Thrombocytopenia in Septic Patients - An Observational Cohort Study in Medical Intensive Care Unit

Research Article

Austin Crit Care J. 2016; 3(1): 1016.

Thrombocytopenia in Septic Patients - An Observational Cohort Study in Medical Intensive Care Unit

Lakshman R1*, Purushothaman SS2, Balakrishnan S2 and Nair SG2

1Fortis Memorial Research Institiute, Gurgaon, Inida

2Department of Anaesthesiology & Critical Care, Amrita Institute of Medical Sciences, Kochi, India

*Corresponding author: Ramachandran Lakshman, 112, Ashoka Enclave, Sector-34/35, Faridabad, Haryana, India

Received: September 16, 2015; Accepted: May 30, 2016; Published: June 01, 2016


Context: Correlation of platelet count with mortality in patients with sepsis.

Introduction: Early detection of sepsis in critically ill patients and suitable intervention is known to decrease mortality. Fall in platelet count has been seen to occur early and is associated with poorer prognosis in previous studies in surgical and trauma patients in Intensive Care Units (ICU). The aim of this study was to evaluate the incidence, risk factors and outcome in septic patients who developed thrombocytopenia in a medical ICU. The time course of change in platelet counts in these patients was also compared with the established prognostic markers like APACHE IV in predicting mortality.

Design: 30-bedded MICU in a tertiary care center

Methodology: All septic patients >12 years admitted in the ICU with duration of stay > 48 hours were included in the study. The platelet counts were daily recorded along with severity scores like APACHE IV. The primary end point was 28-day mortality. Receiver-Operator Characteristic (ROC) curve and Kaplan-Meier survival analysis was done to determine the cutoff level and the survival probability of the patients with a falling platelet count.

Results: 104 septic patients were studied. Sixty three (60%) of patients developed thrombocytopenia out of which 35 (33%) patients were thrombocytopenic at admission. Time to reach the nadir platelet value was 5.3 days. No risk factors were found to be associated with thrombocytopenia. Nadir thrombocytopenia, instead of admission thrombocytopenia was found to be a better marker for predicting mortality p=0.016. Nadir thrombocytopenia had a higher discriminative value for mortality prediction than admission APACHE IV score on ROC curve. A platelet count drop by >30% was found to be associated with higher mortality.s

Conclusion: Thrombocytopenia is frequent in critically ill medical patients. No risk factors were responsible for its development. Nadir thrombocytopenia and decline in platelet count by >30% has a significant predictive value for 28- day mortality.

Keywords: Sepsis, Thrombocytopenia, Prognosis, 28-day mortality, APACHE IV


Development of sepsis in patients admitted in the Intensive Care Unit (ICU) is associated with a mortality of 20-30% which may go up to 50-60% if associated with septic shock [1,2]. Early detection and intervention (golden hour) in sepsis has improved survival considerably [3]. Many biomarkers such as C-Reactive Protein (CRP), Procalcitonin (PCT), Total Leucocyte Count (TLC), Triggering Receptor Expressed On Myeloid Cell1 (TREM-1), serum albumin levels, etc, have been investigated for early diagnosis and prognosis in sepsis [4]. On the other hand, biological variables like Central Venous Oxygen Saturation (ScVO2) and serum lactate have already been included in the accepted management protocol of sepsis as biomarkers for its early detection [5]. Platelet count is another acute phase reactant under investigation. Measurement of platelet count being cost effective, easily available, can be done serially and may be a useful biomarker, especially in resource constrained setups.

Platelets have a pivotal role in haemostasis and thrombus formation as well as in host defence and hence, a reduction in platelet count may potentially influence the outcome of the critically ill patients [6]. Thrombocytopenia has already been shown to be associated with worsening prognosis in earlier studies on surgical and trauma patients [7].

Thrombocytopenia is a common occurrence in critically ill patients. Various mechanisms like increased platelet destruction, hemodilution, decreased marrow production and increased splenic sequestration are postulated for the development of thrombocytopenia in ICU [6,7]. Sepsis has been found to be most commonly associated with thrombocytopenia [8,9] On the other hand, thrombocytopenia has also been shown to be an independent prognostic marker and thus complimentary to establish markers like APACHE, SOFA, SAPS, etc., in patients of sepsis, septic shock or merely with evidence of new onset blood stream infection in ICU [10].

The advantage of using platelets as a predictor of mortality in critically ill patients is the dynamic nature of the daily platelet count, which takes the disease progression into account in contrast to various mortality scores which use only the worst parameters within the first 24 hr after admission or at admission [11]. Various studies on the adult patients have shown that it is not the absolute level of platelets but the change (drop) in the platelet levels that are more suggestive of poorer prognosis in terms of mortality and longer ICU stay [11,21]. Absolute platelet count and a fall in platelet count as prognostic and diagnostic markers of sepsis has not been evaluated frequently in many Indian ICUs. Agrawal et al. studied the variations in platelet count with the mortality in paediatric ICU. They concluded that a drop in platelet count and absolute thrombocytopenia were independently related to mortality [24]. However, similar data is lacking in Indian scenario, where being a cost effective diagnostic modality it may be a promising marker. Hence, to study the trend of platelet count in patients of sepsis and comparing it with the present established markers of severity of diseases might be useful as platelet count estimation is a simple, easily available and relatively cheap investigation. Our primary objective was to study the incidence of thrombocytopenia and its prognostic value in predicting mortality and Length of Stay (LOS) in critically ill septic patients. The secondary objective was to study the time trend of platelet count and its association with mortality and LOS. We also compared the efficacy of thrombocytopenia in predicting the above outcomes vis-à-vis other present prognostic markers like CRP, ScVO2, serum lactate, APACHE IV score.

Subjects and Methods

The study was a prospective, observational, cohort study and was approved by the ethical committee of the hospital. We enrolled all patients admitted from August 2010 till August 2011 in a 30 bedded medical. Sepsis was defined as per the current guidelines [12]. All patients who presented with sepsis on admission or developed new sepsis during their stay in ICU were included. Patients excluded were those with history of haematological malignancies, past use of chemotherapeutic drugs, platelet disorders, patients with mechanical cardiac valves, patients with splenectomy or hypersplenism, alcohol abuse, non-septic causes of SIRS like trauma, surgery, burns and immune-complex mediated diseases like dengue and SLE. All patients who died within 48 hours of inclusion were also excluded from the study. The patients were followed from the day of admission in MICU to their discharge, death or continued stay in ICU.

Platelet counts were determined daily throughout the ICU stay by automated cell counter. Thrombocytopenia was defined as a platelet count < 150 ×109/L. Patients with thrombocytopenia were further subdivided into mild (101-149×109/L), moderate (51-100 ×109/L), severe (21-50×109/L) and very severe (= 20 ×109/L), as in the recent Sepsis-Related Organ Failure Assessment score study [13,14]. Nadir platelet count was defined as the lowest platelet count recorded during the ICU stay. Percentage drop in the platelet count was taken as a percentage of the difference between the admission platelet count and the nadir platelet count for each patient. ICU acquired thrombocytopenia was considered when the patient was admitted with normal platelet count which dipped below 150×109/L subsequently during ICU stay. All patients received standard ICU care as per our protocols for antibiotics, mechanical ventilation, nutrition, blood and blood product transfusion and inotropic support. Data collected included age, sex, source of sepsis, use of medications in the past and during the present stay in the ICU which can affect the platelet count like heparin, NSAIDS, furosemide, β-lactams and antiplatelet drugs, use of mechanical ventilation and requirement of inotropic supports. Prognostic markers of sepsis like ScVO2 and serum lactate levels were also noted within 24 hours of the ICU admission or at the onset of the sepsis.

Acute Physiological and Chronic Health Evaluation IV (Apache IV) scoring system was used to estimate the severity of the disease or the number of organ failures within 24 hours of the admission [15]. Statistical analysis was performed using statistical software SPSS 14. Results are expressed as numerical values (percentage) for the categorical variables, and median (Interquartile Range [IQR] for continuous variables). Continuous variables were compared with student’s T test for normally distributed variables and mannwhitney test was used for non-parametrically distributed variables. The chi-square test and fisher’s exact test were used to compare the categorical variables. Receiver-Operator Characteristic (ROC) curve analysis was done to see the prediction of mortality by platelet count and to determine the cut-off level for platelet count for determining increased mortality. We also tried to determine the percentage decline of the platelet count from the admission which predicts the increased mortality again by using the ROC curve. After categorizing the platelet decline into four categories (<10%, 10-30%, 30-60 %, > 60%) we used the kaplan-meier survival analysis to determine the survival probability of the patients with falling platelet count. All p-values were two-sided and were considered significant at < 0.05.


762 patients were admitted to our ICU over a period of one year. Of these, 467 patients were diagnosed as having sepsis. 319 patients did not fit into the inclusion criteria and thus were excluded. 148 patients formed the study group. Of these, 43 died within 48 hours of inclusion. Hence, the final data analysis was done for 105 patients (Figure 1). The Mean age of the study group was 56.4 years (range=17-84). Major sources of sepsis as well as the characteristic distribution of the study patients are demonstrated in Table 1.