136 Clinical Advances in Hematology & Oncology Volume 4, Issue 2 February 2006
Management of Adult Idiopathic
Ibrahim N. Nakhoul, MD, Peter Kozuch, MD, Mala Varma, MD
Dr. Nakhoul is a Fellow, Dr. Kozuch is an
Assistant Professor of Clinical Medicine,
and Dr. Varma is an Attending Physician
in the Division of Hematology-Oncology
at St. Luke’s-Roosevelt Hospital Center, of
the Continuum Cancer Centers of
Address correspondence to:
Mala Varma, MD, St. Luke’s-Roosevelt
Hospital Center, Continuum Cancer
Centers of New York, 1000 10th Avenue,
Suite 11C02, New York, NY 10019;
Tel: (212) 523-7281; Fax: (212) 523-2004;
Abstract: Idiopathic thrombocytopenic purpura (ITP) is defined as
isolated thrombocytopenia without a clinically apparent cause. It is
categorized as acute, chronic, and refractory. Its clinical presenta-
tion ranges from acute to insidious and the bleeding may vary from
minimal to severe. The target platelet count with therapy is more
than 30,000/µL in sedentary individuals. Since studies regarding
therapies for ITP have been mostly uncontrolled case series, the treat-
ment recommendations are largely derived from expert opinion. This
review paper summarizes the data on available therapies for adult
acute and chronic/refractory ITP. The therapies include splenectomy,
steroids, intravenous immunoglobulin, anti-Rh(D), monoclonal anti-
bodies, danazol, chemotherapy, plasma exchange, and others.
originally called Werlhof’s disease. ITP is divided into two types:
acute, lasting for less than 6 months, and chronic, persisting
for more than 6 months. Refractory ITP is a term attributed to
persistent thrombocytopenia despite adequate steroid treatment
The pathogenesis of ITP is unclear but it is postulated that
antibody-coated platelets undergo reticuloendothelial phagocytosis
resulting in reduced platelet survival. However, not all patients
have these auto-antibodies.1 T cell–mediated cytotoxicity, anti-
body-mediated complement activation causing platelet lysis, and
antibody-mediated suppression of megakaryocyte production have
been suggested as other possible mechanisms.2
The incidence of ITP is 1.6/10,000 per year. Whereas some
report that the disease is more common in women, others report no
difference in gender distribution.3
The diagnostic hallmark of ITP is a low platelet count without
identification of alternative causes of thrombocytopenia by history,
physical, and laboratory evaluations. Tests should include peripheral
blood smear examination, HIV testing in at-risk patients, and bone
marrow biopsy to rule out myelodysplastic syndrome in patients
above the age of 60.4 Assays for antiplatelet antibodies are not used
diopathic thrombocytopenic purpura (ITP) is defined as iso-
lated thrombocytopenia without a clinically apparent cause.
Paul Gottlieb Werlhof first described it in 1735, and it was
ITP, idiopathic thrombocytopenic purpura, steroid,
splenectomy, monoclonal antibodies, chemotherapy.
Clinical Advances in Hematology & Oncology Volume 4, Issue 2 February 2006 137
M A N A G E M E N T O F A D U LT I T P
routinely.4 Platelet-associated immunoglobulin G (IgG)
testing, though sensitive, lacks specificity. Assays for plate-
let antigen–specific antibodies are less sensitive but more
specific; they may be helpful in distinguishing immune
from nonimmune thrombocytopenias.5
Clinicians should be cognizant of other important
possible diagnoses associated with thrombocytopenia
including thrombotic thrombocytopenic purpura–hemo-
lytic uremic syndrome, disseminated intravascular
induced thrombocytopenia, bacterial and viral infec-
tions (hepatitis, HIV), hypersplenism, myelodysplasia,
acquired pure megakaryocytic aplasia, and congenital
The clinical presentation in ITP ranges from acute to
insidious and bleeding can vary from minimal to severe.
In children, ITP usually has a self-limiting course resolv-
ing within 2–8 weeks in 80% of cases.4,6 The majority of
adults develop chronic ITP.4 Bleeding in ITP is mucocu-
taneous and manifests as petechiae, purpura, easy bruis-
ing, epistaxis, gingival bleeding, and menorrhagia. The
destruction of platelets by antibodies leads to an increase
in the production of young platelets that are more effective
in controlling hemostasis.7 Thus, bleeding manifestations
are milder in patients with ITP compared with those of
patients with thrombocytopenia of other etiologies. Seri-
ous bleeding rarely occurs if the platelet count is greater
than 10,000/µL.8 About 40% of patients with platelet
counts less than 10,000/µL develop major bleeds, includ-
ing gastrointestinal bleeds, hematuria, and intracranial
bleeding. The rate of fatal hemorrhage in untreated ITP is
estimated to be 5%.4
Initial therapies for ITP are used to avert the risk of
bleeding by promptly increasing the platelet count and to
buy time for spontaneous remissions to occur. The target
platelet count with therapy is more than 30,000/µL in
sedentary individuals and more than 50,000–80,000/µL
in patients with physically active occupations/lifestyles.9
Studies regarding therapies for ITP have been mostly
uncontrolled case series. Treatment recommendations
are therefore largely derived from expert opinion.4 The
management of ITP should be approached according to
the type of ITP and is summarized in Figure 1. When
compared with acute ITP, the management of chronic/
refractory ITP is challenging, but it is becoming more
exciting with the emergence of new therapies.
This review summarizes the data on available
therapies for adult acute and chronic ITP. A review of the
Medline database from 1958 through March 2005 was
performed. Keywords used were idiopathic thrombocy-
topenic purpura, immune thrombocytopenic purpura,
and ITP. While response criteria have not been histori-
cally uniform, platelet counts greater than 150,000/µL
and platelet counts of 50,000–150,000/µL have typically
defined complete response (CR) and partial response
(PR), respectively. In most studies, sustained response was
defined as a response lasting for more than 6 months.
Management of Acute ITP
The first report of a successful therapy for ITP was in
1916, when Paul Kaznelson described a response to
splenectomy. Splenectomy became first-line therapy for
the next 35 years (Table 1). A recent review of a six-decade
experience of splenectomy as secondary treatment for ITP
by Kojouri and colleagues10 reported a CR rate of 66%.
Relapses occurred in a median of 15% (range 0–51%)
of patients with a median follow-up of 33 months
(range 3–153 months). The time to relapse following
splenectomy ranged from less than 1 month to more than
10 years.11 The complication rate was 21.9% with lapa-
rotomy and 9.6% with laparoscopy.10 The mortality rate
was 1% with laparotomy and 0.2% with laparoscopy.10
The death rate due to ITP or therapy complications in
splenectomy-refractory patients was 15.7%.11 Since the
Consider dexamethasone 40 mg qd
No active bleeding
Dexamethasone 40 mg qd
Danazol, azathioprine, vinca alkaloids, cyclosporine, cyclophosphamide,
combination chemotherapy, alemtuzumab, clinical trials
Figure 1. Suggested algorithm for the management of ITP.
ITP = idiopathic thrombocytopenic purpura; IVIG = intravenous immunoglobulin.
144 Clinical Advances in Hematology & Oncology Volume 4, Issue 2 February 2006
N A K H O U L E T A L
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