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To estimate the prevalence of thrombocytopaenia and its role as prognostic marker in patients of paediatric intensive care unit
*Corresponding author: Gurudutt Joshi, Department of Paediatrics, Surat Municipal Institute of Medical Education and Research, Surat, Gujarat, India. joshigurudutt@yahoo.com
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Received: ,
Accepted: ,
How to cite this article: Joshi G, Budh H. To estimate the prevalence of thrombocytopaenia and its role as prognostic marker in patients of paediatric intensive care unit. Karnataka Paediatr J 2022;37:13-8.
Abstract
Objectives:
Platelets play an important role in normal homeostasis and thrombus formation. They help in reducing vascular permeability, mediating inflammatory processes, promoting wound healing and host defence mechanisms. The aim of this was to estimate the prevalence of thrombocytopaenia, to categorise thrombocytopaenia according to the severity and to evaluate the role of thrombocytopaenia as a prognostic marker in patients admitted in PICU.
Materials and Methods:
This was a prospective observational study over a period of 15 months. One hundred and eighty patients of age 1 month–17 years, critically ill, admitted in PICU or transferred from paediatric ward were enrolled. Those, who had thrombocytopaenia during admission or during PICU stay, were labelled as ‘Thrombocytopaenia’ group, while the remaining patients who did not have thrombocytopaenia were grouped as ‘No thrombocytopaenia’ group.
Results:
The prevalence of thrombocytopaenia in PICU was 37.78% category wise, 35.29%, 33.82%, 19.12% and 11.76% of patients had mild, moderate, severe and very severe thrombocytopaenia, respectively. Mean duration of stay in PICU was more with severe and very severe thrombocytopaenia, followed by moderate and mild thrombocytopaenia, which was statistically significant (P = 0.00037). Mortality was higher in thrombocytopaenic group as compared to non-thrombocytopaenic patients expired, which was statistically significant (P = 0.001013).
Conclusion:
The prevalence of thrombocytopaenia in this study was similar to other studies. Severity of thrombocytopaenia correlated well with the duration of PICU stay. Overall mortality was 22.22% in this study.
Keywords
Thrombocytopaenia
Prevalence
Paediatric intensive care unit
INTRODUCTION
The circulating life span of platelets is 10–14 days. Normal platelet count is 150–450 × 109/L. Decrease in platelet count below 150 × 109/L is labelled as thrombocytopaenia. Disseminated intravascular coagulation, increased destruction, reduced production, increased consumption and abnormal sequestration are mechanism of thrombocytopaenia. Thrombocytopaenia is a common complication in patients admitted to PICUs and may require transfusions.[1-5] The prevalence of thrombocytopenia varies in PICUs ranging from 13% to 60%.[6-9] Some of the drugs such as beta-lactams, linezolid, vancomycin and anticonvulsants such as phenytoin and valproic acid also cause decrease in platelet counts.[10-13] Implications of platelet count and its outcome have been studied in adult medical intensive care units but there are few studies and scarce data available, as regards prevalence of thrombocytopaenia and its outcome in paediatric intensive care units (PICU), particularly in Indian setup; hence, this study was planned. Outcome of this study finding may add to the existing literature.
MATERIALS AND METHODS
This study was a prospective observational study conducted in PICU, over a period of 15 months (from 1 December 2018 to 29 February 2020). A study was approved by the ‘Institutional Ethics Committee’ and a written informed consent from the parent/guardian of enrolled patients was obtained. A total of 246 patients were enrolled, out of which 18 expired within 48 h of admission, 11 patients were discharged against medical advice (DAMA), 19 were transferred to paediatric ward after stabilisation of vitals within 48 h of PICU stay, 12 had deranged coagulation profile, five had received platelet transfusion in other setup before admission in PICU of our hospital and one patient had Glanzmann thrombasthenia, all these patients were excluded from this study. In addition, those patients, whose parents did not give consent, who had deranged coagulation profile, platelet function disorder and received platelet transfusion, were also excluded from the study. The remaining 180 patients were studied in detail and subjected to statistical analysis. Patients were studied for their entire duration of PICU stay (till discharge, transfer to paediatric wards, DAMA or death).
Sampling method
Platelet counts were performed as a part of routine investigations at the time of admission and as per treating physician but it was ensured that minimum of two investigations was done during the entire PICU stay. Any discrepancy in platelet count was counter confirmed by expert faculty. Patients with any of the platelet counts showing thrombocytopaenia during the duration of PICU stay were grouped into ‘Thrombocytopaenic’ group while the remaining patients who did not develop thrombocytopaenia during PICU stay duration were grouped into ‘No thrombocytopaenic’ group. Data were entered into predesigned pro forma. The lowest platelet count on admission or during PICU stay was used to grade the severity of thrombocytopaenia.
Statistical analysis
The sample size was calculated as per the average annual admissions in the PICU. The level of significance was 95%. The sample size calculated was 178 for the present study. Qualitative data were presented in the form of frequency (number) and percentage. Association between ‘Thrombocytopaenia’ and ‘No thrombocytopaenia’ with the qualitative variables was assessed by Chi-square test for 2 × 2 tables along with Yates correction and Fisher’s exact test where Chi-square was not valid because of small counts. This analysis was done with the help of OpenEpi software. Quantitative data were represented by mean ± SD. For more than 2 rows and columns, R X C table for Chi-square testing was used for statistical analysis in OpenEpi software. Independent t-test and ANOVA test were applied for the evaluation of quantitative data wherever applicable. Odds ratio was applied for the evaluation of association between thrombocytopaenia and risk factors. Results were graphically represented where deemed necessary. Statistical analysis was done by MS Excel 2007, OpenEpi software (version 3.01) and SPSS 20 software. Graphical representation was done in MS Word 2007 and MS Excel 2007. P < 0.05 was considered statistically significant and confidence interval was at 95% confidence limit.
RESULTS
The classification of thrombocytopaenia[14] is as shown in [Table 1]. As shown in [Table 2], out of the 180 patients studied, 68 patients (37.78%) had thrombocytopaenia at least on a single occasion, while the duration of PICU stay, whereas 112 patients (62.22%) had platelet counts within the normal range. Fifty-nine patients from 68 patients had thrombocytopaenia on admission, whereas nine patients developed thrombocytopaenia during the PICU stay. The prevalence of thrombocytopaenia was observed to be 37.78% (i.e., 68 patients out of 180). Out of 180 patients, 92 patients (51.11%) are male and 88 patients are female (48.89%). Sex: Male predominance was observed with M: F ratio of 1.04:1. Age: The majority of the patients 64 (35.56%) were in the age group of 1–12 months, followed by 6–10 years and 11–15 years with 16 patients (16.11%) each. Mean age of the study population was 5.40 ± 5.94 years.
As shown in [Table 3], 68 patients had thrombocytopaenia, out of 180 patients enrolled, 24 patients (35.29%) had mild thrombocytopaenia, 23 patients (33.82%) had moderate thrombocytopaenia, 13 patients (19.12%) had severe thrombocytopaenia and 8 patients (11.76%) had very severe thrombocytopaenia.
Mean duration of PICU stay was 5.21 (~5) days and majority that is, 109 patients (60.59%) had <5 days of PICU stay. Ten patients (5.56%) had PICU stay of 5 days whereas 61 patients (33.89%) had PICU stay of more than 5 days, based on the mean duration of PICU stay, the study population was divided into three groups, with PICU stay lesser than, equal to and more than mean duration. As shown in [Table 4], the majority of thrombocytopaenic patients (51.47%) had PICU stay more than mean, while the majority of nonthrombocytopaenic patients (71.43%) had PICU stay of lesser than mean. Statistically significant difference (P = 0.0003749) was observed with regard to the duration of PICU stay between the two groups. Hence, thrombocytopaenic patients required longer PICU stay duration as compared to nonthrombocytopaenic patients.
As shown in [Table 5], the mean duration of PICU stay for patients with thrombocytopaenia was 6.62 days, while it was 4.36 days in patients without thrombocytopaenia. Statistically significant difference was observed on comparison of mean PICU stay between the two groups (P = 0.00003585); hence, mean PICU stay was longer in thrombocytopaenic patients as compared to non-thrombocytopaenic patients.
As shown in [Table 6], mean PICU stay duration was more in severe thrombocytopaenia (10.15 days) followed by very severe thrombocytopaenia (8 days). There was statistically significant difference (P = 0.00037) observed on comparison of mean PICU stay with severity of thrombocytopaenia. Hence, the mean PICU duration is more for patients with severe and very severe thrombocytopaenia as compared to patients with mild and moderate thrombocytopaenia. No statistical test could be applied as it does not meet Cochrane criteria for Pearson Chi-square testing between severity of thrombocytopaenia and gender as well as age.
[Table 7] reflects that overall mortality observed in this study was 22.22% (40 patients out of total 180 patients studied). From the 140 patients (77.78%) that survived during the period of this study, 129 patients (71.67%) were given discharge after the completion of treatment whereas 11 patients (6.11%) had taken DAMA due to varied reasons such as personal, social or economical issues after being vitally stable and transferred to paediatric ward. Patients who had taken DAMA during the course of treatment and vitally unstable have been excluded from this study. Only those patients who had taken DAMA after being vitally stable and transferred to paediatric ward have been included in the study. Gender and age were not found to be statistically significant, as risk factors for thrombocytopaenia, as p value for both was 0.7019 and 0.6458, respectively.
[Table 8] depicts that 35.29% of thrombocytopaenic patients expired, while only 14.29% of non-thrombocytopaenic patients expired. Statistically significant difference was observed on comparison of mortality and thrombocytopaenia. Hence, mortality was more in patients with thrombocytopaenia as compared to patients without thrombocytopaenia. When gender was considered as risk factor for mortality in thrombocytopaenic patients, it was found to be statistically insignificant as P = 0.3858. No statistical test can be applied, to age, as a risk factor for mortality in thrombocytopaenic patients, as it did not meet Cochrane criteria for Pearson Chi-square testing.
| Grade of thrombocytopaenia | Platelet counts (μL) |
|---|---|
| Mild | 100,000–150,000 |
| Moderate | 50,000–100,000 |
| Severe | 20,000–50,000 |
| Very severe | <20,000 |
| Thrombocytopaenia | Number | Percentage |
|---|---|---|
| Present | 68 | 37.78 |
| Absent | 112 | 62.22 |
| Total | 180 | 100 |
| Severity of thrombocytopaenia | Number | Percentage |
|---|---|---|
| Mild | 24 | 35.29 |
| Moderate | 23 | 33.82 |
| Severe | 13 | 19.12 |
| Very severe | 8 | 11.76 |
| Duration of PICU stay | Number | Percentage | Thrombocytopaenia | Total | |||
|---|---|---|---|---|---|---|---|
| Present | Present | ||||||
| Number | Percentage | Number | Percentage | ||||
| <5 days | 109 | 60.56 | 29 | 42.65 | 80 | 71.43 | 109 |
| 5 days | 10 | 5.55 | 4 | 5.88 | 6 | 5.36 | 10 |
| More than 5 days | 61 | 33.89 | 35 | 51.47 | 26 | 23.21 | 61 |
| Total | 180 | 100 | 68 | 100 | 112 | 100 | 180 |
| Chi-square tests | Value | df | P-value | Association | |||
| Pearson Chi-square | 15.78 | 2 | 0.0003749 | Significant | |||
Mean duration of PICU stay of the study population was 5.21±3.63 days
| Thrombocytopaenia | Number of patients | Mean±SD | Minimum | Maximum | |||
|---|---|---|---|---|---|---|---|
| Present | 68 | 6.62±4.04 | 2 | 16 | |||
| Absent | 112 | 4.36±3.07 | 2 | 22 | |||
| Total | 180 | 5.21±3.62 | 2 | 22 | |||
| Independent t-test | Value | df | Lower limit | Upper limit | Mean difference | P-value | Association |
| Equal variance | 4.24 | 178 | 1.208 | 3.311 | 2.26 | 0.00003585 | Significant |
| Severity of thrombocytopaenia | No. of patients | Mean PICU stay±SD | Min | Max | ||
|---|---|---|---|---|---|---|
| Mild | 24 | 3.96±3.97 | 2 | 12 | ||
| Moderate | 23 | 6.91±4.07 | 2 | 13 | ||
| Severe | 13 | 10.15±4.26 | 3 | 16 | ||
| Very severe | 8 | 8.00±4.05 | 4 | 12 | ||
| ANOVA test | Value | df | Mean square | P-value | Association | |
| Equal variance | 348.97 | 3 | 116.325 | 0.00037 | Significant | |
As shown in [Table 9], the mean PICU stay duration is longer in expired thrombocytopaenic patients as compared to thrombocytopaenic patients who survived and these data were statistically significant (P = 0.000029). Maximum PICU stay was longer in expired thrombocytopaenic patients as compared to survived ones. Hence, longer PICU stay was associated with mortality in thrombocytopaenic patients and may be used as a mortality predictor in thrombocytopaenic patients.
DISCUSSION
Prevalence
The prevalence of thrombocytopaenia observed in various studies ranges from 25 to 60%. In this study, the prevalence was 37.78%. This is similar to the results shown in the studies conducted by Sah et al.[15] and Kaur et al.[1] where the prevalence of thrombocytopaenia was 34% and 32.36%, respectively. Relatively higher prevalence was observed in the studies conducted by Divecha et al.[8] (60.3%), Yilmaz et al.[6] (59.57%) and Mussa et al.[16] (44.61%), respectively, while relatively lower prevalence was observed in the studies conducted by Krishnan et al.[17] (25.3%) and Agrawal et al.[7] (25%). The difference in the prevalence of thrombocytopaenia may be attributed to the varying inclusion criteria of the different studies. Moreover, patients with burns have a separate ICU and hence not included in the present study. Almost all above studies had also male preponderance.
Age
Maximum age range was 1 month–18 years in the study of Mundkur et al.[18] The mean age of the patients in the present study was 5.4 years which is similar to the studies conducted by Mittal et al.[19] and Mussa et al.[16] The range of age groups of the study population in this study was 1 month–17 years, which is similar to that of the study by Mundkur et al.[18] who had included patients from 1 month to 18 years of age. The median age observed in our study was 36 months (3 years), which is similar to the study by Agrawal et al.[7] (2008), where a median age was 32 months. Yilmaz et al. (2013)[6] conducted a study which showed the median age of 24.
Severity of thrombocytopaenia
In this study, maximum patients 24 out of total 68 thrombocytopaenic patients that is, 35.29% had mild thrombocytopaenia followed in decreasing order by moderate thrombocytopaenia (33.82%), severe thrombocytopaenia (19.12%) and very severe thrombocytopaenia (11.76%). Similar results were observed in the study conducted by Sah et al.[15] where maximum (41.7%) patients had mild thrombocytopaenia (platelet count <150 × 109/L) followed by 32.3% of patients with moderate thrombocytopaenia (platelet count <100 × 109/L) and 26.4% of patients with severe thrombocytopaenia (platelet count <50 × 109/L). Studies conducted by Mundkur et al.[18] and Kaur et al.[1] who showed higher prevalence of severe thrombocytopaenia 51% (platelet count <50 × 109/L) whereas the study by Yilmaz et al.[6] showed lower prevalence (7.45%) of severe thrombocytopaenia as compared to our study. Thus, there is varying prevalence of severity of thrombocytopaenia.
| Final outcome | Total no. of patients | Percentage |
|---|---|---|
| Survived | 140 | 77.78 |
| Expired | 40 | 22.22 |
| Total | 180 | 100.00 |
| Outcome | Thrombocytopaenia | Total | ||
|---|---|---|---|---|
| Yes (n=68) | No (n=112) | |||
| Survived | ||||
| No. | 44 | 96 | 140 | |
| % | 64.71% | 85.71% | 77.78% | |
| Expired | ||||
| No. | 24 | 16 | 40 | |
| % | 35.29% | 14.29% | 22.22% | |
| Total | ||||
| No. | 68 | 112 | 180 | |
| % | 100.00% | 100.00% | 100.00% | |
| Chi-square tests | Value | df | P-value | Association |
| Pearson Chi-square | 10.8 | 1 | 0.001013 | Significant |
| Outcome | Number of patients | Mean PICU stay duration Mean±SD |
Min. | Max. | ||
|---|---|---|---|---|---|---|
| Expired | 24 | 9.58±4.04 | 2 | 16 | ||
| Survived | 44 | 5.00±4.01 | 2 | 12 | ||
| Total | 68 | 6.62±4.04 | 2 | 16 | ||
| Statistical test | Value | df | Mean difference | P-value | Association | |
| Independent t-test | 4.48 | 66 | 0.1464 | 0.000029 | Significant | |
Duration of PICU stay
In this study, the mean duration of PICU stay was found to be 5.21 (±3.63) days. The majority of patients (60.56%) had PICU stay duration of <5 days whereas 5.55% had PICU stay duration of 5 days and 33.89% had more than 5 days of PICU stay. The study conducted by Mundkur et al.[18] who showed that the median duration of PICU stay in mild and moderate thrombocytopaenia was 4 days and in severe thrombocytopaenia was 3 days. The median duration of PICU stay was 8 days (3–120 days) in the study by Yilmaz et al.[6] In the study by Mussa et al.,[16] PICU stay duration was divided into <7 days, 7–14 days and >14 days with 56.2%, 25.4% and 18.5% of study population, respectively. Agrawal et al.[7] found that 99 (71.1%) patients had PICU stay duration of <7 days while 20 (14.5%) had more than 14 days of PICU stay and 19 (13.8%) PICU stay of 7–14 days. The duration of PICU stay would depend on the type of diagnosis of the patients admitted in the PICU, treatment protocols and the outcome.
Duration of PICU stay and thrombocytopaenia
In this study as well as studies by Yilmaz et al.,[6] Mussa et al.,[16] Agrawal et al.[7] and Krishnan et al.,[17] longer duration of stay was observed in thrombocytopaenia group as compared to non-thrombocytopaenia group, which was statistically significant whereas in a study of Mittal et al.,[19] this difference was insignificant.
Outcome
Mortality was 22.22% in this study, which was comparable to Sah et al.[15] (26%), Mittal et al.[19] (20%) and Kaur et al.[1] (19.64%), whereas it was 37.2% and 53.07% in Yilmaz et al.[6] and Mussa et al.[16] study. The difference may be attributed to the different diagnosis of the patients and admission criteria in different studies.
Thrombocytopaenia and mortality
In this study, 35.29% of thrombocytopaenic patients expired while only 14.29% of non-thrombocytopaenic patients expired and this was statistically significant. Similarly, statistically significant association between mortality and thrombocytopaenia was observed in various studies as shown in table below. Kaur et al.[1] and Mittal et al.[19] observed that mortality among thrombocytopaenic and nonthrombocytopaenic patients was similar to this study. Higher mortality was observed among thrombocytopaenic patients in the studies by Sah et al.,[15] Yilmaz et al.,[6] Mussa et al.[16] and Agrawal et al.[7] while lower mortality was seen among thrombocytopaenic patients in studies by Mundkur et al.[18] and Krishnan et al.[17] Sah et al.[15] observed that there were 18 times more risk of mortality among thrombocytopaenic patient compared to non-thrombocytopaenic patients with odds ratio 18 at 95% CI. Mortality including this study was statistically significant in thrombocytopaenic group as compared to non-thrombocytopaenic group in all studies.
CONCLUSION
The prevalence of thrombocytopaenia in the PICU observed in this study was 37.78%, of which mild thrombocytopaenia was predominant (35.29%). Male preponderance was observed in this study. Duration of stay in PICU correlated well with a severity of thrombocytopaenia, also thrombocytopaenic patients had statistically higher risk of death; hence, thrombocytopaenia may be considered as an important risk factor for mortality.
Limitation of the study
Patients with burns could not be recruited in this study, as there was separate burns ward in the institute. Association of risk factors with a severity of thrombocytopaenia because could not be correlated as they were not meeting Cochrane criteria for statistical testing. The role of thrombocytopaenic drugs in causing thrombocytopaenia was not assessed.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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