Lynn K. Boshkov

Heparin-induced thrombocytopenia and thrombosis: clinical and laboratory studies.

Summary. Heparin‐induced thrombocytopenia is one of the most common and important immunological complications of drug therapy. Most patients with heparin‐induced thrombocytopenia have isolated thrombocytopenia, which by itself seldom causes serious morbidity. However, a small proportion of patients also develop an acute arterial thrombotic episode which can be fatal. It remains uncertain why some patients have only isolated thrombocytopenia, whereas others have thrombotic complications. In this report we describe 53 patients with heparin‐induced thrombocytopenia in whom the diagnosis was confirmed using the platelet 14C‐serotonin release assay. The intent of the study was to look for laboratory or clinical characteristics that could be used to predict which patients will have the less serious thrombocytopenia and which patients will have thrombocytopenia plus thrombotic complications. The laboratory markers included AT‐III, protein C, protein S and heparin cofactor II. No serological result identified whether a patient was at risk of having isolated thrombocytopenia or an acute thrombotic event. However, during the acute thrombocytopenic episode, there was evidence of global activation of the coagulation cascade as evidenced by reductions in the level of protein C, heparin cofactor II and antithrombin III. Following resolution of the thrombocytopenia, these inhibitory factors returned to normal indicating that the thrombotic complications were not caused by a familial deficiency.

Use of Intravenous Gammaglobulin as an Immune Replacement and an Immune Suppressant

I N 1890 the first Nobellaureate, von Behring, recognized antibodies in serum to diphtheria toxin and introduced passive immune prophylaxis against the disease. About 60 years later, the potential of this treatment became apparent when Bruton,1 and Good and Varco,z and Barandun et al used gammaglobulin (IgG) to successfully treat infections in children with X-linked infantile agammaglobulinemia. This treatment was quickly extended to other patients as treatment and as prophylaxis. For the next 30 years, most physicians used a standard dose of 100 to 200 mg/kg of IgG every 4 weeks for immune replacement. This dose did not raise the plasma concentration of IgG to normallevels, but higher doses could not be used because the preparation could only be given by intramuscular injection. In the late 1970s, safe and effective IgG preparations that could be administered intravenously (IV) became available. The ability to give the preparation IV meant that very high doses of IgG could be given, and this led to the recognition that IgG could act as an immune suppressant. As will be discussed, intravenous gammaglobulin (IV IgG) has provided insights into the role of IgG in both physiological and pathological cell clearance. In this review, we will summarize the various preparations of IgG that can be given IV and the efficacy of IV IgG as an immune replacement and an immune suppressant, and we will discuss the adverse effects of IV IgG.

HLA‐DR expression by platelets in acute idiopathic thrombocytopenic purpura

Induction of expression of MHC class II antigens on the surface of cells that do not ordinarily express these proteins has been implicated in the pathogenesis of autoimmunity in diabetes mellitus and autoimmune thyroiditis. Platelets express class I but not class II HLA antigens. In this report, we describe a child with acute idiopathic thrombocytopenic purpura who at the time of the thrombocytopenic episode had class II (HLA‐DR) antigens on his platelets. Following recovery, the HLA‐DR antigens were no longer present on the platelets. We postulated that class II had been induced on his megakaryocytes by a cytokine such as interferon gamma, and that the induced expression of class II antigens contributed to the autoimmune disorder. To substantiate this possibility we next studied class I and II antigen expression on an erythroleukaemia cell line (HEL), which has many megakaryocytic features. Following treatment of HEL cells with interferon gamma, class I expression was increased and HLA‐DR antigens were induced. These observations suggest that cytokine‐mediated induced HLA‐DR expression may contribute to the pathogenesis of a subset of thrombocytopenias.