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C H A P T E R 131

DISEASES OF PLATELET NUMBER: IMMUNE

THROMBOCYTOPENIA, NEONATAL ALLOIMMUNE

THROMBOCYTOPENIA, AND POSTTRANSFUSION PURPURA

Donald M. Arnold, Michelle P. Zeller, James W. Smith, and Ishac Nazy

Platelets are anucleate cells that are required for primary hemostasis. Epidemiology
Platelets have a life span of 7–10 days in the circulation, after which
time they are cleared by the cells of the reticuloendothelial system The natural history of ITP is different in children and adults. For the
(RES), including the spleen. Platelet production is stimulated by majority of children, ITP presents acutely and resolves within several
thrombopoietin (TPO), a hormone that is constitutively secreted by weeks, often in the absence of intervention. Seasonal variability sug-
the liver. TPO binds to c-Mpl, its receptor on platelets, hematopoietic gests that viral infections may trigger the disease in many children.
progenitor cells, and bone marrow (BM) megakaryocytes. When Conversely, adult-onset ITP tends to be insidious in onset and is
bound to c-Mpl, TPO is internalized, degraded, and removed from characterized by a chronic or remitting and relapsing course.
the circulation; thus when the platelet count is low, free TPO levels
are high, and more platelets are produced. In contrast, when platelet
counts are high, circulating TPO levels are low, and platelet produc- Incidence and Prevalence of Immune
tion declines. This primitive feedback system is very effective at Thrombocytopenia in Children
maintaining the platelet count at a stable level. Recent evidence in
mice has shown that the Ashwell-Morell receptor on murine hepato- The incidence of acute ITP in children is estimated at 1.9–6.4 per
cytes binds platelets that have lost sialic acid residues on their surface. 100,000 per year. Nearly 70% of childhood ITP occurs between the
Binding activates a JAK-STAT signaling pathway, resulting in ages of 1 and 10 years with the peak prevalence between 4 and 6 years.
increased hepatic TPO mRNA expression and TPO production. The Most studies in children report an overall male predominance in early
role of this pathway in normal human thrombopoiesis is not yet childhood and equalization or reversal to female predominance in older
known. children. Reported prevalence estimates are 12.6 per 100,000 for girls
Immune-mediated platelet disorders disrupt normal regulation and 9.3 per 100,000 for boys in the older age groups.
of platelet number because of antibody-mediated or cell-mediated
platelet destruction or platelet underproduction. Antibodies that
target self (autoimmune) or nonself (alloimmune) antigens on plate- Incidence and Prevalence of Immune
lets can cause severe thrombocytopenia. Immune thrombocytopenia Thrombocytopenia in Adults
(ITP) is an autoimmune disorder characterized by antibodies directed
against platelet glycoproteins (GPs). Neonatal alloimmune thrombo- Incidence estimates for adult-onset ITP are reported to be between
cytopenia (NAIT) is a thrombocytopenic syndrome caused by platelet 1.6 and 3.9 per 100,000 per year. A retrospective analysis from the
alloantibodies. Posttransfusion purpura (PTP) has features of both United Kingdom described a bimodal distribution for men, with
alloantibody- and autoantibody-mediated processes. These platelet peak incidences before the age of 18 years and between 75 and 84
disorders have related immunologic features with distinct clinical years of age. Relatively stable incidence rates were found in women
characteristics (Table 131.1). The pathophysiology, clinical manifes- up to the age of 60 years with a steady increase thereafter. The inci-
tations, and management of these disorders are discussed in this dence of ITP has been reported to double in patients over 60 years
chapter. of age.
The overall prevalence of ITP in adults has been estimated at 9.5
per 100,000, and ranges from 4.1 per 100,000 in younger ages
IMMUNE THROMBOCYTOPENIA (19–24 years) to 16 per 100,000 in older age groups (55–64 years).
Male and female prevalence rates are 16.6 and 27.2 per 100,000
ITP is a common autoimmune disease characterized by a low platelet adults, respectively, for those 18–64 years of age, with prevalence rates
count that can be associated with an increased risk of bleeding. increasing significantly after the age of 65 years. The female predomi-
Increased platelet destruction resulting from platelet autoantibodies nance is attenuated in older age groups and may revert to a male
is a hallmark of ITP. Recently, however, it has become evident that predominance after the age of 65 years. Indeed, the prevalence of ITP
relative platelet underproduction is also an important mechanism for in older men is reported to be as high as 38.3 per 100,000. Increasing
the thrombocytopenia in ITP. Conventional treatments, including incidence and prevalence rates may reflect a true rise in disease fre-
corticosteroids, intravenous immunoglobulin (IVIg), immunosup- quency with age or ascertainment bias because of the higher likeli-
pressant drugs, and splenectomy are aimed at preventing platelet hood of discovering incidental thrombocytopenia with more frequent
destruction. TPO receptor agonists are medications that work by medical visits in older individuals.
increasing platelet production. They represent the most significant
advance in ITP management since the first description of IVIg as a
treatment for ITP in the early 1980s. TPO receptor agonists have Pathophysiology
1,2
been shown to be effective in clinical trials and were the catalyst
for several key initiatives in ITP including the standardization of ITP is caused by increased platelet destruction and impaired platelet
3
terminology (2009) and the development of the American Society production. Until recently, the pathogenesis of immune-mediated
of Hematology (ASH) Guidelines on diagnosis and management of thrombocytopenia was mainly attributed to platelet-reactive autoan-
ITP (2011). 4 tibodies; however, it is now evident that the pathophysiology of ITP
1944