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5 Gurbel PA, Bliden KP, Hayes KM, Yoho JA, Herzog WR, Tantry
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7 Aleil B, Ravanat C, Cazenave JP, Rochoux G, Heitz A, Gachet C.
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the detection of clopidogrel resistance in patients with ischemic cardiovascular diseases. J Thromb Haemost 2005; 3: 85–92.
8 Jilma B. Platelet function analyzer (PFA-100): a tool to quantify
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9 Golanski J, Pluta J, Baraniak J, Watala C. Limited usefulness of the
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10 Mueller T, Haltmayer M, Poelz W, Haidinger D. Monitoring aspirin
100 mg and clopidogrel 75 mg therapy with the PFA-100 device in
patients with peripheral arterial disease. Vasc Endovascular Surg 2003;
37: 117–23.
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14 Raman S, Jilma B. Time lag in platelet function inhibition by clopidogrel in stroke patients as measured by PFA-100. J Thromb Haemost
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More on: platelet function analyzer (PFA)-100 closure time
in the evaluation of platelet disorders and platelet function
J . K O S C I E L N Y , * H . K I E S E W E T T E R * and G . - F . V O N T E M P E L H O F F *Institute for Transfusion Medicine, Universitätsmedizin Berlin, Charité, Berlin; and Clinic for Gynecology and Obstetrics, City Hospital of
Ruesselsheim, Ruesselsheim, Germany
To cite this article: Koscielny J, Kiesewetter H, von Tempelhoff G.-F. More on: Platelet function analyzer (PFA)-100 closure time in the evaluation
of platelet disorders and platelet function. J Thromb Haemost 2006; 4: 1426–7.
See also Hayward CPM, Harrison P, Cattaneo M, Ortel TL, Rao AK. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet
disorders and platelet function. J Thromb Haemost 2006; 4: 312–9.
We read with interest the recent review on the PFA-100 (PFA)
by Hayward et al. (Working Group on PFA-100, ISTH-SSC
Platelet Physiology Subcommittee) [1]. The article covers well
the considerable body of literature pertaining to the use of PFA
in detecting acquired and inherited platelet disorders. The
various reports cited also show clearly that in most cases very
few patients were studied, an indication that larger trials are
needed in order to better assess the utility of PFA. Indeed, the
Correspondence: J. Koscielny, Institute for Transfusion Medicine,
Universitätsmedizin Berlin, Charité, Campus Charité Mitte,
Schumannstr. 20–21, 10117 Berlin, Germany.
Tel.: +49 45 052 5181; fax: +49 45 052 5906; e-mail:
juergen.koscielny@charite.de
Received 29 March 2006, accepted 4 April 2006
authors state that Ôadequately powered clinical studies…are
required to establish a role for the PFA-100 [closure time (CT)]
in predicting clinical outcomesÕ [1]. We agree, and that is why it
came as a surprise to note their rather negative comment
concerning the value of the PFA CT in preoperative assessment,
referring to our recently published clinical trial data [2]. In fact,
this study is in line with the Working Party’s recommendation,
having been conducted with well over 5000 patients.
In brief, we studied prospectively 5649 patients, administering a bleeding history and performing preoperative screening
(including PFA testing) [2]. A negative bleeding history was
found in 5021 (89%) patients, and among these individuals
only nine (0.2%) had a positive screening test, all because of an
abnormal activated partial prothromboplastin time (APTT).
The remaining 628 (11%) patients had a positive bleeding
history and/or evidence of impaired hemostasis, for example
drug ingestion. Among these latter individuals, 256 (41%) had
2006 International Society on Thrombosis and Haemostasis
Letters to the Editor 1427
Fig. 1. Patients with a positive bleeding history having either completely
normal screening results or at least one abnormal screening test. Hemostatic disorders were determined by a battery of diagnostic tests including
coagulation factor deficiency analysis, platelet aggregometry (ristocetin,
ADP, collagen and arachidonic acid) and flow cytometry analysis for
platelet glycoprotein abnormalities (CD41a, CD42b, CD61, CD62,
CD63). (Coagulation: dysfibrinogenemia, n ¼ 1; factor VII deficiency,
n ¼ 1). Patients in the group with negative bleeding history: 615 of 5021
(12.2%)* perioperative blood transfusions. *Chi-squared test after Pearson (asymptomatic significance doubleside): P ¼ 0.389 (not significant).
PD, platelet disorder; VWD, von Willebrand disease; GT, Glanzmann’s
thrombasthenia; BSS, Bernard-Soulier syndrome; coag, coagulopathy.
at least one positive result with the following screening tests:
complete blood count, PFA CT with collagen-epinephrine
(CEPI) and collagen-ADP (CADP), prothrombin time and
APTT. Of these screening tests, PFA CEPI CT was abnormal
in 250 (98%) of the patients. In all 628 patients with a positive
bleeding history and/or evidence of impaired hemostasis, for
example drug ingestion, diagnostic testing for von Willebrand
disease and platelet and coagulation disorders was performed
as described on pages 197 and 198, and included comprehensive platelet aggregometry and flow cytometry studies [2]. Thus,
a response to Hayward et al. [1] is warranted.
The original Figs 1 and 2 from our study [2] have been
modified and are shown here. Of the 628 patients with a positive
bleeding history and/or evidence of impaired hemostasis, for
example drug ingestion, 256 had a positive screening test, while
372 had a negative screening test. Diagnostic evaluation in the
two groups revealed the various disorders as shown. It is
noteworthy that none of the patients with a positive bleeding
2006 International Society on Thrombosis and Haemostasis
history (and/or evidence of impaired hemostasis, e.g. drug ingestion) and a negative screening test was found to have any hemostatic disorder. However, the bleeding history and/or evidence of
impaired hemostasis, for example drug ingestion was not highly
suggestive in the majority of these patients. For example, the
bleeding tendency was often related to an underlying disease
rather than to a ÔtrueÕ bleeding disorder, for example nosebleeds
in 59 patients with hypertension, gumbleeds in 45 patients
with periodontitis, profuse menstruation in 18 patients with
uterine myomas. On the other hand, the PFA-100 did not detect
platelet dysfunction in 43 patients receiving antiplatelet drugs.
Based on these findings and the screening results, we
calculated the following sensitivity, specificity, positive and
negative predictive values for CEPI CT: 90.8%, 86.6%, 81.8%,
and 93.4%, respectively. Moreover, in our follow-up article [3]
we showed that screening with CEPI CT enabled significant
improvement of Ômeaningful clinical outcomesÕ. Patients with a
positive bleeding history (and/or evidence of impaired hemostasis, e.g. drug ingestion) and a positive screening test (n ¼ 256)
who were treated with dermopressin acetate (DDAVP) prior to
surgery had the same transfusion needs as patients with a
negative (n ¼ 5021) or positive bleeding history (and/or evidence of impaired hemostasis, e.g. drug ingestion) (n ¼ 372)
but negative screening test who were not treated with dermopressin acetate (DDAVP) (Fig. 1). This contrasts dramatically
with a similar group of patients with a positive bleeding history
(and/or evidence of impaired hemostasis, e.g. drug ingestion)
and abnormal CEPI CT, from an earlier companion study
(n ¼ 5102), who were not pretreated with DDAVP [3]. These
patients experienced 8-fold more transfusion needs than
patients with a negative bleeding history and normal CEPI
CT (P < 0.001). Therefore, from these two studies on preoperative assessment with more than 10 000 patients [2,3], it
can be concluded that the PFA-100 CEPI test meets the
requirements both as a useful tool for screening and
possible predicting clinically relevant bleeding.
References
1 Hayward CPM, Harrison P, Cattaneo M, Ortel TL, Rao AK. Platelet
function analyzer (PFA)-100 closure time in the evaluation of platelet
disorders and platelet function. J Thromb Haemost 2006; 4: 312–9.
2 Koscielny J, Ziemer S, Radtke H, Schmutzler M, Pruss A, Sinha P,
Salama A, Kiesewetter H, Latza R. A practical concept for preoperative
identification of patients with impaired primary hemostasis. Clin Appl
Thromb Hemost 2004; 10: 195–204.
3 Koscielny J, von Tempelhoff G-F, Ziemer S, Radtke H, Schmutzler M,
Sinha P, Salama A, Kiesewetter H, Latza R. A practical concept for
preoperative management of patients with impaired primary hemostasis. Clin Appl Thromb Hemost 2004; 10: 155–66.