Thrombocytopenia immune-mediated

GP Ilb/IIIa inhibitors may increase the risk of bleeding, especially if given in the setting of recent (<4 hours) administration of fibrinolytic therapy. An immune-mediated thrombocytopenia occurs in about 5% of patients. 

Besides bleeding, the most frequent adverse effect of UFH is immune-mediated thrombocytopenia, which occurs in up to 5% of patients. 

J Heparin-induced thrombocytopenia (HIT) is a serious immune-mediated problem that requires immediate intervention. For patients receiving therapeutic UFH doses, a baseline platelet count should be obtained before therapy is initiated and then every-other-day for 14 days or until therapy is stopped, whichever occurs first. HIT should be suspected if a patient develops a thromboembolic event (e.g., DVT, PE, stroke, myocardial infarction, limb artery occlusion) during or soon after receiving UFH. The platelet... 

These agents interact directly with thrombin and do not require antithrombin to have antithrombotic activity. They are capable of inhibiting both circulating and clot-bound thrombin, which is a potential advantage over UFH and the LMWHs. They also do not induce immune-mediated thrombocytopenia and are widely used for the treatment of HIT. 

Heparin, which has an anticoagulation action, may give rise to heparin-induced thrombocytopenia, which is an immune-mediated condition that usually develops 5-10 days after the administration of the drug. When heparin is used, a platelet count should be measured before treatment and if administration is repeated, platelet counts should be monitored regularly. Signs of thrombocytopenia include a reduction in platelet count. It may present with spontaneous haemorrhage and heparin should be stopped. Factor VIII is used in the treatment and prophylaxis of haemorrhage in patients with haemophilia. 

Hypersensitivity reactions, such as pruritus, cutaneous vasculitis, and thrombocytopenia, are seen in some patients, and an immune-mediated systemic flulike syndrome with thrombocytopenia also has been described. Rifampin imparts a harmless red-orange color to urine, feces, saliva, sweat, tears, and contact lenses. Patients should be advised of such discoloration of body fluids. 

A serious complication of HIV infection is HIV-associated thrombocytopenia, This results from immune-mediated platelet destruction and decreased or defective platelet production due to infection of megakaryocytes with HIV-1 (211). HIV-related thrombocytopenia may be associated with an accelerated progression to AIDS and decreased survival rates. Hence management of thrombocytopenia in AIDS patient is crucial to prevent severe complications, Severe bleeding complications in HIV-infected hemophilia patients treated with protease inhibitors... 

Nikolsky E, Dangas GD. Percutaneous interventions in patients with immune-mediated heparin-induced thrombocytopenia. Semin Thromb Hemost 2004 30 305-3 14. 

The most devastating complication is heparin induced thrombocytopenia (HIT) (I). In contrast with other immune mediated thrombocytopenia, HIT is associated with thrombosis. 

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. 

Frank hemolysis has also been reported in rare instances, including, rarely, immune-mediated hemolysis (87,88). Leukopenia has been reported (SED-12, 673). Thrombocytopenia has been reported in several instances and also occurs with lipid formulations (89,90). 

In an analysis of 447 adverse effects in 194 patients worldwide (5), 20 had blood abnormahties, including two cases of agranulocytosis and one of granulocytopenia. One of these patients, who was sensitive to pyrazolone, had taken a pyrazolone compound as well. Immune-mediated agranulocytosis and thrombocytopenia have been reported (SEDA-16,110). 

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). 

Interferon alfa has direct myelosuppressive effects and can also cause hematological disorders by immune blood cell destruction, as suggested by reports of immune-mediated thrombocytopenia, immune hemolytic anemia (205,206), or a positive direct Coombs test, with or without hemolysis (207-209). 

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). 

Quinine can cause a variety of immune-mediated syndromes, most commonly isolated thrombocytopenia, but rarely microangiopathic hemoljdic anemia with thrombocytopenia and acute renal insufficiency (hemolytic-uremic syndrome). Two reports of immune-mediated syndromes following the use of quinine for leg cramps have helped to provide an immunopathological explanation for the diversity of such presentations (29,30). 

Agranulocytosis (probably due to toxicity rather than hypersusceptibility) can be caused by sulindac (13), as can bone marrow aplasia (14) and severe thrombocytopenia (15,16), which may be the consequence of autoimmune platelet destruction in the presence of sulindac or its metabolite (SEDA-7, 109). Immune-mediated hemolytic anemia with a positive direct antiglobulin test has been reported (SEDA-18,103). 

Seidman AD, Schwartz M, Reich L, Scher HI. Immune-mediated thrombocytopenia secondary to suramin. Cancer 1993 71(3) 851. ... 

Immune-mediated reactions to penicillin G include anaphylaxis (a type 1 hypersensitivity reaction), hemolytic anemia and thrombocytopenia (type II hypersensitivity reactions). Anaphylactic reactions can be fatal, so epinephrine... 

Two forms of heparin-induced thrombocytopenia (HIT) have been observed. The first (HIT I) is a transient, mild, and benign thrombocytopenia seen soon after initiation of heparin therapy (normally within 2 days) and is felt to be due to inherent plateletaggregating properties of heparin. A second, more severe form of HIT (HIT II) is typically seen later and is immune-mediated. The incidence of HIT II is estimated at 3-5%. The onset is generally 3-14 days after initiation of heparin therapy but may occur sooner with repeat exposure. HIT II may occur with any dose and type of heparin, but the frequency is highest with continuous intravenous infusions of unfractionated heparin. HIT with subsequent thrombosis is a feared complication. These thrombi can form in the venous or arterial circulation. Thrombotic complications include necrotic skin lesions, myocardial infarction, stroke, and gangrene. Hyperkalemia may be seen with heparin therapy due to aldosterone synthesis inhibition. 

Besides bleeding, the most frequent adverse effect of UFH is an immune-mediated clotting disorder, heparin-induced thrombocytopenia, which occurs in up to 5% of patients treated with UFH. Heparin-induced thrombocytopenia is less common in patients receiving low-molecular-weight heparins (LMWHs)." ... 

Two types of thrombocytopenia associated with heparin use have been described. " As many as of 25% of patients receiving heparin therapy develop a benign, mild reduction in platelet counts referred to as non-immune-mediated heparin-associated thrombocytopenia (HAT) or previously called HIT type 1. HAT produces a transient fall in platelet count that occurs early, typically between days 2 and 4, during the course of therapy. The degree of thrombocytopenia is usually mild, with platelet counts rarely going below 100,000/mm . It is not necessary to discontinue heparin therapy in these patients because platelet counts generally rebound to baseline values despite continued use. The exact mechanism of HAT is unknown, but it may be the result of platelet aggregation, a dilutional effect, or diminished platelet... 

The second type of thrombocytopenia associated with heparin use is known as immune-mediated HIT (formally known as HIT type jjj p jg severe pathologic adverse effect of heparin... 

Thrombocytopenia is a relatively common feature in both acute and chronic liver disease and is proportional to the extent of liver disease. The etiology of thrombocytopenia in liver disease is multifactorial, but involves primarily hypersplenism with pooling of platelets, immune-mediated destruction, and the inability of the bone marrow to compensate for the accelerated removal. The bone marrow depression may be related to alcohol, drugs, and nutritional deficiencies associated with the cirrhotic process. ... 

Heparin can cause at least two types of thrombocytopenia. The first is a mild, reversible, non-immune-mediated reaction that occurs 2 to 4 days after the initiation of therapy. The platelet count slowly returns to normal following an initial decline, despite continued heparin therapy. This benign condition is thought to result from weak activation of platelets, leading to sequestration. No major sequelae develop from this type of heparin-induced thrombocytopenia. 

Murphy MF, Riordant T, Minchinton RM, et al. Demonstration of an immune-mediated mechanism of penicillin-induced neutropenia and thrombocytopenia. Br J Haematol 1983 55 155-160. 

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