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Keywords:

  • platelet indices;
  • mean platelet volume;
  • platelet deviation width;
  • platelet-large cell ratio;
  • thrombocytopenia

Summary

  1. Top of page
  2. Summary
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

We investigated the significance of the platelet indices, mean platelet volume (MPV), platelet size deviation width (PDW), and platelet-large cell ratio (P-LCR), in the diagnosis of thrombocytopenia by comparing these levels in 40 patients with hypo-productive thrombocytopenia (aplastic anaemia; AA) and 39 patients with hyper-destructive thrombocytopenia (immune thrombo-cytopenia; ITP). The sensitivity and specificity of platelet indices to make a diagnosis of ITP were also compared. All platelet indices were significantly higher in ITP than in AA, and platelet indices showed sufficient sensitivity and specificity. The area under the curve (AUC) of the receiver operating characteristics curve of platelet indices was large enough to enable the diagnosis of ITP. P-LCR and PDW had the largest AUCs, which indicated that these values were very reliable for immune thrombocytopenia. Our results suggest that these indices provide clinical information about the underlying conditions of thrombocytopenia. More attention should be paid to these indices in the diagnosis of thrombocytopenia.

In evaluating the mechanism of thrombocytopenia, it is necessary to know which is more dominant, hypo-productive thrombocytopenia or hyper-destructive thrombocytopenia. For this purpose, bone marrow aspiration, platelet-associated immunoglobulin G (PAIgG), and molecular markers for disseminated intravascular coagulation (DIC) are often evaluated. Bone marrow aspiration provides information about platelet production, such as the number of megakaryocytes and the degree of platelet production, while PAIgG identifies the presence of anti-platelet antibodies that lead to platelet destruction. Bone marrow examination, which is an invasive test, is necessary for aplastic anaemia (AA), but there is no agreed consensus regarding its necessity for immune thrombocytopenia (ITP) (George et al, 1996; Mak et al, 2000; Marsh et al, 2003). PAIgG is often elevated in ITP, but it is not specific to ITP and an increased PAIgG level is often found in many other diseases (Mueller-Eckhardt et al, 1980; Von dem Borne et al, 1986; Kelton et al, 1989). In fact, the necessity for both bone marrow aspiration and PAIgG in ITP was not accepted in the recent guidelines (British Committee for Standards in Haematology General Haematology Task Force, 2003). However, these two diagnostic approaches are actually overused in the diagnosis of ITP.

Recent advances in automated blood cell analysers have made it possible to measure various blood cell parameters automatically. Among these parameters, platelet indices, such as mean platelet volume (MPV), platelet size deviation width (PDW), and platelet large cell ratio (P-LCR), provide some important information (Threatte, 1993; Niethammer & Forman, 1999; Park et al, 2002), but are not accepted for routine clinical use. If these indices really are informative regarding platelet kinetics, they might become very useful laboratory measures for thrombocytopenia. We investigated the significance of these platelet indices in the diagnosis of thrombocytopenia by comparing the levels in hypo-productive (AA) and hyper-destructive thrombocytopenia (ITP). The sensitivity and specificity of platelet indices to enable the diagnosis of ITP were also evaluated.

Patients and methods

  1. Top of page
  2. Summary
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

Seventy-nine patients with thrombocytopenia (platelet count < 100·0 × 109/l) were entered into this study. There were 47 women and 32 men. Their ages ranged from 20 to 84 years (median age, 58 years). All patients gave written informed consent for this study. The Ethics Committee for Biomedical Research of the Jikei University School of Medicine approved this study in July 2003. Patients were divided into two groups according to the diagnosis of thrombocytopenia; AA and ITP. There were 40 patients with AA and 39 patients with ITP. The degree of thrombocytopenia is shown in Table I. The diagnosis and severity of AA were based on haematological, pathological, radiological, and chromosomal analyses (International Agranulocytosis and Aplastic Anemia Study, 1987), and the diagnosis of ITP was based on the guidelines previously reported (George et al, 1996). The AA group comprised two severe AA, 11 moderate AA, and 27 mild AA patients. Four patients had a history of blood transfusion, but there were no patients who had a history of blood transfusion in the previous 5 years. The Sysmex-XE2100 automated blood cell analyzer (Sysmex, Kobe, Japan) was used to measure platelet indices. MPV was calculated by the following formula, MPV (fL) = [(plateletcrit (%)/platelet count (×109/l)] × 105. Plateletcrit was the ratio of the platelet volume to the whole blood volume. PDW and P-LCR were analysed from a histogram of platelet size distribution. The distribution width at the level of 20% (the peak of the histogram is 100%) was defined as PDW, and the percentage of platelets with a size of more than 12 fL was defined as P-LCR (Fig 1).

Table I.  Characteristics of the evaluated patients.
Diagnosis (n)Female/maleAge, years (median)No. of cases according to the platelet count (×109/l)
10–2020–4040–6060–8080–100
AA (40)27/1326–84 (52)2710138
ITP (39)20/1920–84 (55)01111710
image

Figure 1. Histogram of platelet size distribution and the definition of platelet size deviation width (PDW), and platelet-large cell ratio (P-LCR). The distribution width at the level of 20% was defined as PDW, and the percentage of the platelets with a size of more than 12 fL was defined as P-LCR.

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The sensitivity and specificity of platelet indices to make a diagnosis of ITP were calculated under various cut-off ranges, and the receiver operating characteristic (ROC) curves were drawn. Sensitivity was calculated as the ratio of the number of positive tests to the number of ITP (39), and specificity was calculated as the ratio of the number of negative tests to the number of AA (40). The false-positive ratio (%) was calculated as 100−specificity (%).

Results are presented as the mean ± standard error (SE), and Fisher's protected least significant difference test and Pearson's correlation test were used for statistical analysis. P < 0·05 was considered statistically significant.

Results

  1. Top of page
  2. Summary
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

The platelet count and platelet indices were compared between AA and ITP and are shown in Table II. The platelet count was similar in both groups. All platelet indices were significantly higher in ITP than in AA (P < 0·0001). In particular, PDW and P-LCR showed marked differences between the two types of thrombocytopenia.

Table II.  Comparison of platelet count and platelet indices between aplastic anaemia and immune thrombocytopenia.
 AAP-valueITP
  1. AA, aplastic anaemia; ITP, immune thrombocytopenia; MPV, mean platelet volume; PDW, platelet size deviation width; P-LCR, platelet-large cell ratio.

Platelet (×109/l)5·9 ± 0·4ns6·0 ± 0·4
MPV (fL)10·2 ± 0·2<0·000112·2 ± 0·2
PDW (fL)11·6 ± 0·3<0·000116·8 ± 0·5
P-LCR (%)25·7 ± 1·1<0·000142·2 ± 1·5

The correlation between the platelet count and evaluated parameters is shown in Fig 2. In patients with AA, there were significant inverse correlations between PDW and the platelet count and between P-LCR and the platelet count. However, no significant correlation between platelet indices and the platelet count was found in ITP.

image

Figure 2. Correlations between the platelet count and evaluated parameters. An inverse correlation was found between the platelet count and both platelet size deviation width and platelet-large cell ratio in aplastic anaemia. However, no significant correlation between platelet indices and platelet count was found in immune thrombocytopenia.

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The sensitivity and specificity of platelet indices to make a diagnosis of ITP were calculated under various cut-off ranges. The referential ranges at our institute were 8·4–12·0 fL for MPV, 8·0–14·0 fL for PDW, and 10–30% for P-LCR. Under these cut-off ranges, platelet indices, especially PDW and P-LCR, showed favourable sensitivity and specificity (Table III).

Table III.  Sensitivity and specificity for the diagnosis of ITP under various cut-off ranges.
Cut-off valueSensitivity (%)Specificity (%)
  1. ITP, immune thrombocytopenia; MPV, mean platelet volume; PDW, platelet size deviation width; P-LCR, platelet-large cell ratio.

MPV (fL)
 >11 87·2 80·0
 >12 59·0 95·0
 >13 11·1100
PDW (fL)
 >13 92·3 75·0
 >14 76·9 90·0
 >15 71·8 95·0
P-LCR (%)
 >25100 45·9
 >30 91·4 73·0
 >40 62·9100

The ROC curves of MPV, PDW, and P-LCR are shown in Fig 3. A laboratory test with the ROC curve shifted to the upper left indicates a better test. As apparent from these figures, ROC curves of MPV, PDW, and P-LCR showed upper left-shift. The area under the curve (AUC) of the platelet indices was very large, 9104·8 for MPV, 9305·0 for P-LCR, and 9343·4 for PDW. Among these three indices, P-LCR and PDW were more reliable for immune thrombocytopenia.

image

Figure 3. Receiver operating characteristic (ROC) curves of mean platelet volume (MPV), platelet size deviation width (PDW), and platelet-large cell ratio (P-LCR) to distinguish immune thrombocytopenia from thrombocytopenic patients. ROC curves of MPV, PDW, and P-LCR were shifted to the upper left of the graph, which indicates that these parameters are sufficient to distinguish the two types of thrombocytopenia. The area under the curve was larger in PDW and P-LCR than MPV.

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Discussion

  1. Top of page
  2. Summary
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

It is very important to know whether thrombocytopenia is a result of hypo-production of platelets or hyper-destruction of platelets. ITP is diagnosed by the absence of other diseases that cause thrombocytopenia, such as systemic lupus erythematosus, malignancy, and DIC. For this purpose, PAIgG and bone marrow aspiration are sometimes used. However, elevated levels of PAIgG are often found in various diseases, such as infection, autoimmune disease, and liver cirrhosis (Mueller-Eckhardt et al, 1980; Von dem Borne et al, 1986; Kelton et al, 1989), and PAIgG was not recommended as a diagnostic measure in recent guidelines (British Committee for Standards in Haematology General Haematology Task Force, 2003). Bone marrow sampling is invasive and not necessary as the first-line diagnostic procedure; it was recommended that it should be reserved for older patients, or patients with atypical features (George et al, 1996; Mak et al, 2000; Marsh et al, 2003). Thus, a new non-invasive diagnostic approach for thrombocytopenia is needed. Recent advances in technology have made it possible to record various platelet indices, such as MPV, PDW, and P-LCR, with an automated haematology analyser. There have been some reports about these platelet indices and platelet disorders (Bessman et al, 1985; Karnad & Poskitt, 1985; Endler et al, 2002; Henning et al, 2002). However, they are not clinically accepted as conventional checkpoints for thrombocytopenia. We evaluated the efficacy of these indices by comparing their values between hypo-productive thrombocytopenia (AA) and hyper-destructive thrombocytopenia (ITP).

Mean platelet volume and PDW were elevated in ITP (Gardner & Bessman, 1983); increasing the number of megakaryocytes and supporting the diagnosis of ITP was associated with larger MPV (Rajantie et al, 2004). However, little is known about P-LCR and thrombocytopenia, and whether platelet indices are satisfactory laboratory tests for thrombocytopenia has not fully been discussed. In our evaluation, not only MPV and PDW, but also P-LCR was significantly higher in ITP than in AA. Therefore, these indices were effective in distinguishing these two types of thrombocytopenia. The sensitivity and specificity of platelet indices were sufficient to enable a diagnosis of ITP. The ROC curve is useful in comparing the superiority of different laboratory tests, and a laboratory test with larger AUC is thought to be more reliable, with less misdiagnosis than a test with smaller AUC. Our results indicated that these platelet indices showed favourable ROC curves and large AUC. Among the three parameters, PDW and P-LCR were more reliable markers for distinguishing hyper-destructive thrombocytopenia from hypo-productive thrombocytopenia.

It is not always possible to record platelet indices. In severe thrombocytopenia, and in the presence of red cell fragmentation, a platelet histogram cannot be adequately drawn, and the indices cannot be recorded. Thus, platelet indices have a limited use as an indicator for thrombocytopenia. Of course, the possibility of many other diseases that cause thrombocytopenia should be ruled out by routine work up. However, our results suggested that these indices could help to distinguish hyper-destructive thrombocytopenia and hypo-productive thrombocytopenia very easily. Platelet indices, if reported, provide a lot of clinical information about the underlying conditions of thrombocytopenia. Whether platelet indices are useful in other conditions that cause thrombocytopenia, except ITP and AA, remains unknown. More attention should be paid to these indices for the diagnosis of thrombocytopenia.

References

  1. Top of page
  2. Summary
  3. Patients and methods
  4. Results
  5. Discussion
  6. References
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