Idiopathic Thrombocytopenic Purpura

Background

ITP or idiopathic thrombocytopenic purpura is defined as isolated thrombocytopenia (decreased platelet count) with normal bone marrow in the absence of other causes for thrombocytopenia. There are 2 distinct clinical syndromes manifest as an acute condition in children and a chronic condition in adults.

Acute ITP often follows an acute infection and has a spontaneous resolution within 2 months. Chronic ITP persists longer than 6 months without a specific cause. In adults, it may follow a viral infection. Since there are many causes of a decreased platelet count, secondary causes should all be excluded before this diagnosis is established. Important secondary causes include drugs, renal disease, infection, and malignancies.

Patients usually present with signs and symptoms of hemorrhage including nonpalpable petechiae occurring in dependent regions, hemorrhagic bullae on mucous membranes, purpura, and gingival bleeding. More severe bleeding from the GI tract or uterus may occur. The most serious bleeding is intracranial hemorrhage, with possible neurological symptoms and deficits. If the platelet count drops to under 20,000 (normal range 150,000-450,000), spontaneous hemorrhage may occur.

SYNONYMS ATP
Autoimmune thrombocytopenic purpura
Primary immune thrombocytopenic purpura

INCIDENCE New cases of chronic refractory ITP are approximately 10 per 1,000,000 per year

United States
In adults is approximately 66 per 1,000,000 per year
In children is 50 per 1,000,000 per year

Worldwide

AGE RANGE-MEDIAN
Peak incidence occurs in adults aged 20-50 years
Peak incidence occurs in children aged 2-9 years

Approximately 40% of all patients <10 years

SEX (M:F)

Acute ITP
Usually in children an equal distribution exists between males (52%) and females (48%)

Chronic ITP
Female-to-male ratio is 2.6:1
More than 72% of patients older than 10 years are female.

DISEASE ASSOCIATIONS CHARACTERIZATION

Prevalence and clinical significance of elevated antiphospholipid antibodies in patients with idiopathic thrombocytopenic purpura.

Stasi R, Stipa E, Masi M, Oliva F, Sciarra A, Perrotti A, Olivieri M, Zaccari G, Gandolfo GM, Galli M, et al.

Department of Hematology, University of Rome Tor Vergata, S. Eugenio Hospital, Italy.

Blood 1994 Dec 15;84(12):4203-8 Abstract quote

Antibodies against phospholipid antigens (APA) have been demonstrated in idiopathic thrombocytopenic purpura (ITP), but their clinical and pathogenetic significance has remained elusive.

In this study we analyzed the prevalence and clinical features of ITP patients with elevated APA. In addition, we prospectively evaluated APA levels after treatment with corticosteroids and compared them with platelet-associated immunoglobulin (PAIgG) titers. We studied 149 patients with newly diagnosed ITP. Of these, 78 had a platelet count less than 50 x 10(9)/L and received an initial treatment with oral prednisone (PDN). In 71 asymptomatic cases with platelet counts between 50 x 10(9)/L and 120 x 10(9)/L, no therapy was scheduled. However, in five of them, the platelet count fell below 50 x 10(9)/L after more than 12 months; these patients were treated with PDN. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay and the detection of the lupus-like anticoagulant (LA) activity with coagulation tests that included kaolin-clotting time, dilute Russel's Viper venom time, activated partial thromboplastin time (aPTT), and dilute aPTT. Controls consisted of 174 apparently healthy subjects. Either LA or elevated ACA was seen in 69 patients (46.3%) at diagnosis. LA and ACA were both elevated in 24 cases (16.1% of the overall patient population and 34.8% of patients with high APA concentrations). No correlation was found between LA ratio values and ACA-IgG or -IgM titers, or between ACA-IgG and ACA-IgM levels. The presence of these antibodies was not associated with sex, age, platelet count, or the severity of hemorrhages. PAIgG was detected in 106 of 127 cases (83%). Again, no relationship was observed with clinical parameters or with APA levels. However, all cases with elevated APA also had increased PAIgG. With regard to the clinical course, we were not able to detect any significant difference between patients with normal and elevated APA. An initial complete response to prednisone treatment was observed in 43 of 83 cases (51.8%), with 13 (15.7%) achieving a prolonged complete remission. APA levels were not significantly modified after PDN therapy and on relapse.

We conclude that APA positivity is a common finding in patients with ITP and does not select a category with different clinical features. APA levels are not influenced by immunosuppressive therapy with steroids and are not related to the activity of the disease. Therefore, we do not support a role for APA in the pathogenesis of ITP.

Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: a prospective cohort study.

Diz-Kucukkaya R, Hacihanefioglu A, Yenerel M, Turgut M, Keskin H, Nalcaci M, Inanc M.

Divisions of Hematology and Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Turkey.

Blood 2001 Sep 15;98(6):1760-4 Abstract quote

The pathogenetic role and the clinical importance of the presence of antiphospholipid antibodies (APAs) in patients with immune thrombocytopenic purpura (ITP) are not clear. In this study, the prevalence and clinical significance of APAs were investigated in patients with ITP.

Eighty-two newly diagnosed ITP patients were prospectively studied. They were evaluated for the presence of lupus anticoagulant (LA) and immunoglobulin G/M anticardiolipin antibodies (ACAs). Thirty-one patients (37.8%) were APA positive at diagnosis. No statistically significant differences were found between the APA-positive and APA-negative groups regarding gender, initial platelet counts, or response to methylprednisolone therapy. After 5 years of follow-up, cumulative thrombosis-free survival of APA-positive (n = 31) and APA-negative (n = 51) ITP patients was 39% and 97.7%, respectively. A significant difference was found between these groups by log-rank test (P =.0004). In addition, LA was an important risk marker for the development of thrombosis in ITP patients. After a median follow-up of 38 months, 14 ITP patients (45%) who had APA positivity developed clinical features (thrombosis or fetal losses) of antiphospholipid syndrome (APS). There were no differences between the APA-positive patients with and without APS regarding the initial platelet counts, response to the therapy, or ACA positivity. The positivity rate for LA was significantly higher in those patients with ITP who developed APS (chi(2): P =.0036; relative risk 7.15; 95% confidence interval, 1.7-47).

In conclusion, this study indicates that a significant proportion of patients initially presenting with ITP and APA positivity developed APS. In patients with ITP, the persistent presence of APAs is an important risk factor for the development of APS.

PATHOGENESIS CHARACTERIZATION

Autoimmune process
ITP primarily is a disease of increased peripheral platelet destruction, with most patients having antibodies to specific platelet membrane glycoproteins

Relative marrow failure may contribute to this condition, since studies show that most patients have either normal or diminished platelet production

Immunoglobulin G (IgG) autoantibodies on the platelet surface

PROGNOSIS AND TREATMENT CHARACTERIZATION

Prognostic Factors
Hemorrhage represents the most serious complication with intracranial hemorrhage is the most significant

Older age and previous history of hemorrhage increase the risk of severe bleeding in adult ITP

In children, disease is usually self-limited

Survival
Mortality from hemorrhage is approximately 1% in children and 5% in adults

Spontaneous remission occurs in children in greater than 80% of cases, but it is uncommon in adults

Recurrence Chronic cases

Treatment
Short course of corticosteroids

Splenectomy may be indicated if the patient does not respond to prednisone

Oral danazol
High dose gamma globulin injections
Passage of the blood over a Protein A (Prosorba) column
Plasmapharesis

Principles of Transfusion Medicine. Second Edition. Rossi EC, etal. Williams and Wilkins. 1996.

Commonly Used Terms

Autoimmune Disorders

Coagulation

Internet Links

Medical Associations or Patient Support Groups

Last Updated 11/13/2001

SYNONYMS	ATP Autoimmune thrombocytopenic purpura Primary immune thrombocytopenic purpura
INCIDENCE	New cases of chronic refractory ITP are approximately 10 per 1,000,000 per year
United States	In adults is approximately 66 per 1,000,000 per year In children is 50 per 1,000,000 per year
Worldwide
AGE RANGE-MEDIAN	Peak incidence occurs in adults aged 20-50 years Peak incidence occurs in children aged 2-9 years Approximately 40% of all patients <10 years
SEX (M:F)
Acute ITP	Usually in children an equal distribution exists between males (52%) and females (48%)
Chronic ITP	Female-to-male ratio is 2.6:1 More than 72% of patients older than 10 years are female.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Prognostic Factors	Hemorrhage represents the most serious complication with intracranial hemorrhage is the most significant Older age and previous history of hemorrhage increase the risk of severe bleeding in adult ITP In children, disease is usually self-limited
Survival	Mortality from hemorrhage is approximately 1% in children and 5% in adults Spontaneous remission occurs in children in greater than 80% of cases, but it is uncommon in adults
Recurrence	Chronic cases
Treatment	Short course of corticosteroids Splenectomy may be indicated if the patient does not respond to prednisone Oral danazol High dose gamma globulin injections Passage of the blood over a Protein A (Prosorba) column Plasmapharesis