Platelet Antibody Profile

Platelet antibodies can be autoimmune (directed against endogenous, i.e., the patient's own platelet antigens) or alloimmune (directed against antigens on exogenous platelets encountered through pregnancy or transfusion). Platelet antibodies may be directed to a number of antigenic “targets” carried on platelet cytoplasmic membranes.^1-6 This platelet antibody profile is designed to detect antibodies to HLA class I and platelet glycoprotein IV (CD36) antigens, and to polymorphic epitopes on the platelet GPs IIb/IIIa, Ib/IX, and Ia/IIa.⁴ Platelet glycoprotein (GP) IV antigen deficiency is rare in Caucasians but frequent in Asians and Africans.^4,7,8 The IIb/IIIa glycoprotein complex plays a central role in platelet adhesion by binding fibrinogen, fibronectin, vitronectin, and von Willebrand factor.² Glycoprotein Ib/IX is the main receptor for von Willebrand factor and glycoprotein Ia/IIa is involved in collagen adhesion.² The congenital absence of IIb/IIIa results in Glanzmann thrombasthenia and the absence of Ib/IX causes Bernard-Soulier syndrome.

Platelet antibodies may be involved in several clinical situations described below^3,9:

Immune Thrombocytopenic Purpura (ITP), formerly referred to as idiopathic thrombocytopenic purpura, occurs when platelet autoantibodies with broad reactivity against common epitopes on platelet glycoprotein complexes destroy an individual's platelets and result in a persistent thrombocytopenia.^3,9-11 Antiplatelet autoantibodies also are thought to impair platelet production by megakaryocytes.^9,12,13 ITP in children often can be associated to a transient viral infection. Approximately 15% of childhood ITP cases become chronic.² ITP in adults often has an insidious onset, resulting in chronic thrombocytopenia that rarely remits spontaneously.^1,2 This condition can be idiopathic, or in some cases, associated with another autoimmune condition (e.g., SLE) or malignancy.¹ The majority of autoantibodies identified in patients with ITP are directed against components of platelet glycoprotein IIb/IIIa. Antibodies to glycoprotein Ib/IX also are observed. Some authors have found that identification of platelet associated antibodies has prognostic significance in ITP and can help in understanding the underlying mechanism of thrombocytopenia.^14-16 According to the American Society for Hematology practice guideline, routine evaluation for platelet reactive antibodies in the evaluation of ITP is not recommended while testing for HIV and HCV should be considered in all patients with acute ITP.¹¹

Neonatal alloimmune thrombocytopenia (NAIT) typically occurs when fetal platelets have an antigen from the father that is absent in the mother.^1,5,17 In this condition, which can be considered to be the platelet equivalent of hemolytic disease of the newborn (HDN), maternal antibodies cross the placenta and destroy fetal platelets. This condition occurs in 1 in 1200 live births in the Caucasian population, and unlike HDN, frequently occurs during the first pregnancy.^1,2 Affected infants may have severe thrombocytopenia and are at increased risk for intracranial bleeding.^1,18 As a component of the work-up, diagnostic testing of the mother's blood is performed for the presence of platelet antibody. Evaluation should also include typing maternal and paternal platelet glycoproteins. In Caucasians, 80% of NAIT is caused by alloimmunization to HPA-1a (a component of platelet glycoprotein IIb/IIIa) in HPA-1a-negative mothers.⁵ Other antigens, including HPA 2, 3, 4, 5, and 15, are less frequently implicated.^18,19 The majority of platelet reactive antibodies identified in patients with NAIT are directed against components of platelet glycoprotein IIb/IIIa, most commonly HPA-1a.¹ Antibodies to HPA-5b (detected as anti-Ia/IIa) are frequently observed in pregnancy but tend to be associated with milder thrombocytopenia.¹ Antibodies to HLA also have been associated with NAIT.¹ Platelet antigen incompatibility is necessary but not sufficient to cause NAIT.¹⁸ Neonatal serum or plasma samples are less sensitive for circulating antibody detection than maternal samples since the antibodies may be attached to platelets or cleared.

Post-transfusion purpura (PTP) is a rare condition where a patient suffers from an acute episode of severe immune-mediated thrombocytopenia that occurs 5 to 14 days after a platelet-containing transfusion.^1,2,20,21 The patient's own platelets also are destroyed along with transfused platelets, a phenomenon thought to be caused by panreactive platelet reactive antibodies.^20,22 Antigen sensitization can frequently be traced to exposure to exogenous platelet antigen either through pregnancy or previous transfusion. Like NAIT, the majority of autoantibodies identified in patients with PTP are directed against components of platelet glycoprotein IIb/IIIa, most commonly HPA-1a.^1,2

Platelet transfusion refractoriness is a condition characterized by the lack of expected platelet count increment after a platelet transfusion.¹ As many as 70% of patients receiving multiple platelet transfusions for thrombocytopenia will exhibit some degree of refractoriness.^1,23 This condition is most common in patients treated for malignant hematopoietic disorders.¹ While platelet antibody production can cause platelet refractoriness, other potential causes include sepsis, disseminated intravascular coagulation (DIC), or drug-induced thrombocytopenia. Immune-mediated platelet refractoriness is most commonly caused by antibodies to HLA antigens but has also been observed in association with antibodies to platelet-specific antigens.^1,2,23-25