Rapid responses are electronic comments to the editor. They enable our users
to debate issues raised in articles published on bmj.com. A rapid response
is first posted online. If you need the URL (web address) of an individual
response, simply click on the response headline and copy the URL from the
browser window. A proportion of responses will, after editing, be published
online and in the print journal as letters, which are indexed in PubMed.
Rapid responses are not indexed in PubMed and they are not journal articles.
The BMJ reserves the right to remove responses which are being
wilfully misrepresented as published articles or when it is brought to our
attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not
including references and author details. We will no longer post responses
that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
Dear Sir – Investigating 56 consecutive patients taking 325 mg/day
ASA presenting with a history of coronary heart disease Friend et al.
claimed (1) that patients with reduced ASA responsiveness had
significantly higher concentrations of total cholesterol and LDL-
cholesterol. They than may need higher doses of ASA or further reduction
in (LDL-) cholesterol. That cholesterol should be treated to target levels
is out of debate. But does a single platelet function test done allow
these conclusions? The authors were measuring platelet aggregation in
whole blood. Although fasted (the time interval to blood withdrawal is not
given) there is a significant correlation to triglycerides (VLDL) most
likely due to the difference in light transmission (2). This also may be –
at least in part – responsible for the different response to ASA under
these artefactual conditions. Also the time interval between blood
withdrawal and aggregometry with up to 4 hours was quite long, already
after 2 hours ex-vivo platelets may exhibit an altered behaviour to
aggregation – inducing agents as well inhibitory ones such as ASA.
Elevated triglycerides (due to insufficient fasting or metabolic syndrome)
may significantly influence (3) data obtained. Other components in whole
blood due to active (inflammatory) disease may interfere with the findings
as well. Cyclooxygenase 2-expression (4)if even (5)is of minimal
influence. Furthermore, repeated assessment of platelet function may
reveal different response (6). Other limitations of platelet function
studies showed be considered as well.
For assessing the platelet response to ASA platelets need to be isolated
and washed. In order to substantiate the authors´ claim in the conclusion
that data derived from this inconclusive in-vitro approach might extend to
the far-going clinical recommendation to treat the non-responders with
higher ASA doses might be premature. Evidence based data so far show a
dose-dependency of side effects of aspirin but not of benefits.
Antithrombotic Trialists Collaboration. Collaborative metaanalysis of
randomised trials of antiplatelet therapy for prevention of death,
myocardial infarction and stroke in high-risk patients (7).
Is it
justified on this basis of a small-sized descriptive, uncontrolled in-vivo
study to expose patients to an eventually elevated risk without documented
evidence to improve benefit? Furthermore, recently a decreased
responsiveness of platelets on clopidogrel has been reported as well (8).
Are these the same patients exhibiting a different response?
What is the in-vivo clinical impact of in-vitro platelet resistance to
certain drugs under a great variety of different conditions? Which test?
A very careful analysis of available information and prospective studies
on basic aspects and clinical consequences of aspirin and clopidogrel
responsiveness of platelets are necessary before giving non-evidence based
for going and eventually harmful therapeutic recommendations.
Contributor: Helmut Sinzinger, MD, Prof.. Institute for Diagnosis and
Treatment of Atherosclerosis and Lipid Disorders (ATHOS), Nadlergasse 1, A
-1090 Vienna, Austria
e-mail: helmut.sinzinger@univie.ac.at
1. Friend M, Vucenik I, Miller M. Platelet responsiveness to aspirin
in patients with hyperlipidaemia. Brit Med J 2003; 326: 82-3.
2. Carvalho AGA, Colman RW, Lees RS. Platelet function in
hyperlipoproteinemia. N Engl Med 1974; 290: 434-8.
3. Nordoy A, Strom E, Gjesdal K. The effect of alimentary
hyperlipaemia and primary hypertriglyceridaemia
on platelets in man. Scand J Haematol 1974; 12: 829-34.
4. Weber A.A, Zimmermann K, Meyer-Kirchrath J. Cyclooxygenase-2 in
human platelets as a possible factor in aspirin resistance. Lancet 1999;
353: 900.
5. Reiter R, Resch U, Sinzinger H. Do human platelets express COX-2?
Prostagl Leukotr Essential Fatty Acids 2001; 64: 299-305.
6. George JN, Shottil SJ. The clinical importance of acquired
abnormalities of platelet function. New Engl J Med 1991; 324: 27-39.
7. Antithrombotic Trialists Collaboration. Collaborative meta-
analyses of randomized trials of antiplatelet therapy for prevention of
death, myocardial infarction, and stroke in high risk patients. Brit Med J
2002; 324: 71-86.
8. Gurbel PA, Bliden KP. Interpretation of platelet inhibition by
clopidogrel and the effect of non-responders. J Thromb Haemost 2003; 1:
1318-9.
there is debate on dose of aspirin which has been steadily
downgraded from 325mg to the present recommended dose of 50-75mg/day. the
above study has highlighted the presence of aspirin resistance in
hyperlipidaemia, also described in heart failure, diabetes, and ischaemic
heart diseases. thus the current recommended dose of aspirin (50-75mg) may
not be appropriate for all patients. also it is not routinely feasible to
determine platelet aggregation. most patients with above conditions
especially ihd and diabetes are on ACE-inhibitors. reports that high
aspirin doses may inhibit actions of ACE-inhibitors will be compounding
the problem. the alternate solution, rather than increasing aspirin dose,
as stated rightly in this article may be combining the current aspirin
dose with clopidogrel especially in those cases where resistance to
aspirin is anticipated.
Platelet responsiveness on ASA in hyperlipidaemics
Dear Sir – Investigating 56 consecutive patients taking 325 mg/day
ASA presenting with a history of coronary heart disease Friend et al.
claimed (1) that patients with reduced ASA responsiveness had
significantly higher concentrations of total cholesterol and LDL-
cholesterol. They than may need higher doses of ASA or further reduction
in (LDL-) cholesterol. That cholesterol should be treated to target levels
is out of debate. But does a single platelet function test done allow
these conclusions? The authors were measuring platelet aggregation in
whole blood. Although fasted (the time interval to blood withdrawal is not
given) there is a significant correlation to triglycerides (VLDL) most
likely due to the difference in light transmission (2). This also may be –
at least in part – responsible for the different response to ASA under
these artefactual conditions. Also the time interval between blood
withdrawal and aggregometry with up to 4 hours was quite long, already
after 2 hours ex-vivo platelets may exhibit an altered behaviour to
aggregation – inducing agents as well inhibitory ones such as ASA.
Elevated triglycerides (due to insufficient fasting or metabolic syndrome)
may significantly influence (3) data obtained. Other components in whole
blood due to active (inflammatory) disease may interfere with the findings
as well. Cyclooxygenase 2-expression (4)if even (5)is of minimal
influence. Furthermore, repeated assessment of platelet function may
reveal different response (6). Other limitations of platelet function
studies showed be considered as well.
For assessing the platelet response to ASA platelets need to be isolated
and washed. In order to substantiate the authors´ claim in the conclusion
that data derived from this inconclusive in-vitro approach might extend to
the far-going clinical recommendation to treat the non-responders with
higher ASA doses might be premature. Evidence based data so far show a
dose-dependency of side effects of aspirin but not of benefits.
Antithrombotic Trialists Collaboration. Collaborative metaanalysis of
randomised trials of antiplatelet therapy for prevention of death,
myocardial infarction and stroke in high-risk patients (7).
Is it
justified on this basis of a small-sized descriptive, uncontrolled in-vivo
study to expose patients to an eventually elevated risk without documented
evidence to improve benefit? Furthermore, recently a decreased
responsiveness of platelets on clopidogrel has been reported as well (8).
Are these the same patients exhibiting a different response?
What is the in-vivo clinical impact of in-vitro platelet resistance to
certain drugs under a great variety of different conditions? Which test?
A very careful analysis of available information and prospective studies
on basic aspects and clinical consequences of aspirin and clopidogrel
responsiveness of platelets are necessary before giving non-evidence based
for going and eventually harmful therapeutic recommendations.
Contributor: Helmut Sinzinger, MD, Prof.. Institute for Diagnosis and
Treatment of Atherosclerosis and Lipid Disorders (ATHOS), Nadlergasse 1, A
-1090 Vienna, Austria
e-mail: helmut.sinzinger@univie.ac.at
1. Friend M, Vucenik I, Miller M. Platelet responsiveness to aspirin
in patients with hyperlipidaemia. Brit Med J 2003; 326: 82-3.
2. Carvalho AGA, Colman RW, Lees RS. Platelet function in
hyperlipoproteinemia. N Engl Med 1974; 290: 434-8.
3. Nordoy A, Strom E, Gjesdal K. The effect of alimentary
hyperlipaemia and primary hypertriglyceridaemia
on platelets in man. Scand J Haematol 1974; 12: 829-34.
4. Weber A.A, Zimmermann K, Meyer-Kirchrath J. Cyclooxygenase-2 in
human platelets as a possible factor in aspirin resistance. Lancet 1999;
353: 900.
5. Reiter R, Resch U, Sinzinger H. Do human platelets express COX-2?
Prostagl Leukotr Essential Fatty Acids 2001; 64: 299-305.
6. George JN, Shottil SJ. The clinical importance of acquired
abnormalities of platelet function. New Engl J Med 1991; 324: 27-39.
7. Antithrombotic Trialists Collaboration. Collaborative meta-
analyses of randomized trials of antiplatelet therapy for prevention of
death, myocardial infarction, and stroke in high risk patients. Brit Med J
2002; 324: 71-86.
8. Gurbel PA, Bliden KP. Interpretation of platelet inhibition by
clopidogrel and the effect of non-responders. J Thromb Haemost 2003; 1:
1318-9.
Competing interests:
None declared
Competing interests: No competing interests