Immune Thrombocytopeni c Purpura

Author: Craig M Kessler, MD, MACP; Chief Editor: Emmanuel C Besa, MD more...

Updated: Apr 21, 2014
Practice Essentials
Immune thrombocytopenic purpura (ITP) is a clinical syndrome in which a decreased number of circulating platelets
(thrombocytopenia) manifests as a bleeding tendency, easy bruising (purpura), or extravasation of blood from
capillaries into skin and mucous membranes (petechiae). Although most cases of acute ITP, particularly in children,
are mild and self-limited, intracranial hemorrhage may occur when the platelet count drops below 10 10
9
/L (<10
10
3
/L);
[1]
this occurs in 0.5-1% of children, and half of these cases are fatal.
[2]
Signs and Symptoms
ITP is a primary illness occurring in an otherwise healthy person. Signs of chronic disease, infection, wasting, or poor
nutrition indicate that the patient has another illness. Splenomegaly excludes the diagnosis of ITP.
An initial impression of the severity of ITP is formed by examining the skin and mucous membranes, as follows:
Widespread petechiae and ecchymoses, oozing from a venipuncture site, gingival bleeding, and hemorrhagic
bullae indicate that the patient is at risk for a serious bleeding complication
If the patient's blood pressure was taken recently, petechiae may be observed under and distal to the area
where the cuff was placed and inflated
Suction-type electrocardiograph (ECG) leads may induce petechiae
Petechiae over the ankles in ambulatory patients or on the back in bedridden ones suggest mild
thrombocytopenia and a relatively low risk for a serious bleeding complication
Findings suggestive of intracranial hemorrhage include the following:
Headache, blurred vision, somnolence, or loss of consciousness
Hypertension and bradycardia, which may be signs of increased intracranial pressure
On neurologic examination, any asymmetrical finding of recent onset
On fundoscopic examination, blurring of the optic disc margins or retinal hemorrhage
See Clinical Presentation for more detail.
Diagnosis
On complete blood cell count, isolated thrombocytopenia is the hallmark of ITP. Anemia and/or neutropenia may
indicate other diseases. Findings on peripheral blood smear are as follows:
The morphology of red blood cells (RBCs) and leukocytes is normal
The morphology of platelets is typically normal, with varying numbers of large platelets
If most of the platelets are large, approximating the diameter of red blood cells, or if they lack granules or have
an abnormal color, consider an inherited platelet disorder
Many children with acute ITP have an increased number of normal or atypical lymphocytes on the peripheral smear,
reflecting a recent viral illness. Clumps of platelets on a peripheral smear prepared from ethylenediaminetetraacetic
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acid (EDTA)anticoagulated blood are evidence of pseudothrombocytopenia.
[3]
This diagnosis is established if the
platelet count is normal when repeated on a sample from heparin-anticoagulated or citrate-anticoagulated blood.
Aspects of bone marrow aspiration and biopsy are as follows:
The value of bone marrow evaluation for a diagnosis of ITP is unresolved
[4]
Biopsy in patients with ITP shows a normal-to-increased number of megakaryocytes in the absence of other
significant abnormalities
In children, bone marrow examination is not required except in patients with atypical hematologic findings, such
as immature cells on the peripheral smear or persistent neutropenia.
[5]
In adults older than 60 years, biopsy is used to exclude myelodysplastic syndrome or leukemia
In adults whose treatment includes corticosteroids, a baseline pretreatment biopsy may prove useful for future
reference, as corticosteroids can change marrow morphology
Biopsy is performed before splenectomy to evaluate for possible hypoplasia or fibrosis
Unresponsiveness to standard treatment after 6 months is an indication for bone marrow aspiration
See Workup for more detail.
Management
ITP has no cure, and relapses may occur years after seemingly successful medical or surgical management.
[6]
Most
children with acute ITP do not require treatment, and the condition spontaneously.
[7, 8]
Treatment is as follows:
Corticosteroids remain the drugs of choice for the initial management of acute ITP
Oral prednisone, IV methylprednisolone, or high-dose dexamethasone may be used
[9, 10, 11]
IV immunoglobulin (IVIG) has been the drug of second choice for many years
[12, 13]
For Rh(D)-positive patients with intact spleens, IV Rho immunoglobulin (RhIG) offers comparable efficacy, less
toxicity, greater ease of administration, and a lower cost than IVIG
[14, 15]
RhIG can induce immune hemolysis (immune hemolytic anemia) in Rh(D)-positive persons and should not be
used when the hemoglobin concentration is less than 8 g/dL
Sporadic cases of massive intravascular hemolysis,
[16]
disseminated intravascular coagulation (particularly in
elderly individuals), and renal failure
[17]
have been reported with RhIG
Rituximab is third-line therapy
Platelet transfusions may be required to control clinically significant bleeding but are not recommended for
prophylaxis
If 6 months of medical management fails to increase the platelet count to a safe range (about 30,000/L),
splenectomy becomes an option
Thrombopoietin receptor agonists (ie, eltrombopag, romiplostim) may maintain platelet counts at safe levels in
adults with chronic ITP refractory to conventional medical management or splenectomy
Pregnant women require special consideration for delivery, as follows
[18]
:
If the platelet count is greater than 50 10
9
/L (>50 10
3
/L), the risk of serious hemorrhage is low, but
beginning oral prednisone a week before delivery is a reasonable precaution
If the platelet count is less than 50 10
9
/L (50 10
3
/L) before delivery, treatment with oral prednisone and
IVIG is recommended
Avoiding the use of IV RhIG in this situation until safety data are available is advisable
Rarely, splenectomy may be required to manage acute hemorrhage
[19]
See Treatment and Medication for more detail.
Image library
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Peripheral blood smear froma patient with immune thrombocytopenic purpura (ITP) shows a decreased number of platelets, a normal-
appearing neutrophil, and normal-appearing erythrocytes. ITP is diagnosed by excluding other diseases; therefore, the absence of other
findings fromthe peripheral smear is at least as important as the observed findings. This smear demonstrates the absence of immature
leukocytes (as in leukemia) and fragmented erythrocytes (as in thrombotic thrombocytopenic purpura) and no clumps of platelets (as in
pseudothrombocytopenia).
Background
Immune thrombocytopenic purpura (ITP) is a clinical syndrome in which a decreased number of circulating platelets
(thrombocytopenia) manifests as a bleeding tendency, easy bruising (purpura), or extravasation of blood from
capillaries into skin and mucous membranes (petechiae).
In persons with ITP, platelets are coated with autoantibodies to platelet membrane antigens, resulting in splenic
sequestration and phagocytosis by mononuclear macrophages. The resulting shortened life span of platelets in the
circulation, together with incomplete compensation by increased platelet production by bone marrow megakaryocytes,
results in a decreased platelet count.
Peripheral blood smear froma patient with immune thrombocytopenic purpura (ITP) shows a decreased number of platelets, a normal-
appearing neutrophil, and normal-appearing erythrocytes. ITP is diagnosed by excluding other diseases; therefore, the absence of other
findings fromthe peripheral smear is at least as important as the observed findings. This smear demonstrates the absence of immature
leukocytes (as in leukemia) and fragmented erythrocytes (as in thrombotic thrombocytopenic purpura) and no clumps of platelets (as in
pseudothrombocytopenia).
No single laboratory result or clinical finding establishes a diagnosis of ITP; it is a diagnosis of exclusion. The
differential diagnosis includes such other causes of thrombocytopenia as leukemia, myelophthisic marrow infiltration,
myelodysplasia, aplastic anemia, and adverse drug reactions. Pseudothrombocytopenia due to platelet clumping is
also a diagnostic consideration.
For discussion of ITP in pregnancy, see Immune Thrombocytopenia and Pregnancy. For patient education
information, see the First Aid and Injuries Center, as well as Bruises.
Pathophysiology
In immune thrombocytopenic purpura (ITP), an abnormal autoantibody, usually immunoglobulin G (IgG) with specificity
for 1 or more platelet membrane glycoproteins (GPs), binds to circulating platelet membranes.
[20, 21, 22]
Autoantibody-coated platelets induce Fc receptor-mediated phagocytosis by mononuclear macrophages, primarily but
not exclusively in the spleen.
[23]
The spleen is the key organ in the pathophysiology of ITP, not only because platelet
autoantibodies are formed in the white pulp, but also because mononuclear macrophages in the red pulp destroy
immunoglobulin-coated platelets.
[24]
If bone marrow megakaryocytes cannot increase production and maintain a normal number of circulating platelets,
thrombocytopenia and purpura develop. Impaired thrombopoiesis is attributed to failure of a compensatory increase in
thrombopoietin and megakaryocyte apoptosis.
Frequency
United States
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The annual incidence of immune thrombocytopenic purpura (ITP) is estimated to be 5 cases per 100,000 children and
2 cases per 100,000 adults,
[2]
but these data are not from large population-based studies. Most cases of acute ITP,
particularly in children, are mild and self-limited and may not receive medical attention. Therefore, estimated
incidences of ITP are difficult to determine and are likely to understate the full extent of the disease. The age-adjusted
prevalence of ITP in Maryland was reported as 9.5 per 100,000 persons by Segal and Powe.
[25]
Mortality/Morbidity
Hemorrhage: The primary cause of long-term morbidity and mortality in patients with immune thrombocytopenic
purpura (ITP) is hemorrhage.
[26]
Intracranial hemorrhage: The most frequent cause of death in association with ITP is spontaneous or accidental
trauma-induced intracranial bleeding. Most cases of intracranial hemorrhage occur in patients whose platelet
counts are less than 10 10
9
/L (<10 10
3
/L).
[1]
This situation occurs in 0.5-1% of cases in children, and half
of those are fatal.
[2]
In one study, 17% of children experienced a major hemorrhage.
[27]
Treatment-related morbidity: Maintaining the platelet count in a safe range in patients with chronic treatment-
resistant ITP may require a long-term course of corticosteroids, other immunosuppressive medications, or
splenectomy. Morbidity and mortality in patients with ITP can be related to treatment, reflecting the
complications of therapy with corticosteroids or splenectomy.
Sex
In children, ITP is more common in boys than in girls.
[28]
In middle-aged adults, women are affected more frequently than men.
[2]
Age
Children may develop ITP at any age, but the incidence peaks in children aged 1-6 years.
[28]
Adults may be affected at any age, but most cases are diagnosed in women aged 30-40 years.
Onset in a patient older than 60 years is uncommon, and a search for other causes of thrombocytopenia is
warranted. The most likely causes in these persons are myelodysplastic syndromes, acute leukemia, and
marrow infiltration (myelophthisis). Persons with ITP who are 70 years or older are at increased risk for
spontaneous bleeding and treatment-related adverse events.
[29]

Contri butor Informati on and Di scl osures
Author
Craig M Kessler, MD, MACP Professor, Department of Medicine and Pathology, Division of
Hematology/Oncology, Georgetown University School of Medicine; Director, Clinical Coagulation Laboratory,
Lombardi Comprehensive Cancer Center, Georgetown University Hospital
Disclosure: NovoNordisk Honoraria Consulting; NovoNordisk Grant/research funds Other; Baxter-Immuno Honoraria
Consulting; Octapharma Honoraria Speaking and teaching; Octapharma Grant/research funds None; Amgen
Consulting fee Consulting; Bayer Review panel membership
Coauthor(s)
S Gerald Sandler, MD, FACP, FCAP Professor of Medicine and Pathology, Director, Transfusion Medicine,
Department of Laboratory Medicine, Georgetown University Hospital
S Gerald Sandler, MD, FACP, FCAP is a member of the following medical societies: American Association of
Blood Banks, College of American Pathologists, and International Society of Blood Transfusions
Disclosure: Nothing to disclose.
Specialty Editor Board
Michael Paul Kosty, MD Associate Director, Associate Professor, Department of Internal Medicine, Divisions of
Supportive Care Services and Hematology and Oncology, Ida M and Cecil H Green Cancer Center, Scripps Clinic
Michael Paul Kosty, MD is a member of the following medical societies: American College of Physicians, American
Society of Hematology, and Phi Beta Kappa
Immune Thrombocytopenic Purpura http://emedicine.medscape.com/article/202158-overview
4 of 12 5/1/2014 8:43 PM
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Ronald A Sacher, MB, BCh, MD, FRCPC Professor, Internal Medicine and Pathology, Director, Hoxworth Blood
Center, University of Cincinnati Academic Health Center
Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for
the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological
Association, American Society for Clinical Pathology, American Society of Hematology, College of American
Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis,
and Royal College of Physicians and Surgeons of Canada
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching
Rajalaxmi McKenna, MD, FACP Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan
Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical
Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.
Chief Editor
Emmanuel C Besa, MD Professor, Department of Medicine, Division of Hematologic Malignancies and
Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, J efferson Medical College of Thomas J efferson
University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer
Education, American College of Clinical Pharmacology, American Federation for Medical Research, American
Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.
Additional Contributors
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author S
Gerald Sandler, MD, FACP, FCAP, to the development and writing of this article.
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthor
Rumina Bhanji, MD to the development and writing of this article.
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