REFRACTORY ITP SURVEY:
- Case Vignettes:
- A 3 year-old previously healthy F presents with diffuse bruising,
petechiae, and a few wet purpura over the oral mucosa. She is found
to have isolated thrombocytopenia (4k), with platelet size variance
on smear review (including large and giant platelets), and some
reactive-appearing lymphocytes, but no blasts or other morphological
abnormalities consistent with a diagnosis of Acute ITP. Parents are
extremely anxious about ongoing injuries for this active toddler,
and also live ~3 hours from the nearest major
medical center. Therefore, the decision is made to proceed with
frontline platelet-directed therapy. She receives IVIG 1 g/kg, and
although cutaneous symptoms are slightly improved ~5
days later, platelet count remains <10k. She is started on
oral prednisone 4 mg/kg/day divided BID at this point; and CBC one
week later reveals platelet count remaining fairly unchanged, at
12k. She has had no major bleeding events, but continues to have
some mild intermittent wet purpura, and diffuse cutaneous symptoms;
with significant anxiety from parents. Blood type is A-; so the
decision is made to proceed with a second dose of IVIG 1 g/kg
following which, symptoms briefly improve, but return to baseline
within 1 week, at the time CBC reveals platelet count remaining at
10k.
- Would you consider this refractory ITP? Yes/No
- Would you work this patient up for alternate etiologies of
thrombocytopenia at this time (vs. continued observation, or
second-line management)? Yes/No
- If so, what additional work-up would you obtain? (check all that
apply)
- HIV
- Hepatitis
- H. Pylori
- CMV and/or EBV
- ANA Profile
- Immunoglobulins
- Lymphocyte subsets
- Complement levels
- ALPS work-up
This patient continues to have cutaneous symptoms and platelet count
fluctuating between 10k and 30k over the next several months, but no
major bleeding events. After ~1 year, parents feel that
patient’s quality of life is suffering significantly (due to activity
and environment restrictions), and they would like to be able to send
her to pre-K safely, without major restrictions. Therefore, the decision
is made to initiate second-line therapy, and parents choose TPO-RA
therapy. After several weeks of therapy, patient shows minimal platelet
response with romiplostim; and is transitioned to eltrombopag therapy.
Again, cutaneous symptoms are improved, but platelet count remains
fairly unchanged (<50k).
Would you consider this refractory ITP? Yes/No
Would you work this patient up for alternate etiologies of
thrombocytopenia at this time (vs. continued observation, or
second-line management)? Yes/No
If so, what additional work-up would you obtain? (check all that
apply)
- HIV
- Hepatitis
- H. Pylori
- CMV and/or EBV
- ANA Profile
- Immunoglobulins
- Lymphocyte subsets
- Complement levels
- ALPS work-up
Given continued concern from parents, lifestyle restrictions, and
intermittent minor bleeding events, the decision is made to continue
pursuing other potential second-line therapies. She is treated with
rituximab (375 mg/m2/week x4), and shows an excellent clinical and
platelet response (100k – 200k range).
Would you consider this refractory ITP? Yes/No
Would you work this patient up for alternate etiologies of
thrombocytopenia at this time (vs. continued observation, or
second-line management)? Yes/No
If so, what additional work-up would you obtain? (check all that
apply)
- HIV
- Hepatitis
- H. Pylori
- CMV and/or EBV
- ANA Profile
- Immunoglobulins
- Lymphocyte subsets
- Complement levels
- ALPS work-up
After ~9 months, patient’s platelet counts again begin
trending downward, eventually to her former baseline
~10k – 30k; and similar clinical symptoms return. The
decision is made to proceed with splenectomy at this point, and patient
responds very well with post-surgical platelet count to a peak of
~500k.
Would you consider this refractory ITP? Yes/No
Would you work this patient up for alternate etiologies of
thrombocytopenia at this time (vs. continued observation, or
second-line management)? Yes/No
If so, what additional work-up would you obtain? (check all that
apply)
- HIV
- Hepatitis
- H. Pylori
- CMV and/or EBV
- ANA Profile
- Immunoglobulins
- Lymphocyte subsets
- Complement levels
- ALPS work-up
- A 4 year-old previously healthy M presents with diffuse bruising and
petechiae, along with recent epistaxis episodes, all resolving in
<5 minutes. He is found to have isolated thrombocytopenia
(6k), with platelet size variance on smear review (including large
and giant platelets), and some reactive-appearing lymphocytes, but
no blasts or other morphological abnormalities consistent with a
diagnosis of Acute ITP. Given his lack of significant bleeding
symptomatology, and parental comfort level, the decision is made to
proceed with thorough education, return precautions, and
observational management. Patient returns in ~2-3
weeks, with no major bleeding events or concerns, and platelet count
remaining <10k. Observation is continued. However,
~2 weeks later, patient presents with hematuria, and
is admitted for platelet-directed therapy. IVIG 1 g/kg is
administered, but platelet count remains ~unchanged
over the subsequent 48 hours, and patient’s hematuria persists, with
Hgb dropping from 11.8 to 9 g/dL. IV methylprednisolone is
initiated, at 30 mg/kg (max 1 g) IV daily doses; but the following
day, patient’s hematuria has not improved, and Hgb is now 8 g/dL.
Patient is DAT negative, blood type O+, and has no evidence of renal
dysfunction. Therefore, anti-D immune globulin 75 mcg/kg is
administered; but again, patient’s platelet count remains
<10k over the next ~36 hours (on continued
methylprednisolone as well), with Hgb trending down to
~7 g/dL. Romiplostim 10 mcg/kg is administered x1,
and patient is planned for slow platelet drip/transfusion.
- Would you consider this refractory ITP? Yes/No
- Would you work this patient up for alternate etiologies of
thrombocytopenia at this time (+/- continued emergent/second-line
ITP management)? Yes/No
If so, what additional work-up would you obtain? (check all that
apply)
- HIV
- Hepatitis
- H. Pylori
- CMV and/or EBV
- ANA Profile
- Immunoglobulins
- Lymphocyte subsets
- Complement levels
- ALPS work-up
- An 8 year-old M presents with increased bruising and episodes of
epistaxis over the past ~month, and is found to have
isolated thrombocytopenia (to 18k), with elevated immature platelet
fraction (13%), and smear review showing platelet size variance
(including large and giant platelets), and no other morphological
abnormalities (including of RBC’s or WBC’s). Thyroid function, renal
function, liver function, and nutritional evaluation is all within
normal limits; and he is diagnosed with Acute ITP. Given lack of
significant bleeding symptomatology or risk, observational
management is recommended. Throughout ~3-4 months of
follow-up, symptoms are unchanged, and platelet count remains
between 10k - 20k. However, he subsequently presents with worsening
epistaxis, now lasting up to 15-20 minutes before resolving,
occurring more frequently, and resulting in a mild anemia (Hgb
~10 g/dL). The decision is made to proceed with
platelet-directed therapy, and he is given IVIG 1 g/kg, with
excellent clinical response. Additionally, platelet count 3 days
later has increased to 170k; and remains >100k for
~4 weeks. About 2 months after IVIG therapy,
however, patient again develops worsening epistaxis/bleeding, and is
found to have platelet count 15k. He is ~6 months
from initial diagnosis, with persistent ITP; and declines any
“long-term” treatment options. However, as symptoms
persist/worsen, he requests to proceed with another dose of IVIG. He
is given another 1 g/kg; but this time with peak platelet count to
80k, and returning to baseline (between 10k-20k) within
~2 weeks. Subsequently, he wishes to proceed with a
trial of short-term prednisone, and receives 2 mg/kg/day divided BID
for 2 weeks with excellent response (platelet count to 120k near the
end of 2 weeks’ prednisone therapy). However, platelet count returns
to baseline within ~2 weeks. He continues
observation for another ~month; but again requests
short-term prednisone therapy when epistaxis worsens. Peak platelet
count is ~70k, and returns to baseline within
~1 week of therapy. Discussions are re-initiated
regarding second-line treatment options, given patient’s lack of
sustained response to front-line/rescue treatment options, and the
persistent need for ITP therapy, in light of his persistent bleeding
symptoms.
- Would you consider this refractory ITP? Yes/No
- Would you work this patient up for alternate etiologies of
thrombocytopenia (vs. proceeding with second-line ITP management)?
Yes/No
If so, what additional work-up would you obtain? (check all that
apply)
- HIV
- Hepatitis
- H. Pylori
- CMV and/or EBV
- ANA Profile
- Immunoglobulins
- Lymphocyte subsets
- Complement levels
- ALPS work-up
- A 13 year-old F presents with increased bruising and mild
menorrhagia over the past 1-2 months, and is found to have isolated
thrombocytopenia (to 13k), with elevated immature platelet fraction
(12%), and smear review showing platelet size variance (including
large and giant platelets), and no other morphological abnormalities
(including of RBC’s or WBC’s). Thyroid function, renal function,
liver function, and nutritional evaluation is all within normal
limits; and she is diagnosed with Acute ITP. Given lack of
significant bleeding symptomatology or risk, observational
management is recommended. Throughout ~3-4 months of
follow-up, however, she reports extreme fatigue, preventing her from
participating in prior extracurricular activities or completing
school work as before. She is treated for iron deficiency (with
improvement in iron stores); and initiated on hormonal control for
menorrhagia (with regulation of cycles and flow per report);
although remaining non-anemic throughout this period of follow-up.
No platelet-directed therapy is initiated throughout these first 3-4
months, and platelet count remains unchanged, between 10k - 20k. She
begins to report falling grades in school; and parents are very
concerned with her level of fatigue, and inability to participate in
routine activities. Therefore, patient is treated with a one-time
course of prednisone (2 mg/kg/day), with excellent platelet
response, to a peak of 160k, and some improvement in
fatiguethroughout this course of short-term prednisone therapy. At
~6 months from time of diagnosis, discussion
regarding potential second-line therapies are initiated, and she
chooses a trial of eltrombopag therapy. Again, platelet response is
achieved (to ~100k, stably); with no notable side
effects; but she reports only slight improvement in fatigue after
~2-3 months of TPO-RA therapy.
- Would you consider this refractory ITP? Yes/No
- Would you work this patient up for alternate etiologies of
thrombocytopenia (vs. continuing with second-line ITP-directed
management and/or evaluating for secondary ITP)? Yes/No
If so, what additional work-up would you obtain? (check all that
apply)
- HIV
- Hepatitis
- H. Pylori
- CMV and/or EBV
- ANA Profile
- Immunoglobulins
- Lymphocyte subsets
- Complement levels
- ALPS work-up
Categorical Questions:
- Is a patient who does not respond at all to first line therapies
refractory? Y/N
- Is a patient who has a transient response to first line treatments but
quickly loses that response refractory? Y/N
- Is a patient who requires ongoing treatment to maintain a response
refractory? Y/N
- Is a patient who fails to respond to one or more second line
treatments (regardless of first line therapy responses) refractory?
- Is a patient with ongoing symptoms (fatigue) regardless of platelet
count responses refractory? Y/N