PRACA ORYGINALNA

ORIGINAL ARTICLE

DIAGNOSTIC ROLE OF SYSTEMIC INFLAMMATION, BLOOD COAGULATION AND PADUA PREDICTION SCORE IN LUNG THROMBOSIS RISK ESTIMATION IN HOSPITALIZED PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA

DIAGNOSTYCZNA ROLA MARKERÓW UKŁADOWEGO STANU ZAPALNEGO, ZABURZEŃ UKŁADU KRZEPNIĘCIA KRWI ORAZ SKALI PADEWSKIEJ W OCENIE RYZYKA WYSTĄPIENIA ZATORU PŁUCNEGO U PACJENTÓW HOSPITALIZOWANYCH Z POWODU ZEWNĄTRZSZPITALNEGO ZAPALENIA PŁUC

Tetyana Pertseva1, Tetyana Kireieieva1, Mariia Krykhtina1, Kseniia Bielosludtseva1, Kateryna Dyagovets2

1Department of internal medicine 1, State Institution “Dnipropetrovsk Medical Academy of Ministry of Health of Ukraine”, Dnipro, Ukraine

2Department of histology, State Institution “Dnipropetrovsk Medical Academy of Ministry of Health of Ukraine”, Dnipro, Ukraine

ABSTRACT

Introduction: Some coagulation and thrombotic disorders during severe CAP could lead to some intravascular disorders and even be the reason of lethal end in hospitalized patients with CAP. But this fact hadn’t been established to the end yet.

The aim was to study the intravascular changes in patients with severe CAP and to estimate the role of parameters of systemic inflammation (procalcitonin (PCT), C-reactive protein (CRP)), blood coagulation test (fibrinogen, D-dimer, heparin time, prothrombin time) and risk of thrombosis in patients with moderate and severe CAP.

Materials and methods: The main group was 63 patients with moderate to severe CAP. The mean age was 54.0 [37.0–63.0] years old, men – 46 (73.0%)). Depending on the severity all patients of the main group were divided into 2 subgroups: subgroup 1 – 36 patients with moderate CAP (the mean age was 51.0 [32.5–62.5] years old, men – 29 (80.5%)), subgroup 2 – 27 patients with severe CAP (the mean age was 56.0 [46.0–68.0] years old, men – 17 (63.0%). Subgroups had no significant difference according to age (p=0,348) and sex (p=0,237). Received results were compared with values in control group. The control group was 10 healthy people (the mean age was 52.0 [35.6–62.0] years old, men – 5 (50.0%)).

Results and conclusions: Patients with severe CAP had significantly higher levels of PCT, CRP, D-dimer, prothrombin time, heparin index and the lowest level of heparin time. This fact shows the highest risk of thrombosis in patients with severe CAP on the background of severe systemic inflammation. The mean level of scores by Padua scale in patients with severe CAP was 5.0 [5.0–6.0] scores, which was significantly higher than in patients with moderate CAP, who had 1.0 [1.0–2.0] scores.

On autopsy of 5 died patients with severe CAP we found thrombosis of lung vessels which differ from embolism or post-mortem blood clots. These changes maybe reflect systemic thrombosis at patients with severe CAP and could be the reasons of increased mortality in this category of patients.

Key words: CAP, thrombosis, Padua scale, inflammation, markers

Wiad Lek 2019, 72, 2, 149-153

Introduction

Сommunity-acquired pneumonia (CAP) is one of the most common causes of mortality among other infectious diseases all over the world. The mortality rate of patients with CAP depends on the severity of the disease and comorbidity [1]. To improve the outcomes in the management of CAP there has recently been a significant attention paid to evidence-based scoring systems and biological markers. They can objectively help to predict the severity, to justify hospital or ICU admission [2]. The role of inflammatory markers had already established rather good. But researchers believe that some coagulation and thrombotic disorders during severe CAP could lead to some intravascular disorders and even be the reason of lethal end in hospitalized patients with CAP [3, 4, 5]. But this fact hadn’t been established to the end yet.

The aim

That’s why the aim was to study the intravascular changes in patients with severe CAP and to estimate the role of parameters of systemic inflammation (procalcitonin (PCT), C-reactive protein (CRP)), blood coagulation test (fibrinogen, D-dimer, heparin time, prothrombin time) and risk of thrombosis in patients with moderate and severe CAP.

Materials and methods

The main group was 63 patients with moderate to severe CAP. The mean age was 54.0 [37.0–63.0] years old, men – 46 (73.0%)). Depending on the severity all patients of the main group were divided into 2 subgroups: subgroup 1 – 36 patients with moderate CAP (the mean age was 51.0 [32.5–62.5] years old, men – 29 (80.5%)), subgroup 2 – 27 patients with severe CAP (the mean age was 56.0 [46.0–68.0] years old, men – 17 (63.0%). Subgroups had no significant difference according to age (p=0,348) and sex (p=0,237).

The formulation of diagnosis CAP and assessment of its severity were determined according to the international guidelines [6] and SMRT-CO scale [7].

General clinical analysis, blood coagulation test, determination of systemic inflammation biomarkers (PCT and CRP) were performed after hospitalization before starting of antibacterial treatment.

Blood coagulation test was done routinely including such parameters as recalcification test, heparin time, heparin index, prothrombin time and ptothrombin index.

The determination of serum PCT levels was by immunochemical electrochemiluminescence method, D-dimer and CRP levels were estimated by immunoturbodimetric method [8, 9].

Received results were compared with values in control group. The control group was 10 healthy people (the mean age was 52.0 [35.6–62.0] years old, men – 5 (50.0%)).

The risk of thrombosis was estimated with the help of Padua Prediction Score for risk of lung thrombosis [10].

At died patients we observed autopsy data including electronic microscope investigations.

Statistical processing of the results in research was carried out using the methods of biometric analysis, implemented in software packages EXCEL-2003 (№ 74017-641-9475201-57075) and STATISTICA 6.0 (№ 31415926535897) [11].

RESULTS AND DISCUSSION

Analyzing the data of main group patients we detect that during hospitalization everybody has clinical symptoms of CAP combining with mono- or bilateral lung infiltration on chest X-ray.

The severity according to the SMRT-CO scale of patients in subgroup 1 was 0.0 [0.0–1.0] scores, in subgroup 2 – 3.0 [3.0–5.0] scores (p=0.000), which proved the right distribution of patient among subgroups.

During investigation of systemic inflammatory markers we found that in both subgroup 1 and subgroup 2 the mean levels of CRP and PCT were higher than in control group (table I). Detailed analysis showed that patients with severe CAP had significantly higher levels of these parameters.

During investigation of blood coagulation test and D-dimer we found that in both subgroup 1 and subgroup 2 the mean levels of D-dimer and prothrombin time were higher than in control group, the mean level of heparin time was lower than in control croup (table II). Detailed analysis showed that patients with severe CAP had significantly higher levels of D-dimer, prothrombin time, heparin index and the lowest level of heparin time. This fact shows the highest risk of thrombosis in patients with severe CAP.

The mean level of scores by Padua scale in patients with severe CAP was 5.0 [5.0–6.0] scores, which was significantly higher than in patients with moderate CAP, who had 1.0 [1.0–2.0] scores (p=0.000) (Fig.1).

Besides the level of Padua scale score correlated significantly with SMRT-CO score, CRP, fibrinogen, heparin time and prothrombin time (Table III, Fig. 2), which demonstrates its relationships with CAP severity by both vital and inflammatory parameters.

During treatment all patients received antibacterial treatment according to standards depending on the severity of disease, mucolytic, oxygenation, symptomatic treatment. Besides, patients with severe CAP received anticoagulants in prophylactic doses.

Unfortunately despite treatment 5 (8%) patients with severe CAP died. On autopsy of we found such pathomorphological signs: macroscopically – thrombosis of small or large branches of the pulmonary artery on the background of expressed purulent-destructive changes (Fig. 3A), microscopically – wall clots, partly with obturating growth, necrosis of surrounding tissues, lymphohystioid and neutrophil infiltration; the organization of the thrombus with the recanalization of the vessels (Fig. 3B).

So we defined that died patients with CAP have thrombosis of lung vessels which differ from embolism or post-mortem blood clots. These changes maybe reflect systemic thrombosis at patients with severe CAP and could be the reasons of increased mortality in this category of patients.

Conclusions

1. Died patients with severe CAP are characterized by lung vessels thrombosis, which could be the reason of high lethality of patients with this disease.

2. Severe CAP is characterized by very high risk of thrombosis by Padua scale, which was confirmed on autopsy. Padua scale could be used in hospitalized patients with CAP for predicting the risk of thrombosis.

3. Increased levels of CRP and PCT are correlated with high risk of lung vessels thrombosis and show the direct connection between systemic inflammation and thrombotic disorders in patients with moderate to severe CAP.

4. Decreased heparin time and increased prothrombin time could be the predictors of thrombotic complications in patients with moderate to severe CAP.

References

1. Torres A, Peetermans WE, Viegi G, Blasi F. Risk factors for community-acquired pneumonia in adults in Europe: a literature review. Thorax 2013; 68: 1057–65.

2. Vail GM, Xie YJ, Haney DJ, Barnes CJ. Biomarkers of thrombosis, fibrinolysis, and inflammation in patients with severe sepsis due to community-acquired pneumonia with and without Streptococcus pneumoniae. Infection 2009; 37:358–64.

3. Violi F, Cangemi R, Calvieri C. Pneumonia, thrombosis and vascular disease. J Thromb Haemost 2014; 12: 1391–400.

4. Clayton TC, Gaskin M, Meade TW. Recent respiratory infection and risk of venous thromboembolism: case–control study through a general practice database. Int J Epidemiol 2011; 40:819–27.

5. Ribeiro DD, Lijfering WM, van Hylckama Vlieg A, Rosendaal FR, Cannegieter SC. Pneumonia and risk of venous thrombosis: results from the MEGA study. J Thromb Haemost 2012; 10:1179–82.

6. Niederman MS, Luna CM. Community-acquired pneumonia guidelines: a global perspective. Semin Respir Crit Care Med 2012; 33(3):298-310.

7. Charles P. GP. and others. SMART-COP: A Tool for Predicting the Need for Intensive Respiratory or Vasopressor Support in Community-Acquired Pneumonia. Clinical Infectious Diseases 2008, 47 (3):375–84.

8. Hedlund J, Hansson L O. Procalcitonin and C-reactive protein levels in community-acquired pneumonia: correlation with etiology and prognosis. Infection 2000; 28:68–73.

9. Gosselin RC, Owings JT, Utter GH. A new method for measuring D-dimer using immunoturbidometry: a study of 255 patients with suspected pulmonary embolism and deep vein thrombosis. Blood Coagul Fibrinolysis 2000; 11(8):715–21.

10. Barbar S, Noventa F, Rossetto V, Ferrari A. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 2010; 8(11):2450–7.

11. Hollander M., Wolfe D.A., Chicken E. (2014). Nonparametric Statistical Methods, John Wiley & Sons.

Authors’ contributions:

According to the order of the Authorship.

Conflict of interest:

The Authors declare no conflict of interest.

CORRESPONDING AUTHOR

Mariia Krykhtina

Department of internal medicine 1,

State Institution “Dnepropetrovsk Medical Academy

of the Ministry of Health of Ukraine”

Street 9, V. Vernadskogo, 49044, Dnipro, Ukraine

e-mail: mariakryhtina@gmail.com

Received: 10.09.2018

Accepted: 12.01.2019

Table I. Levels of systemic inflammation parameters in patients with moderate to severe CAP, Me [25-75%]

Parameter

Main group

Control group

p

subgroup 1

subgroup 2

CRP,

mg/l

136.9

[95,9–192,0]

223.8

[187,8–324,6]

4.5

[3,4–5,5]

Pc-s1=0.000

Pc-s2=0.000

Ps1-s2=0.000

PCT,
mcg/ml

1.5

[0,7–2,4]

0.7

[0,6 – 12,0]

0.01

[0,04–0,09]

Pc-s1=0.045

Pc-s2=0.007

Ps1-s2=0.846

Fibrinogen,
mcg/ml

2.9

[2,4–3,1]

9.2

[5,8–13,3]

2.7

[2,4–3,0]

Pc-s1=0.648

Pc-s2=0.000

Ps1-s2=0.001

Pc-s1 – between control group and subgroup 1;

Pc-s2 – between control group and subgroup 2;

Ps1-s2 – between subgroup 1 and subgroup 2.

Table II. Levels of blood coagulation test parameters and D-dimer in patients with moderate to severe CAP, Me [25-75%]

Parameter

Main group

Control group

p

subgroup 1

subgroup 2

D-dimer,

ng/ml

1382.7

[989,4–2940,0]

1802.1

[1389,6–5325,3]

264.0

[254,0–294,0]

Pc-s1=0.000

Pc-s2=0.001

Ps1-s2=0.679

Heparin time,
seconds

40.0

[37,0–40,0]

23.0

[21,0–39,5]

56.0

[55,0–57,0]

Pc-s1=0.000

Pc-s2=0.000

Ps1-s2=0.007

Heparin index,
%

140.0

[122,0–142,0]

132.0

[122,0–140,0]

105.0

[98,0–112,0]

Pc-s1=0.000

Pc-s2=0.007

Ps1-s2=0.557

Prothrombin time,
seconds

18.0

[16,0–20,0]

22.0

[20,0–25,0]

13.0

[12,0–14,0]

Pc-s1=0,000

Pc-s2=0,000

Ps1-s2=0,000

Prothrombin index,
%

82.0

[72,0–90,0]

86.0

[76,0–90,0]

100.0

[98,0–108,0]

Pc-s1=0.000

Pc-s2=0.000

Ps1-s2=0.692

Recalcification time, seconds

100.0

[92,0–104,0]

92.5

[74,5–102,0]

61.0

[55,0–66,0]

Pc-s1=0.000

Pc-s2=0.000

Ps1-s2=0.105

Pc-s1 – between control group and subgroup 1;

Pc-s2 – between control group and subgroup 2;

Ps1-s2 – between subgroup 1 and subgroup 2.

Table III. Relationships between Padua scale and other parameters

Parameter

R

P

SMRT-CO

0,751

0,000

CRP

0,389

0,002

PCT

0,490

0,263

Fibrinogen

0,689

0,000

D-dimer

0,393

0,146

Heparin time

-0,356

0,017

Heparin index

-0,233

0,197

Prothrombin time

0,534

0,000

Prothrombin index

0,037

0,803

Recalcification time

-0,144

0,354

Median

25%-75%

Min-Max.

Outliers

1

2

subgroup

0

1

2

3

4

5

6

7

8

9

Fig. 1. Medians of score levels by Padua scale in subgroups

A

B

Fig.3. Macro- and microscopically data of lung autopsy died from CAP

Fig. 2. Correlation of score levels by Padua scale and SMRT-CO scale in hospitalized patients with CAP: subgroup 1 (A), subgroup 2 (B).