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Blood, 15 September 2001, Vol. 98, No. 6, pp. 1993-1994
CORRESPONDENCE
To the editor:
Increased Lipoprotein(a) levels are not a steady
prothrombotic defect
We have read the paper by Nowak-Göttl and
coworkers1 on the meaning of combined
prothrombotic defects for recurrence of venous thrombosis in childhood
with great interest and congratulate the authors for their work.
However, we would like to comment on their findings with regard to
Lipoprotein(a) [Lp(a)]. In their paper, the authors describe Lp(a) as
the second most prevalent "prothrombotic defect" for recurrent and
nonrecurrent venous thromboembolism (VTE) in childhood, using a cut-off
of 300 mg/L (30 mg/dL). We had the chance to examine Lp(a) concentrations in a small
group of pediatric patients (n = 7) treated for acute
lymphoblastic leukemia (ALL) or lymphoma on the ALL- or NHL-BFM
(non-Hodgkin lymphoma-Berlin-Frankfurt-Muenster) trial 95, respectively. These 2 trials were used by Nowak-Göttl et
al2 to study the incidence of increased Lp(a) and its
possible relationship to the incidence of venous thrombosis in this
setting. We found that Lp(a) was significantly decreased during therapy
on the BFM trial 95 (Figure 1), with
every patient showing reduction of Lp(a) concentration. A patient with
an increased Lp(a) of 325 mg/L displayed a decrease to a nadir of 58 mg/L, only to end the first block of therapy with a level of 111 mg/L.
Mean Lp(a) fell by 75% from 116.1 mg/L on day 8, to 28.9 mg/L on day
16 (P = .049, Figure 1). It is very likely that these
changes in Lp(a) concentrations were due to the use of L-asparaginase,
as described by other investigators in a different
setting.3
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| Figure 1.
Lp(a) levels can be unsteady: the course of
Lp(a) concentration during L-asparaginase containing chemotherapy is
displayed and a significant decrease can be seen.
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Variation of Lp(a) levels with albumin concentrations has been
described4 as well as with the state of thyroid
function.5,6 Also, Lp(a) levels have repeatedly been
linked to acute-phase responses.7-10 On the other hand,
negative acute-phase characteristics and decreases in catabolic
states have also been shown to occur.11,12 In vitro
experiments show that Lp(a) messenger RNA (mRNA) expression can be
positively regulated by interleukin-6 (IL-6), whereas it can be
suppressed by transforming growth factor  1 (TGF-1) and tumor necrosis factor- (TNF-), suggesting that in vivo Lp(a) levels may be dependent on the balance between stimulatory and inhibitory cytokines,13 which could help to explain the
variation of Lp(a) levels with regard to different clinical settings. In a case control study with patients and controls matched for age and
sex, the authors also considered acute-phase responses to control for
"falsely" increased Lp(a) concentrations14; in this
study, no increased risk for VTE with increased Lp(a) concentrations could be demonstrated. Epidemiologically, there seems to be a relationship between increased
Lp(a) concentrations and VTE. However, given the fact that a clearly
defined pathophysiologic model on how increased Lp(a) concentrations
can convey an increased prothrombotic risk is still missing, we suggest
that increased Lp(a) levels should not be looked at as a
"prothrombotic defect" but rather a "surrogate risk
marker." This view is important in light of the
above data, showing that Lp(a) levels are (although largely genetically
determined) not "fixed" to a certain concentration. Therefore, disregarding circumstances (such as comorbidity or treatment
effects) that might cause variation of Lp(a) levels could lead
to false estimation of numbers of patients at risk for VTE in a given
population. In addition, an increased Lp(a) concentration cannot be
assumed to be a stable risk marker of VTE during chemotherapy with
asparaginase-containg regimens, since asparaginase greatly reduces
Lp(a) levels.
Wolfgang Korte, Jeanette Greiner, Andreas Feldges, and Walter F. Riesen
Correspondence: Wolfgang Korte, Institute for Clinical Chemistry
and Haematology, Kantonsspital, 9007 St Gallen, Switzerland; e-mail:
wolfgang.korte{at}ikch.ch
Acknowledgments
Data on Lp(a) during the BFM 95 trials was reported in poster
form at the Annual Meeting of the Gesellschaft für Thrombose-und Hämostaseforschung, in Freiburg, Germany, February 16-19, 2000.
References
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Risk of recurrent venous thrombosis in children with combined prothrombotic risk factors.
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2001;97:858-862[Abstract/Free Full Text].
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Ramharack R, Barkalow D, Spahr MA.
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