Introduction: Platelet activation, thrombocytopenia and coagulation abnormalities have been described in coronavirus disease 2019 (COVID-19). Routinely generated platelet indices may offer inexpensive markers of disease severity. Objective: To evaluate changes in platelet parameters measured on a five-part haematology analyser and D-dimer levels in patients with COVID-19 and to assess their association with intensive cardiac care unit (ICCU) admission. Methods: This cross-sectional study included 100 patients with COVID-19 confirmed by reverse transcription polymerase chain reaction or rapid antigen testing. Fifty patients were admitted to the ICCU and 50 to the ward. Admission samples were analysed for platelet count, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), mean platelet component (MPC), mean platelet mass (MPM), platelet-large cell count (P-LCC), platelet-large cell ratio (P-LCR), platelet-to-lymphocyte ratio (PLR) and D-dimer. Results: ICCU patients had lower platelet count, PLR and PCT, and higher MPV, PDW, MPM, P-LCR and D-dimer than ward patients. Platelet count was 102.86±61.23 versus 315.60±146.57×10³/µL and D-dimer was 2559.12±1661.18 versus 389.44±161.28 ng/mL (both P<0.0001). In multivariable analysis, age, platelet count and D-dimer were independently associated with ICCU admission. Conclusion: Admission platelet indices and D-dimer showed significant associations with higher-acuity care in COVID-19. These routinely available parameters may support early risk stratification when interpreted with clinical findings.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a clinical spectrum ranging from asymptomatic infection to respiratory failure and multiorgan dysfunction. Haematological and thrombotic abnormalities are frequent, and lower platelet counts have been associated with severe disease.1,2 Platelet activation can be reflected by routinely generated indices such as mean platelet volume (MPV), platelet distribution width (PDW) and platelet-large cell ratio (P-LCR), while D-dimer reflects activation of coagulation and fibrinolysis and is associated with COVID-19 severity.3-5 Because these measurements are inexpensive and rapidly available, the present study evaluated admission platelet parameters on a five-part cell counter and D-dimer levels in patients with COVID-19, and assessed their association with ICCU versus ward admission.
Study design and setting: This cross-sectional study was conducted in the Department of Pathology of a tertiary care hospital over an 18-month period ([insert exact study dates]). The study included 100 patients with COVID-19, comprising 50 patients admitted to the ICCU and 50 admitted to the ward. Eligibility criteria: Patients of all ages and both sexes with COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR) or rapid antigen test (RAT) were eligible. Samples that were inadequate for automated analysis, diluted or haemolysed were excluded. Ethics: The study was conducted after approval of the Institutional Ethics Committee ([insert approval number and date]). Written informed consent was obtained from the patient or, where applicable, the parent/legally authorised representative. Laboratory assessment: Peripheral blood collected at admission in an ethylenediaminetetraacetic acid tube was analysed on a Siemens ADVIA 2120 five-part haematology analyser. Platelet count, lymphocyte percentage, absolute lymphocyte count, MPV, PDW, PCT, MPC, MPM and P-LCC were recorded. PLR was calculated as platelet count divided by absolute lymphocyte count. P-LCR was calculated as P-LCC divided by platelet count. Citrated plasma was used for D-dimer measurement on the iCHROMA-D system. Clinical details were obtained from hospital records. Statistical analysis: Data were analysed using IBM SPSS Statistics version 28. Continuous variables are presented as mean±standard deviation and categorical variables as frequency and percentage. Continuous variables were compared between ICCU and ward groups using the independent-samples t-test. Categorical variables were compared using the chi-square test or Fisher exact test when appropriate. Associations with ICCU admission were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Multivariable logistic regression was used to identify independent factors associated with ICCU admission. A two-sided P value <0.05 was considered statistically significant.
A total of 100 patients with confirmed COVID-19 were analysed; 50 were admitted to the ICCU and 50 to the ward. Fever was the most common presenting complaint (62%). Difficulty in breathing was substantially more frequent in ICCU patients than ward patients (56% vs 2%; P<0.001). Headache, sore throat and running nose also differed significantly between the two groups (Table 1).
Table 1. Presenting complaints according to level of care
|
Presenting complaint |
Total n (%) |
ICCU n (%) |
Ward n (%) |
P value |
|
Fever |
62 (62) |
32 (64) |
30 (60) |
0.680 |
|
Headache |
12 (12) |
2 (4) |
10 (20) |
0.028 |
|
Fatigue |
7 (7) |
2 (4) |
5 (10) |
0.436 |
|
Cough |
20 (20) |
11 (22) |
9 (18) |
0.617 |
|
Difficulty in breathing |
29 (29) |
28 (56) |
1 (2) |
<0.001 |
|
Anosmia |
5 (5) |
0 |
5 (10) |
0.056 |
|
Sore throat |
29 (29) |
6 (12) |
23 (46) |
0.010 |
|
Loss of taste |
2 (2) |
1 (2) |
1 (2) |
1.000 |
|
Diarrhoea |
10 (10) |
4 (8) |
6 (12) |
0.741 |
|
Running nose |
7 (7) |
0 |
7 (14) |
0.012 |
|
Drowsiness |
2 (2) |
2 (4) |
0 |
0.495 |
Platelet count, PLR and PCT were significantly lower in ICCU patients, whereas MPV, PDW, MPM, P-LCR and D-dimer were higher (Table 2). Mean platelet count was 102.86±61.23×10³/µL in the ICCU group compared with 315.60±146.57×10³/µL in the ward group (P<0.0001). Mean D-dimer was 2559.12±1661.18 ng/mL in ICCU patients and 389.44±161.28 ng/mL in ward patients (P<0.0001). MPV and PDW were positively correlated (r=0.4263; P<0.0001).
Table 2. Comparison of laboratory parameters between ICCU and ward patients
|
Parameter |
Total mean±SD |
ICCU mean±SD |
Ward mean±SD |
P value |
|
Platelet count (×10³/µL) |
209.23±154.65 |
102.86±61.23 |
315.60±146.57 |
<0.0001 |
|
Lymphocytes (%) |
22.76±13.48 |
22.55±14.96 |
22.97±11.97 |
0.8750 |
|
Absolute lymphocytes (×10³/µL) |
1.53±1.08 |
1.54±1.31 |
1.53±0.81 |
0.9694 |
|
PLR |
165.65±124.16 |
101.16±74.20 |
230.13±130.98 |
<0.0001 |
|
MPV (fL) |
9.32±0.80 |
10.34±1.78 |
8.30±0.80 |
<0.0001 |
|
PDW |
60.57±18.00 |
64.18±19.53 |
56.96±15.70 |
0.0446 |
|
PCT (%) |
0.18±0.12 |
0.10±0.066 |
0.26±0.11 |
<0.0001 |
|
MPC |
25.26±1.74 |
24.84±2.25 |
25.26±1.74 |
0.2980 |
|
MPM |
2.15±0.30 |
2.30±0.34 |
1.99±0.15 |
<0.0001 |
|
P-LCC |
7.86±5.64 |
7.62±6.63 |
8.10±4.49 |
0.2132 |
|
D-dimer (ng/mL) |
1474.28±1602.32 |
2559.12±1661.18 |
389.44±161.28 |
<0.0001 |
|
P-LCR |
0.048±0.043 |
0.068±0.050 |
0.027±0.010* |
<0.0001 |
Abbreviations: ICCU, intensive cardiac care unit; MPV, mean platelet volume; PDW, platelet distribution width; PCT, plateletcrit; MPC, mean platelet component; MPM, mean platelet mass; P-LCC, platelet-large cell count; P-LCR, platelet-large cell ratio; PLR, platelet-to-lymphocyte ratio. *Original source table reported 0.27; 0.027 is an internal-consistency correction and must be verified against the raw dataset before submission.
On univariable analysis, age >47 years, difficulty in breathing, platelet count <150×10³/µL, absolute lymphocyte count ≤1.13×10³/µL, PLR ≤113.64, MPV >8.4 fL, PDW >65.7, PCT ≤0.16%, MPC ≤23.5, MPM >2.09, P-LCC ≤5, D-dimer >500 ng/mL and P-LCR >0.04 were associated with ICCU admission (Table 3). In the multivariable model, age (OR 1.19, 95% CI 1.01–1.39; P=0.029), platelet count (OR 0.007, 95% CI 0.000–0.88; P=0.044) and D-dimer (OR 1.00, 95% CI 1.00–1.01; P=0.023) remained independently associated with ICCU admission.
Table 3. Factors associated with ICCU admission
|
Factor / cut-off |
ICCU |
Ward |
OR |
95% CI |
P value |
|
Age >47 y |
44 |
24 |
7.94 |
2.65–26.40 |
<0.0001 |
|
Difficulty breathing: yes |
29 |
2 |
33.14 |
7.03–300.46 |
<0.0001 |
|
Platelet <150×10³/µL |
40 |
3 |
62.67 |
14.64–354.05 |
<0.0001 |
|
Lymphocytes ≤20.6% |
28 |
23 |
1.49 |
0.63–3.54 |
0.3172 |
|
Absolute lymphocytes ≤1.13 |
27 |
15 |
2.74 |
1.11–6.78 |
0.0150 |
|
PLR ≤113.64 |
35 |
5 |
21.00 |
6.37–78.36 |
<0.0001 |
|
MPV >8.4 fL |
49 |
19 |
79.94 |
11.17–3321.64 |
<0.0001 |
|
PDW >65.7 |
36 |
13 |
7.31 |
2.78–19.52 |
<0.0001 |
|
PCT ≤0.16% |
40 |
6 |
29.33 |
8.82–104.46 |
<0.0001 |
|
MPC ≤23.5 |
17 |
4 |
5.92 |
1.69–25.98 |
0.0014 |
|
MPM >2.09 |
38 |
10 |
12.67 |
4.48–36.72 |
<0.0001 |
|
P-LCC ≤5 |
24 |
14 |
2.37 |
0.96–5.94 |
0.0394 |
|
D-dimer >500 ng/mL |
48 |
13 |
68.30 |
13.77–620.74 |
<0.0001 |
|
P-LCR >0.04 |
35 |
8 |
12.25 |
4.26–36.77 |
<0.0001 |
Figure 1: A positive correlation between MPV and PDW (r-value=0.4263) with highly significant difference of p=<0.0001.
A total of 100 patients with confirmed COVID-19 were analysed; 50 were admitted to the ICCU and 50 to the ward. Fever was the most common presenting complaint (62%). Difficulty in breathing was substantially more frequent in ICCU patients than ward patients (56% vs 2%; P<0.001). Headache, sore throat and running nose also differed significantly between the two groups (Table 1).
Table 1. Presenting complaints according to level of care
|
Presenting complaint |
Total n (%) |
ICCU n (%) |
Ward n (%) |
P value |
|
Fever |
62 (62) |
32 (64) |
30 (60) |
0.680 |
|
Headache |
12 (12) |
2 (4) |
10 (20) |
0.028 |
|
Fatigue |
7 (7) |
2 (4) |
5 (10) |
0.436 |
|
Cough |
20 (20) |
11 (22) |
9 (18) |
0.617 |
|
Difficulty in breathing |
29 (29) |
28 (56) |
1 (2) |
<0.001 |
|
Anosmia |
5 (5) |
0 |
5 (10) |
0.056 |
|
Sore throat |
29 (29) |
6 (12) |
23 (46) |
0.010 |
|
Loss of taste |
2 (2) |
1 (2) |
1 (2) |
1.000 |
|
Diarrhoea |
10 (10) |
4 (8) |
6 (12) |
0.741 |
|
Running nose |
7 (7) |
0 |
7 (14) |
0.012 |
|
Drowsiness |
2 (2) |
2 (4) |
0 |
0.495 |
Platelet count, PLR and PCT were significantly lower in ICCU patients, whereas MPV, PDW, MPM, P-LCR and D-dimer were higher (Table 2). Mean platelet count was 102.86±61.23×10³/µL in the ICCU group compared with 315.60±146.57×10³/µL in the ward group (P<0.0001). Mean D-dimer was 2559.12±1661.18 ng/mL in ICCU patients and 389.44±161.28 ng/mL in ward patients (P<0.0001). MPV and PDW were positively correlated (r=0.4263; P<0.0001).
Table 2. Comparison of laboratory parameters between ICCU and ward patients
|
Parameter |
Total mean±SD |
ICCU mean±SD |
Ward mean±SD |
P value |
|
Platelet count (×10³/µL) |
209.23±154.65 |
102.86±61.23 |
315.60±146.57 |
<0.0001 |
|
Lymphocytes (%) |
22.76±13.48 |
22.55±14.96 |
22.97±11.97 |
0.8750 |
|
Absolute lymphocytes (×10³/µL) |
1.53±1.08 |
1.54±1.31 |
1.53±0.81 |
0.9694 |
|
PLR |
165.65±124.16 |
101.16±74.20 |
230.13±130.98 |
<0.0001 |
|
MPV (fL) |
9.32±0.80 |
10.34±1.78 |
8.30±0.80 |
<0.0001 |
|
PDW |
60.57±18.00 |
64.18±19.53 |
56.96±15.70 |
0.0446 |
|
PCT (%) |
0.18±0.12 |
0.10±0.066 |
0.26±0.11 |
<0.0001 |
|
MPC |
25.26±1.74 |
24.84±2.25 |
25.26±1.74 |
0.2980 |
|
MPM |
2.15±0.30 |
2.30±0.34 |
1.99±0.15 |
<0.0001 |
|
P-LCC |
7.86±5.64 |
7.62±6.63 |
8.10±4.49 |
0.2132 |
|
D-dimer (ng/mL) |
1474.28±1602.32 |
2559.12±1661.18 |
389.44±161.28 |
<0.0001 |
|
P-LCR |
0.048±0.043 |
0.068±0.050 |
0.027±0.010* |
<0.0001 |
Abbreviations: ICCU, intensive cardiac care unit; MPV, mean platelet volume; PDW, platelet distribution width; PCT, plateletcrit; MPC, mean platelet component; MPM, mean platelet mass; P-LCC, platelet-large cell count; P-LCR, platelet-large cell ratio; PLR, platelet-to-lymphocyte ratio. *Original source table reported 0.27; 0.027 is an internal-consistency correction and must be verified against the raw dataset before submission.
On univariable analysis, age >47 years, difficulty in breathing, platelet count <150×10³/µL, absolute lymphocyte count ≤1.13×10³/µL, PLR ≤113.64, MPV >8.4 fL, PDW >65.7, PCT ≤0.16%, MPC ≤23.5, MPM >2.09, P-LCC ≤5, D-dimer >500 ng/mL and P-LCR >0.04 were associated with ICCU admission (Table 3). In the multivariable model, age (OR 1.19, 95% CI 1.01–1.39; P=0.029), platelet count (OR 0.007, 95% CI 0.000–0.88; P=0.044) and D-dimer (OR 1.00, 95% CI 1.00–1.01; P=0.023) remained independently associated with ICCU admission.
Table 3. Factors associated with ICCU admission
|
Factor / cut-off |
ICCU |
Ward |
OR |
95% CI |
P value |
|
Age >47 y |
44 |
24 |
7.94 |
2.65–26.40 |
<0.0001 |
|
Difficulty breathing: yes |
29 |
2 |
33.14 |
7.03–300.46 |
<0.0001 |
|
Platelet <150×10³/µL |
40 |
3 |
62.67 |
14.64–354.05 |
<0.0001 |
|
Lymphocytes ≤20.6% |
28 |
23 |
1.49 |
0.63–3.54 |
0.3172 |
|
Absolute lymphocytes ≤1.13 |
27 |
15 |
2.74 |
1.11–6.78 |
0.0150 |
|
PLR ≤113.64 |
35 |
5 |
21.00 |
6.37–78.36 |
<0.0001 |
|
MPV >8.4 fL |
49 |
19 |
79.94 |
11.17–3321.64 |
<0.0001 |
|
PDW >65.7 |
36 |
13 |
7.31 |
2.78–19.52 |
<0.0001 |
|
PCT ≤0.16% |
40 |
6 |
29.33 |
8.82–104.46 |
<0.0001 |
|
MPC ≤23.5 |
17 |
4 |
5.92 |
1.69–25.98 |
0.0014 |
|
MPM >2.09 |
38 |
10 |
12.67 |
4.48–36.72 |
<0.0001 |
|
P-LCC ≤5 |
24 |
14 |
2.37 |
0.96–5.94 |
0.0394 |
|
D-dimer >500 ng/mL |
48 |
13 |
68.30 |
13.77–620.74 |
<0.0001 |
|
P-LCR >0.04 |
35 |
8 |
12.25 |
4.26–36.77 |
<0.0001 |
Figure 1: A positive correlation between MPV and PDW (r-value=0.4263) with highly significant difference of p=<0.0001.
The present study demonstrates that several admission platelet parameters and D-dimer differed significantly between patients requiring ICCU care and those managed in the ward. The most marked differences were a lower platelet count and PCT, together with higher MPV and D-dimer in ICCU patients. These findings support the concept that both platelet consumption/turnover and coagulation activation accompany more severe COVID-19.1,2,6 Difficulty in breathing was strongly associated with ICCU admission, which is clinically expected in patients with more severe respiratory involvement. Similar studies have reported dyspnoea and other lower respiratory tract symptoms more frequently among patients requiring intensive care.7,8 In contrast, drowsiness was uncommon and was not statistically different between groups in the present dataset; this has been corrected from the earlier draft. The mean platelet count was substantially lower in ICCU patients. Lippi et al. reported in a meta-analysis that platelet counts were lower in severe COVID-19 and that thrombocytopenia was associated with an increased risk of severe disease.2 Yardımcı et al. likewise found lower platelet counts and PCT in patients transferred to intensive care.8 Platelet consumption in microvascular thrombosis, immune-mediated destruction and altered megakaryopoiesis are plausible contributors to thrombocytopenia in severe infection. MPV and PDW were higher in ICCU patients, and MPV correlated positively with PDW. Larger and more heterogeneous platelets may reflect accelerated platelet turnover and release of younger, more reactive platelets. Aydınyılmaz et al. observed associations of MPV and PDW with disease severity and mortality.9 Liu et al. also reported an association between platelet parameters and mortality in COVID-19.10 These observations support the potential value of platelet size indices as adjunctive markers, although analyser-specific differences and timing of sampling should be considered. PLR was lower in the ICCU group in this study, whereas other reports have described higher PLR in severe disease.11,12 This apparently discordant finding may be explained by the pronounced reduction in platelet count in the ICCU group, because PLR is directly dependent on platelet count as well as lymphocyte count. Therefore, PLR should not be interpreted in isolation, particularly in populations with substantial thrombocytopenia. D-dimer showed one of the largest between-group differences, with markedly higher levels in ICCU patients. Elevated D-dimer is a consistent feature of severe COVID-19 and reflects enhanced coagulation and fibrinolysis. Liao et al. found significantly higher D-dimer levels in critically ill patients,13 and Yao et al. reported that D-dimer was associated with disease severity and mortality.5 In the present multivariable model, D-dimer remained independently associated with ICCU admission together with age and platelet count. The clinical implication of these findings is pragmatic: platelet indices are automatically generated with routine complete blood counts and incur little or no additional cost. When combined with D-dimer and clinical assessment, they may help identify patients who need closer observation or escalation of care. However, these parameters should be viewed as supportive risk markers rather than stand-alone prognostic tests. The study has limitations. It was a single-centre cross-sectional study with a modest sample size and an equal number of ICCU and ward patients, which may not represent the natural distribution of disease severity. Measurements were analysed only at admission, so temporal trends could not be evaluated. Important potential confounders such as comorbidities, medications, inflammatory markers, vaccination status and clinical outcomes were not included in the available dataset. Cut-offs were assessed within the study sample and require external validation.
In patients with COVID-19, admission platelet count, MPV, PDW, PCT, MPM, P-LCR and D-dimer differed significantly between ICCU and ward groups. Older age, lower platelet count and higher D-dimer were independently associated with ICCU admission. Because platelet indices are routinely available from automated haematology analysers, they may provide a simple, low-cost adjunct to clinical assessment and D-dimer for early risk stratification. Prospective multicentre studies with serial measurements and external validation are required before specific cut-offs are used for clinical decision-making.
Ethics approval: Institutional Ethics Committee approval obtained
Consent to participate: Written informed consent was obtained from participants or their legally authorised representatives, as applicable.
Funding: NIL
Conflicts of interest: NIL