Keywords
ITP - steroids - immunosuppressants - partial splenic artery embolization
Introduction
The first-line treatment of immune thrombocytopenia (ITP) usually includes corticosteroids,
intravenous gamma globulin, and other immunosuppressive agents.[1] Sometimes high doses of steroid therapy may be required, and long-term use can cause
potential side effects. When patients are refractory to first-line therapy, they may
often require splenectomy or costly drugs like rituximab.[2] Embolization of splenic artery has been used to treat hypersplenism.[3] Later studies of partial embolization of splenic artery showed benefits over complete
embolization.[4]
[5] The effectiveness of partial splenic artery embolization (PSE) for ITP has been
reported by Ji et al[6] and Miyazaki et al.[7] Partial splenic artery embolization retains the immunogenic function of the spleen
and vaccinations against capsulated microorganisms, which are given before the usual
splenectomy, can be avoided.[8] However, there are not many studies in India that evaluate the efficacy of PSE in
patients with ITP and hence this pilot study.
Materials and Methods
Partial splenic artery embolization was performed in the year 2016 from the month
of August to November in six patients who attended the hematology clinic of our hospital.
As there are no definite guidelines till now, we formed our own guidelines which are
follows:
-
Chronic ITP (> 1 year) not responding to medical treatment (high-dose steroids and
immunosuppressants).
-
Platelet count < 10,000/cumm during treatment on at least four occasions (four different
hospital visits with platelet count < 10,000/cumm; while during other visits the platelets
were > 10000/cumm).
-
One severe life-threatening bleeding episode (those requiring platelet and red blood
cell transfusion and intracranial bleeds) while on treatment.
-
Patients who cannot compromise with logistics of splenectomy (fear, scar, vaccinations)
or other expensive treatment (rituximab).
-
Unacceptable side effects of high dose of medications continued for a long time (hyperglycemia,
dyselectrolytemia, weight gain, fluid retention, increased risk for infections, osteoporosis,
bone marrow suppression).
Each of our patients fulfilled at least three of the above criteria. Five were females
and one was male with their age ranging from 30 to 53 years with a mean age of 41
years. Five of six patients were cases of chronic ITP who were not responding to medical
treatment and one of the patients had 1-month history of ITP and a PSE was done to
withdraw steroids. The lowest platelet count before PSE ranged from 2,000 to 12,000
which was confirmed by checking the peripheral smear manually. All patients had taken
various medications before embolization, including methyl prednisolone and other immunosuppressive
drugs.
An antibiotic prophylaxis was given to all the patients with ciprofloxacin 500 mg
two times for 7 days starting from the day of procedure. The procedure was done under
local anesthesia. Splenic artery angiogram was performed using 4F Glide Yashiro (Terumo)
catheter which showed nonenlarged spleen morphology. Multiple splenic artery branches
supplying the lower pole were cannulated using Progreat microcatheter and were embolized
with polyvinyl alcohol (PVA) particles of size 300 to 500 microns and Gelfoam (Ferrosan
Medical Devices) ([Fig. 1]). For most of the patients, PVA was the first choice of embolic agent. In some patients
after embolization of splenic bed with PVA with slow flow in the parent artery, Gelfoam
was used to further occlude the parent artery to reduce the procedure costs. End point
of embolization was when contrast stasis is achieved for three cardiac cycles. Post-procedure
angiogram ([Fig. 2]) showed around 70 to 75% reduction in splenic parenchymal blush with sluggish flow
in the embolized vessels. Mean proportion of spleen embolized was 60 to 75%. The mean
duration of hospital stay was 6 days and then was followed up in outpatient clinic.
The therapeutic effect was evaluated on the basis of platelet count at the last follow-up.
A good response to the treatment was considered when there is improvement in platelet
count (> 10,000/cumm) with reduction in the dosage of drugs used for treatment (steroids,
immunosuppressants) ([Table 1]).
Fig. 1 Splenic artery angiogram showing splenic parenchymal blush: (a) Catheter in splenic artery. (b) Splenic vein. (c) Splenic blush.
Fig. 2 Postembolization splenic angiogram showing residual splenic blush in 25% of parenchyma.
(a) Splenic artery. (b) Residual splenic parenchymal blush.
Table 1
The clinical data of the patients who had undergone PSE in the year 2016 and their
prognosis during follow–up
|
Sl. no
|
Age (years)
|
Sex
|
Date of diagnosis
|
Indications for PSE
|
Date of procedure
|
Lowest platelet count before procedure
|
Drugs given
|
Dose After PSE (mg)
|
% of dose reduction after PSE
|
Duration of follow–up after PSE
|
Latest platelet count (/cumm)
|
|
Abbreviation: SAH, subarachnoid hemorrhage.
(1/7)—once a week.
(2/7)—twice a week.
(3/7)—thrice a week.
|
|
1.
|
32
|
F
|
Sep 2012
|
Ecchymoses, hematuria Persistent low platelet count
|
12–8–2016
|
2000
|
Steroids Azathioprine Dapsone
|
10
50
|
73%
0%
100%
|
1 year
|
46,000
|
|
2.
|
30
|
M
|
Jan 2015
|
Persistent low platelet count not responding to first line therapy
|
6–9–2016
|
3000
|
Steroids Azathioprine Dapsone MMF
|
6
(3/7)
50
(1/7)
–
–
|
74%
93%
100%
100%
|
1.5 years
|
74,000
|
|
3.
|
40
|
F
|
Aug 2016
|
Melaena Persistent low platelet count
|
13–9–2016
|
5000
|
Steroids Azathioprine Dapsone
|
15
100
–
|
37%
0%
100%
|
1 year
|
26,000
|
|
4.
|
42
|
F
|
Oct 2010
|
Gum bleeding Persistent low platelet count
|
21–9–2016
|
3000
|
Steroids Azathioprine Dapsone
|
6
(3/7)
–
–
|
89%
100%
100%
|
7 months
|
18,5000
|
|
5.
|
51
|
F
|
Aug 2007
|
Persistent low platelet count not responding to first–line therapy
|
6–10–2016
|
10000
|
Steroids
|
6
|
75%
|
1.5 years
|
15,0000
|
|
6.
|
53
|
F
|
Aug 2012
|
Gum bleeding, SAH Persistent low platelet count
|
18–11–2016
|
12000
|
Steroids Azathioprine Dapsone
|
6
(3/7)
50
(3/7)
100
(2/7)
|
78%
78%
71%
|
1.5 years
|
26,000
|
Results
Partial splenic artery embolization brought about a good response in all six patients.
All of them had an increase in platelet count and the drug dosage could be tapered
down. The embolization was technically successful in all cases. The pre- and post-procedure
platelet count done on days before and after the day of procedure was compared that
showed an immediate rise of platelet count ([Table 2]). No major complications were confronted. But a few minor complications did occur,
such as transient fever, abdominal pain, referred pain to shoulder, vomiting and were
controlled with appropriate antibiotics, analgesics, and antiemetics. Neither infections
nor pleural effusions were seen. As per the Society of Interventional Radiology adverse
events reporting criteria, our patients had only class B minor complications. One
out of six patients had low-grade fever lasting for 3 days and subsided with antipyretics.
Three of the patients had abdominal pain which subsided with analgesics and antispasmodics;
two of them also had associated vomiting managed with antiemetics like ondansetron.
One patient had left shoulder pain which was a referred pain and was controlled with
analgesics. No minor or major complications were found in one patient.
Table 2
Pre– and post–procedure platelet count
|
Case
|
Pre–procedure (/cumm)
|
Post–procedure (/cumm)
|
|
1
|
1,18,000
|
1,30,000
|
|
2
|
4,000
|
23,000
|
|
3
|
6,000
|
8,000
|
|
4
|
49,000
|
66,000
|
|
5
|
95,000
|
10,1000
|
|
6
|
10,000
|
25,000
|
The mean lowest platelet count of patients before procedure was 5,833/cumm (ranging
from 2,000 to 12,000/cumm) and post-procedure was 26,500/cumm (ranging from 4,000
to 65,000/cumm). The average value of platelet count at the last follow-up was 84,500
(ranging from 26,000 to 1,85,000/cumm). The cost of the procedure and the hospital
stay was around 100,000 rupees.
Discussion
Thrombocytopenia in patients with chronic ITP responds to medical therapy (steroids
and immunosuppressants) variedly. Only < 40% of ITP respond to steroids.[9] Success rate of medical treatment in ITP with steroids is found to be only 20% who
go into complete remission.[10] Splenectomy is the next choice, when the patient cannot be withdrawn from moderate
dose of the drugs given as treatment (steroids and immunosuppresants) or does not
respond to even high dose of these drugs given for a sufficiently long time. The success
rate of splenectomy is 66%.[10] The spleen is a major source of platelet antibodies and lymphocyte production and
it enhances the phagocytosis of white blood cells. Although splenectomy eliminates
the hypersplenism that causes blood cell destruction, it increases the risk of systemic
infection by capsulated microorganisms. PSE, therefore, was developed to achieve the
occlusion of arteries only in certain areas of the spleen and to overcome the limitations
of splenectomy. A study done by Miyazaki et al[7] on PSE for the treatment of chronic ITP in 26 patients showed that it brought about
a complete response in 33%, a partial response in 38%, and no response in 29%. No
serious complications had occurred in these patients. Ji et al[6] in his study of PSE in 21 patients with chronic ITP found that the response attained
3 months after embolization with transcatheter vessel occlusion is similar to the
reported results of splenectomy. In addition to the reduced morbidity and mortality
associated with surgical splenectomy, the noninfarcted spleen after PSE may continue
to provide immunologic functions. Splenectomy can result in serious complications
like infections and venous thromboembolism.[10] Open and laparoscopic splenectomy is associated with a mortality rate of 1 and 0.2%,
respectively.[11] PSE does not require general anesthesia and has not been associated with severe
complications. The long-term prognosis in patients who underwent PSE was studied by
Kaiho et al.[12] Of the 13 patients, 8 were followed up for 6 months. The platelet count after PSE
increased more remarkably in the effective cases than in the noneffective ones (p < 0.01), which could predict the prognosis after PSE. One patient whose platelet
count increased enough after PSE had splenectomy later and resulted in complete remission.
However, another patient whose platelet count did not increase enough after PSE revealed
that there was no effect even after splenectomy. So, PSE done for the treatment of
ITP could sometimes predict the effectiveness of a future splenectomy. If PSE is effective,
splenectomy may produce complete remission. On the other hand, if PSE is not effective
subsequent, splenectomy also may not produce remission. Togasaki et al who had done
a study in 91 patients with steroid resistant ITP undergoing PSE found that the complete
response rate (a platelet count of > 1,00,000/cumm) was found to be 51% and overall
response rate was 84% (a platelet count of > 30,000/cumm).[13] Therefore, PSE could be an alternative therapy of splenectomy because it is less
invasive. The cost of PSE is likely to be less than a laproscopic splenectomy.
Conclusion
Chronic ITP has become a very common clinical challenge for physicians and hematologists.
Various modalities are available for the treatment of ITP of which splenectomy is
considered as the best treatment for attaining long-term remission or cure. Splenectomy
is a major surgical procedure limited by logistics, costs, and fear of surgery. PSE
gives us an outcome which is quite similar to splenectomy and is less invasive. Our
preliminary observations from this short case series has shown that most of the patients
are continuing without major bleeding and minimum medications for a long time. However,
we need results from more Indian patients to make this treatment popular.
