgery.
Outcome Analysis for Treatment in 100 Patients with Deep Vein Thrombosis
Authors: Baker William F.
Published: November 2007

The treatment of acute deep vein thrombosis has been the subject of much research aimed at delineat ing the safest and most effective approach to diagnosis and treatment. Studies regarding long-term treatment have been limited by the narrow scope of laboratory and clinical analyses of many patients. In this study of 100 patients with a history of deep vein thrombosis, treated on an outpatient basis by a diverse group of clinicians, follow-up data were retrieved in order to determine the outcomes of various approaches to acute and long-term care. Among individuals followed for > 1 year, in only two patients (2%) was death attributable to a thrombotic event related to the etiology of the first episode of deep vein thrombosis. Most deceased patients succumbed to unrelated causes (11%). Among the 77 survivors, most (52%) received long-term antiplatelet therapy. All individ uals with a plasma coagulation defect, whether inherited or acquired, received anticoagulation with either heparin or warfarin. Since the long-term clinical outcome of most patients with deep vein thrombosis is dependent upon the underlying factor predisposing to thrombosis, the most important treatment decision is to select the therapy most likely to provide benefit without causing hemorrhage. An tiplatelet therapy, heparin, or warfarin may be chosen as appropriate for the individual patient.
Acute Myocardial Infarction: Diagnosis and Management
Authors: Leya Ferdinand , Fareed Jawed , Walenga Jeanine
Published: November 2007

Acute myocardial infarction is caused by abrupt thrombotic coronary occlusion. About 1.5 million patients will suffer a heart attack and 10 to 20% of them will die in the U.S.A. annually. Accurate diagnosis and early reopening (reperfusion) of infarct-related coronary artery will lower mortality (2 to 7%) and morbidity of patients and improve their post-MI recovery. There are several effective therapies available to reopen closed infarct-related coronary arteries. Thrombolytic or clot dissolving therapy can be safely used in about one-third of heart attack stricken patients. The expected effectiveness of thrombolytic therapy in treated patients is 70 to 80% of reperfusion rates and 7 to 8% mortality rates. Direct coronary angioplasty of the infarct-related coronary artery represents the most aggressive, yet the most effective reperfusion modality available to all patients suffering from acute MI. Direct angioplasty, when used appropriately, will result in 97 to 99% reperfusion rates and 2 to 3% mortality rates. Aggressive approach to the diagnosis and the treatment of acute MI using either thrombolytic therapy or direct coronary angioplasty holds the greatest promise for clinical success.
State-of-the-Art Review: Optimal Anticoagulation in Cardiovascular Surgery
Authors: Pifarré Roque
Published: November 2007

Despite current developments in anticoagulant drugs, unfractionated heparin has remained the drug of choice for anticoagulation during cardiopulmonary bypass surgical procedures. The use of heparin has been associated with problems. Heparin-induced thrombocytopenia, intra- and postoperative bleeding, heparin resistance, and heparin rebound after heparin neutralization are the major complications. The complexity of hemostatic control during cardiopulmonary bypass (CPB) must be emphasized. The protocol for anticoagulation during CPB has varied greatly from institution to institution. With the use of the activated clotting time (ACT) and the heparin analyzer, control of anticoagulation has become more uniform and neutralization of heparin with protamine more accurate. The preferred initial dose of heparin is controversial. It varies from 200 U/kg to 450 U/kg. In our institution the initial dose used is 200 U/kg. During cardiopulmonary bypass the ACT is maintained above 400 s. Several doses of 2,000-3,000 U of heparin are added to the oxygenator, if needed, to maintain that level. Monitoring anticoagulation with the ACT and the heparin analyzer has convinced us that the lower dose is safe and the higher dose unnecessary. Once CPB is discontinued, the dose of protamine for heparin reversal is calculated with the use of the Hepcon heparin analyzer. The total dose is divided into two: 75% is given once the lines have been removed, and the other 25% is administered once the blood from the oxygenator and the cell saver has been reinfused into the patient. With this method heparin rebound is prevented. The large surface of the extracorporeal circulation apparatus acts as a massive thrombotic stimulus. The early reactions that lead to activation of the contact system of plasma proteins, white cells, fibrinolysis, platelets, and complement are not inhibited because heparin acts near the end of the coagulation cascade. The consequences of these early reactions are potential bleeding, thrombotic complications, and inflammatory reactions associated with cardiopulmonary bypass. The introduction of aprotinin has decreased perioperative bleeding by inhibiting the inflammatory cascades associated with contact activation and by acting as an antifibrinolytic agent. Newly developed anticoagulants, such as r-hirudin, peptides, plasma-derived agents, and glycoprotein targeting drugs, may be useful as a adjunct to or replacement for heparin.
State-of-the-Art Review: Gamma Knife Radio Isurgery Treatment of Cerebral AVMs
Authors: Weiner Richard L.
Published: November 2007

Gamma knife stereotactic radiosurgery has been shown to be a relatively safe, cost-effective, and less invasive neurosurgical intervention for the treatment of intracranial arteriovenous malformations (AVMs). Total AVM obliteration rates at 3 years postradiosurgery approach 90%, with minimal morbidity and no mortality.
Common Thrombotic Disorders Defined by CBC Platelet Parameters
Authors: Willans David J. , Mill Sharon C. , Ranney E. Kenneth
Published: November 2007

The Coulter STKS mean platelet volume (MPV), platelet distribution width (PDW), mean corpuscular volume (MCV), and hematocrit (HCT) are assessed in thrombotic diseases. Complete blood counts (CBCs) were studied retrospectively in 645 consecutive hospital cases and, 850 "CBCs with blood films to the pathologist." Because the MPV and PDW are time dependant, nomograms and tables were created for the 0-25- and 26-40-min elapsed time intervals. In this study, abnormal CBC platelet parameters were found in the majority of patients with common thrombotic diseases, such as diabetes, atherosclerosis, hypertension, congestive heart failure, deep vein thrombosis (DVT), and toxemia. Thrombotic disease-related CBC categories include combined elevated MPV and PDW, elevated MPV or PDW alone, "MCV/MPV mismatch" (failure of physiologic "MCV/MPV match"), rheologic problem of elevated HCT and MPV, and mild thrombocytopenia with decreased MPV and high PDW. Anticoagulants and steroids often decrease the MPV. CBC platelet parameter abnormalities provide a new useful classification of thrombotic diseases in daily practice.
Changes in Clotting and Fibrinolytic Parameters Produced by Venous Stasis
Authors: Altman Raul , Scazziota Alejandra , Rouvier Jorge
Published: November 2007

Vascular endothelial cells have thrombosis- prevention properties through the release of some fibri nolytic factors. This capacity of endothelium was studied using the venous occlusion test (VOT) and measuring proteins released during stasis. Blood samples were col lected before and after 10 and 20 min VOT in tubes con taining sodium citrate at pH 7.0 or 4.3. A significant shortening of the euglobulin clot lysis time (ECLT) was obtained 10 and 20 min after VOT in plasma collected in citrate pH 7.0 or 4.3. No statistical difference was noted between results obtained 10 and 20 minutes after VOT. The shortening was related to the increase of tissue plas minogen activator (t-PA) released during VOT. No differ ence was detected in the concentration of tissue plasmin ogen activator inhibitor 1 (PAI-1), but PAI-1 activity mea sured in plasma from blood collected in citrate pH 7.0 decreased progressively from 10.8 ± 9.2 arbitrary units (AU)/ml to 3.76 ± 4.5 AU/ml and 0.8 ± 1.02 AU/ml (p < 0.001) after 10 and 20 min, respectively, of stasis. When the PAI-1 activity was determined in blood collected in citrate pH 4.3 for preventing in vitro complexing of PAI-1 and t-PA, results were different: PAI-1 activity decreased from a basal value of 29.2 ± 15.3 AU/ml to 24.9 ± 12.2 ( p = NS) and 18.7 ± 11.5; p < 0.02) 10 and 20 min after VOT. As result of fibrinolytic activation, other factors were modified: increase of plasminogen activators, de crease of plasminogen, and increase of D-dimer. Fibrin ogen, fibronectin, protein C, protein S, von Willebrand factor, and tissue factor pathway inhibitor concentration remained unchanged after VOT. According to our find ings, VOT can be performed with a stasis of 10 min. Good responders are related to the endothelial capacity for re leasing t-PA and urokinase-type PA (u-PA) and defined as those with an ECLT of <60 min after 10 min VOT when blood was collected in sodium citrate pH 7.0.
Sinus Venous Thrombosis Associated with a Nephrotic Syndrome in an Eight-Year-Old Child
Authors: Mira Yolanda , Mendizabal Santiago , Vayá Amparo , Sanchis Nuria , Villa Piedad , Aznar Justo
Published: November 2007

The nephrotic syndrome (NS) is reportedly as sociated with an increased risk of thromboembolic dis ease. We describe the case of an 8-year-old child with a steroid-responsive NS who developed a longitudinal si nus venous thrombosis. No family thrombophilic ten dency was found. To our knowledge, this is the second case published with these clinical characteristics. We sug gest that the sinus venous thrombosis was precipitated by the low levels of antithrombin III and hypoalbuminemia. Moreover, steroids probably played an etiological role. Key Words: Nephrotic syndrome—Sinus venous throm bosis—Venous thrombosis—Antithrombin III.
State-of-the-Art Review : Management of Patients Who Require Invasive Procedures Immediately Following Thrombolytic Therapy
Authors: Lanzkron Sophie M. , Bell William R.
Published: November 2007

In recent years the use of thrombolytic ther apy has been demonstrated to be valuable in the treat ment of patients with acute myocardial infarction. Often, because of the frequency of reocclusion of the infarct- related artery, identification of a treatable vascular le sion, or, rarely, failure of thrombolytic therapy, patients will require more invasive procedures to prevent further ischemic injury to the myocardium. These procedures in clude anything from cardiac catheterization to emergency coronary bypass surgery. The perioperative evaluation and management of patients who have recently received thrombolytic therapy requires an understanding of the changes in coagulation proteins that occur with the use of these therapeutic agents. The appropriate understanding and use of antifibrinolytic agents and blood products will allow for these procedures to be performed safely with a minimum of bleeding complications.
ABO Blood Groups as Risk Factors for Thrombosis
Authors: Lourenço Dayse M. , Miranda Fausto , Lopes Letícia H. C.
Published: November 2007

To evaluate the relationship between ABO blood group and thrombosis, we studied 127 patients tak ing oral anti-vitamin K drugs for thromboembolism pro phylaxis and compared them with 700 voluntary blood donors. There were 68 patients with venous thrombosis (VT)—68 with deep vein thrombosis and 8 with pulmo nary embolism—and 51 patients with arterial embolism (AE). There were 61 men and 66 women. Mean age at diagnosis was lower for all women, regardless of if they had VT or AE (43 years) than for men (55 years; Kruskal- Wallis test, p < 0.01). There was an imbalance between blood group A and O frequencies in patients with VT versus blood donors, with a higher frequency of blood group A or a lower frequency of blood group O, repre sented by a high A/O ratio. A/O ratio for blood donors was 0.63; it was 1.50 for men (Fisher test, p = 0.028) and 1.44 for women (Fisher test, p = 0.010). Patients with AE showed the same discrepancy, but it was significant for women (A/O = 2.25; Fisher test, p = 0.026) and not for men (A/O = 0.86; Fisher test, p = 0.836), suggesting that men with AE might have other risk factors for thrombo sis. These data are not conclusive about the causes of the association between ABO blood groups and thrombosis, and prospective studies are needed to verify whether blood typing could have a predictive value for prophylatic measures in clinical and surgical patients.
Optimal Duration for Prophylaxis of Deep Vein Thrombosis: The New Focus?
Authors: Toulemonde Francis , Kher André
Published: November 2007

It is usual to stop prophylaxis of most surgical patients at hospital discharge. However, there is increas ing evidence that some patients are at risk of thromboem bolism after treatment is stopped. Some evidence and several proposals from the literature are presented, but to date, the situation remains unclear.
Tamoxifen-Induced Changes in the Plasma Fibrinolytic Factors in Menopausal Women with Breast Cancer
Authors: Lox Charles D. , Ronaghan Catherine A. , Cobos Everardo , Messer Robert H.
Published: November 2007

There is evidence that tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and the plasminogen activator inhibitors 1 and 2 (PAI-1, PAI-2), are involved in the invasion and metastasis of breast tumors. Menopausal controls and menopausal women with breast cancer, who were taking tamoxifen, 10 mg b.i.d., had plasma antigenic levels of tPA, uPA, PAI-1, and PAI-2 determined by enzyme-linked immunosorbent assay (ELISA). In addition, five women being placed on this tamoxifen regimen also had these same determinations made before and after 6 months. Significant increases were observed for tPA, uPA, and PAI-1 in the 26 tamoxifen-treated patients. The percent increase in tPA and uPA combined were greater than that of PAI-1. Nonsignificant increases were also seen in the five women evaluated before and after initiation of treatment. Linear correlations were seen for tPA and PAI-1 over time length of exposure to tamoxifen. Ratios of tPA/PAI- 1 and UPA/PAI-1 were not significantly different, but were correlated and linear. From these data, it appears that tamoxifen increases the fibrinolytic factors in these patients and that this was not proportional as the ratios of the factors were not different after treatment. The increase in activators was greater than inhibitors, which could be detrimental in terms of the potential for invasion and metastasis of the tumor cell. As a negative correlation was seen for tPA over time while PAI- was positively correlated, this may help explain why some patients taking tamoxifen are at risk for thromboembolytic events. Key Words: TPA—uPA—PAI-1—PAI-2—Tamoxifen—Breast cancer.
The Use of Dextran 70 as a Plasma Expander Increases the Intraoperative Bleeding in Total Hip Replacement
Authors: Seest Jørgensen P. , Rasmussen S.W. , Tørholm C.
Published: November 2007

In total hip replacement (THR) dextran 70 is widely used as a plasma expander and as a thromboprophylactic agent. In a rec-hirudin multicenter dose-finding study approximately one third of the patients in our center received dextran 70 as a plasma expander at the beginning of the operation, the remainder received Haemaccel preoperatively. The average intraoperative bleeding was 1,572 ml (770-3,950 ml) in group 1 (dextran) and 1,160 ml (500-2,400 ml) in group 2. This difference is statistically significant ( p = 0.002). The average postoperative bleeding was in group 1,273 ml (50-675 ml) and in group 2, 229 ml (0-870 ml), the difference is not significant. Total bleeding was in average 1,846 ml (850-4,250 ml) in group 1 and 1,451 ml (620-2,810 ml) in group 2; this difference is statistically significant ( p = 0.012). Regarding the transfusion requirement measured in units; a median of 2, 5 units (0-8 units) were used in group 1 as opposed to 1.7 units (0-7 units) in group 2 (p = 0.055). The use of dextran 70 as a plasma expander led to significantly increased intraoperative bleeding. Key Words: Bleeding—Dextran—Hiparthroplasty.
Whole Blood Lumiaggregation: Evaluation of Reagents
Authors: Vucenik Ivana , Podczasy John J.
Published: November 2007

We evaluated the whole blood lumiaggregation system, which analyzed the optimal sample dilutions and ago nist concentrations. We also showed that platelet aggregation using the whole blood impedance technique, as compared to the platelet-rich plasma optical method, yielded similar informa tion. In the extension of that study, we further evaluated the stability of the reagents used in platelet aggregation. The most commonly used agonists thrombin, ristocetin, arachidonic acid, adenosine diphosphate, and collagen were monitored over a 1-year period. Throughout the entire period, aliquots of the reconstituted reagents were stored at -20°C, -50°C, and -70°C, with the exception for collagen, which was kept at 4°C. Every 2 weeks tests were performed using the whole blood from the same healthy volunteer. Platelet aggregation and aden osine diphosphate release were measured after stimulation with 1.0 U/mL thrombin, 1.0 mg/mL ristocetin, 0.5 mM arachidonic acid, 10 μM adenosine diphosphate or 3 μg/mL collagen. The results indicated that thrombin was stable at all temperatures over the 1-year period. Platelet agglutination with ristocetin was similar among samples for about 2 months; after that time some deterioration of ristocetin was noticed, especially at -20°C. Reconstituted arachidonic acid, frozen at -20°C, was stable for about 1 month, and at the lower temperatures this agonist was good for 4 months. On the contrary, adenosine diphosphate and collagen exhibited stability throughout the 1- year period. Based on the information provided by this study, we encourage more laboratories to use whole blood lumiaggre gation to evaluate platelet function.
Soluble Plasma Thrombomodulin Levels in Patients with Chronic Myeloproliferative Disorder
Authors: Randi Maria Luigia , Meneghin Cristina , Zerbinati Patrizia , Sbarai Alessandra , Rampin Ernesto , Pasini Roberto , Zanin Lara , Girolami Antonio , Cella Giuseppe
Published: November 2007

The plasma levels of soluble thrombomodulin (TM) were measured in 44 patients with chronic myeloprolif erative disorder, 15 with polycythemia vera (PV), 29 with es sential thrombocythemia (ET), and a group of 62 matched healthy controls. The younger patients had significantly lower TM levels (mean: 15.6 ± 4.8 ng/mL) than the older patients (mean: 28.6 ± 8.2 ng/mL, p < .001). Moreover, a significant negative correlation between platelet counts and plasma TM levels in healthy persons was noted (r = 0.317, p < .05). The only significant difference we found in plasma TM levels be tween patients and controls or among patients was between the young patients with ET (mean: 29.0 ± 19.2 ng/mL) and young healthy controls (mean: 15.6 ± 4.8 ng/mL). It is possible that younger ET patients with more active platelets are more sus ceptible to earlier vascular damage. The lack of any significant difference compared with the older patient population supports this hypothesis. Key Words: Thrombomodulin—Essential thrombocythemia—Polycythemia vera.
Acquired von Willebrand Disease Due to Increasing Platelet Count Can Readily Explain the Paradox of Thrombosis and Bleeding in Thrombocythemia
Authors: Michiels Jan Jacques
Published: November 2007

The arterial microvascular thrombotic events in thrombocythemia including erythromelalgia, atypical and typi cal cerebral and ocular transient ischemic attacks, and acute coronary syndromes already occur at platelet counts >400 x 109/L and are sensitive to low-dose aspirin, which does not elicit bleedings at platelet counts <1,000 x 109/L. An increasing platelet count in thrombocythemia to above 1,000 x 109/L is accompanied by the acquisition of a von Willebrand factor deficiency due to the loss of intermediate and large von Will ebrand factor multimers. The arterial thrombotic condition in thrombocythemia changes into an overt spontaneous bleeding tendency at mean platelet counts of about 2,000 ± 1,000 x 109/L due to an acquired von Willebrand disease type II with normal values for von Willebrand factor antigen concentration but absence of intermediate and large von Willebrand factor multimers in plasma. At platelet counts between 1,000 and 2,000 × 109/L, thrombosis and bleeding frequently occur in sequence or paradoxically, and low-dose aspirin does prevent thrombotic complications but aggravates or may elicit bleeding symptoms. Reduction of the platelet count <1,000 x 109/L significantly restores the von Willebrand factor deficiency with the reappearance of the intermediate and some of the large von Willebrand factor multimers and the disappearance of the bleeding tendency, but the thrombotic tendency per sists as long as platelet counts are above the upper limit of normal. The acquisition of von Willebrand factor deficiency at increasing platelet counts can readily explain the paradox of thrombosis and bleeding in thrombocythemia and has impor tant clinical implications.
Do Hemophilia A and von Willebrand Disease Protect Against Carotid Atherosclerosis? A Comparative Study Between . Coagulopathics and Normal Subjects by Means of Carotid Echo-Color Doppler Scan
Authors: Bilora Franca , Dei Rossi Camilla , Girolami Bruno , Casonato Alessandra , Zanon Ezio , Bertomoro Antonella , Girolami Antonio
Published: November 2007

Atherosclerosis is a multifactorial disease caused by genetic and environmental factors with important clinical sequelae. The aim of this study was to evaluate the degree of carotid atherosclerosis by echo-color Doppler scan in a group of patients affected by hemophilia A and von Willebrand dis ease versus a group of normal subjects apparently free of ath erosclerotic risk factors. All coagulopathics and normal patients who came to our Internal Medicine Department (Padua Hospi tal) underwent physical exam, blood analysis, standard electro cardiogram, chest x-ray, echo-color Doppler scan, and a thor ough history. We examined 156 subjects, 76 coagulopathics (46 men, 30 women) and 77 normals (37 men, 40 women). Coagulopathics were affected by hypertension in 28.9% of cases, diabetes mellitus in 6.5%, dislipidemia in 17.1%, smoke in 39.4%, and obesity in 36.8% (p < .05). Echo-color Doppler scan revealed carotid plaques in 27.2% of control patients ver sus 13.1% of coagulopathics (p < .05). Hemophilics and sub jects with von Willebrand disease with a more serious illness had fewer plaques than those with lighter defects. Coagulopath ics showed 23.6% of the plaques we revealed on the whole, versus 76.3% of control subjects (p < .01), with a lighter degree of stenosis (p < .01). Our data demonstrate that patients with hemophilia A and von Willebrand disease have fewer carotid plaques and a smaller degree of carotid stenosis than normal subjects of the same sex and age. These data seem to strengthen the hypothesis that blood coagulation defects may allow pro tection against carotid atherosclerosis and its sequelae.
Aspirin and Platelet-Lowering Agents for the Prevention of Vascular Complications in Essential Thrombocythemia
Authors: Michiels Jan Jacques
Published: November 2007

Low-risk essential thrombocythemia patients in clude patients aged 18 to < 80 years with no vascular risk fac tor or previous thrombosis, no associated disease, a normal life expectancy, and a platelet count between 400 and 1,000 x 109/L up to 1,500 x 109/L. Asymptomatic essential thrombo cythemia patients may be at risk for microvascular circulation disturbances. The indication for low-dose aspirin in asymptom atic essential thrombocythemia patients is uncertain, therefore randomization for aspirin 50 mg versus placebo is recom mended. Symptomatic essential thrombocythemia patients with erythromelalgia and its ischemic complications, atypical tran sient ischemic attacks, minor stroke, visual disturbances and "superficial thrombophlebitis" in the absence of bleeding, vas cular risk factors, or vascular disease have a clear indication for aspirin in a regular dose. To determine whether 50 mg/day is as effective as 100 mg/day for the prophylaxis of microvascular circulation disturbances in essential thrombocythemia, a ran domized trial comparing low-dose aspirin 50 mg versus 100 mg at platelet counts between 400 and 1,000 up to 1,500 x 109/L is recommended. To address the question whether reduction of the platelet count to normal (<350 x 109/L) is as effective as low-dose aspirin for the long-term relief of microvascular cir culation disturbances, a randomized study comparing low-dose aspirin with the correction of platelet count to normal by anagrelide is recommended. High-risk essential thrombocythe mia patients have a clear indication for platelet reductive therapy, including: (a) platelets >1,500 x 109/L, history of ma jor thrombosis (myocardial infarction, stroke, peripheral occlu sive vascular disease), or presence of vascular disease (e.g., arteriosclerosis); (b) history or presence of spontaneous or ma jor bleedings, bleedings elicited by low-dose aspirin for the secondary prevention of vascular complications in essential thrombocythemia at platelet counts <1500 x 109/L, and side effects of long-term aspirin treatment such as gastritis; and © progression from low- to high-risk essential thrombocythemia patients during follow-up or progressive myeloproliferative disease such as significant splenomegaly, myelofibrosis, leu kocytosis, etc. To address the question of optimal treatment of high-risk essential thrombocythemia patients, randomization for anagrelide versus interferon at < 65 years of age and anagrelide versus hydroxyurea at an age > 65 years is recom mended.
An Analysis of Tenure and House Structure Type by Household Composition
Authors: Vanderford Stephanie E. , Mimura Yoko , Sweaney Anne L. , Carswell Andrew T.
Published: November 2007

This study examined the relation of household composition and characteristics with each of two variables, tenure status and structural type of residence. Past research related to tenure status has considered household composition and characteristics in a limited manner, and very little empirical work has addressed the relations of those variables with house structure type. The three structure types assessed were manufactured housing, multifamily site‐built homes, and single‐family site‐built homes. The authors extended past research by considering more complicated household compositions and also identified the importance of knowing more complete information about all the residents of a home to understand both tenure and house structure type. Family composition and the presence of extended family members, an unmarried partner, and other unrelated individuals all explained di ferences in tenure and house structure type. The findings suggest the significance of family and household characteristics when understanding variations in tenure and house structure type.
Pharmaceutical care in oncology pharmacy practice: A method for using outcome indicators
Authors: Broadfield Larry
Published: November 2007

A method is discussed for design and implementation of a set of toxicity outcome indicators, linked to each chemotherapy protocol ordered for routine patient care. Pharmacists, as integral members of the systemic treatment team, participate in the monitoring of patient toxicities to chemotherapy, and the treatment and/or prevention of adverse effects. Rating scales vary from protocol to protocol, depending on the drugs in each specific protocol, and the unique toxicities associated with that combination of agents. Both objective and subjective toxicities are measured and monitored in a standardized format. Aside from assisting in the care of individual patients, these toxicity ratings may also be analyzed for various administrative purposes, including quality audit and planning of future services (including pharmaceutical care pro grams), and may be used for population-based descriptive research.
A multiparous pregnant woman receiving chemotherapy for breast cancer
Authors: Cass Y. , Uziely B. , Heching N. , Ramu N. , Pappo Y. , Peretz T.
Published: November 2007

Cancer is the second leading cause of death in women during the childbearing years. Breast can cer is the most common malignancy presenting during pregnancy and lactation. Treatment with antineoplastic agents in this group of patients is problematic due to their potential teratogenicity. A case report is presented of a pregnant woman who received neo-adjuvant chemotherapy for locally advanced carcinoma of the breast. The patient received a total of four courses of cyclophospha mide, doxorubicin and 5-fluorouracil, before deliv ery of a child healthy in all systems. We discuss the use of cytotoxic drugs during pregnancy and indi cate some of the dilemas facing the treating physi cian. The authors join in the call for the establish ment of an international registry of children born to mothers who receive cytotoxic drugs during pregnancy.
Review : Angiogenesis: A new target for antineoplastic therapy
Authors: Dover Kristi R. , Valley Amy W.
Published: November 2007

Objective. To review the pathophysiologic rationale and therapeutic applications of inhibiting angiogenesis in solid tumor growth.

Data Sources. A MEDLINE search of articles published from 1985 to 1995 and a CancerLit search of articles published from 1988 to 1995, using the MESH heading "neovascularization" and text words "angiogenesis" and "antiangiogenesis." References listed in identified publications were reviewed for additional pertinent literature.

Study Selection. All human trials evaluating angiogenesis inhibitors in malignant disease and pre- clinical trials that illustrate potential mechanisms of action of such agents were included.

Data Synthesis. Angiogenesis, the formation of new blood vessels, is necessary for the development of significant solid tumor growth. Inhibition of angio genesis is a unique mechanism of antineoplastic ther apy that does not use traditional cytotoxic actions. Four investigational antiangiogenic agents are cur rently being evaluated in phase I and II trials. Poten tially beneficial applications of angiogenesis inhibitors include suppression of occult and premalignant le sions, symptomatic control of angiogenesis-depen dent malignancies, and combination therapy with traditional antineoplastic agents.

Conclusion. Inhibition of angiogenesis is a new pharmacologic strategy that may prove useful in controlling malignant growth. A number of agents with antiangiogenic activity have been developed, and further study of these drugs will define their role in antineoplastic therapy.
Review : Taste disturbances during chemotherapy
Authors: Gilbar Peter
Published: November 2007

Objective. The purpose of this review is to highlight drugs that have been involved in causing taste dys function during cancer chemotherapy and discuss possible management strategies. To illustrate the po tentially damaging consequences that can occur, a case study, describing a taste disturbance with levami sole, is presented.

Data sources. A variety of literature sources, including manual and on-line (Medline, IDIS) search ing were used. Taste or taste disorders linked with antineoplastic agents or individual drug names were used as the primary search terms.

Study selection. Any articles mentioning taste disturbances during cancer chemotherapy were con sidered.

Conclusion. Taste alteration is a poorly re ported and often neglected side effect of drug treat ment. The initial treatment of taste disturbance in volves isolating the cause and correction of any contributing factors. Withdrawal of the offending drug commonly leads to resolution of symptoms. However, if this is inappropriate, management or temporary relief of symptoms often can be achieved. The consequences of taste disturbances can be con siderable, ranging from reduction in a patient's quality of life to cessation of a potentially curative treatment. Pharmacists should be aware of this adverse effect and the possible damaging impact it can have on therapeutic outcome.