Thrombocytopenic Purpura, Autoimmune
Description
Autoimmune thrombocytopenic purpura is characterized by a low platelet count, normal bone marrow, and the absence of other causes of thrombocytopenia. It is principally a disorder of increased platelet destruction mediated by autoantibodies to platelet-membrane antigens (George et al., 1994).
Clinical FeaturesIn children, AITP is usually acute and self-limited, whereas in adults, it is most often chronic. The presenting features are bruising, petechiae, and/or mucosal bleeding (epistaxis, hematuria, and rarely intracerebral hemorrhage) (George et al., 1994).
Cines and Blanchette (2002) and Imbach et al. (2002) provided comprehensive reviews.
InheritanceKarpatkin et al. (1981) described autoimmune thrombocytopenic purpura in a woman and 3 of her 4 children (a son and 2 daughters). Bound platelet antibody was demonstrated. They found reports of 4 families of probable similar disorder.
Laster et al. (1982) described chronic immune thrombocytopenic purpura in monozygotic twins.
Imbach et al. (2002) cited Dohrn in Germany as describing purpura hemorrhagica in a neonate and his mother.
PathogenesisHarrington et al. (1951) observed a child with purpura born to a mother with chronic idiopathic thrombocytopenic purpura. The child's purpura resolved spontaneously within 3 weeks while the mother remained thrombocytopenic. Harrington argued that transfer of a humoral antiplatelet factor from the mother to her baby occurred. He then administered plasma from patients with chronic AITP to himself and to 9 volunteers with a normal platelet count. Eight of the recipients immediately developed transient thrombocytopenia and some of them purpura as well. One of the volunteers, in spite of an earlier splenectomy, also responded with thrombocytopenia, indicating a secondary role of the spleen. Imbach et al. (2002) stated that Harrington's experiment clearly suggested an antiplatelet factor in the plasma as the cause of AITP. They also noted that evidence for the role of autoantibodies in chronic AITP was first reported by van Leeuwen et al. (1982).
Clinical ManagementGasbarrini et al. (1998) reported that successful eradication of Helicobacter pylori infection in ITP patients, as assessed by the urea breath test, resulted in a significant increase in platelet counts and, in 6 of the 8 patients, in the disappearance of anti-platelet antibodies.
Fujimura et al. (2005) analyzed more than 200 ITP patients and observed a benefit from successful eradication of H. pylori in most patients. Complete remission was 23% in the successfully treated group, 12 months after eradication.
Asahi et al. (2008) observed increased platelet numbers following anti-H. pylori treatment only in H. pylori-positive ITP patients. Before treatment, monocytes from H. pylori-positive patients exhibited enhanced phagocytic capacity and low levels of the inhibitory FCGR2B (604590) receptor. Treatment suppressed the activated monocyte phenotype and improved autoimmunity parameters and modulation of the balance of Fc-gamma receptors. Asahi et al. (2008) suggested that platelet recovery in successfully treated ITP patients is mediated through a change in Fc-gamma receptor balance toward the inhibitory FCGR2B type.
Molecular GeneticsBreunis et al. (2008) found that an ORF allele of the FCGR2C gene (612169) was significantly overrepresented in patients with autoimmune thrombocytopenic purpura, with 34% of AITP patients having at least 1 ORF allele.