Authorship and contributorship
Can platelet indices predict obstruction level of pulmonary vascular bed in patients with acute pulmonary embolism?
Article first published online: 31 JUL 2013
© 2013 John Wiley & Sons Ltd
The Clinical Respiratory Journal
Volume 8, Issue 1, pages 33–40, January 2014
How to Cite
Günay, E., Sarinc Ulasli, S., Kacar, E., Halici, B., Unlu, E., Tünay, K., Ozkececi, G., Koken, T. and Unlu, M. (2014), Can platelet indices predict obstruction level of pulmonary vascular bed in patients with acute pulmonary embolism?. The Clinical Respiratory Journal, 8: 33–40. doi: 10.1111/crj.12031
E.G. designed, analysed the data and write the manuscript; S.S.U. retrospectively collected the data of the participants and critically revised the manuscript; E.K. and E.U. had a role in the measurement of tomographic index; B.H. retrospectively collected the data of the participants and literature review; K.T. retrospectively collected the data of the participants; G.O. collected and evaluated echocardiographic data of patients; T.K. analysed and determined blood samples results of subjects; M.U. had a role in design, analysis and interpretation of data, critical revision and final version of the manuscript.
The study protocol was approved by the Local Ethics Committee of Afyon Kocatepe University, School of Medicine, Afyonkarahisar, Turkey
Conflict of interest
The authors have stated explicitly that there are no conflicts of interest in connection with this article.
In the present study, the mean value of mean platelet volume (MPV), platelet distribution width (PDW) levels, platelet counts and red cell distribution width levels were higher in pulmonary embolism (PE) groups than in control subjects (P < 0.05). There were statistically significant differences in terms of hospital length of stay (HLS), mean value of MPV, computed tomography pulmonary arterial obstruction index ratio (CTPAOIR) and systolic pulmonary arterial pressure (sPAP) in addition to systolic arterial pressure between massive and submassive PE patients (P < 0.05 for all). CTPAOIR was positively correlated with HLS, clinical probability scores, D-Dimer level, MPV, PDW levels and sPAP. These results suggest that platelet indices, MPV and PDW, can be used for the determination of disease severity, and considering therapeutic strategies for pulmonary embolism patients.
- Issue published online: 6 JAN 2014
- Article first published online: 31 JUL 2013
- Accepted manuscript online: 27 MAY 2013 04:16AM EST
- Manuscript Accepted: 20 MAY 2013
- Manuscript Revised: 9 APR 2013
- Manuscript Received: 11 MAR 2013
- acute pulmonary embolism ;
- computed tomography pulmonary arterial obstruction index ratio ;
- computerised tomography ;
- mean platelet volume ;
- platelet indices ;
- severity of pulmonary embolism
Computed tomography pulmonary arterial obstruction index ratio (CTPAOIR) is related with the severity of pulmonary embolism (PE). Platelet indices including mean platelet volume (MPV), platelet distribution width (PDW) are reported to be increased in acute PE.
In this study, we aimed to evaluate the relationship between CTPAOIR and platelet indices and the utility of these parameters in the determination of PE severity.
Materials and Methods
We retrospectively analysed the demographic data, clinical probability scores, laboratory data and echocardiographic findings of 63 acute PE patients who were diagnosed by pulmonary arterial computed tomography angiography.
The hospital records of 38 (60.3%) male and 25 (39.7%) female patients with acute PE and 29 (58%) male and 21 (42%) female healthy control were evaluated (P = 0.803). The mean value of MPV, PDW levels, platelet counts and red cell distribution width levels were higher in PE groups than in control subjects (P < 0.05). Massive PE was present in 33.3% of PE patients. There were statistically significant differences in terms of hospital length of stay (HLS), mean value of MPV, CTPAOIR and systolic pulmonary arterial pressure (sPAP) in addition to systolic arterial pressure between massive and submassive PE patients (P < 0.05 for all). CTPAOIR was positively correlated with HLS, clinical probability scores, D-Dimer level, MPV, PDW levels and sPAP.
Platelet indices, MPV and PDW, can be used for the determination of disease severity, and lead to therapeutic strategies for PE patients.
Acute pulmonary embolism (PE) is a common pulmonary emergency state. Hypercoagulability, venous stasis, deteriorations in the platelet functions and inflammatory processes were found to be associated with venous thromboembolism and other common thrombotic vascular conditions (1, 2). Thus, depending on the occlusion level of pulmonary vascular bed, PE may lead to a life-threatening condition .
In the literature, there are some reports showing the clinical effectiveness of the computed tomography pulmonary arterial obstruction index (CTPAOI) and CTPAOI ratio (CTPAOIR) on the degree and the extent of the thrombotic pulmonary arterial occlusion in patients with acute PE. Additionally, it is shown that CTPAOIR have been correlated with clinical probability scores (Wells scoring system), echocardiographic findings and systolic arterial pressure of the patients with PE [4-6].
Previous studies have showed that platelet activation occurs in patients with thrombotic disorders as well as in patients with acute PE [7, 8]. Platelet count, mean platelet volume (MPV) and platelet distribution width (PDW) are commonly used and easily accessible markers of platelet activation that was routinely examined in the complete blood count (CBC) tests [9-11]. Increased MPV is an indicator of activated, increased and hyperfunctional platelets and is related to increase the propensity of thrombotic events [12, 13].
The purpose of this study is to evaluate the relationships among clinical probability scores, D-Dimer, high-sensitive cardiac troponin T (hs-cTnT) levels, platelet indices, parameters of arterial blood gas (ABG) analysis and CTPAOIR and the importance of these relations in clinical practice.
Materials and methods
We retrospectively analysed the hospital records of 92 patients diagnosed as acute PE by spiral and multidetector pulmonary arterial computed tomography angiography (PCTA) admitted to outpatient and emergency clinics of our university hospital between 1 August 2010 and 31 December 2011. And we enrolled only 63 (68.4%) of them whose complete clinical data including symptoms, past medical history, smoking habits, laboratory records (CBC, D-Dimer, hs-cTnT and ABG at the first admission), clinical probability scores (Wells score and Geneva score), PCTA images and echocardiography results on admission and hospital length of stay could be accessed. Twenty-nine (31.5%) of the patients missing one or more data above-mentioned were excluded from the study.
The control group included 50 age- and sex-matched healthy subjects without any risk factors and concomitant diseases who were admitted to outpatient clinics for routine check-up. So, blood samples for CBC were also taken from control group.
This study was conducted with the permission of our local ethical committee.
The PE group divided into two subgroups according to the disease severity as ‘submassive embolism group’ and ‘massive embolism group’. Massive embolism was defined as the presence of cardiogenic shock and/or arterial hypotension (systolic arterial pressure less than 90 mmHg), presence of pulmonary arterial hypertension and/or right ventricular dysfunction in echocardiographic evaluation and thrombus in one or both common pulmonary arteries or more than 50% occlusion of pulmonary vascular bed by a thrombus [4, 14]. Thrombolytic treatment (recombinant tissue plasminogen activator infusion at rate of 100 mg/2 h) was applied to all patients with massive PE and no contraindications.
After collection of blood samples in the potassium ethylenediaminetetraacetic acid tubes (dipotassium EDTA tube), the Sysmex-XE 2000i automated blood cell analyser (Sysmex, Kobe, Japan) was used to measure CBC within 1 h after venipuncture. This duration is standard for our university hospital laboratory and helps to prevent EDTA-induced swelling. 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 platelet large cell ratio were analysed from a histogram of platelet size distribution. D-Dimer levels were measured by a quantitative latex assay (D-DI2; Roche Diagnostics, Mannheim, Germany) on a Cobas C 501 analyser (Roche Diagnostics). Serum hs-cTnT levels were measured by an electrochemiluminescence assay [troponin T hs (high-sensitive) Short Turn Around Time] with the Elecsys 2010 analyser (Roche Diagnostics). When the result for hs-cTnT was <0.001, it was evaluated as ‘0’.
Pulmonary arterial computed tomography angiography
All patients were scanned on a contrast-enhanced multislice spiral computed tomography scanner (Philips medical systems; Cleveland, OH, USA) from the lung apices to the lowest level of the hemidiaphragm in a supine position during the patients were holding their breaths. All multiplanar reconstructions of computed tomography images were evaluated and scored by two radiologists according to the previously described methods as CTPAOI and CTPAOIR [5, 6].
The echocardiographic assessments of acute PE patients on the same day of the diagnosis were evaluated. Echocardiographic findings of PE, such as right ventricular a/hypokinesis, interventricular septal shift and paradoxical movement and systolic pulmonary arterial pressure (sPAP) in addition to left ventricular ejection fraction were noted. Either interatrial septal defect (patent foramen ovale) or interventricular septal defect was not present in PE groups.
The Statistical Package for the Social Sciences 20.0 (SPSS Inc, Chicago, IL, USA) was used for statistical analysis. The Kolmogorov–Smirnov test was used to evaluate whether the variables were distributed normal or not. Continuous variables were expressed as mean (±) standard deviation or median (min-max) according to distribution state. Nominal variables were expressed as percentage. Student's t-test and/or Mann–Whitney U-test were used to compare parametric or nonparametric variables between the PE and the control groups and between the massive and the submassive PE patients. The relationships between CTPAOIR and the laboratory values [red cell distribution width (RDW), platelet, MPV, PDW, D-Dimer, hs-cTnT and arterial oxygen pressure (PaO2)], clinical probability scores (Wells and Geneva) were examined using the Spearman correlation coefficient analysis. Statistically significance was set at P value < 0.05.
The hospital records of 38 (60.3%) male and 25 (39.7%) female patients with acute PE and 29 (58%) male and 21 (42%) female healthy control were evaluated (P = 0.803). Mean ages of acute PE group and control group were 57.76 ± 18.49 years and 56.02 ± 8.03 years, respectively (P = 0.081). There was no statistically significant difference in case of smoking status demonstrated in Table 1.
|Characteristics||PE (n = 63)||Control (n = 50)||P value*|
|Male n, %||38 (60.3)||29 (58.0)||0.803|
|Female n,%||25 (39.7)||21 (42.0)|
|Age, years||57.76 ± 18.49||56.02 ± 8.03||0.081|
|Smoker, n||34 (54.0)||27 (54.0)||0.997|
|Smoking consumption, pack-years||37.59 ± 29.08||36.44 ± 15.12||0.844|
All patients had one or more symptoms. The most common symptoms were chest pain (84.1%), dyspnoea (82.5%) and palpitation (11.1%). The most common risk factors in PE group were immobilisation (14.3%), surgery (11.1%) and malignancies (11.1%). Twenty-four (38.1%) patients were free of any risk factors.
The mean MPV and PDW values of patients with acute PE group were 10.92 ± 1.37 fL and 13.31 ± 2.22 fL, respectively. These values of healthy control subjects were 10.23 ± 1.61 fL and 12.15 ± 1.78 fL, respectively. There were statistically significant differences between groups in terms of MPV and PDW values (P = 0.015 and P = 0.003, respectively). The mean value of RDW was significantly different between two groups (P < 0.001). All the other CBC findings of both groups were shown in Table 2.
|WBC, ×103 μL||9.58 ± 2.71||7.92 ± 2.83||0.002|
|Haemoglobin, g/dL||12.97 ± 1.93||14.33 ± 1.39||<0.001|
|RDW, %||15.05 ± 2.12||13.59 ± 1.80||<0.001|
|Platelet, ×103 μL||246.67 ± 82.15||281.28 ± 87.44||0.032|
|MPV, fL||10.92 ± 1.37||10.23 ± 1.61||0.015|
|PDW, fL||13.31 ± 2.22||12.15 ± 1.78||0.003|
Hospital length of stay, clinical probability scores, laboratory results including D-Dimer, hs-cTnT levels, ABG analysis results, computed tomography obstruction indices and sPAP and other echocardiography findings of acute PE patients were presented in Table 3.
|Clinical and laboratory findings||PE|
|Hospital length of stay, days||12.84 ± 4.62|
|Clinical Probability Scores|
|Wells score||6.21 ± 1.53|
|Geneva score||6.87 ± 1.46|
|Systolic arterial pressure, mmHg||105.24 ± 20.09|
|D-Dimer, μg/mL [Median (min.-max.)]||2.73 (0.10–27.20)|
|hs-cTnT, ng/mL [Median (min.-max.)]||0.01 (0–0.19)|
|PaO2, mmHg||64.37 ± 11.40|
|SaO2, %||90.56 ± 6.24|
|Computed tomography obstruction index|
|CTPAOI [Median (min.-max.)]||8.00 (2.00–40.00)|
|CTPAOIR [Median (min.-max.)]||0.20 (0.05–1.00)|
|sPAP, mmHg||43.89 ± 12.96|
|Left ventricular EF, %||59.55 ± 9.36|
One (1.6%) patient with submassive embolism had low probability based on both clinical scoring systems. Based on the Wells scoring system, moderate and high clinical probabilities were detected in 40 (63.5%) and 22 (34.9%) cases, respectively. On the other hand, based on the Geneva scoring system, moderate and high probabilities were detected in 52 (82.5%) and 10 (15.9%) cases, respectively.
Massive PE was present in 21 (33.3%) of PE patients. There was a statistically significant difference in terms of hospital length of stay, mean value of MPV, CTPAOI, CTPAOIR and sPAP in addition to systolic arterial pressure between massive and submassive PE patients (P < 0.05 for all) (Table 4).
|Submassive PE, N = 42||Massive PE, N = 21||P value*|
|Demographics and Findings|
|Age, years||58.23 ± 17.73||56.81 ± 20.35||0.775|
|Sex, M/F (% males)||25/17 (59.5)||13/8 (61.9)||0.857|
|Smoking, pack-years||36.48 ± 0.50||39.91 ± 31.23||0.753|
|Hospital length of stay, days||11.83 ± 4.72||14.86 ± 3.74||0.013|
|Wells scores||6.1 ± 1.45||6.36 ± 1.70||0.584|
|Geneva scores||6.74 ± 1.64||7.14 ± 1.01||0.305|
|Systolic arterial pressure, mmHg||117.26 ± 12.36||81.19 ± 5.22||<0.001|
|D-Dimer, μg/mL [Median (min.-max)]||2.25 (0.1–16.00)||4.60 (0.56–27.20)||0.102|
|hs-cTnT, ng/mL [Median (min.-max)]||0.027 (0–0.15)||0.01 (0–0.19)||0.404|
|PaO2, mmHg||65.50 ± 11.13||62.11 ± 11.86||0.269|
|SaO2, %||91.61 ± 5.20||88.45 ± 7.63||0.057|
|WBC, ×103 μL||9.65 ± 2.96||9.45 ± 2.19||0.202|
|Haemoglobin, g/dL||12.72 ± 1.99||13.46 ± 1.75||0.153|
|RDW, %||14.76 ± 1.87||15.63 ± 2.51||0.125|
|Platelet, ×103 μL||245.19 ± 72.82||249.62 ± 100.18||0.842|
|MPV, fL||10.53 ± 1.12||11.71 ± 1.50||0.001|
|PDW, fL||12.94 ± 2.26||14.04 ± 2.01||0.064|
|CTPAOI||6.93 ± 5.54||22.05 ± 8.23||<0.001|
|CTPAOIR||0.17 ± 0.14||0.55 ± 0.21||<0.001|
|sPAP, mmHg||38.16 ± 8.20||57.50 ± 12.25||<0.001|
|Left ventricular EF, %||59.42 ± 8.89||59.88 ± 11.04||0.911|
There was a negative significant correlation between mean value of Geneva scores and the mean PaO2 levels (r = −0.26, P = 0.04). CTPAOIR was correlated with Wells scores and Geneva scores (r = 0.466, P = 0.008 and r = 0.386, P = 0.022, respectively) (Table 5).
|Parameters||Correlations with CTPAOIR|
|Hospital length of stay||0.506||<0.001|
|Systolic arterial pressure||−0.720||<0.001|
The mean D-Dimer levels was positively correlated with CTPAOIR (r = 0.294, P = 0.02).
There was not a relationship between the mean RDW levels and CTPAOIR (r = −0.022, P = 0.865) (Table 5).
Platelet count was not correlated with CTPAOIR (r = −0.28, P = 0.158) (Table 5). The mean value of MPV levels was positively correlated with the mean value of CTPAOIR (r = 0.428, P < 0.001) (Fig. 1) and the mean value of sPAP (r = 0.419, P = 0.03). The mean value of MPV levels was correlated with Wells scores (r = 0.587, P = 0.002), Geneva scores (r = 0.406, P = 0.032) and hospital length of stay (r = 0.660, P < 0.001). There was a significant correlation between mean value of PDW levels with hospital length of stay (r = 0.308, P = 0.014). A significant correlation was found between the mean value of PDW levels and the mean value of CTPAOIR (r = 0.342, P = 0.006) (Table 5).
Thrombolytic treatment was applied to 14 (22.2%) massive PE patients without any contraindications. No complication was occurred after thrombolytic treatments. The rest of the patients with submassive PE and remainder massive PE were treated initially with low-molecular weight heparin. There was no deceased patient after diagnosis of PE.
It has shown that PE represents an acute and potentially fatal disease. So that, it is important to determine the extent of the disease in order to begin an appropriate treatment modality as soon as possible before patient is deceased [15-17]. In the present study, we examined the predictor role of platelet indices and computed tomography scores in the determination of acute PE severity (massive/submassive), and the main finding was the presence of relationships between CTPAOIR and platelet indices with PE severity.
There are many studies to determine the relationship between the severity of PE and the radiological scoring systems evaluated with the digital subtraction pulmonary angiograms (Miller index) and computerised tomography (4, 5, 18–22). Qanadli et al.  proposed a computed tomography index that was correlated with clinical outcomes, like systolic blood pressure, echocardiographic findings and Miller index. In the literature, there are so many studies evaluating the accuracy and the effect of this index in predicting mortality [5, 18-22]. In this study, we determined the degree of occlusion (CTPAOI and CTPAOIR) with the formula that was proposed by Qanadli et al. (5), and we showed that CTPAOI and CTPAOIR were significantly increased in massive PE (P < 0.001 for both). The significant relationship between CTPAOIR and clinical probability scores have been reported in the literature . In this study, in addition to the relationship between CTPAOIR and both clinical probability scores (Wells and Geneva scores), there is a positive correlation between CTPAOIR and D-Dimer level (r = 0.293, P = 0.02), and negative correlation between CTPAOIR and PaO2 and arterial oxygen saturation (SO2) levels (r = −0.262, P = 0.038; r = −0.288, P = 0.023, respectively).
Increased platelet activation in patients with PE has been demonstrated in the previous studies [7-9, 23]. Mechanism of this activation has not been clearly explained . In the literature, there are limited studies evaluating MPV levels in patients with acute PE [8, 9]. Varol et al.  determined the increased MPV levels in patients with acute PE compared with controls. They showed a correlation between increased levels of MPV and right ventricular diameters. Kostrubiec et al.  found that MPV levels were similar in control subjects and PE patients. However, MPV values were differed between low and intermediate or high risk. In our study, we found statistically higher MPV levels in PE group compared with controls. In parallel with the literature, there were also relationships between MPV values and the mean value of both clinical probability scores (P < 0.05 for both). Furthermore, the mean MPV levels were correlated with the mean value of sPAP as a preliminary result of the present study which should be verified in further investigations.
Vagdatli et al.  reported that both the PDW and MPV are increased in diseases associated with platelet activation. However, they underlined PDW as a more specific marker of platelet activation than MPV because PDW was not affected during simple platelet swelling. To our knowledge, there has been no study comparing the level of PDW of PE patients and healthy subjects in the literature. In our study, we found that PDW levels were significantly higher in PE patients when compared with healthy controls (P = 0.003). Donzé et al.  showed that anaemia is common in patients with PE, and decreased haemoglobin level is independently associated with an increased mortality. In the present study, we also found that the mean haemoglobin level was significantly lower than the control group. RDW is a quantitative measurement of the size variation of erythrocytes [2, 25]. Elevated RDW level was supposed to be a result of inflammatory processes in patients with pulmonary hypertension, cardiovascular and thrombotic diseases [2, 25-27]. Ozsu et al.  showed that RDW is an independent predictor of mortality in patients with PE. However, authors did not compare RDW levels of PE patients with control groups. In our study, we found a significantly increased RDW value in patients with PE compared with controls. Based on these results, we suggest that PDW and RDW levels may be used in the assessment of PE.
When we compared all these laboratory data in patients with massive and submassive PE, we found that higher MPV levels in massive PE patients than submassive PE (Table 5). Moreover, MPV was significantly correlated with hospital length of stay. These results also support our hypothesis that MPV can predict disease severity in PE patients.
To our knowledge, this is the first study investigating the relationship between laboratory findings and computed tomography indices in PE patients. In this study, we found that MPV, PDW and D-Dimer levels were correlated with the pulmonary arterial occlusion level assessed by CTPAOIR. These findings suggest that pulmonary arterial occlusion level that was the indicator of the massive PE can be predicted with the increased level of MPV, PDW and D-Dimer.
Main limitation of this study was retrospective design. Another important limitation was the small number of patients with PE. Moreover, further prospective studies including larger participants are needed to confirm and explore these results.
In conclusion, MPV and PDW as potential markers of platelet activation can be used in the determination of disease severity, hospital length of stay and lead therapeutic options for PE patients.
- 4The value of the computed tomographic obstruction index in the identification of massive pulmonary thromboembolism. Diagn Interv Radiol. 2012;18: 255–260., , , . , .
- 8Platelet indices in patients with acute pulmonary embolism. Scand J Clin Lab Invest. 2011;71: 163–167., , , .