Antibodies against platelets

Topol, E. J., Califf, R. M., Weismann, H. F. el al. (1994). Randomized trial of coronary intervention with antibody against platelet Ilb/IIIa integrin for reduction of clinical restenosis Results at 6 months. Lancet 343, 881-886. 

Idiopathic thrombocytopenic purpura is an immune-mediated disease in which immunoglobulin, either as antibody directed against platelet antigens or nonspecifically bound to platelets, is present in increased quantities on platelets. This leads to increased destruction of platelets and, in many instances, megakaryocytes. Standard treatment consists of corticosteroids and splenectomy (72). When these measures fail, treatment may include androgenic steroids, administration of intravenous 7-globulin, or injection of vinca alkaloids. 

Deep vein thrombosis refers to clot formation within the vascular system, usually in the lower extremities. It requires prompt medical attention, as it not only disrupts blood flow in the affected area but can also lead to the formation of emboli, with serious, often fatal, medical consequences (Chapter 9). Such thrombi may be pinpointed by immunoscintigraphy, utilizing a radio-labelled antibody directed against platelets or, more often, flbrin. 

Bates, E. R., McGillem, M. J., Mickelson, J. K, Pitt, B., and Mancini, G. B. (1991). A monoclonal antibody against the platelet glycoprotein Ilb/IIIa receptor complex prevents platelet aggregation and thrombosis in a canine model of coronary angioplasty. Circulation 84, 2463-2469. 

The EPIC Investigators (1994). Use of a monoclonal antibody directed against platelet glycoprotein Ila/IIIb in high risk coronary angioplasty. N. Engl.J. Med. 330, 956-961. 

Shebuski RJ, Storer BL, Fujita T (1988) Effect of thromboxane synthetase inhibition on the thrombolytic action of tissue-type plasminogen activator in a rabbit model of peripheral arterial thrombosis. Thromb Res 52 381-392 Yasuda T, Gold HK, Fallon JT et al. (1988) Monoclonal antibody against the platelet glycoprotein (GP) Ilb/IIIa receptor prevents coronary artery reocclusion after reperfusion with recombinant tissue type plasminogen activator. J Clin Invest 81 1284-1291... 

This makes the blood cells antigenic and results in the production of IgG antibodies against them. The antibodies so produced activate the complement system. Complement destroys the blood cells. This can lead to haemolytic anaemia if red blood cells are involved and can occur in response to penicillin. If white blood cells are the target of the reaction then the result is agranulocytosis this can occur for example with carbimazole (used to treat an overactive thyroid gland, see Chapter 6). Thrombocytopenia can be the result if the cells involved are platelets this can happen in response to heparin (used in thrombotic disorders, see Chapter 4). 

The results of immunoblotting with antibodies against CP indicate that CP is more or less exclusively expressed in smooth muscle in vivo (Takahashi et al., 1987 Gimona et al., 1990). It is not found in skeletal or cardiac muscle and is absent in nonmuscle tissues, including brain (Takahashi et al., 1987), kidney, liver, and spleen (Gimona et al., 1990). But there are detectable amounts in blood platelets (Takeuchi et al., 1991), cells that express other proteins typical for smooth muscle (Turner and Burridge, 1989), and it has also been reported to occur in adrenal medulla (Takahashi etal., 1987). In the latter case, however, the investment of vascular tissue makes it difficult to exclude the possibility of the presence of contaminating smooth muscle. 

Heparin-induced thrombocytopenia (platelet count <150,000/ml or a 50% decrease from the pretreatment value) occurs in about 0.5% of medical patients 5 to 10 days after initiation of therapy with standard heparin. The incidence of thrombocytopenia is lower with low-molecular-weight heparin. Thrombotic complications that can be life threatening or lead to amputation occur in about one-half of the affected heparin-treated patients and may precede the onset of thrombocytopenia. The incidence of heparin-induced thrombocytopenia and thrombosis is higher in surgical patients. Venous thromboembolism occurs most commonly, but arterial thromboses causing limb ischemia, myocardial infarction, and stroke also occur. Bilateral adrenal hemorrhage, skin lesions at the site of subcutaneous heparin injection, and a variety of systemic reactions may accompany heparin-induced thrombocytopenia. The development of IgG antibodies against complexes of heparin with... 

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