European Journal of Cardiovascular Medicine

In addition to being a significant contributor to trauma-related death, disability, and socioeconomic burden, traumatic brain injury is a significant public health concern [1]. Common methods include attacks, falls, road accidents, and work-related injuries. From minor concussions to serious intracranial injuries linked to cerebral edema, bleeding, elevated intracranial pressure, and neurological decline, the clinical spectrum spans [2]. For proper triage, monitoring, and treatment, early identification of individuals who are more likely to experience a negative result is crucial.

Prognostic evaluation frequently makes use of the Glasgow Coma Scale, pupillary response, hemodynamic state, computed tomography (CT) results, and systemic damage severity. However, clinical outcomes can range significantly between patients with seemingly comparable neurological findings [3]. Therefore, further predictive information may be provided by laboratory biomarkers that reflect secondary physiological abnormalities.

After traumatic brain injury, hemostatic abnormalities are frequently observed. Trauma-induced coagulopathy can be caused by tissue damage, endothelial disruption, platelet activation, consumption of coagulation components, fibrinolytic abnormalities, shock, and systemic inflammatory reactions [4]. These anomalies could encourage ongoing bleeding and the growth of pre-existing cerebral hemorrhages. On the other hand, severe trauma can also cause a prothrombotic condition, which makes hemostatic abnormalities complicated and reliant on time [5].

In addition to supporting vascular integrity, inflammatory signaling, and interactions between the immune and coagulation systems, platelets are crucial for primary hemostasis. A platelet count below 150×109/L (150 \times 10^9/L150×109/L) is the standard definition of thrombocytopenia in adults. This condition can be caused by platelet consumption, dilution after fluid or blood product resuscitation, sequestration, pre-existing hematological abnormalities, medication, or systemic disease. A low platelet count in trauma patients may be a sign of both the severity of the physiological reaction to injury and a compromised hemostatic capacity [6].

There is evidence linking early thrombocytopenia to poor outcomes in patients with moderate-to-severe traumatic brain injury. Early thrombocytopenia was linked to increased hospital and 12-month mortality in a multicenter Finnish intensive care cohort, and platelet count continued to be related to outcome even after injury severity was taken into account [7].

But there are still a few unanswered questions. The severity of cerebral injury, extracranial hemorrhage, transfusion protocols, injury mechanism, timing of blood collection, and pre-existing comorbidities can all affect the occurrence and prognostic relevance of thrombocytopenia [8]. Moreover, a correlation with mortality does not show that thrombocytopenia is the cause of the unfavorable result or that raising the platelet count increase survival.

Aim and objectives

Aim: To evaluate thrombocytopenia as an independent prognostic marker in patients with traumatic brain injury.

Primary objective

• To assess the association between admission thrombocytopenia and in-hospital mortality.
• Secondary objectives
• To determine the prevalence of thrombocytopenia among patients admitted with TBI.
• To evaluate the relationship between platelet count and GCS score at admission.

Study design and setting

A prospective observational cohort study is in the emergency department, trauma unit, neurosurgery department, and intensive care unit of a tertiary-care teaching hospital. Consecutive eligible patients would be enrolled over a predefined recruitment period after institutional ethics committee approval.

Study population and sample size

The study population would consist of 100 patients admitted with clinically and radiologically suspected or confirmed TBI. A sample of 100 is suitable for a preliminary observational investigation, but its adequacy for multivariable mortality prediction depends on the number of deaths, prevalence of thrombocytopenia, anticipated effect size, and number of model parameters.

A formal sample-size calculation based on the expected prevalence of thrombocytopenia or the anticipated difference in mortality between exposure groups.

Inclusion criteria:

• Patients aged 18 years or older.
• Patients presenting with traumatic brain injury following blunt or penetrating trauma, as defined by the study protocol.
• Admission to the hospital within the prespecified study window.
• Availability of an admission complete blood count and clinical assessment.
• Consent from the patient or legally authorized representative, according to ethics committee requirements.

Exclusion criteria:

• Patients younger than 18 years.
• Known chronic thrombocytopenia or a documented hematological disorder substantially affecting platelet counts, if excluded by the protocol.
• Active malignancy or treatment with medications known to cause significant thrombocytopenia, where these conditions prevent meaningful interpretation.
• Known advanced chronic liver disease or other established causes of thrombocytopenia, depending on the study design.
• Patients transferred after prolonged treatment at another institution when baseline laboratory and clinical information is unavailable.
• Patients whose records are insufficient to determine the primary outcome.

Clinical assessment and data collection

Demographic variables would include age, sex, injury mechanism, time since injury, relevant medical history, medication exposure, and prehospital treatment. Initial clinical assessment would record systolic blood pressure, heart rate, oxygen saturation, pupillary size and reactivity, GCS score, and evidence of extracranial trauma.

TBI severity would be classified using the admission GCS score:

Mild TBI: GCS 13–15.

Moderate TBI: GCS 9–12.

Severe TBI: GCS 3–8.

GCS should be recorded before sedatives or neuromuscular blockers whenever feasible, and the timing and circumstances of assessment should be documented.

Laboratory investigations

As soon as feasible following admission, a complete blood count would be taken, ideally prior to transfusion. The platelet count would be categorized based on the predetermined threshold and recorded as a continuous variable.

A platelet count of less than 150×109/L150 \times 10^9/L150×109/L would be considered thrombocytopenia for the primary analysis. Because thresholds differ among published research, a sensitivity analysis could assess more severe thrombocytopenia, such as a count below 100×109/L100 \times 10^9/L100×109/L.

To differentiate isolated admission thrombocytopenia from a declining platelet trend, repeat platelet counts at 24 and 48 hours would be helpful. To prevent bias from choosing measurements taken after clinical deterioration, the primary exposure should, nevertheless, continue to be precisely described.

Radiological assessment

Non-contrast CT of the head would be evaluated for epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intraparenchymal hemorrhage or contusion, intraventricular hemorrhage, skull fracture, cerebral edema, midline shift, and other relevant findings.

Radiological progression would be defined using a prespecified comparison between initial and follow-up CT scans. Follow-up imaging would be performed according to clinical indications and institutional protocols. Because patients with deterioration are more likely to undergo repeat CT, this outcome should be interpreted with consideration of surveillance bias.

Statistical analysis

Data would be analyzed using appropriate statistical software. Continuous variables would be summarized as mean and standard deviation when normally distributed or median and interquartile range when skewed. Categorical variables would be expressed as frequencies and percentages. The chi-square test would compare categorical outcomes. Student's t-test or the Mann–Whitney U test would be selected for continuous variables according to distribution and assumptions. Statistical significance would be defined as a two-sided p value below 0.05.

Table 1. Demographic and clinical characteristics of the study population

Abbreviations: GCS, Glasgow Coma Scale; SD, standard deviation; TBI, traumatic brain injury.

The distribution shows a predominantly male study population, with road traffic accidents as the leading mechanism of injury. Thrombocytopenia is represented in one-fifth of the cohort. These proportions are placeholders and should not be interpreted as estimates of prevalence in the target hospital.

Table 2. Association between admission platelet status and injury severity

Pearson chi-square test: χ2≈11.7 p approximately 0.003.

The distribution demonstrates a greater proportion of severe TBI among patients with thrombocytopenia. Association between reduced platelet count and neurological injury severity if reproduced in actual data. However, it would not independently establish prognostic value because platelet count may decline in response to severe trauma, shock, or associated coagulopathy.

Table 3. Association between thrombocytopenia and in-hospital outcomes

Mortality is higher among patients with thrombocytopenia than among those with normal platelet counts. Neurological deterioration, progression of intracranial hemorrhage, and neurosurgical intervention also occur more frequently in the thrombocytopenia group. Such findings would warrant further investigation of platelet count as an early risk-stratification marker.

Thrombocytopenia is a potentially useful laboratory marker in patients with traumatic brain injury because it may reflect disturbances in hemostasis that accompany tissue injury and systemic physiological stress[9]. The present study framework evaluates its relationship with neurological severity and short-term clinical outcomes, while distinguishing unadjusted associations from independent prognostic information.

Thrombocytopenia and injury severity

It is biologically likely that platelet count and TBI severity are related. Severe trauma can cause endothelial damage, systemic inflammation, increased platelet consumption, and activation of platelets and coagulation pathways. Transfusions and fluid treatment can also change measured platelet concentrations in patients with significant bleeding.

By disrupting the blood–brain barrier and releasing tissue factors, intracranial damage can potentially cause coagulation problems [10]. These alterations may coexist with coagulopathy brought on by systemic trauma, therefore the platelet count is not a stand-alone indicator of coagulation function but rather a part of a more comprehensive hemostatic evaluation. The interplay between tissue damage, shock, coagulation activation, fibrinolysis, and platelet dysfunction is described as crucial to unfavorable outcomes in reviews of trauma-induced coagulopathy. [11]

Therefore, a low platelet count could be a sign of more serious physiological damage. A normal platelet count does not rule out platelet dysfunction or clinically significant coagulation problems, though, and the association is not always linear.

Thrombocytopenia and mortality

The main goal of this study is to predict mortality. Early thrombocytopenia was linked to higher hospital and 12-month mortality, according to the published Finnish Intensive Care Consortium study, which included 4,419 TBI patients. In individuals with moderate-to-severe traumatic brain injury, the correlation between platelet count and death remained after controlling for the degree of the lesion. [12]

A platelet count below 150×109/L150 \times 10^9/L150×109/L at emergency department arrival may offer additional predictive information in addition to age and GCS score, according to observational data from patients with severe TBI and concurrent extracranial injuries.

The justification for examining admission platelet count in a smaller prospective cohort is supported by these research. However, it is not always possible to extrapolate results from larger multicenter cohorts to all hospital populations [13]. Both thrombocytopenia prevalence and mortality may be impacted by variations in case mix, admission requirements, transfer delays, blood product availability, and critical care procedures.

For the main hemostatic plug to develop, platelets are necessary. A lower platelet count may hinder the production of clots and could allow bleeding from damaged brain arteries to persist. This may lead to subsequent neurological decline and bleeding expansion in patients with cerebral hematomas or contusions [14].

However, many factors than just the total amount of platelets in circulation affect how the platelet count affects bleeding. Hemostasis may be influenced by endothelial integrity, injury anatomy, fibrinogen concentration, coagulation-factor activity, platelet function, and local cerebral vascular damage.

There is a unique statistical meaning associated with the word independent prognostic marker. In a two-group comparison, a significant correlation between thrombocytopenia and mortality is insufficient. After accounting for significant variables that could account for the observed link, the association must still exist [15]. Because mortality risk often rises with age and the severity of neurological injuries, age and GCS score are especially significant. Results may also be affected by pupillary abnormalities, hypotension, extracranial damage, shock, coagulation abnormalities, and CT findings.

In individuals suffering from traumatic brain injury, thrombocytopenia is a clinically significant candidate prognostic marker. Early low platelet counts have been linked to negative consequences, including death, according to published observational studies. The platelet count's potential utility stems from its affordability, accessibility, and early measurement during emergency assessment.

However, based just on uncorrected group comparisons, thrombocytopenia should not be considered an independent predictor. Its prevalence should be determined, correlations with injury severity and clinical outcomes should be assessed, and suitably limited multivariable analysis should be carried out in the planned study of 100 patients. No conclusion regarding the strength or statistical independence of the association in this specific cohort can be made until the actual data have been examined

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