Decreased hemoglobin levels are associated with higher plasma level of fibrinogen, irrespective of age.

BACKGROUND: Increased plasma levels of fibrinogen are been associated with an increased risk of cardiovascular accident. We aimed at verifying whether the changes of fibrinogen levels are associated with red blood cell (and/or hemoglobin) concentration. METHODS: A group of 381 carefully selected healthy volunteers (219 male and 162 female), aged from 18 to 101 years, were enrolled in this study. Fasting blood samples were taken and all measurements (fibrinogen plasma level, whole blood viscosity, hemoglobin concentration, hematocrit value, red blood cell and white blood cell count, platelet count, glucose, total cholesterol and triglycerides plasma concentration, and C-reactive protein level) were obtained with standardized methodology using appropriate equipment, procedures, and controls. RESULTS AND CONCLUSIONS: In the male but not in the female group, plasma fibrinogen concentration inversely correlated with hemoglobin (P < 0.0001) and hematocrit value (P < 0.01). In a post hoc analysis, plasma fibrinogen level inversely correlated with hemoglobin in the subgroup of the 93 premenopausal women and directly correlated with age and inversely correlated with platelet count in the subgroup of the 69 postmenopausal women. Results of multiple regression analysis revealed that in all the subjects, except in the postmenopausal women, hemoglobin level is an independent predictor of fibrinogen plasma level. Considering the physiopathologic role of increased plasma fibrinogen concentration and the scarcity of pharmacologic approaches to decrease its level, these findings could be important in designing a preventive therapy of cardiovascular disease.

Induction of CD95 upregulation does not render chronic lymphocytic leukemia B-cells susceptible to CD95-mediated apoptosis.

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a progressive accumulation of long-lived and well-differentiated clonal B-lymphocytes in peripheral blood, lymphoid tissue and bone marrow. Although B-CLL pathogenesis is not entirely understood, the progressive increase in lymphocyte counts coupled with the very low proportion of proliferating cells suggests that B-CLL may be primarily determined by defective apoptosis. Consistently, freshly analyzed CLL B-cells express very low levels of membrane CD95, one of the best-known receptors involved in triggering apoptosis. In this study, CD95 upregulation on CLL B-cells was induced by culturing clonal B-cells in the presence of supernatants from preactivated autologous T-lymphocytes. Intracellular cytokine staining of preactivated autologous T-lymphocytes using monoclonal antibodies (moAbs) specific for Th1 or Th2 cytokines, namely interleukin (IL)-2, IL-4, IL-5, IL-10 and interferon (IFN)-gamma, showed these cells to be positive for IL-2 and IFN-gamma. Blocking experiments using moAbs specific for IL-2 and/or IFN-gamma revealed that CD95 upregulation on CLL B-cells was mainly driven by IFN-gamma. However, CD95-expressing CLL B-cells were demonstrated to be resistant to CD95-mediated apoptosis, thus arguing against strategies aimed at exploiting CD95-mediated apoptosis for immunotherapy of B-CLL.

Triclonal gammopathy in an extranodal non-Hodgkin lymphoma patient.

The case of a patient with an extranodal non-Hodgkin lymphoma and three M-components (IgGkappa + IgGlambda + IgMlambda) in the serum is described. Three separate populations of M-component producing cells have been identified. Since a kappa-->lambda chain switch is not demonstrated, the synthesis of IgGkappa and IgGlambda by two distinct clones is obvious. IgMlambda and IgGlambda M-components are synthesized by two different plasma cell populations that could represent two unrelated cell clones or, alternatively, two subclones originated by a common precursor. After chemotherapy the IgGlambda M-component is replaced by heavy gamma chains without evidence of lambda light chains.

Differences in constitutive and activation-induced expression of CD69 and CD95 between normal and chronic lymphocytic leukemia B cells.

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a sustained accumulation of long-lived and well-differentiated B lymphocytes in lymphoid tissues, peripheral blood and bone marrow. Although the pathogenesis of this disease is not entirely understood, altered apoptosis is believed to play a relevant role in B-CLL. In this study, we compared the expression of CD95, the best characterized surface molecule involved in triggering the apoptotic machinery, on normal and CLL B cells before and after in vitro activation with polyclonal stimulators. Cell activation was monitored by verifying the induced expression of the early activation antigen CD69. Freshly analyzed CLL B cells showed significantly lower levels of CD95 than normal B cells. Moreover, following in vitro culture with phorbol 12-myristate 13-acetate (PMA) + ionomycin, phytohemagglutinin, or pokeweed mitogen, CLL B cells failed to upregulate CD95 expression as efficiently as normal B cells. Impairment of CD95 upregulation was mainly observed following PMA + ionomycin treatment. In contrast, CLL B cells were shown to express CD69 as well as normal B cells, regardless of the activator used, indicating that CLL B cells retain the ability to respond to activating stimuli but are unable to efficiently implement the CD95-mediated activation-induced cell death (AICD) program. In conclusion, these results suggest that prolonged survival of CLL B cells may be contributed to by alterations in AICD mechanisms.

Macroamylasemia in a patient with multiple myeloma.

We report a rare case of a patient with multiple myeloma who developed hyperamylasemia not associated to hyperamylasuria and without symptoms of pancreatic or salivary disease. This condition suggested the occurrence of macroamylasemia, consisting of macromolecules of amylase bound with immunoglobulins, which are not filtered by the kidneys. Hyperamylasemia was not present at the diagnosis of myeloma and appeared at the relapse of the disease, simultaneously with the appearance of an additional gamma-chain oligoclonal component, suggesting a possible role of these chains in producing macroamylasemia. To our knowledge, this is the first report of macroamylasemia in a patient with multiple myeloma.

A case of congenital dyserythropoietic anemia type II, Gilbert's syndrome and malleolar trophic ulcers.

A case of a woman with congenital dyserythropoietic anemia type II (CDA-II), Gilbert's syndrome (GS) and trophic malleolar ulceration is described. The association of CDA-II and GS caused early gallstone formation that led the patient to undergo cholecystectomy at the age of 15. GS is typified by increased production of both unconjugated and monoconjugated bilirubin, which is more lithogenic. The development of ulcers is not typical of CDA-II, even though they are associated with many of the hemolytic anemias, and were thought in our patient to be due to a thrombophilic tendency which manifest with Antithrombin III and Protein C deficiency.

C1 inhibitor infusion modifies platelet activity in hereditary angioedema patients.

CONTEXT: C1 inhibitor (C1-INH) is an alpha2-globulin that blocks esterolytic activity of the first component of the classic complement cascade. The alpha-granules of normal human platelets also contain C1-INH, which is expressed on the platelet surface during platelet secretion in healthy patients, but it is clearly reduced in patients with hereditary angioedema (HAE). OBJECTIVE: To evaluate the effects of in vivo C1-INH concentrate infusion on platelet responsiveness and coagulation system activity in patients with HAE. DESIGN: Assessment of the platelet activity and plasma levels of C1-INH, activated factor XII (XIIa), and prothrombin fragment F1.2 (F1.2) before and after infusion of 15 U/kg of C1-INH concentrate. PATIENTS: In 6 patients (4 men and 2 women), HAE was diagnosed according to the accepted clinical and laboratory criteria. MEASUREMENTS: Platelet aggregation (final concentrations: adenosine diphosphate, 0.5, 1.25, and 2.5 microM; collagen, 5 microg/mL), C1-INH antigen (radial immunodiffusion), C1-INH activity (chromogenic substrates), and XIIa and F1.2 (enzyme-linked immunosorbent assay). RESULTS: After C1-INH infusion, we observed a prompt increase of C1-INH level and a slow return toward its plasma preinfusion values within 4 to 7 days, a significant decrease of both adenosine diphosphate- and collagen-induced platelet aggregation versus preinfusion values (maximum after 1-2 days; P <.001), and a rapid decrease of high basal values of XIIa and F1.2 in 30 and 120 minutes, respectively. CONCLUSIONS: These data show a role of C1-INH in the control of platelet activity and that its deficiency increases platelet aggregability and plasma levels of XIIa and F1.2 in patients with HAE.

Development of a transient monoclonal gammopathy after chemotherapy in a patient with biphenotypic acute leukemia.

The development of a IgGk monoclonal gammopathy after a phase of bone marrow aplasia following chemotherapy is described in a patient suffering from biphenotypic acute leukemia (BAL). Paraprotein was followed by the relapse of the disease and disappeared during a further chemotherapy. Paraprotein could have been caused by an additional chemotherapy-induced genetic mutation or by a dysfunction in T-B cooperation observed in the phase of reconstitution of the immune system after medullar aplasia.

Altered constitutive and activation-induced expression of CD95 by B- and T-cells in B-cell chronic lymphocytic leukemia.

Expression of CD95, a molecule involved in activation-induced cell death (AICD), might contribute to explain accumulation of leukemic B-cells and functional impairment of T-cells in B-cell chronic lymphocytic leukemia (B-CLL). There-fore, we compared constitutive and activation-induced expression of CD95 and CD69 by B- and T-cells in CLL patients and in healthy donors.