BLOOD MANAGEMENT
Romiplostim in the management of the thrombocytopenic
surgical patient
Ariela L. Marshall,1,2 Katayoon Goodarzi,1 and David J. Kuter1
BACKGROUND: Thrombopoietin receptor agonists
increase platelet (PLT) counts and are approved for the
treatment of chronic immune thrombocytopenia (ITP).
These agents may also be useful for the management of
thrombocytopenia in patients requiring surgical
procedures.
STUDY DESIGN AND METHODS: We conducted a
retrospective review of patients with thrombocytopenia
(baseline PLT count, <150 3 109/L) who received
romiplostim before planned operative procedures. We
characterized patient demographics, dosing and duration
of romiplostim use, success in achieving PLT counts high
enough for surgery, and clinical outcomes.
RESULTS: Eighteen patients underwent a total of 22
operative procedures, including three Jehovahs
Witnesses who underwent five procedures. Etiologies of
thrombocytopenia included mild ITP (not on romiplostim
at baseline), liver disease, hematologic malignancy, and
drug-related thrombocytopenia. Median PLT count at
romiplostim initiation was 47 3 109/L (range, 11 3 109-
120 3 109/L). All patients experienced a PLT count
increase over a median of 4 weeks; median PLT count at
surgery was 144 3 109/L (range, 28 3 109-370 3 109/L).
PLT counts increase to more than 150 3 109/L in four of
five Jehovahs Witness patients by the time of surgery.
There were no surgical delays or cancellations due to
thrombocytopenia. Four bleeding events occurred; none
were fatal and none occurred at a PLT count of fewer
than 80 3 109/L. No definitive thromboembolic events
occurred.
CONCLUSION: Romiplostim successfully increased
preoperative PLT counts allowing operative interventions,
was well tolerated, did not lead to any significant
thromboembolic events, and avoided the need for
transfusion. Romiplostim may be of clinical utility in the
preoperative management of thrombocytopenic patients,
especially those unable to receive or unresponsive to
PLT transfusion.
T
hrombocytopenia, especially when severe, is
associated with increased risk of bleeding and
may prevent patients from undergoing elective
or emergent surgical procedures. In general,
patients with platelet (PLT) counts of fewer than 50 3
109/L are considered to be at increased risk of bleeding
during most general surgical procedures.1 Recent evi-
dence suggests that patients with moderate to severe
thrombocytopenia (<100 3 109/L) who undergo surgical
procedures are at significantly increased risk of requiring
blood transfusion and have an increased 30-day postpro-
cedure mortality.2 Several guidelines suggest the use of
preoperative PLT targets of 50 3 109 to 80 3 109/L for
most nonneuraxial surgical procedures (depending on the
invasiveness of the procedure) and 100 3 109/L for neuro-
surgical procedures.3,4
PLT production is regulated by the glycoprotein
thrombopoietin (TPO), which is synthesized primarily in
the liver (and in smaller amounts in the kidney and mar-
row). TPO acts via binding to its receptor (c-Mpl) on meg-
akaryocytes and their precursors, resulting in downstream
signaling, which ultimately leads to PLT production.5 The
development of thrombopoietic growth factors represents
a major advancement in the treatment of thrombocytope-
nia. Early studies with recombinant TPO molecules
(recombinant human TPO and pegylated recombinant
human megakaryocyte growth and development factor)
showed their effectiveness in increasing PLT counts in
ABBREVIATIONS: ITP 5 immune thrombocytopenia; TPO 5
thrombopoietin.
From the 1Department of Hematology, Massachusetts General
Hospital; and the 2Department of Hematology and Medical
Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Address reprint requests to: Ariela Marshall, MD, 55 Fruit
Street, Professional Office Building Room 221, Boston, MA
02114; e-mail address: ariela_marshall@dfci.harvard.edu.
Received for publication January 30, 2015; revision
received April 13, 2015; and accepted April 20, 2015.
doi:10.1111/trf.13181
C 2015 AABB
V
TRANSFUSION 2015;55;25052510
Volume 55, October 2015 TRANSFUSION 2505
MARSHALL ET AL.

several settings.6-8 However, further development of these

molecules was stopped because patients developed neu- TABLE 1. Patient and procedural demographics*
tralizing antibodies.9 The TPO receptor agonists were Age (years) 61 (47-74)
developed to evade this problem.10 Sex
Romiplostim is a peptide TPO receptor agonist that Male 10 (56)
Female 8 (44)
binds to and activates the TPO receptor, leading to an Etiology of thrombocytopenia (some
increase in PLT count. Romiplostim is currently Food and patients with more than etiology)
Drug Administration approved for the treatment of chronic Mild ITP 8
Liver disease 12
immune thrombocytopenia (ITP). Early work showed that Hepatitis C 5
many patients with ITP could achieve a PLT count of at Hepatitis B 2
least 50 3 109/L (or higher) in a dose-dependent fashion.11 Alcoholic cirrhosis 2
Hepatocellular carcinoma 2
A subsequent randomized placebo-controlled trial in Steatohepatitis 1
patients with chronic ITP found that the majority of Hematologic malignancy 4
patients responded to romiplostim over a period of Lymphoma 2
Myelodysplastic syndrome 1
approximately 24 weeks without significant adverse events Multiple myeloma 1
or the development of anti-TPO or anti-romiplostim anti- Drug related 3
bodies.12 Ongoing data continue to show that patients Chemotherapy 2
Antibiotic related 1
treated with romiplostim for up to 156 weeks continue to Procedure planned
benefit in terms of sustained increases in PLT counts.13,14 Orthopedic 6 (27)
Romiplostim has also been shown to increase PLT counts Total hip replacement 3
Total knee replacement 1
in patients with myelodysplastic syndrome.15,16 Reduction or fixation 1
Romiplostim may be useful in a variety of other clini- Spinal fusion 1
cal settings where thrombocytopenia complicates care, Cardiac 4 (18)
Open cardiac surgery 3
including before surgical procedures. Currently, data are Angioplasty and stenting 1
limited regarding the use of romiplostim in the preopera- Gastrointestinal 5 (23)
tive setting. Clinicians at our institution have empirically Cholecystectomy 2
Upper endoscopy or colonoscopy 2
used romiplostim for management of preoperative throm- Liver biopsy 1
bocytopenia. We examined the indications for romiplos- Other 7 (32)
tim use and dosing patterns as well as the surgical Biopsy of a mass 2
Dental extraction 1
outcomes in these patients to establish the general utility Eyelid resection 1
of romiplostim in this setting and explore opportunities Lung resection 1
for further prospective investigations. Prostate surgery 1
Transarterial chemoembolization 1
* Data are reported as median (range), number (%), or number.
MATERIALS AND METHODS
Study population
This study was approved by the institutional review board within 30 days of the procedure, number of perioperative
of the Massachusetts General Hospital. Between 2010 and PLT and red blood cell (RBC) transfusions, any delays or
2014, all adult patients (18 years of age or older) who cancellations of surgery due to thrombocytopenia, and
received romiplostim were identified via the electronic date and cause of death or last known date alive.
medical record system and pharmacy records. All those
who received romiplostim for the management of preoper- Statistical analysis
ative thrombocytopenia were selected for further analysis. Analysis was conducted with computer software (Micro-
soft Excel 2010, Microsoft Corp., Redmond, WA; and
Data collection GraphPad Prism, GraphPad, Inc., San Diego, CA).
Baseline data included patient age and sex, the cause(s) of
thrombocytopenia, the type of procedure, and PLT count RESULTS
before administration of romiplostim. Treatment data
included date of romiplostim initiation; dose at initiation; Patient demographics
and PLT count at initiation as well as weekly PLT counts, Of 74 patients who received romiplostim, 18 did so for the
dates and amounts of any dose changes, date of romiplos- purpose of increasing the PLT count before a surgical pro-
tim discontinuation, and dose and PLT count at the time cedure. Patient demographics and other baseline data are
of discontinuation. Clinical information included proce- reported in Table 1. Some patients had more than one
dures performed, any bleeding or thromboembolic events cause of thrombocytopenia. Procedures performed

2506 TRANSFUSION Volume 55, October 2015


Fig. 1. Pre- and postromiplostim PLT counts. Median PLT
counts (625%-75% IQR) before romiplostim treatment and
at the time of the procedure.
included six orthopedic procedures, four cardiac proce-
dures, five gastrointestinal procedures, and seven other
procedures. Of the 18 subjects, 11 had PLT counts of fewer
than 50 3 109/L at baseline, and all but two subjects had
baseline PLT counts of less than 100 3 109/L. Three
patients were Jehovahs Witnesses (including both patients
with baseline PLT counts of more than 100 3 109/L).
These three patients underwent five procedures: cardiac
surgery, two orthopedic surgeries, a gastrointestinal pro-
cedure, and a cholecystectomy.
Romiplostim dosing and PLT response
Romiplostim was started at a median dose of 2.5 (range,
1-7.5) mg/kg and the median duration of treatment before
the procedure was 4.2 (range, 0.6-50) weeks. At the time of
surgery, the median dose of romiplostim was 3 (range, 1-
6) mg/kg. Dose was changed on average once over the
treatment period; doses were increased for seven proce-
dures and decreased for two procedures. The median PLT
count at romiplostim initiation was 47 3 109/L (range, 11
3 109-119 3 109/L) and the median PLT count at the time
of surgery was 144 3 109/L (range, 28 3 109-370 3 109/L),
shown in Fig. 1. All patients experienced an increase in
PLT counts and the median increase was 98 3 109/L
(range, 17 3 109-252 3 109/L). Baseline PLT count pre-
dicted PLT count achieved at the time of surgery (r 5 0.73,
p 5 0.0003). For the three Jehovahs Witness patients, the
preromiplostim PLT counts of 45 3 109, 49 3 109, 114 3
109, 119 3 109, and 120 3 109/L increased to 107 3 109,
140 3 109, 164 3 109, 235 3 109, and 370 3 109/L, respec-
tively, by the time of surgery.
ROMIPLOSTIM IN THROMBOCYTOPENIC SURGICAL PATIENTS
Figure 2 illustrates the clinical course of one repre-
sentative patient. Few patients experienced a precipitous
decrease in PLT count after romiplostim discontinuation.
At least one PLT count after discontinuation was available
for 15 of the 21 cases. In those 15 cases, the median PLT
count at romiplostim initiation was 47 3 109/L and the
median postdiscontinuation PLT count (drawn at a
median of 6 days after discontinuation) was 140 3 109/L.
While many of these patients did have a lower PLT count
at a median of 6 days after discontinuation than on the
day of discontinuation, only three patients had a decrease
of greater than 50 3 109/L between the time of discontin-
uation and the first measured PLT count after discontinu-
ation (one patient from 184 3 109 to 125 3 109/L, the
second from 141 3 109 to 82 3 109/L, and the last from
140 3 109 to 31 3 109/L).
Procedure outcomes
Clinical outcomes during treatment and for the 30 days
after the procedure are presented in Table 2. There were
no surgical delays or cancellations due to thrombocytope-
nia. Four postoperative bleeding episodes occurred at PLT
counts ranging from 82 3 109 to 185 3 109/L; three of the
four occurred within the first 2 postoperative days. Over-
all, four patients received blood product transfusions. One
patient received 2 units of PLTs and 1 unit of RBCs intra-
operatively during a spinal fusion surgery (preoperative
PLT count of 99 3 109/L), one patient received 1 unit of
PLTs during a right lobectomy and pleurectomy and resec-
tion of lung cancer (preoperative PLT count 184 3 109/L),
one patient successfully underwent aortic valve replace-
ment but developed cardiac tamponade several days later,
and received 1 unit of PLTs and a total of 7 units of RBCs
for management including reexploratory surgery (PLT
count 41 3 109/L at the time of transfusion), and one
patient developed a thigh hematoma after total hip
arthroplasty and received 5 units of RBCs but no PLT
transfusions (preoperative PLT count 164 3 109/L).
Although one patient developed a Foley catheterassoci-
ated clot after prostate surgery (PLT count 48 3 109/L at
the time of the clot), there were no other thromboembolic
events recorded during the time of romiplostim adminis-
tration and for up to 30 days after the last dose. None of
the Jehovahs Witness patients had a bleeding event or
thrombotic event.
DISCUSSION
Thrombocytopenia is a common clinical problem which
in many patients results from mild ITP, liver disease, sple-
nic sequestration, or underlying marrow dysfunction.
Despite the absence of clinical trials on this matter, many
surgeons are reluctant to perform procedures on patients
with PLT counts under 50 3 109/L and, if performed, such
Volume 55, October 2015 TRANSFUSION 2507
MARSHALL ET AL.

Fig. 2. Example of preoperative romiplostim administration. A Jehovahs Witness patient with known cirrhosis and a baseline
PLT count of 51 3 109/L was started on romiplostim at a dose of 2 mg/kg (Day 0). PLT count at the time of the first dose was 49
3 109/L. On Day 7, the PLT count was 51 3 109/L and the romiplostim dose was increased to 4 mg/kg. She received a second
dose of romiplostim at 4 mg/kg on Day 13 (PLT count of 98 3 109/L), a third dose on Day 20 (PLT count of 179 3 109/L), and a
fourth and final dose on Day 27 (PLT count of 140 3 109/L). This was followed by an uncomplicated cholecystectomy on Day 29
with a postoperative PLT count of 114 3 109/L on Day 34. The same patient required an elective colonoscopy the following year.
She was started at the prior successful dose of romiplostim, 4 mg/kg, on Day 0 with PLT count at that time of 45 3 109/L. On
Day 7, PLT count was 61 3 109/L and she received a dose of 4 mg/kg. On Day 13, PLT count was 172 3 109/L and she received 4
mg/kg. On Day 20 PLT count was 163 3 109/L and she received 4 mg/kg, on Day 27 PLT count was 121 3 109/L and she received 4
mg/kg, and on Day 34 PLT count was 107 3 109/L and she again received 4 mg/kg. She underwent an uncomplicated colonoscopy
on Day 42 without further administration of romiplostim.

procedures are rarely performed without PLT transfusion.
In this setting many thrombocytopenic Jehovahs Witness
patients are refused surgery. We reviewed the clinical
course of 18 patients with thrombocytopenia resulting
from a variety of causes including ITP and liver disease
who were treated with romiplostim to increase their pre-
operative PLT count. All patients showed an increase in
PLT count between the time of initiation of romiplostim
and the time of surgery, and baseline PLT count was corre-
lated with increase in PLT count achieved by the time of
surgery. All patients were able to undergo a total of 22 pro-
cedures including major orthopedic and cardiac surgeries
without delays or cancellations due to thrombocytopenia.
Bleeding was infrequent and most patients were able to
avoid PLT transfusion.
Treatment with the TPO receptor agonist eltrombo-
pag has previously been shown to increase the PLT count
within 4 weeks in patients with hepatitis Crelated throm-
bocytopenia, allowing treatment with antiviral therapy.17
Eltrombopag has further been used to increase PLT counts
in patients with cirrhosis and thrombocytopenia before
surgery, leading to a significant reduction in the number
of perioperative PLT transfusions but also a relative
increase in the frequency of portal venous thromboses,
which ultimately resulted in early study discontinuation.18
Although this study was incomplete in not using pretreat-
ment ultrasound to assess the portal veins, there has been
concern about the potential thrombogenic effects of TPO
agents in the perioperative setting. However, eltrombopag
was used successfully before tympanoplasty in a pediatric
patient with MYH9-related thrombocytopenia and
boosted PLT counts from 10 3 109 to 70 3 109/L over a 4-
week period and obviated the need for PLT transfusions
without any reported thrombotic events.19 In addition, in

2508 TRANSFUSION Volume 55, October 2015


TABLE 2. Clinical outcomes of patients receiving romiplostim
Perioperative bleeding
Type
Thigh hematoma
Hematemesis
Melena
Oozing after tooth extraction
Perioperative thromboembolic event
Location
Foley catheter associated
Perioperative and postoperative PLT transfusions
Type of surgery
Spinal fusion
Right lobectomy or pleurectomy
Reexploration after cardiac surgery
a series of 35 patients with cirrhosis and thrombocytope-
nia related to hepatitis C who underwent a variety of sur-
gical procedures (including orthopedic surgery, hernia
repair, and cataract surgeries), romiplostim produced an
increase in PLT counts in all patients without any reported
thrombotic events within 60 postoperative days.20
The results reported here expand our knowledge
regarding the utility of TPO receptor agonists in the pre-
operative setting with regard to the dosing and timing of
this treatment. Romiplostim increased PLT counts in all
patients with a wide variety of thrombocytopenic disor-
ders and allowed them all to undergo surgical procedures
with minimal delay. The median dose of 3 mg/kg was less
than that generally required for patients with ITP (4-5 mg/
kg) and patients achieved a median PLT count increase of
almost 100 3 109/L in a median of 4 weeks. Few patients
required PLT transfusions or bled. While other studies
have evaluated patients with a single underlying etiology
of thrombocytopenia (i.e., liver disease), this series exam-
ined use in the setting of thrombocytopenia related to sev-
eral causes. Additionally, patients underwent a large
variety of procedures (including major procedures such as
cardiac and thoracic surgeries). Of the five procedures
performed on Jehovahs Witness patients, all were done at
PLT counts of more than 100 3 109/L and none were com-
plicated by bleeding events.
The limitations of this study include those of any retro-
spective study. Selection bias may have influenced the
patient population who received romiplostim. The results
may not be generalizable to all thrombocytopenic patients
requiring surgery. However, this population with underlying
chronic mild ITP and liver disease is likely fairly representa-
tive of the overall population of thrombocytopenic patients
who would be considered for surgical procedures who
require an increase in PLT counts before the procedure.
Preoperative romiplostim administration may also
reduce the need for transfusion. Although lacking a con-
ROMIPLOSTIM IN THROMBOCYTOPENIC SURGICAL PATIENTS
PLT count at time Postoperative day on
of bleed (3109/L) which bleed occurred
185 1
98 2
88 19
82 1
PLT count at time Postoperative day on
of clot (3109/L) which clot occurred
48 1
PLT count (3109/L) Number of units transfused
99 2
184 1
41 1
trol group not treated with romiplostim, most of the
patients in this study would likely have received prophy-
lactic PLT transfusion for their procedures, had they even
been deemed eligible for the procedure.
Administration of both recombinant TPO and TPO
receptor agonists has been associated with some potential
complications including reticulin fibrosis and thrombosis.
Some patients on romiplostim developed a dose-
dependent increase in marrow reticulin fibrosis,21,22 but
the fibrosis decreased or fully reversed upon discontinua-
tion of the drug. The limited duration of administration
necessary for preoperative use seems to preclude signifi-
cant concern regarding fibrosis. Furthermore, even long-
term use of romiplostim has been associated with an
acceptable safety profile in the setting of chronic ITP.13,14
There may be some concern that using a stimulating
agent in the already prothrombotic setting of surgery
especially orthopedic, cardiac, or other high-risk proce-
duresmay potentiate the risk of thrombosis in these
patients. However, the one Foley catheterrelated clot in
our series was likely not related to romiplostim adminis-
tration, and no other thromboembolic events occurred.
While patients with ITP and liver disease are certainly at
increased risk for perioperative thrombotic events, we did
not find any significant risk of thrombosis in these
patients. Close monitoring for clinical signs of thrombosis
and appropriate use of prophylaxis (pharmacologic if pos-
sible, especially as these patients all achieved PLT counts
high enough to undergo procedures and therefore cer-
tainly high enough for pharmacologic prophylaxis) should
be pursued, as for all surgical patients.
In conclusion, we have found that romiplostim was
effective in increasing PLT counts in patients with throm-
bocytopenia related to chronic ITP or liver disease such
that these patients were able to undergo a variety of
planned surgical procedures including those with high
risk of bleeding (cardiac and orthopedic procedures).
Volume 55, October 2015 TRANSFUSION 2509
MARSHALL ET AL.
Most avoided the use of PLT transfusion. This may be a
major supportive care treatment for thrombocytopenic
Jehovahs Witness patients as well as for patients with sig-
nificantly low PLT counts at baseline, for whom certain
surgical procedures might otherwise be precluded. The
success of this treatment modality suggests a role for fur-
ther evaluation in the setting of a clinical trial as well as
the assessment of the potential cost-effectiveness of this
form of preoperative treatment.
ACKNOWLEDGMENTS
AM designed the research study, collected the data, analyzed the
data, and wrote/revised the manuscript; KG designed the
research study and critically revised the manuscript; and DK
designed the research study and critically revised the manuscript.
CONFLICT OF INTEREST
The authors have disclosed no conflicts of interest.
REFERENCES
1. Kuter DJ, Bussel JB, Lyons RM, et al. General aspects of
thrombocytopenia, platelet transfusions, and thrombo-
poietic growth factors. In: Kitchens CS, Kessler CM, Konkle
BA, editors. Consultative hemostasis and thrombosis. Phila-
delphia: Elsevier Saunders; 2013. p 103-116.
2. Glance LG, Blumberg N, Eaton MP, et al. Preoperative
thrombocytopenia and postoperative outcomes after non-
cardiac surgery. Anesthesiology 2014;120:62-75.
3. Provan D, Stasi R, Newland AC, et al. International consen-
sus report on the investigation and management of primary
immune thrombocytopenia. Blood 2010;115:168-86.
4. Kaufman RM, Djulbegovic B, Gernsheimer T, et al. Platelet
transfusion: a clinical practice guideline from the AABB. Ann
Intern Med 2015;162:205-13.
5. Kaushansky K. Thrombopoietin: the primary regulator of
platelet production. Blood 1995;86:419-31.
6. Vadhan-Raj S, Verschraegen CF, Bueso-Ramos C, et al.
Recombinant human thrombopoietin attenuates
carboplatin-induced severe thrombocytopenia and the need
for platelet transfusions in patients with gynecologic cancer.
Ann Intern Med 2000;132:364-8.
7. Harker LA, Carter RA, Marzec UM, et al. Correction of
thrombocytopenia and ineffective platelet production in
patients infected with human immunodeficiency virus (HIV)
by PEG-rHuMGDF therapy. Blood 1998;92:707a.
8. Kuter DJ, Goodnough LT, Romo J, et al. Thrombopoietin
therapy increases platelet yields in healthy platelet donors.
Blood 2001;98:1339-45.
2510 TRANSFUSION Volume 55, October 2015
9. Li J, Yang C, Xia Y, et al. Thrombocytopenia caused by the
development of antibodies to thrombopoietin. Blood 2001;
98:3241-8.
10. Kuter DJ. Milestones in understanding platelet production: a
historical overview. Br J Haematol 2014;165:248-58.
11. Bussel JB, Kuter DJ, George JN, et al. AMG 531, a
thrombopoiesis-stimulating protein, for chronic ITP. N Engl
J Med 2006;355:1672-81.
12. Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim
in patients with chronic immune thrombocytopenic pur-
pura: a double-blind randomised controlled trial. Lancet
2008;371:395-403.
13. Bussel JB, Kuter DJ, Pullarkat V, et al. Safety and
efficacy of long-term treatment with romiplostim in
thrombocytopenic patients with chronic ITP. Blood 2009;
113:2161-71.
14. Kuter DJ, Bussel JB, Newland A, et al. Long-term treatment
with romiplostim in patients with chronic immune throm-
bocytopenia: safety and efficacy. Br J Haematol 2013;161:
411-23.
15. Kantarjian H, Fenaux P, Sekeres MA, et al. Safety and efficacy
of romiplostim in patients with lower-risk myelodysplastic
syndrome and thrombocytopenia. J Clin Oncol 2010;28:
437-44.
16. Giagounidis A, Mufti GJ, Fenaux P, et al. Results of a
randomized, double-blind study of romiplostim versus
placebo in patients with low/intermediate-1-risk myelo-
dysplastic syndrome and thrombocytopenia. Cancer 2014;
120:1838-46.
17. McHutchison JG, Dusheiko G, Shiffman ML, et al.
Eltrombopag for thrombocytopenia in patients with cir-
rhosis associated with hepatitis C. N Engl J Med 2007;
357:2227-36.
18. Afdhal NH, Giannini EG, Tayyab G, et al. Eltrombopag before
procedures in patients with cirrhosis and thrombocytopenia.
N Engl J Med 2012;367:716-24.
19. Favier R, Feriel J, Favier M, et al. First successful use of
eltrombopag before surgery in a child with MYH9-related
thrombocytopenia. Pediatrics 2013;132:e793-5.
20. Moussa MM, Mowafy N. Preoperative use of romiplostim
in thrombocytopenic patients with chronic hepatitis C
and liver cirrhosis. J Gastroenterol Hepatol 2013;28:335-
41.
21. Douglas VK, Tallman MS, Cripe LD, et al. Thrombopoietin
administered during induction chemotherapy to patients
with acute myeloid leukemia induces transient morphologic
changes that may resemble chronic myeloproliferative disor-
ders. Am J Clin Pathol 2002;117:844-50.
22. Kuter DJ, Mufti GJ, Bain BJ, et al. Evaluation of bone marrow
reticulin formation in chronic immune thrombocytopenia
patients treated with romiplostim. Blood 2009;114:
3748-56.