Blood, 1 October 2001, Vol. 98, No. 7, pp. 2282-2283
CORRESPONDENCE
To the editor:
The natural history of refractory idiopathic thrombocytopenic
purpura
Portielje et al1 recently reported a
study on the natural history of idiopathic thrombocytopenic purpura
(ITP). Although the design of their study still falls short of a
"gold-standard" inception cohort, prospective study required to
reliably assess the natural history of a disease,2 their
study represents the best available to date to assess the prognosis of
adult patients with ITP. The study reaffirmed previous analysis of data
that patients with mild and moderate thrombocytopenia have a benign course.3 Portielje et al1 now show that these
patients do not have their life expectancy (LE) compromised. But they
also show that patients with refractory ITP with persistently low
platelet counts (below 30 000/µL) have 4.2-fold increased mortality
risk in comparison with the general population. In this population the
authors calculated the death rate of 0.019 cases per
patient-year at risk. They compared this estimate with our
estimate of the fatal bleeding rate in patients with refractory ITP of
0.0162 to 0.0389 cases per patient-year at risk.4 Our
estimate, based on pooled data available in literature up to year 1998, showed a considerable compromise in LE in patients with refractory,
untreated ITP.4 But by analyzing the cause of death,
Portielje et al1 pointed out that half of the deaths were
due not to bleeding but rather to the lethal infections likely related
to the treatment.
To investigate whether this suggested estimate of the fatal
bleeding rate would change calculation of LE in refractory ITP, we
assumed that the bleeding rate in refractory, untreated patients would
amount to half of the death rate calculated by Portielje et al
(= 0.019 / 2). Even with this new assumption, our
model4 again demonstrates that LE and QALE
(quality-adjusted life expectancy) in patients with refractory ITP are
severely compromised (Figure 1). For a
typical 30-year-old female, LE is decreased by 10.43 years (an average
LE for a 30-year-old healthy female is 49.57 years and an average LE
for a 30-year-old female with refractory ITP calculated in our model is
39.14 years) and by 8.72 of QALE (36.21-27.49). This result is based on
the constant bleeding risk. We also analyzed the model assuming
age-dependent bleeding risk (as was done in our original model).
Unfortunately, Portielje et al did not provide death-rate calculations
according to age. But since their estimate was quite close to ours (see
above), we redid the analysis by assuming half of the
fatal-bleeding age-adjusted risk in our original model. As expected,
under these assumptions LE and QALE do not change significantly from
the model based on the constant bleeding risk for younger patients but
are significantly affected for older patients. For example,
under the constant-bleeding risk model (Figure 1), a 60-year-old female
with untreated refractory ITP will have LE decreased by 2.6 years
compared with a healthy 60-year-old female. Under the age-adjusted risk
model, a 60-year-old female would have LE decreased by almost 10 years
(results not shown).
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| Figure 1.
Life expectancy in refractory patients with ITP with persistently low
(below 30 000/µL) platelet counts based on data for fatal bleeding
risk by Portielje et al.1 QALY indicates quality-adjusted
life years.
|
|
In conclusion, the best data so far indicate that patients with
refractory, untreated ITP have a poor prognosis. If we are to believe
the current data, then it is difficult to justify complacency in terms
of a watchful waiting strategy. A separate issue is whether current available treatments do more good than harm, which
neither our model nor Portielje et al's study was designed to answer. As we noted,4 the only way to settle the issue of
prognosis is to perform a well-designed prospective inception cohort
study of patients with refractory ITP. Until that study is done,
recommendations that patients with refractory ITP and low counts should
be merely observed is difficult to justify.
Benjamin Djulbegovic and Yael Cohen
Correspondence: Benjamin Djulbegovic, H. Lee Moffitt
Cancer Center & Research Institute, University of South Florida,
Interdisciplinary Oncology Program, 12902 Magnolia Dr, Tampa, FL 33612;
e-mail: djulbebm{at}moffitt.usf.edu
References
1.
Portielje JEA, Westendorp RGJ, Kluin-Nelemans HC, Brand A.
Morbidity and mortality in adults with idiopathic thrombocytopenic purpura.
Blood.
2001;97:2549-2554[Abstract/Free Full Text].
2.
Sackett DL, Richardson WS, Rosenberg W, Haynes BR.
Evidence-based medicine. How to practice and teach EBM. New York, NY: Churchill Livingstone Inc; 1997.
3.
George JN, Woolf SH, Raskob GE, et al.
Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology.
Blood.
1996;88:3-40[Free Full Text].
4.
Cohen YC, Djulbegovic B, Shamai-Lubovitz O, Mozes B.
The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts.
Arch Intern Med.
2000;160:1630-1638[Abstract/Free Full Text].
Response:
Mortality in adults with ITP
We thank Drs Djulbegovic and Cohen for their comments on our
recently published study.1 As they point out, we estimated the rate of fatal hemorrhage for patients with refractory idiopathic thrombocytopenic purpura (ITP) at 0.019 cases per patient-year at risk
(where time at risk was defined as time with fewer than 30 × 109/L platelets), using a method previously
described by Cohen et al.2 Unfortunately, Drs Djulbegovic
and Cohen erroneously assumed that nonhemorrhagic deaths were included
in the death rate of 0.019. But this rate only represents fatal
hemorrhages and is entirely in accordance with their original estimates
obtained from pooled information from 17 case series.
Here we want to address 2 other important issues: First,
nonhemorrhagic deaths should also be addressed when defining to
what extent ITP compromises life expectancy. This led us to suggest that the only reliable estimate of the risk to die from ITP is obtained
by comparing the mortality risk of patients with ITP with mortality
risks in the general population, the method applied in our study.
Second, hemorrhagic and nonhemorrhagic deaths should be differentiated.
In our population, deaths due to lethal infections exceeded deaths due
to bleeding, necessitating a discussion about the severe adverse
effects of presently available treatment options for refractory ITP.
Therefore, although we did not advocate a "watchful waiting
strategy," our results underscore the fact that risks of hemorrhages and the risks of serious adverse effects must be carefully
weighed when administering second-line treatment for refractory ITP.
Johanna E. A. Portielje, Rudi
G. J. Westendorp, Hanneke C. Kluin-Nelemans, and Anneke Brand
Correspondence: Johanna E. A. Portielje, Department Medical
Oncology, Daniel den Hoed Kliniek, Rotterdam Cancer Institute, Groene
Hilledijk 301, Rotterdam 3075 EA, The Netherlands; e-mail:
portielje{at}onch.azr.nl
References
1.
Portielje JEA, Westendorp RGJ, Kluin-Nelemans HC, Brand A.
Morbidity and mortality in adults with idiopathic thrombocytopenic purpura.
Blood.
2001;97:2549-2554.
2.
Cohen YC, Djulbegovic B, Shamai-Lubovitz O, Mozes B.
The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts.
Arch Intern Med.
2000;160:1630-1638.
