The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice.     

Preoperative pulmonary assessment of the older adult

Postoperative pulmonary complications in the elderly are common and are a significant source of morbidity, mortality, and prolonged length of stay. Risk factors differ from the well-known risk factors for cardiac complications and can be divided into patient- and procedure-related factors. Patient-related factors include COPD, recent cigarette use, poor general health status as defined by Goldman or ASA class, dependent functional status, and laboratory parameters including abnormal chest radiograph, renal insufficiency, and low serum albumin. Age is a minor risk factor when adjusted for comorbidities and confers approximately a two-fold increase in risk. Elderly patients who are otherwise acceptable surgical candidates should not be denied surgery based solely on age and concern for postoperative pulmonary complications. The surgical site is the single most important predictor of pulmonary complications. High-risk surgeries include thoracic, upper abdominal, aortic, neurosurgery, and peripheral vascular. Other procedure-related risk factors include surgery lasting longer than 3 hours, the use of general anesthesia, pancuronium use, and emergency surgery. Clinicians should not recommend routine preoperative spirometry before high-risk surgery because it is no more accurate in predicting risk than clinical evaluation. Patients who might benefit from preoperative spirometry include those who have unexplained dyspnea or exercise intolerance and those who have COPD or asthma in whom uncertainty exists as to the status of airflow obstruction when compared with baseline. After identifying patients at risk for postoperative pulmonary complications, clinicians can recommend strategies to reduce risk throughout the operative period. In addition to minimizing or avoiding the above risk factors, optimization of COPD or asthma, deep breathing exercises, incentive spirometry, and epidural local anesthetics reduce the risk of postoperative pulmonary complications in elderly surgical patients.     

Anti-factor VIII antibodies of hemophiliac patients are frequently directed towards nonfunctional determinants and do not exhibit isotypic restriction

A significant proportion of hemophilia A patients receiving transfusions of factor VIII (FVIII) develop a specific antibody response towards FVIII. These antibodies are usually detected by assays in which they inhibit the function of the molecule, such as the Bethesda clotting test. We have prepared anti-FVIII antibodies by specific immunoadsorption from the plasma of four hemophiliacs with stable inhibitor levels. The isotypic distribution of such antibodies was determined and their capacity to bind to insolubilized FVIII was compared with their inhibitory activity in two functional assays, namely, the Bethesda assay and a chromogenic assay. In addition, the FVIII epitope specificity was determined by competition with monoclonal antibodies for the binding to insolubilized FVIII. We show here that (1) anti-FVIII antibodies are not isotypically restricted; thus, a significant proportion of specific IgG2 was found; (2) antibodies are frequently directed towards epitopes of FVIII that are not directly involved in the function of the molecule and therefore escape detection in the Bethesda method or chromogenic assay; and (3) each patient shows a unique pattern of FVIII epitope recognition. We conclude that evaluation of anti-FVIII antibodies by a functional method does not provide an accurate evaluation of the specific antibody response. These findings have important implications for the comparison of the immunogenicity of FVIII molecules produced by different technologies and for the development of methods to control anti-FVIII antibody production.     

In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease

The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28 present on the latter cells. In this study, benign lymphoid tissues, lymphomas, and extralymphoid inflammatory sites were examined immunohistochemically using anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign transformed germinal center B cells, as it was by B cells of follicular lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of macrophages and dendritic cells in a variety of lymphoid tissues. It was present in abundance on all macrophages constituting sarcoid granulomas in lymph nodes. In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that potentially contributes to the lymphocytic accumulation that is a feature of this condition. CD28+ T cells were seen in all areas where T cells were present. B7+ and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a potential for cellular interaction via these molecules at these sites.     

Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

Management of tandem occlusions in patients who receive rtPA

Journal of Thrombosis and Thrombolysis - Tandem occlusions exist in 17–32% of large vessel occlusion (LVO) strokes. A significant concern is bleeding when carotid stenting is performed in...     

Nucleoli in cells of the granulopoietic proliferating compartment in patients suffering from the refractory anemia of the myelodysplastic syndrome

Granulocytic precursors of the granulopoietic proliferating compartment (GPC) were investigated in patients suffering from refractory anemia (RA) of myelodysplastic syndrome (MDS) to provide an information on the number of nucleoli and incidence of main nucleolar types in these cells stained with the simple cytochemical procedure for the demonstration of RNA. The results demonstrated that the incidence of main nucleolar types in all stages of the granulopoietic proliferating compartment in RA patients of MDS generally did not differ in comparison with that of control patients without a disturbed granulopoiesis. In contrast, the number of nucleoli expressed by the values of the nucleolar coefficient in all stages of GPC in RA patients was significantly smaller than in control persons. In addition, the values of the nucleolar coefficient of myeloblasts in patients with RA of MDS were close to those in patients with acute myeloid leukemias.     

A note on nucleoli in granulocytic precursors of the granulopoietic proliferating compartment in patients suffering from the chronic phase of chronic myeloid leukemia treated with two different drugs with different mode of action

The incidence of main nucleolar types in granulocytic precursors was studied in the granulopoietic proliferating compartment (GPC) of patients suffering from chronic phase of the chronic myeloid leukemia (CML) who were treated by the widely used therapy with two different drugs with different mode of action - hydroxyurea (HU) and interferon alpha (IFN-alpha). In comparison with IFN early stages of GPC, i.e. myeloblasts and promyelocytes in patients treated with HU possessed more frequently micronucleoli which are known to reflect the direct as well as indirect inhibition of the nucleolar biosynthetic activities. On the other hand, the incidence of micronucleoli in these cells of a small percentage of patients treated with IFN also reached the average values of these nucleoli which were noted in patients treated with HU.     

A further study on the number of silver stained granules of active nucleolus organizer regions in mitotic Yoshida and Zajdela rat experimental tumor cells

Yoshida ascitic sarcoma and Zajdela ascitic hepatoma were investigated in Norway rats to provide more information on active nucleolus organizer regions (NORs) represented by silver stained granules (SSGs). Diploid Yoshida sarcoma cells were characterized by the presence of 6 (3 doublets) of SSGs in the metaphase and 3 + 3 SSGs in future daughter nuclei in the anaphase or telophase. In contrast Zajdela hepatoma cells (frequently hypoploid) possessed 6 SSGs less frequently in the metaphase and the number of anaphasic or telophasic cells with 3 SSGs in future daughter nuclei was also reduced. The number of SSGs in future nuclei of anaphasic or telophasic Yoshida sarcoma cells was usually the same, i.e. such anaphases or telophases were symetric. In Zajdela hepatoma cells the number of symetric anaphases and telophases was substantially reduced in favor of asymetric anaphases or telophases which contained different number of SSGs in future nuclei.