Platelet morphology, platelet mass, platelet count andprognosis in patients with myelodysplastic syndromes

In a recent report, Bowles et al (2006) presented data on the

impact of platelet mass on prognosis of patients with myelod-

ysplastic syndromes (MDS). In the authors’ cohort of 58

patients, platelet count as well as median platelet volume

(MPV) significantly influenced survival. Patients with low-

platelet mass had an adverse prognosis. This report prompted

us to analyse the prognostic impact of platelet counts and

platelet volume of patients in the Dusseldorf MDS registry. The

MPV had been assessed at the time of diagnosis by using the

same blood specimen which was used for platelet count in 167

patients. Platelet counts and platelet volumes were analysed

using an automated analyser (Sysmex, Norderstedt, Germany).

There were 17 patients with refractory anaemia (RA) or RA

with ringed sideroblasts (RARS), 57 patients refractory

cytopenia with multilineage dysplasia RCMD or refractory

sideroblastic cytopenia with multilineage dysplasia (RSCMD),

40 patients presented as RA with excess blasts (RAEB) I or

RAEB II, 20 patients had chronic myelomonocytic leukaemia

(CMML) and 33 patients were diagnosed as RAEB in

transformation (RAEB-T) according to the French–Ameri-

can–British and World Health Organisation classifications

(Bennett et al, 1982; Bennett, 2000).

The median platelet count was 118 · 109/l (3–907 · 109/l),

MPV was 10Æ1 fl (5Æ8–13Æ8) and median platelet mass,

calculated as the MPV x platelet count was 1Æ5 ml/l (0Æ2–

9Æ9). As expected, a platelet count of <100 · 109/l was

associated with a median survival time of 12 months as

compared with 31 months in patients with a platelet count

‡100 · 109/l (P ¼ 0Æ0008). Patients with a unilineage MDS

(RA or RARS) had a MPV of 9Æ4 fl as compared with 10Æ5 fl in

patients with RCMD or RSCMD (P ¼ 0Æ03). There were no

significant differences between the International Prognostic

Scoring System (Greenberg et al, 1997) groups as far as MPV

was concerned. We could not confirm any prognostic impact

of MPV. Neither a cut-off point of 8Æ5 fl, as proposed by

Bowles et al (2006), nor any other cut-off point was able to

distinguish distinct risk groups (Table I).

When analysing the prognostic impact of the platelet mass, we

could confirm that patients with a platelet mass of <0Æ6 ml/l had

an adverse prognosis, with a median survival of 10 months as

compared with 20 and 31 months in those patients with a

platelet mass of 0Æ6–1Æ2 and >1Æ2 ml/l respectively (P ¼ 0Æ009).

However, when we analysed separately patients with a platelet

count of <100 · 109/l and then with a platelet count of

‡100 · 109/l the difference in survival was no longer demon-

strable. The same was true when we investigated only two groups

of platelet mass, using a cut-off point of ‡ or <1Æ0 ml/l.

In addition, we were not able to find an association between

platelet volume and risk of bleeding at diagnosis or death

because of bleeding. Although low-platelet mass, as well as the

presence of giant platelets and platelet anisometry is associated

with an adverse prognosis, all these parameters do not provide

additional prognostic information to the platelet count.

These findings are in contrast to the data presented by

Bowles et al (2006). The shortcomings of platelet mass as

a prognostic marker seem to become evident by a more

detailed analysis of the present data. In the entire population,

we also could show that a low-platelet mass was associated

with a poor prognosis. When taking into account the

overwhelming prognostic meaning of low-platelet counts, is

it obvious that the influence of the platelet number on the

platelet mass is more important than the platelet volume.

It is not known whether the number and volume of platelets

are responsible for worsening the prognosis or if there are

other mechanisms that have to be taken into account. There

Table I. Prognostic impact of different parameters regarding platelet

count, platelet morphology and platelet mass.

Variable %

Median

survival/months Log-rank P

Platelet count

‡100 · 109/l 56 31 11Æ15 0Æ0008

<100 · 109/l 44 12

MPV

>8Æ5 fl 85 23 0Æ07 NS

>8Æ5 fl 15 23

Giant platelets

present 18 17 7Æ78 0Æ02

Not present 82 25

Platelet anisometry

Yes 35 17 8Æ6 0Æ0034

No 65 26

Platelet mass (all patients)

<0Æ6 ml/l 47 31 9Æ38 0Æ009

0Æ6–1Æ2 ml/l 25 20

>1Æ2 ml/l 28 11

Platelet mass (‡100 · 109 platelets/l)

<0Æ6 ml/l 82 25 0Æ15 NS

0Æ6–1Æ2 ml/l 83 31

>1Æ2 ml/l 17 29

Platelet mass (£100 · 109 platelets/l)

<0Æ6 ml/l 33 11 0Æ1 NS

0Æ6–1Æ2 ml/l 67 16

>1Æ2 ml/l

MPV, median platelet volume; NS, not significant.

Correspondence

ª 2007 The AuthorsJournal Compilation ª 2007 Blackwell Publishing Ltd, British Journal of Haematology, 138, 396–403 399

must be at least some other mechanisms platelet dysfunction

that influence the risk of bleeding. As long as the molecular

mechanisms of dysplasia and dysfunction of platelets in MDS

are unknown, we can only rely on platelet counts.

Ulrich Germing,1

Uwe Platzbecker,2

Aristoteles Giagounidis3

and Carlo Aul3

1Department of Haematology, Oncology and Clinical Immunology,

Heinrich-Heine-University, Dusseldorf, 2Department of Haematology

and Oncology University, Dresden, and 3Department of Haematology,

Oncology and Clinical Immunology, St Johannes Hospital, Duisburg,

Germany

E-mail: germing@med.uni-duesseldorf.de

References

Bennett, J.M. (2000) World Health Organization classification of the

acute leukemias and myelodysplastic syndromes. International

Journal of Hematology, 72, 131–133.

Bennett, J.M., Catovsky, D., Daniel, M.T., Flandrin, G., Galton, D.A.G.,

Gralnick, H.R. & Sultan, C. (1982) Proposals for the classification of

the myelodysplastic syndromes. British Journal of Haematology, 51,

189–199.

Bowles, K.M., Warner, B.A. & Baglin, T.P. (2006) Platelet mass has

prognostic value in patients with myelodysplastic syndromes. British

Journal of Haematology, 135, 198–200.

Greenberg, P., Cox, C., LeBeau, M.M., Fenaux, P., Morel, P., Sanz, G.,

Sanz, M., Vallespi, T., Hamblin, T., Oscier, D., Ohyashiki, K.,

Toyama, K., Aul, C., Mufti, G. & Bennett, J. (1997) International

scoring system for evaluating prognosis in myelodysplastic

syndromes. Blood, 89, 2079–2088.

Keywords: platelet count, platelet morphology, platelet mass,

myelodysplastic syndromes.

First published online 6 June 2007

doi:10.1111/j.1365-2141.2007.06655.x

Recurrent venous thromboembolism during coumarin therapy.Data from the computerised registry of patients with venousthromboembolism

Current guidelines from the American College of Chest

Physicians recommend that patients with venous thrombo-

embolism (VTE) be treated initially with heparin, followed by

long-term treatment with anti-vitamin K (AVK) drugs (Buller

et al, 2004). However, even after adequate anticoagulant

therapy some 3–5% of patients have recurrence of their VTE

(Douketis et al, 2000; Prandoni et al, 2002; Veeger et al, 2005).

The computerised registry of patients with venous thrombo-

embolism (RIETE) is an ongoing, multicentre, observational

registry of consecutive patients with acute VTE (Monreal et al,

2003; Trujillo-Santos et al, 2006). We compared the clinical

characteristics, treatment patterns and 3-month outcome in

patients with new VTE (group 1), those with recurrent VTE

after termination of AVK (group 2), and those with recurrent

VTE during AVK therapy (group 3).

Consecutive patients with symptomatic, acute deep vein

thrombosis (DVT) or pulmonary embolism (PE), confirmed

by objective tests are enrolled in RIETE. The following

parameters are recorded: patient’s baseline characteristics; risk

factors for VTE; the treatment received upon diagnosis; and

the outcome within 3 months. Fatal PE, in the absence of

autopsy, was defined as death shortly after PE, in the absence

of any alternative cause of death. Fatal bleeding was defined as

any death occurring shortly after a major bleed. Bleeding

complications were classified as ‘major’, if they were overt and

required a transfusion of 2 units of blood or more, or were

retroperitoneal or intracranial.

During the observation period, special attention was paid to

any signs or symptoms suggesting either VTE recurrences or

bleeding complications. Each episode of clinically suspected

recurrent DVT or PE was documented by repeat objective

tests. The statistical package for the social sciences (spss)

version 11.5 (SPSS Inc., Chicago, IL, USA) was used to

calculate odds ratios and corresponding 95% confidence

intervals, and a P-value <0Æ05 was considered to be statistically

significant.

Of the 15 862 patients with acute VTE who had been

followed for 3 months as of July 2006, 2538 (16%) had

a prior episode of VTE. In 177 (7Æ0%) the current episode

developed during AVK therapy. Ninety-nine further patients

taking AVK for other reasons (i.e. atrial fibrillation and heart

diseases) were not considered in this analysis. Thus, there

were 13 324 patients in group 1; 2361 in group 2 and 177 in

group 3.

Correspondence

ª 2007 The Authors400 Journal Compilation ª 2007 Blackwell Publishing Ltd, British Journal of Haematology, 138, 396–403