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.
138 Clinical Advances in Hematology & Oncology Volume 4, Issue 2 February 2006
N A K H O U L E T A L
introduction of steroids for the treatment of ITP in the
1950s, splenectomy is no longer considered first-line
therapy. While splenectomy may still be considered as sec-
ond-line therapy if a 4–6 week course of steroids does not
induce a sustained response, this operation is increasingly
being deferred until other medical interventions, detailed
below, have been attempted.
Steroid therapy as treatment of ITP was first reported in
1958.12 It is believed that steroids inhibit phagocytosis
of antibody-coated platelets13 and inhibit autoantibody
production.14 Steroids also appear to strengthen capillar-
ies; bleeding manifestations often decrease before platelet
Steroid use in oral and intravenous formulations,
in continuous and pulse schedules, and in “regular” and
“high” dosages have been explored in both acute and
chronic ITP. The most commonly used steroid regimen
is prednisone at a dosage of 1 mg/kg per day orally for a
duration of 2 weeks to 6 months. CR rates varied from
14% to 50% and PR rates from 2% to 40% when steroids
were used as initial therapy.12,13,15-18 The rate of sustained
CR following discontinuation of steroids varied from 14%
to 32%. Continuation of steroids beyond 30–45 days
did not confer additional benefit. Although short-term
steroid use for ITP is well tolerated in general, reversible
cushingoid features, gram-negative sepsis, and aspergillo-
sis have been reported.19,20 Opportunistic infections have
also been reported to complicate short-term steroid use
in patients with AIDS.21 Therefore, in our practice, we
usually avoid steroids in patients with AIDS-related ITP.
Oral and intravenous high-dose dexamethasone have
been used in acute and chronic/refractory ITP, at a dos-
age of 40 mg/day for 4 days every 4 weeks. Cheng and
associates22 treated 125 patients with newly diagnosed
ITP with a single course of dexamethasone. Platelet
counts increased by at least 20,000/µL by the third day
of treatment in 85% of patients. The overall response rate
(ORR; CR+PR) was 85%; 50% had a sustained response
for more than 6 months after a single course. Relapse rates
were 43% and 50% at 3 and 6 months, respectively. Borst
and coworkers23 treated 18 patients with newly diagnosed
ITP and another 18 patients with recurrent ITP with up
to 6 cycles of oral dexamethasone. An acute response with
an increase in platelet count to a level above 50,000/µL
was seen in 83% of patients. When high-dose steroids
were given as first-line treatment, the ORR was 89% and
was sustained in 61% of patients at a median follow-up
of 8.5 months. As second-line modality, ORR was also
89%, but was sustained in only 28% of patients at a
median follow-up of 6 months. The efficacy of high-dose
dexamethasone in chronic, refractory ITP has not been
consistently demonstrated, although one study did show
an overall response rate of 100% and a sustained CR rate
of 100%.24 High-dose dexamethasone is generally well
tolerated with minor adverse effects comprised mainly
of increased appetite and difficulty sleeping.25 Because of
its efficacy and favorable adverse-effect profile, high-dose
dexamethasone is our preferred steroid regimen for initial
therapy of ITP.
Intravenous immunoglobulin (IVIG) at a dosage of
400 mg/kg per day for 5 days or 1 g/kg per day for 2 days
has been used in the management of ITP. In 1983,
Salama and colleagues26 postulated that low titers of red
cell alloantibodies contained in IVIG cause Fc receptor
blocking. It was then demonstrated that following infu-
sions of IVIG, clearance of autologous radiolabelled anti-
Rh(D)–sensitized red cells is decreased, suggesting that
IVIG works through Fc receptor blockade.27,28 The allo-
antibodies induce hemolysis and divert macrophages from
antibody-bound platelet destruction.26 IVIG can induce
Number of Patients,
Regular dose Ste-
High dose steriods†22-25
* Prednisone 15–120 mg or 0.3–3 mg/kg, prednisolone, methylprednisone, cortisone, or adrenocor-
† Dexamethasone 40 mg per day for 4 days (single or multiple courses).
IVIG = intravenous immunoglobulin.
Table 1. Management of Acute Idiopathic Thrombocytopenic Purpura
Clinical Advances in Hematology & Oncology Volume 4, Issue 2 February 2006 139
M A N A G E M E N T O F A D U LT I T P
an increase in platelet count to more than 50,000/µL in
70% of patients.10,26-30 The response is usually rapid; 7%
and 79% of patients achieve platelet counts of more than
50,000/µL on the second and fifth day, respectively, fol-
lowing the start of IVIG therapy.30 Thus, IVIG therapy
is ideal when a rapid increase in platelet count is desired
in patients with life-threatening bleeding.9 It can also be
combined with steroids and platelet transfusions in these
situations.9 Responses to IVIG usually last about 3 weeks
and repeat cycles are frequently needed. However, the
expense of this therapy and the length of infusion (8 hours
daily for 2 days) limit its use in the chronic setting.
Anti-Rh(D) is a plasma-derived immune globulin con-
taining a high titer of antibodies to Rh(D) antigens.
In contrast, IVIG has a distribution of IgG subclasses
similar to that of normal plasma. Anti-Rh(D) binds to
the Rh(D) antigen, and it is believed that the complex
competitively inhibits reticuloendothelial phagocytosis of
IgG-coated platelets.31 In 1984, Salama and colleagues32
reported on treatment of 10 Rh(D)-positive patients with
chronic ITP with anti-Rh(D). Platelet counts increased
in 8 out of 10 patients. Treatment response was poorer in
the splenectomized (n=4) than in the nonsplenectomized
(n=6), with mean platelet increments of 16,000/µL versus
60,000/µL, respectively. In a study of 27 Rh(D)-positive,
HIV-negative, nonsplenectomized patients with acute
ITP and platelet counts of less than 30,000/µL, a dose
of 75 µg/kg of intravenous anti-Rh(D) induced a median
overnight increase in platelet count of 43,000/µL with a
median duration of response of 46 days.33 In HIV-related
ITP, the effect of anti-Rh(D) was shown to last a mean of
11.6 days longer than that of IVIG (26.8 vs 15.2 days).34
Cooper and coauthors35 treated 28 patients with
ITP refractory to steroids with intermittent anti-Rh(D).
Anti-Rh(D) was infused whenever the platelet count was
30,000/µL or below. Twenty-six (93%) patients responded
to the initial infusion of anti-Rh(D); 19 (68%) patients
had repeated responses. At a median of 26 months,
12 (43%) of 28 patients had been off therapy for more
than 6 months without undergoing splenectomy;
8 underwent splenectomy. The cost of anti-Rh(D) used
in all 28 patients plus the cost of 8 splenectomies was
less than the expected cost if splenectomies had been
performed in all 28 patients. Thus, maintenance therapy
with anti-Rh(D) may abrogate the need for splenectomy
in more than 40% of patients.
Anti-Rh(D) is also less expensive than IVIG
and requires a much shorter time period for infusion
(5–10 minutes). The toxicity profile of anti-Rh(D),
which includes mild hemolysis and infusional fever and
chills, is more favorable than that of steroids. Although
considerably more expensive than steroid therapy, anti-
Rh(D) should be considered for first-line therapy of ITP
in the immunocompromised unsplenectomized Rh(D)-
positive population. The efficacy of anti-Rh(D) therapy
in splenectomized patients with accessory spleens has not
Management of Chronic/Refractory ITP
Patients who have ITP persisting for more than 6 months
(chronic ITP) or who have not responded to the treat-
ments described above (refractory ITP) will ultimately
need to be treated with the options outlined below and
summarized in Table 2.
Rituximab Rituximab (Rituxan, Genentech) is a chime-
ric murine/human monoclonal antibody directed against
the B-cell antigen CD20. It can induce profound B-cell
depletion that may involve the autoreactive B-cell clone.36
The regimen used in almost all studies is 375 mg/m2
weekly for 4 consecutive weeks. There are two types of
responses: early responses, occurring after the first or
second infusion, and late responses, occurring at weeks
6–8.37 It is postulated that a mechanism of macrophage
blockade by opsonized B cells may account for the early
responses.36 The ORRs range from 23% to 100%.36-40 In
the study by Cooper and coworkers,38 32% of patients
had a sustained response at more than 1 year; half of those
patients had not undergone prior splenectomy. The toxic-
ity profile of rituximab is favorable; most adverse effects
are limited to first infusion reactions. Due to its efficacy
and favorable adverse effect profile, it may be preferable
for patients with chronic/refractory ITP to try therapy
with rituximab before undergoing splenectomy.
Alemtuzumab Alemtuzumab (Campath 1-H, Berlex)
is a humanized anti-CD52 monoclonal antibody. CD52
is highly expressed on lymphocytes and monocytes. It is
a 12–amino acid cell-surface glycoprotein that lies close
to the cell membrane. Its function is not clear, but it may
promote cell-cell adhesion or protect cells from insult.
Reports of alemtuzumab therapy for ITP are
emerging. ORRs range from 44% to 80%.41,42 Lim and
colleagues42 reported a response in 4 of 5 patients with
refractory ITP treated with intravenous alemtuzumab.
One response occurred after 3 days of therapy; the other
responses occurred after 4–6 weeks. Responses lasted more
than 4–9 months in 3 patients. It is believed that T-lym-
phocyte as well as B-lymphocyte depletion are mechanisms
through which alemtuzumab is effective in ITP.41-43
Adverse effects of intravenous alemtuzumab include
140 Clinical Advances in Hematology & Oncology Volume 4, Issue 2 February 2006
N A K H O U L E T A L
fever, rigors, rash, nausea, hypotension, transient pancyto-
penia, prolonged lymphopenia, and opportunistic infec-
tions. Alemtuzumab is effective and has less hypotension,
rash, and nausea when given subcutaneously.44
Danazol, a synthetic androgen, is believed to restore
suppressor T-cell function and decrease antibody produc-
tion,45 decrease the number of available Fc receptors,46 and
decrease capillary wall permeability.47 The conventional
dose ranges from 200 to 800 mg orally daily.
The initial study published by Ahn and cowork-
ers,45 who treated 22 patients with danazol for at least
2 months, demonstrated an ORR of 59% with a median
duration of response of 9 months. These results were not
reproduced in subsequent smaller studies where the dura-
tion of therapy was only 2–3 months.48-50 Subsequently,
two large studies by Ahn and colleagues51 and Maloisel
and colleagues52 in which danazol was given for mean
durations of 17.8 and 22.6 months, respectively, reported
ORRs of 61.4%–67%. The median time to response was
3.1 months.51,52 Of note, 10–15% of patients responded
after 6 or more months of therapy.51,52 Therefore a thera-
peutic trial of danazol should last at least 6 months.
Long-term remissions with danazol have been
reported. Maloisel and colleagues52 reported a median
duration of remission of 119 months and a sustained
remission at 10 years in 42% of patients. Retreatment
usually induces a response.51,52
Some patients who do not respond to danazol
400–800 mg daily respond to 50 mg daily.53 Notably,
the time to response is longer with the lower dose.51-53
Sustained responses have been reported in some nonsple-
nectomized patients, indicating that danazol may be an
alternative to splenectomy.51,52,54 Danazol is well-toler-
ated. Adverse effects include weight gain or loss, lethargy,
myalgias, liver dysfunction, skin rash, pruritus, and mild
virilization. These adverse effects generally abate after sev-
eral weeks of therapy or with a reduction in dose.
Azathioprine Azathioprine is given at a daily dose of
1–4 mg/kg (usually 150 mg) orally and modified accord-
ing to the leukocyte count. Time to response varies from
2 to 10 months. Thus 6 months of treatment are needed
* Chemotherapy regimens (repeated every 28 days):
· CVP: cyclophosphamide 400–650 mg/m2 IV on days 1 and 8, prednisone 40 mg/m2 orally on days 1–14, vincristine 2 mg IV on
days 1 and 8.
· CMOPP: cyclophosphamide 400–650 mg/m2 IV on days 1 and 8, prednisone 40 mg/m2 orally on days 1–14, vincristine 2 mg on
days 1 and 8, procarbazine 100 mg/m2 orally on days 1–14.
· CEP: cyclophosphamide 400–650 mg/m2 IV on days 1 and 8, prednisone 40 mg/m2 orally on days 1–14, etoposide 100 mg/m2
IV on days 14, 15, and 16.
Table 2. Management of Chronic/Refractory Idiopathic Thrombocytopenic Purpura
Clinical Advances in Hematology & Oncology Volume 4, Issue 2 February 2006 141
M A N A G E M E N T O F A D U LT I T P
for assessment of its effectiveness. The reported CR and
PR rates range from 17% to 71% and 5% to 83%, respec-
tively.18,55-57 Therapy should be continued for 18 months
in responders.58 Response duration ranges from months
to years. The major adverse effects are cytopenias, gas-
trointestinal symptoms, and secondary malignancy in
Vinca Alkaloids The mechanism of action of vinca
alkaloids could be related to inhibition of phagocytic cell
function. Vincristine is given intravenously in 1–2 mg
weekly doses for several weeks. Vinblastine is admin-
istered 0.1 mg/kg weekly for 5 weeks and repeated at
biweekly then monthly intervals as maintenance therapy
once a CR or PR is attained.59 Although intravenous
bolus and slow infusions (over 6 hours) of vinblastine
yield equivalent responses,60 slow infusional therapy of
vincristine and vinblastine was associated with less hair
loss and neutropenia than bolus injection therapy.61 Time
to response is rapid (7–10 days). CRs and PRs range from
0 to 55% and 17% to 44%, respectively.18,59-67 Many of the
reported responses are transient.59,62,64 The major adverse
effects are peripheral neuropathy, alopecia, constipation,
and extravasational injuries. If a sustained response is not
achieved, vincristine therapy should be discontinued after
4–6 doses to avoid peripheral neuropathy.58
Cyclosporine Cyclosporine A (CyA) is typically started
at a daily dose of 5–6 mg/kg orally. Response rates
vary from 30% to 75% and from 8% to 33% for CR
and PR, respectively.68-70 In a study by Kappers-Klunne
and colleagues,68 5 out of 10 unsplenectomized patients
with chronic refractory ITP responded to CyA, but
9 ultimately required a splenectomy. Thus, CyA treat-
ment may not obviate but rather may delay splenectomy
in chronic ITP. Emilia and coworkers70 treated 12 patients
with refractory ITP with CyA for a median of 40 months.
CR was achieved in 9 out of 12 (75%) patients and PR
in 1 (8%) patient. A sustained response was seen in 60%
of responders after discontinuation of CyA at a mean of
28.6 months after completion of therapy. Thus, CyA can
be useful in a subgroup of patients with corticosteroid-
and splenectomy-refractory ITP. However, treatment
toxicity is significant, and it necessitated discontinuation
of therapy in 30% of patients in one study.68 Adverse
effects consist of renal insufficiency, hepatotoxicity, hyper-
tension, tremor, hirsutism, headache, muscle ache, gum
hyperplasia, hypomagnesemia, and secondary cancer.
Cyclophosphamide Cyclophosphamide is given orally
at dose of 1–2 mg/kg per day (usually 150 mg daily),
or intravenously at a pulse dose of 1.0–1.5 g/m2 every
3–4 weeks. Time to response is about 6–8 weeks.58 CR
and PR range from 34% to 75% and 14% to 25%, respec-
tively.18,66,71-73 Treatment should continue for 3 months
beyond platelet count normalization.58 Verlin and associ-
ates71 reported that remission rate appears to be related
to duration of disease. Presence of disease for less than 1
year is associated with a response rate of 73% compared
with disorders lasting over 2 years in which response rates
were 40%. In a study by Reiner and colleagues,72 sustained
CRs were seen in 8 out of 13 responders during follow-
up intervals ranging from 7 months to 7 years (median
2.5 years) and sustained PRs were seen in 2 of 4 respond-
ers at 10-month and 4-year follow-up. Upon recurrence of
ITP, 2 out of 5 patients responded to subsequent courses of
cyclophosphamide. However, when relapse occurs, long-
term risks such as secondary malignancy must be weighed
against the benefits of resuming therapy. Adverse effects
include cytopenias, hemorrhagic cystitis, gastrointestinal
symptoms, sterility, and secondary cancers.
Huhn and colleagues73 treated 14 adults with
chronic refractory ITP with high-dose cyclophosphamide
(50 mg/kg per day) followed by autologous lymphocyte-
depleted peripheral blood stem cell transplantation. With
up to 42 months follow-up, 6 patients had sustained CRs
and 2 had sustained PRs; the ORR was 57%.
2-Chlorodeoxyadenosine Seven patients with refrac-
tory ITP were treated with 1–3 cycles of 2-chlorode-
oxyadenosine administered by continuous infusion at a
dosage of 0.1 mg/kg per day for 7 days. No improvement
in platelet counts was observed.100
Figueroa and associates74 published the results of combina-
tion chemotherapy in chronic refractory ITP (Table 2). Ten
splenectomized patients were treated with up to 6 cycles
of cyclophosphamide, prednisone, and one or more other
agents (vincristine, procarbazine, and/or etoposide as in
CVP, CEP, and CMOPP protocols). Six patients attained
CRs and responses were sustained in 4 patients for over
11, 30, 54, and 126 months. Two patients attained a PR,
which was sustained in 1 patient for over 9 months follow-
ing completion of therapy. Discontinuation of therapy is
recommended if no response is attained following 2 cycles
of therapy. Responding patients may be given a total of 6
cycles at 4-week intervals.58
Intensive plasma exchange therapy with fresh-frozen
plasma as replacement fluid has been used in the manage-
ment of patients with acute and chronic ITP. The response
rates range from 50% to 80% for CRs and 0 to 23% for
PRs.75-77 Marder and colleagues75 followed 14 patients
with ITP for 1 year after plasma exchange therapy.
142 Clinical Advances in Hematology & Oncology Volume 4, Issue 2 February 2006
N A K H O U L E T A L
Exchange was performed prior to splenectomy in 8 of
9 patients with acute ITP and following splenectomy in
5 patients with chronic ITP. In the 9 patients with acute
ITP, CR was attained in 5 patients (sustained for 80 weeks
in 4 patients) and PR was seen in 1 patient. None of
the patients with chronic ITP attained a response. Thus
plasma exchange may be considered for the management
of acute but not chronic ITP.
Interferon alpha 2b has been used in refractory ITP, typi-
cally at a dosage of 3 million units subcutaneously 3 times
a week for 4 weeks.78-80 Responses range from 0 to 100%
and 0 to 60% for CR and PR, respectively.78-80 In a study
by Vianelli and coworkers80 none of 9 patients had any
response. Retreatment with interferon after relapse may
induce responses.78,79 Adverse effects include flu-like symp-
toms, fever, cytopenias, cardiomyopathy, hypotension,
tachycardia, confusion, hepatotoxicity, depression, and
The possible mechanism of action of colchicines in ITP is
decreased clearance of opsonized platelets secondary to inhi-
bition of microtubule-dependent events in macrophages.81
The recommended dosage is 0.5–0.6 mg 2 or 3 times daily
orally for a minimum of 2 weeks. Response rates range
from 14% to 67% and 7% to 71% for CR and PR, respec-
tively.81-83 Adverse events are usually mild.
Dapsone at a daily dose of 75–100 mg has demonstrated
CR rates ranging from 0 to 25% and PR rates from 25%
and 48%.84-87 The median duration of treatment required
to obtain a response is 21 days. Godeau and colleagues84
reported a sustained response in 19 out of 33 patients with
a 12.5-month follow-up. However, thrombocytopenia
recurs shortly after treatment withdrawal.84 The most
frequent adverse effect is dose-related hemolytic anemia
at the 100-mg dose, which may abate at the lower dose
of 50 mg.85
The first report of vitamin C in the treatment of refrac-
tory ITP was by Brox and colleagues in 1988.88 The
mechanism of action is not known. In subsequent studies
the CR rate was very poor, in the 0–9% range. PR rates
ranged from 0 to 82%.88-91 Adverse effects of vitamin C
include mainly dyspepsia.
Twenty-one patients with refractory ITP were treated
with mycophenolate mofetil (MMF) at a dosage of
1.5–2.0 g/day for a minimum of 12 weeks.92 The ORR
was 62%. Five of 13 responders had a sustained response
with the original dose of MMF for a median of 22 weeks.
MMF was tapered or discontinued in the other 8 respond-
ers and 5 of these 8 responders relapsed as a result of dose
reduction or withdrawal of MMF. Three patients showed
sustained response after withdrawal of MMF, which was
generally well tolerated with only slight nausea and diar-
Protein A Immunoadsorption
It was postulated that protein A immunoadsorption
decreases platelet activation and reduces platelet-binding
immunoglobulin and circulating immune complex lev-
els.93 Snyder and coworkers94 treated 72 splenectomized
patients with chronic refractory ITP with staphylococcal
protein A immunoadsorption. The regimen consisted of
6 treatments of 0.25–2.0 L plasma per procedure over
2–3 weeks. CR was attained in 25% and PR in 21%
of patients. The median time to response was 2 weeks.
Responses were sustained in 36% of patients over a fol-
low-up period of up to 26 months. Hypersensitivity-type
reactions were seen in 30% of cases. Low-dose steroids
(<30 mg/d) can depress the incidence and severity of
Thrombopoietin and Thrombopoietin-like Agents
It was postulated that a mechanism leading to ITP is
autoantibody-induced impairment of megakaryopoiesis
and platelet production.95 In a phase I/II clinical trial,
pegylated recombinant human megakaryocyte growth and
development factor (MGDF) induced a platelet response
in 3 of 4 patients with refractory ITP.96 Neutralizing anti-
bodies and resultant thrombocytopenia have been reported
in healthy volunteers and cancer patients undergoing
chemotherapy treated with MGDF.97 Therefore, develop-
ment of MGDF has been halted. Bussel and colleagues98
initiated a pilot study intended to enroll 12 patients with
refractory ITP for treatment with oprelvekin (Neumega,
Wyeth) 50 µg/kg per day subcutaneously for 21 consecu-
tive days followed by 21 days of observation. The study
was terminated after 7 patients were enrolled because of
substantial toxicity and lack of efficacy. Also in develop-
ment is AMG531 (Amgen), a thrombopoietic peptide. In
a phase II study, 21 patients received a weekly dose of
1 µg/kg or 3 µg/kg for 6 weeks. Ten patients achieved a
platelet count in the target range of 50,000–450,000/µL.
Further development of this drug is in process.99
WEB 2086 BS
Giers and associates101 treated 13 patients with chronic
ITP for 14 days with 120 mg/day of the platelet-activat-
ing-factor antagonist WEB 2086 BS. Clinical bleeding
Clinical Advances in Hematology & Oncology Volume 4, Issue 2 February 2006 143
M A N A G E M E N T O F A D U LT I T P
symptoms remained essentially unchanged in 9 patients
and became more pronounced in the posttreatment
period in 4 patients. In no case was an increase in platelet
In summary, this article describes the therapeutic options
for adult patients with ITP, as outlined in Figure 1. Select-
ing the right treatment depends on many factors that the
treating physician should be aware of, and which are sum-
1. Type of ITP (acute vs chronic/refractory): Whereas
the treatment of acute ITP is straightforward, the treat-
ment of refractory ITP is more challenging given that
the disease is more resistant and the list of available
medications is long. Our preference is to start with
monoclonal antibodies, especially rituximab, before
moving to other available agents.
2. Time to Response: This is especially important when
a quick rise in the platelet count is needed to prevent a
major complication. The agents that produce the fast-
est increase in platelet count are IVIG, anti-Rh(D), and
high-dose steroids. These are our drugs of choice for
ITP patients who present with platelet counts less than
10,000/µL and/or signs or symptoms of bleeding.
3. Adverse Events: As an example, alemtuzumab seems to
have good activity in the treatment of refractory ITP;
however, its toxicity profile may hinder its use. Further
studies are warranted to evaluate the best mode of
administration for efficacy and for toxicity reduction.
4. Cost: Cost may hinder the use of active medica-
tions with minimal toxicities, such as rituximab, as
5. Response Rate: Tables 1 and 2 summarize the response
rates of the drugs used in the management of ITP.
This work is supported by the Hope Sheridan Foundation.
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