Skin Necrosis Associated With Heparin-Induced Thrombocytopenia and Thrombosis.

Skin necrosis is a rare complication of heparin therapy. Strong evidence suggests an immune-mediated mechanism in which heparin-antibody complexes bind to platelets, resulting in platelet aggregation, thromboembolism, and ischemic necrosis. Heparin-induced thrombocytopenia (HIT) may also occur in response to immune-mediated platelet aggregation. The presence, of heparin-dependent antibodies can be confirmed by platelet aggregometry, (14)C-serotonin release assay (SRA), or enzyme-linked immunosorbent assay (ELISA). Clinical suspicion, early detection and immediate cessation of heparin therapy are important in preventing the potentially severe complications of heparin-induced platelet aggregation. Potential therapeutic approaches include plasmapheresis and alternative forms of anticoagulation such as warfarin, aspirin, dipyridamole, or other novel investigational agents.

Technetium-99m Sestamibi Scanning Reflects Marrow Activity in a ß-Thalassemia Patient Treated with an Allogeneic Bone Marrow Transplant.

ß-thalassemia major is a disorder of globin synthesis, resulting in anemia and compensatory bone marrow hyperproliferation. Conventional imaging studies do not measure bone marrow activity reliably. We report on the use of technetium-99m sestamibi (MIBI) in a ß-thalassemia major patient treated with an allogeneic bone marrow transplant. Pre-transplant and early post-transplant MIBI scannings demonstrated generalized marrow uptake, reflecting marrow hyperproliferation. After full engraftment, post-transplant MIBI showed disappearance of abnormal uptake in the skeleton, indicating normalization of the marrow activity. MIBI scan may be used as a noninvasive measure of bone marrow proliferation that may guide hypertransfusion therapy in thalassemia patients.

Relationship between enhanced macrophage phagocytic activity and the induction of interferon by Newcastle disease virus in mice.

The relationship between phagocytic activity of peritoneal macrophages and serum interferon (IF) titers was evaluated in mice challenged with Newcastle disease virus (NDV). Time course studies indicated peak serum IF titers between 6 and 12 hr, whereas Fc receptor-mediated macrophage phagocytosis was maximal 18 hr after viral administration. Both responses decreased in parallel as the inoculated dose of the virus was reduced. Splenectomy, shown by others to decrease the NDV-induced serum IF titers, significantly decreased the stimulation of phagocytosis. The role of T cells in the response to the virus was studied with nude mice raised under germfree conditions. NDV-induced serum IF titers and macrophage phagocytosis were both diminished in BALB/c nudes compared with their heterozygous littermates. Both responses could be partially restored by transfer of thymocytes obtained from heterozygous mice. The results provide further evidence that in vivo macrophage stimulation by NDV is mediated by induced IF. The experiments with nude mice also indicate that the IF response to NDV is regulated by T lymphocytes.

Mononuclear phagocytes: responders to and producers of interferon.

We have provided evidence that in vivo-induced type I IF enhanced Fc-mediated particle uptake by mouse macrophages. Fc-mediated phagocytosis of opsonized erythrocytes by unelicited fresh or cultivated macrophages was stimulated by 4-8 hours of cultivation with 100 ohms/ml IF. A 1-hour pulse was sufficient when followed by incubation in If-free medium. Pactamycin, a protein synthesis inhibitor, and camptothecin, and RNA synthesis inhibitor, blocked the stimulation of phagocytosis, indicating a requirement for macromolecular synthesis. Binding by the macrophages of a radioiodinated monoclonal antibody with anti-Fc receptor II specificity indicated that the stimulation of phagocytosis did not result from an increase in the numbers of available Fc receptors. Inflammatory macrophages, while more phagocytic than resting cells, could be further stimulated by IF in vitro, as could macrophages stimulated with LPS. In contrast, macrophages obtained from animals treated with IF inducers could not be further stimulated by IF. LPS-prestimulated and normal macrophages showed similar time-course and dose-response curves to IF, indicating that the probable mechanism of stimulation is similar in both types of cells. Cultivated bone marrow-derived macrophages found to be sensitive to IF induction by LPS, poly I.C., or NDV. The induction of IF by either LPS or poly I.C. was greater at 26 degrees C than at 37 degrees C, while no such difference was found using NDV. A 2-hour pulse of LPS was sufficient to induce IF in marrow-derived macrophages. The induced IF activity was shown to be type I IF.

Macrophage activation: increased ingestion of IgG-coated erythrocytes after administration of interferon inducers to mice.

In vitro phagocytosis of IgG-opsonized sheep erythrocytes (EA) was used to measure the in vivo activation of mouse peritoneal macrophages. Uptake of EA as enhanced by the extraperitoneal administration of Newcastle disease virus, vesicular stomatitis virus, tilorone or polyinosinic-polycytidylic acid. Ingestion of EA was similarly stimulated by lipopolysaccharide or killed Corynebacterium parvum. Dose-response curves relating concentrations of IgG to phagocytosis were parallel for both treated and control animals. This indicates that the heterogeneity of the macrophage populations did not change and that the overall populations were activated with respect to phagocytic ability. Numbers of macrophages were not increased (except in C. parvum-treated mice), suggesting that resident, rather than newly recruited macrophages, were activated by the different agents.