Idiopathic thrombocytopenia

Fig. 8.14. a Sixty-eight-old-year woman with idiopathic thrombocytopenia that prevented any cosmetic surgical intervention, b One year after the performance of deep chemical peeling... 

In addihon to treahng tumors, and because depleting B cells in humans with rituximab has been found to be safe, Rituxan is now in clinical trials and has shown efficacy for a number of autoimmune disorders. These include rheumatoid arthritis, idiopathic thrombocytopenia purpura (ITP, a platelet-depletion disorder), and lupus. It is expected that depleting B cells with rituximab will be approved in a nononcology indication within several years. 

Autoimmune disorders Auto mmune disorders of multiple target organs have been reported postmarketing, including idiopathic thrombocytopenia, hyper- and hypothyroidism, and rare cases of autoimmune hepatitis. 

Immunoglobulin obtained from pooled plasma obtained from hepatitis B and HIV negative donors is used as an aspecific immunostimulant in immunodeficiency diseases, idiopathic thrombocytopenia, autoimmune hemolytic anemias, Kawasaki syndrome and to prevent infections in immune compromised patients with leukemia or multiple myeloma. Adverse effects include potentially severe hypersensitivity reactions. 

Although corticosteroids possess immunosuppressive properties, their real value is in controlling the inflammation that can accompany transplantation and autoimmune disorders. Virtually all phases of the inflammatory process are affected by these drugs. Corticosteroid therapy alone is successful in only a limited number of autoimmune diseases, such as idiopathic thrombocytopenia, hemolytic anemia, and polymyalgia rheumatica. 

Eltrombopag is a new orally active small molecule agonist at the thrombopoietin receptor licensed for use in idiopathic thrombocytopenia. Because of toxicity concerns, eltrombopag is restricted to use by registered physicians and patients. 

In patients with chronic idiopathic thrombocytopenia (UP) who failed to respond adequately to previous treatment with steroids, immunoglobulins, or splenectomy, romiplostim significantly increased platelet count in most patients. In a 6-week placebo-controlled study in which patients were treated weekly with 1 or 3 mcg/kg, 12 of 16 patients reached the targeted platelet range of 50,000-450,000 platelets/mL. Romiplostim does not appear to decrease the rate of platelet destruction in ITP as platelet counts returned to pretreatment levels after the drug s discontinuation. An open label trial found that many patients maintained a platelet count of 100,000 platelets/mL or higher over a 48-week period and that over half of the patients were able to discontinue other therapies. Romiplostim is initiated as a weekly subcutaneous dose of 1 mcg/kg and then continued at the lowest dose required to maintain a platelet count of at least 50,000 platelets/mL. 

Thrombotic thrombocytopenic purpura is a rare acute or subacute disease in adults, rather similar to the hemolytic uremic syndrome in children, in which there is systemic malaise, fever, skin purpura, renal failure, hematuria and proteinuria. Hemorrhagic infarcts caused by platelet microthrombi occur in many organs in the brain they may cause stroke-like episodes (Matijevic and Wu 2006) although more commonly there is global encephalopathy. The blood film shows thrombocytopenia, hemolytic anemia and fragmented red cells. The differential diagnosis includes infective endocarditis, idiopathic thrombocytopenia, heparin-induced thrombocytopenia with thrombosis, systemic lupus erythematosus, non-bacterial thrombotic endocarditis and disseminated intravascular coagulation. 

A 75-year-old man with idiopathic thrombocytopenia purpura who was treated with intravenous immunoglobulin developed recurrent myocardial ischemia (46). 

Ahn YS, Byrnes JJ, Harrington WJ, et al. Treatment of idiopathic thrombocytopenia with vinblastine-loaded platelets. N Engl J Med 1978 298 1001-1007. 

Rheumatoid factor antibody, rheumatoid arthritis Anti-nuclear antibodies, systemic lupus erythematosus Platelet-associated IgG, idiopathic thrombocytopenia purpura (ITP) Blood typing and crossmatching Transplantation HLA antibodies... 

A 38-year-old man developed rectal bleeding and syncope. He had a history of idiopathic thrombocytopenia but had never previously complained of bleeding. Capsule endoscopy showed areas of petechial hemorrhage and erosions in the small bowel. He worked as a farmer and had prepared animal fodder that contained acetylsalicylic acid, of which he had inhaled a substantial amount. After he recovered, there was no recurrence of bleeding, despite persistent thrombocytopenia. 

The pathogenesis of thrombocytopenia will become clearer when the mechanism of production of autoimmune disease is discussed. Only a few salient points are mentioned here. A number of drugs, among them allylisopropylacetyl carbamide (Sedormid), quinine, quinidine, are known to autosensitize platelets. In affected patients, the combination of platelet, drugs, and serum leads to thrombocytopenia a large number of patients with idiopathic thrombocytopenia have antiplatelet antibodies in their blood. If the blood of such patients is injected to normal individuals, thrombocytopenia occurs. 

Patients with a bleeding disorder including hemophilia, von WiUebrand disease, various factor deficiencies, disseminated intravascular coagulation (DIG), idiopathic thrombocytopenia purpura (ITP), antithrombin in deficiency, or protein C or S deficiency. 

ADAMTS13 was normal in four patients and mildly reduced in two. The authors concluded that the pathophysiology of quinine-associated thrombocjhopenia and schistocytosis is distinct from that seen in most cases of idiopathic thrombocytopenia. They recommended that the term quinine-associated thrombotic microangiopathy should be used. 

Common variable immunodeficiency has been reported in an 8-year-old boy treated with rituximab for idiopathic thrombocytopenia [300 ]. 

MDX-33 (H22) Humanized IgGi CD64 (FcyRI) Idiopathic thrombocytopenia purpura Phase II Aventis Behring, Medarex... 

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