Annals of Oncology Advance Access published April 25, 2012

review

Annals of Oncology
doi:10.1093/annonc/mds074

Oxaliplatin-related thrombocytopenia
D. L. Jardim1*, C. A. Rodrigues1,2, Y. A. S. Novis1, V. G. Rocha1,3 & P. M. Hoff1,3
1

Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo; 2Department of Clinical and Experimental Hematology, Universidade Federal do Estado de
Sao Paulo, Sao Paulo; 3Department of Radiology and Oncology, Instituto do Cancer do Estado de Sao Paulo, Faculdade de Medicina da Universidade de Sao Paulo,
Sao Paulo, Brazil

Received 30 August 2011; revised 17 December 2011; accepted 7 March 2012

introduction
Oxaliplatin is a third generation platinum analog that binds
to DNA forming cross-links which inhibit DNA replication
and transcription, resulting in cell death. Since its approval
by the USA Food and Drug Administration (FDA) for use in
metastatic colorectal cancer (CRC) in 2002, this drug has
been widely used to treat this malignancy and a wide range of
other tumors. Several studies have demonstrated that
oxaliplatin combined with 5-fluorouracil (5-FU) and folinic
acid, in a regimen commonly known as FOLFOX, increases
survival in the metastatic setting and reduces the risk of
disease recurrence when used as a treatment of stage III
CRC [13]. In these major trials, the incidence of
thrombocytopenia of all grade was >70 %, which is
substantially superior than the rate observed when 5-FU and
folinic acid are used without oxaliplatin [1, 2]. In a review of
chemotherapy-induced thrombocytopenia including >47 000
patients with solid tumors, CRC was associated with the
highest prevalence of thrombocytopenia by cancer type, and
most patients had received a platinum-based chemotherapy
regimen [4]. Although grades 34 thrombocytopenia are
noted in only 3%4% of patients exposed to oxaliplatin, this
toxicity is of significant concern since the majority of patients
with CRC will receive this drug in a given moment of their
treatment and the incidence of this toxicity tends to increase
during repeated exposures.
*Correspondence to: Dr D. L. Jardim, Department of Clinical Oncology, Hospital
Sirio Libanes, Adma Jafet Street, 91, Bela Vista, 01308-050, Sao Paulo, Brazil.
Tel: +55-11-31550995; E-mail: jardimde@gmail.com

Even though the major dose-limiting side-effect of

oxaliplatin is neurotoxicity, with the widespread use of
this drug several groups have also shown the need to
discontinue oxaliplatin due to thrombocytopenia [5]. The
presence of significant thrombocytopenia could possibly limit
the benefits of oxaliplatin by preventing appropriate
administration of it at the optimal doses and schedule.
Particularly in the adjuvant setting, where it is used with
curative intent, this issue is a major concern. In addition,
oxaliplatin-based chemotherapy has also been increasingly
used to permit resection of hepatic metastases and
thrombocytopenia, in this context, may increase bleeding
risks, postsurgical morbidity, the need for blood transfusions
and the duration of hospitalization.
Mild bone marrow suppression similar to that of other
platinum-based compounds is the main cause of oxaliplatininduced thrombocytopenia. However, novel mechanisms of
oxaliplatin-induced thrombocytopenia have emerged and may
be associated with different clinical presentation and may even
need different approaches [6, 7]. These novel mechanisms
include an immune-dependent mechanism and splenic
sequestration of platelets due to portal hypertension related to
sinusoidal injury. In Figure 1, we present a schematic
representation of these mechanisms involved in oxaliplatinrelated thrombocytopenia, while Table 1 summarizes the main
features related to them.
In the light of these new mechanisms, this review will provide
a clinical overview of them and management recommendations
for patients presenting a low-platelet count during treatment
with oxaliplatin, including issues related to myelossupresion.

The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: journals.permissions@oup.com

review

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Oxaliplatin is a third generation platinum compound that inhibits DNA synthesis, mainly through intrastrandal crosslinks in DNA. Most of the experience with the clinical use of this drug is derived from colorectal cancer but it is also used
in other tumor types such as ovary, breast, liver and non-Hodgkins lymphoma. Thrombocytopenia is a frequent toxicity
seen during oxaliplatin treatment, occurring at any grade in up to 70 % of patients and leading to delays or even
discontinuation of the chemotherapy. Although myelossupression is recognized as the main cause of oxaliplatin-related
thrombocytopenia, new mechanisms for this side-effect have emerged, including splenic sequestration of platelets
related to oxaliplatin-induced liver damage and immune thrombocytopenia. These new pathophysiology pathways
have different clinical presentations and evolution and may need specific therapeutic maneuvers. This article attempts
to review this topic and provides useful clinical information for the management of oxaliplatin-related thrombocytopenia.
Key words: myelossupression, oxaliplatin, review, thrombocytopenia

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Annals of Oncology

methods
We searched Medline (19982008), UpToDate database and
Embase for case reports and up-to-date manuscripts about
oxaliplatin and thrombocytopenia. We used the search terms
oxaliplatin or chemotherapy, colon cancer in combination
with the terms thrombocytopenia, myelossupression,
bone marrow suppression, allergic reactions,
auto-immune reactions splenic sequestration and
hemolytic uremic syndrome. We mostly selected
publications from the past 6 years but did not exclude
frequently referenced older publications or case reports. We
also searched the reference lists of reports identified by this
search strategy and selected those we judged relevant.
After reviewing all the data, the authors organized a practical
review classifying the information by the different mechanisms of
thrombocytopenia.

Prolonged thrombocytopenia and splenic enlargement can be

observed in some patients receiving oxaliplatin-based

Figure 1. Schematic representation of the mechanisms involved in

oxaliplatin-related thrombocytopenia.

Table 1. Clinical features of the mechanisms involved in oxaliplatin-related thrombocytopenia

Myelosuppression

Immune-mediated

Splenic sequestration

Mechanism

Toxicity to megakaryocytic
progenitors

Oxaliplatin-dependent antibodies to
platelet antigens

Clinical presentation

Asymptomatic thrombocytopenia
usually with anemia and
neutropenia

Diagnostic evaluation

Bone marrow aspirate not routinely

carried out
Dose reduction or treatment delays;
platelet-stimulating agents

Sudden and isolated drop in platelet

levels with clinical bleeding.
Hypersensitivity reactions may
occur
Detection of oxaliplatin-dependent
antibodies by flow cytometry
Definitive discontinuation of
oxaliplatin. Platelet transfusion
frequently needed. Steroids use
uncertain

Oxaliplatin-induced sinusoidal
injury leading to portal
hypertension
Prolonged thrombocytopenia in the
context of splenomegaly and
other features of portal
hypertension
Detection of splenomegaly in image
studies
Temporary discontinuation of
oxaliplatin. PSE produce rapid
increase in platelet count

Management

PSE, partial splenic embolization.

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thrombocytopenia due to sinusoidal injury by oxaliplatin

treatments and a hypothesis to explain this association has been

recently published [7]. Clinical and pathological analyses
following oxaliplatin-based chemotherapy regimens used as
a neoadjuvant treatment for resection of liver metastasis
showed an association between hepatic sinusoidal injury, portal
hypertension and thrombocytopenia [8].
Oxaliplatin-induced sinusoidal injury was described as
a disruption of the sinusoidal barrier leading to subsequent
deposition of collagen in the perisinusoidal space and venoocclusive fibrosis [9]. Some degree of sinusoidal injury can be
observed in up to 78% of patients who receive oxaliplatin and
these hepatic changes appear to be drug-specific, since patients
who receive other agents, such as fluorouracil, or chemo-naive
patients are clearly less affected by sinusoidal injury [9, 10].
Perisinusoidal fibrosis and veno-occlusive lesion induced by
oxaliplatin in the normal liver can lead to portal hypertension
and its complications, including esophageal or hemorrhoidal
varices with bleeding, ascites and splenomegaly with associated
thrombocytopenia [10]. Studies with a series of patients
indicate a median of 12 cycles of oxaliplatin before evidence of
portal hypertension develops [8].
The development of splenomegaly following oxaliplatinbased regimens is clearly more frequent in comparison to
fluorouracil, and the splenic index (SI) can be a surrogate
marker for portal hypertension [11]. The reported rate of
spleen size increase after oxaliplatin treatment is up to 86% [7]
and the mean increase in SI is 45.7% [11]. Single-agent
fluoropyrimidine-treated patients have a mean increase in SI of
only 16.3%, which is significantly lower. Increases in spleen size
were directly correlated with the cumulative amount of
oxaliplatin administered, and the degree of thrombocytopenia
is significantly related to the increase in spleen size. The group
from M. D. Anderson was able to detect thrombocytopenia in
28% of patients who developed splenomegaly and in only 5%
of patients who did not [7]. As increases in spleen size also
correlate with a histopathological grade of sinusoidal injury in
this study, it is logical to view splenomegaly as a marker of
portal hypertension secondary to oxaliplatin-induced
sinusoidal injury and oxaliplatin-related thrombocytopenia
resulting from splenic sequestration of platelets.

Annals of Oncology

oxaliplatin-induced immune thrombocytopenia

Many drugs have been implicated in development of immuneinduced thrombocytopenia, in which drug-dependent
antibodies react to specific platelet membrane glycoproteins
mediating accelerated platelet destruction. Although oxaliplatin
more typically causes thrombocytopenia by suppressing
hematopoiesis, this drug can also cause immune
thrombocytopenia. There are a few case reports that describe
this mechanism, and its exact incidence is not known.
Immune-mediated thrombocytopenia has been identified in 3
of 42 patients presenting allergic reactions to oxaliplatin [14],
and considering that 10% of patients exposed to oxaliplatin
experience allergic reaction [1], we can suppose that
oxaliplatin-induced immune thrombocytopenia (OIIT) affects
<1% of patients. It is noteworthy that this estimate is probably
an underestimation since patients may present with
immune-mediated thrombocytopenia in the absence of an
allergic reaction.
The basic mechanism responsible for OIIT is the induction of
antibodies that bind tightly to normal platelets only in the
presence of the drug. The exact immune pathway mediating
platelet destruction is not completely understood, but current
hypotheses suggest that naturally occurring antibodies with
weak affinity for platelet membrane antigens may be involved.
In the presence of certain drugs, such as oxaliplatin, these
antibodies can increase the strength of their interaction with
such antigens, resulting in platelet destruction and
thrombocytopenia [15]. Oxaliplatin-dependent antibodies
against glycoprotein IIb/IIIa complex have been most
commonly involved in immune-mediated thrombocytopenia
[6], although antibodies against other platelet surface
glycoproteins, such as GP Ia/IIa and GP Ib/IX, have also been
identified [16, 17]. These antibodies react strongly with
platelets only in the presence of oxaliplatin and weakly in the
presence of cisplatin but neither react in the presence of
carboplatin, 5-FU or folinic acid, indicating specificity for
oxaliplatin [6].
The main clinical characteristics of the oxaliplatin-induced
thrombocytopenia case reports were reviewed and are
summarized in supplemental Table S1 (available at Annals of
Oncology online). The usual presentation is an acute and severe
drop in platelet count leading to clinical bleeding or bruising
within a few hours, but sometimes in up to 48 h, after the
administration of a treatment cycle of oxaliplatin. The nadir of
platelet count can be as low as 2 109/l. This complication
most commonly affects female patients with advanced CRC and
prior oxaliplatin exposure, usually occurring during
retreatments. The majority of cases describe this complication
after at least a total of 12 cycles of oxaliplatin. In some cases,
thrombocytopenia can follow the onset of hypersensitivity
reactions, such as skin rash, pruritis, chills and brochospasm
[5].
Although isolated thrombocytopenia is the most common
finding in blood cell counts, acute hemolysis can be present
(Evans syndrome). In these situations, the patient can also
present back pain during infusion, chills and fever after each
cycle, and the direct antiglobulin test is usually positive
[1824]. Oxaliplatin-induced thrombocytopenia can occur in
the rare context of acute immune pancytopenia, which was

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Oxaliplatin-related hepatic injury is associated with increased

postsurgical morbidity, greater transfusion requirements and
longer hospital stays [10]. A low-preoperative platelet count in
this context and a high aspartate aminotransferase to platelet
ratio index score were shown to be good indicators to predict
sinusoidal obstruction syndrome severity [12]. Therefore,
detection of thrombocytopenia in the preoperative setting after
oxaliplatin chemotherapy might have a great clinical relevance,
especially if concomitant with splenomegaly.
Thrombocytopenia due to splenic sequestration presents as
a moderate prolonged thrombocytopenia after a median of 18
weeks of oxaliplatin-based chemotherapy [7]. The mean
platelet count after splenic sequestration due to chemotherapy
is 81 109/l [13], and patients rarely present hemorrhagic
manifestations. Splenomegaly may be associated with other
features of portal hypertension, such as ascites and esophageal
and hemorrhoidal varices, which may eventually lead to
associated bleeding. Bone marrow aspiration should not be
carried out routinely, but, if carried out, it will probably show
normal trilineage hematopoiesis [13]. Imaging studies of the
spleen have probably been already obtained for cancer evaluation
but should be requested if not carried out before. Absence of
splenomegaly should direct clinical judgment to other causes of
thrombocytopenia, including bone marrow suppression and
drug-induced immune thrombocytopenia (DIIT).
The management of these patients depends on the urge to
continue systemic treatment. After discontinuation of
oxaliplatin, platelet counts improve with time, although platelet
recovery is slower for patients with associated splenomegaly. In
this context, 23% of patients will maintain thrombocytopenia
in the first year after completion of chemotherapy and platelet
counts approach the baseline levels in 23 years after
oxaliplatin cessation [7]. There is no clinical treatment of
oxaliplatin sinusoidal injury, although there are some
suggestions that association of bevacizumab to the regimen
might decrease the development of this complication [7].
When the administration of systemic therapy is needed and is
precluded because of thrombocytopenia related to splenic
sequestration, partial splenic embolization (PSE) is a safe and
effective means to produce a rapid increase in platelet count. A
report of the experience with PSE has shown an increase in
mean platelet count from 81 109/l to 293 109/l and a mean
time to a platelet count higher than 150 109/l of 10 days [13].
Most of the patients were submitted to 5-fluorouracil and
oxaliplatin regimens before the procedure and the average time
to resume systemic treatment was 32 days. However, the
indication of PSE should be carefully considered since the
platelets of these patients are usually normofunctional, and
platelet counts >75 109/l should not preclude chemotherapy
administration. Besides, PSE involves some grade of morbidity,
such as infectious complications and prolonged hospital stays.
Other manifestations of portal hypertension should be
screened and appropriately managed, especially through an
upper gastrointestinal endoscopy to detect esophageal varices.
Prophylactic use of nonselective beta-blockers could be
considered when splenic enlargement and clinical consequences
of portal hypertension are detected. Discontinuation of
oxaliplatin also can be considered if high-risk varices or acute
variceal bleeding develops.

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4 | Jardim et al.

thrombocytopenia related to oxaliplatin

myelossupression

Oxaliplatin is associated with mild to moderate bone marrow

suppression similar to that observed with other platinum
compounds. Undoubtedly, this is the main mechanism of
oxaliplatin-related thrombocytopenia and has been reported to
occur in 45%77% of patients receiving oxaliplatin-based
regimens for the treatment of CRC [1, 2, 28]. Decreases in
platelet counts are more pronounced in patients receiving
oxaliplatin as compared with those receiving other regimes
containing 5-FU and folinic acid, with or without irinotecan
(FOLFIRI). Although thrombocytopenia in this context can
occur from direct tumor invasion in the marrow, from
myelossupression caused by distant disease or from the
combination of these mechanisms, myelossupression of
oxaliplatin is assumed to be the main culprit since direct effects
of CRC in the bone marrow are not common. The exact
mechanism through which chemotherapeutic agents affect
platelet production is not completely understood and neither is
the reason why oxaliplatin potentially affects megacaryocytes
more than other agents. Some investigators speculate that
a direct toxicity to megakaryocytic progenitors might induce
apoptosis of this population in an agent-sensitive manner [29].
The patient typically presents platelets counts <75 109/l
10 days after oxaliplatin administration. Symptomatic
thrombocytopenia, manifested by petechiae, purpura and other
mucosal bleeding such as gingival bleeding or epistaxis, is
uncommon since patients rarely present grade 4
thrombocytopenia. Routine blood cell counts usually show
concomitant anemia and neutropenia as a result of the bone
marrow suppression.
Isolated thrombocytopenia in this context is not common
and a falsely low-platelet count must be excluded. The
specimen may have been improperly drawn or underanticoagulated, leading to the presence of small clots and
resultant thrombocytopenia. The blood smear must also be
examined to exclude the possibility that platelet clumping
occurred in an EDTA-containing blood sample. In both cases,
it is recommended that the test be repeated in appropriate
conditions. If an isolated thrombocytopenia is confirmed, one
might consider other causes of oxaliplatin-related
thrombocytopenia. Bone marrow aspirates should not be
carried out routinely, unless tumor invasion or hematological
malignancies are suspected on the basis of the complete blood
count. Unlike what is seen with the other mechanisms of
oxaliplatin-related thrombocytopenia, the bone marrow
aspirates from patients with myelosuppression will show
a decrease in the number of all hematological precursors,
including megakaryocytes.
Most patients with thrombocytopenia related to bone
marrow suppression will require no specific treatment, as
their platelets counts will probably recover rapidly before the
next cycle of chemotherapy. It may be necessary to delay the
programmed treatment if a safe platelet count (75 109/l for
FOLFOX) is not reached. Patients should be given platelet
transfusions in the presence of bleeding manifestations
assigned to a very low-platelet count. The threshold for
prophylactic platelet transfusion is a common issue for
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described in two case reports [16, 25]. In these reports, acute

thrombocytopenia, hemolysis and neutropenia were mediated
through production of oxaliplatin-dependent antibodies to
platelets, red blood cells and neutrophils, respectively.
The clinical diagnosis of drug-induced thrombocytopenia is
made based on established criteria [26]. Unlike others drugs
that are used continuously, the causal relationship of
oxaliplatin-induced thrombocytopenia is easily identified due
to its intermittent use in the chemotherapy cycles, and
a rechallenge is neither necessary nor recommended. Definitive
laboratorial diagnosis can be established by detection of
oxaliplatin-dependent antibodies in patients sera carried out
by flow cytometry. Binding of an IgG antibody is detected when
the patients serum is incubated with normal group O platelets
in the presence of oxaliplatin and the fluorescence intensity is at
least twice that of a normal control [6]. The reaction does not
happen in the absence of the drug. This test in not generally
available at the time of presentation, but it may be helpful to
document oxaliplatin-induced acute thrombocytopenia and to
discontinue the drug. When the test is not available, clinical
judgment may be sufficient to establish the diagnosis.
Additional tests such as peripheral blood smear examination,
direct antiglobulin test and detection of antibodies to
neutrophils are also helpful in assessing immune pancytopenia
and Evans syndrome. Bone marrow aspirates, if carried out, will
probably show the presence of adequate or increased numbers
of megakaryocytes [17].
There is no specific treatment for most of the patients with
OITT. Platelet count usually recovers in a few days after
discontinuation of the oxaliplatin, which is the main
therapeutic maneuver. The patient should not receive
oxaliplatin again and should carry a medical alert to remember
this fact, since drug sensitivity usually persists indefinitely [6].
Subsequent treatments with other chemotherapy agents and
biologic agents are possible. For instance, some case reports
have shown that the administration of 5-FU, folinic acid,
irinotecan and cetuximab could be carried out without
consequences. For patients with major bleeding, appropriate
hematologic support, including platelet transfusion, may be
necessary to keep the platelet count at safe numbers. A
posttransfusion platelet increase should be checked in 1 h
after the procedure to ensure that a satisfactory enhancement
has occurred.
The value of steroids in this context is uncertain. The
approaches described in previous cases varied between no
steroid administration to pulses of methylprednisolone [17].
Whether steroids altered the clinical evolution of these cases is
unknown. Since idiopathic immune thrombocytopenic
purpura cannot initially be distinguished from OIIT, steroids
may be justified. One case report describes a steadily increase in
platelet counts after administration of i.v. immune globulin
[27]. Unlike other causes of oxaliplatin-related
thrombocytopenia, recovery is usually fast and complete after
discontinuation of the drug, although many patients need
repeated transfusions until they can maintain safe numbers on
their own.

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speculative mechanisms

Oxaliplatin treatment can lead to acute thrombocytopenia with

hemolysis mimicking the hemolytic uremic syndrome (HUS)
[38, 39]. In this context, patients also present acute onset of
back pain, dark urine and oliguria. Investigations show an
elevation of lactic dehydrogenase and indirect bilirubin levels,
a drop in concentrations of haptoglobin and blood films
commonly show circulating fragmented red blood cells
(schizocytes). Drug-induced thrombotic microangiopathy may
be related to an immune-mediated phenomenon involving
ADAMTS13 metalloprotease or to a direct endothelial injury,
both following certain drug exposures [40]. Thrombotic
microangiopathies, such as HUS, can be present in patients
with DIIT for reasons that are poorly understood. There are
some associations of these complications in patients receiving
quinine, a drug known to be related to DIIT [41, 42].
In the absence of oxaliplatin-induced antibodies, one may
consider HUS as a distinct mechanism of oxaliplatin-related
thrombocytopenia. In clinical practice, the differential
diagnosis is troublesome. There are few reports of possible HUS
following oxaliplatin administration. In one of them, neither
kidney biopsy nor detection of oxaliplatin-dependent
antibodies against erythrocytes and platelets were carried out
and the diagnosis remains speculative [38]. In the other report,
although hemolysis, thrombocytopenia and acute renal failure
were present, kidney biopsy did not confirm thrombotic
microangiopathy [39]. Fatal HUS has also been reported in

a patient with metastatic pancreatic adenocarcinoma following

administration of gemcitabine and oxaliplatin [43]. Other
chemotherapy agents, such as mitomycin-C and gemcitabine,
have been implicated as causal agents of thrombotic
microangiopathy in a cumulative dose-dependent manner [40,
44]. However, the relation of oxaliplatin to drug-induced
thrombotic microangiopathy is not completely established.
Therefore, thrombocytopenia in this context could be
immune-mediated and a negative oxaliplatin antibody test and
a kidney biopsy consistent with HUS are needed to begin
treatment and that could include fresh frozen plasma and
large-volume plasmapheresis.

conclusions
Oxaliplatin-related thrombocytopenia can prevent the
administration of the optimal dose and schedule of this
important chemotherapy agent and limit its benefits in the
adjuvant or metastatic setting. Mild to moderate bone marrow
suppression is the main cause of thrombocytopenia during and
after treatment with oxaliplatin. In this setting, patients present
thrombocytopenia concomitant to anemia and neutropenia
usually 12 weeks after treatment. Therapeutic approaches will
include dose delays or reduction and consideration of plateletstimulating agents. However, novel mechanisms of oxaliplatinrelated thrombocytopenia should promptly be recognized by
physicians and include an immune-dependent mechanism, as
well as portal hypertension related to sinusoidal injury yielding
splenic sequestration of platelets.
OIIT usually presents a sudden and isolated drop in platelet
counts minutes to hours after oxaliplatin administration,
leading to acute hemorrhagic events. Female patients with
advanced CRC and prior oxaliplatin exposure are more likely to
develop this consequence. Prompt immunological testing
documenting oxaliplatin-mediated platelet destruction leads
to definitive diagnosis. Platelets counts will improve after
discontinuation of treatment and transfusions may be necessary
during the acute phase. Other measures such as corticoid or
immunoglobulin administration are controversial and patients
with documented OIIT should not be rechallenged with
oxaliplatin.
Hepatic sinusoidal injury is a well-known complication of
oxaliplatin treatment and can lead to portal hypertension and
hypersplenism. Thrombocytopenia in this setting demonstrates
a different natural history, with moderate but prolonged
reductions in platelet counts. Splenomegaly and other
complications of portal hypertension are recognized in these
patients. Platelet recovery is slow and usually takes 23 years to
be complete after treatment discontinuation. When a fast
platelet recovery is wanted, splenic embolization might be
considered as a therapeutic measure.
An improvement in the recognition of these mechanisms of
oxaliplatin-related thrombocytopenia will permit a better
documentation of them and help to understand possible risk
factors associated with this complication in different settings.
This information may help the development of new preventive
and therapeutic approaches and allow for a more rational
management of cancer patients treated with oxaliplatin that
present thrombocytopenia.

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count, which may vary according to other conditions such as

infection or other hemostatic abnormalities [30]. In the
absence of risk factors for hemorrhage, a threshold of 10 109
platelets/l might be safely used without an increase in the
bleeding risk and has been recommended by the American
Society of Clinical Oncology guidelines [31].
Currently, one area of great interest is the development of
thrombopoietic growth factors for primary or secondary
prophylaxis of chemotherapy-induced thrombocytopenia. In
clinical studies, IL-11 (oprelvekin, Neumega
, Wyeth,
Pharmaceuticals Inc, Philadelphia, PA) has modestly reduced
the extend of thrombocytopenia and the need of platelet
transfusion [32, 33], being the only agent currently approved
by the USA FDA for chemotherapy-induced
thrombocytopenia. However, the use of this agent is limited
by its narrow therapeutic index. Administration of
recombinant thrombopoietins (TPOs) to patients receiving
chemotherapy with platinum compounds has been shown to
induce enhanced platelet recovery [34, 35], but the
development of these agents has been abandoned because
a high incidence of antibody development leading to
thrombocytopenia [36] and some concerns about
hematological malignancies following administration of
megakaryocyte growth factor to healthy volunteers [37].
First-generation TPO receptor agonists are currently being
evaluated for chemotherapy-induced thrombocytopenia,
including peptide (romiplostim) and nonpeptide
(eltrombopag) mimetics. They might be a future option for
oxaliplatin-treated patients, especially in cases when
maintaining the dose intensity can translate into better
clinical outcomes.

review
acknowledgements
DLFJ and PMGH contributed to the concept and design of the
article. DLFJ and CAR undertook the researching and writing
of this report. PMGH, YASN and VGR were involved in
revising it critically for important intellectual data before final
approval. The authors also thank C.H.Collins for helpful
discussions and suggestions. All authors read and approved the
final manuscript.

disclosure
The authors have declared no conflicts of interest associated
with this manuscript and no external source of funding was
used.

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