Immunoglobulins thrombocytopenia

Delayed thrombocytopenia - Delayed thrombocytopenia (Type II) develops 7 to 12 days after either low-dose or full-dose heparin, can have serious consequences and may reflect the presence of an immunoglobulin that induces platelet aggregation. 

Finally, platelets can be activated by immune complexes following binding of immunoglobulin G (IgG) Fc domains to platelet Fey RII. This process involves tyrosine phosphorylation of a motif designated as ITAM (immunoreceptor tyrosine-based motif) found on the cytoplasmic domain of platelet Fey RII receptors (73). This may play a role in immune complex diseases, particularly in heparin-induced thrombocytopenia. 

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. 

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. 

Lorenzo s oil affected blood platelet counts in 39 patients followed for 1 year (2). Blood platelet aggregation studies in those patients were normal and there were no platelet-associated immunoglobulins. It has been suggested that the thrombocytopenia might be due to platelet activation, resulting from an increase in the concentration of erucic acid in the platelet membrane (1). 

Teeling JL, Jansen-Hendriks T, Kuijpers TW, de Haas M, van De Winkel JG, Hack CE, Bleeker WK. Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers studies in experimental immune thrombocytopenia. Blood 2001 98 1095-9. 

In addition to cancer, too little apoptosis can also result in diseases such as autoimmune lymphoproliferative syndrome (ALPS). This occurs when there is insufficient apoptosis of auto-aggressive T cells, resulting in multiple autoimmune diseases. An overproliferation of B cells occurs as well, resulting in excess immunoglobulin production, leading to autoimmunity. Some of the common diseases of ALPS include hemolytic anemia, immune-mediated thrombocytopenia, and autoimmune neutropenia. The different types of this condition are caused by different mutations. Type 1A results from a mutation in the death domain of the Fas receptor, Type IB results from a mutation in Fas ligand, and Type 2 results from a mutation in caspase 10, reducing its activity. 

Thrombocytopenia after a second exposure to abciximab in nine patients showed that each had a strong immunoglobulin IgG antibody that recognized platelets sensitized with abciximab (23). Five patients also had IgM antibodies. Thrombocytopenia occurred four times as often as after the first exposure. The mechanism is not understood, but these findings suggest that it may be antibody-mediated. These antibodies were also found in 77 of 104 healthy patients, but in the patients the antibodies were specific for murine sequences in abciximab, causing the hfe-threatening thrombocytopenia. 

Type II thrombocytopenia is probably an immune-mediated phenomenon, a fact that has been the subject of much specific investigation (27,37 2). It has been proposed that the diagnosis should depend on two criteria the association of one or more clinical events and laboratory evidence of a heparin-dependent immunoglobulin (36). 

Patients with thrombocytopenia generally tolerate intravenous immunoglobulin well (35). In 16 young patients aged 9 months to 22 years with immune-mediated hemocytopenias (13 with childhood immune thrombocytopenic purpura), who received a total of 210 infusions, minimal adverse effects (transient headaches) were experienced during only four infusions, and later infusions were problem-free in three of the four patients (36). 

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

In a 38-year-old man with end-stage renal insufficiency and thrombocytopenia secondary to systemic lupus erythematosus, pseudohyponatremia occurred after treatment with intravenous immunoglobulin 1 g/kg for 2 days (146). 

Woodruff RK, Grigg AP, Firkin FC, Smith IL. Fatal thrombotic events during treatment of autoimmune thrombocytopenia with intravenous immunoglobulin in elderly patients. Lancet 1986 2(8500) 217-18. 

Interferon alfa-induced immune-mediated thrombocytopenia shares many features with idiopathic thrombocytopenic purpuras and may be therefore coincidental (SED-13, 1094) (SEDA-20, 328) (SEDA-21, 371), but recurrence of thrombocytopenia on interferon alfa readministration strongly supports a causal role of interferon alfa (232). Cross reaction with interferon beta was not found in an isolated report (SEDA-20, 329). Even though severe and even fatal worsening of idiopathic thrombocjdopenic purpura has been observed after administration of interferon alfa (SED-13, 1094) (SEDA-20, 328), interferon alfa was not considered harmful in patients with chronic hepatitis C who were previously positive for platelet-associated immunoglobulin G (233). 

Taliani G, Duca F, dementi C, De Bac C. Platelet-associated immunoglobulin G, thrombocytopenia and response to interferon treatment in chronic hepatitis C. J Hepatol 1996 25(6) 999. 

Two patients developed grade 4 thrombocytopenia (under 25 x 10 /1) after 42 and 151 days of treatment with nevirapine (6). In the first patient, zidovudine and intravenous immunoglobulin were added to continued nevirapine, and the thrombocytopenia resolved by day 89. In the second, nevirapine was discontinued and alternative antiretroviral therapy was started, whereupon the platelet count returned to normal within 22 days. 

Frame JN, Mulvey KP, and Phares JC (1989) Correction of severe heparin-associated thrombocytopenia with intravenous immunoglobulin. Annals of Internal Medicine 111 946-947. 

Hypersensitivity reactions include morbilliform rash in 2—5% of patients and occasionally more serious skin reactions, including Stevens-Johnson syndrome. Systemic lupus erythematosus and potentially fatal hepatic necrosis have been reported rarely. Hematological reactions include neutropenia and leucopenia, or more rarely, red-cell aplasia, agranulocytosis, and thrombocytopenia Lymphadenopathy is associated with reduced immunoglobulin A (IgA) production. Hypoprothrombinemia and hemorrhage have occurred in the newborns of mothers who received phenytoin during pregnancy vitamin K is effective treatment or prophylaxis. 

Hematologic A 3-year-old boy developed immune thrombocytopenic purpura 26 days after a second dose of seasonal influenza vaccine [12. He was given intravenous immunoglobulin and recovered within 2 days. A literature review showed that symptomatic thrombocytopenia occurs in a substantial number of children and adults who require hospitalization for complicated natural influenza infections. In contrast, reports of immune thrombocytopenic purpura after influenza immunization are rare and occur in adults. 

Cooper N. Intravenous immunoglobulin and anti-RhD therapy in the management of immune thrombocytopenia. Hematol Oncol Clin North Am 2009 23(6) 1317-27. 

Rink BD, Gonik B, Chmait RH, O Shaughnessy R. Maternal hemolysis after intravenous immunoglobulin treatment in fetal and neonatal alloimmrme thrombocytopenia. Obstet Gynecol February 2013 121(2 Pt 2 Suppl l) 471-3. 

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