Changes in platelet parameters and secondary brain injury in acute craniocerebral trauma＊☆

Xiaoping Tang, Chao You, Hua Peng, Tao Zhang, Wenguo Tang, Jian Qi, Renguo Luo,Yuanchuan Wang, Ling Feng, Zhangyang Gou, Junwei Duan, Shun Li

1Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China

2Department of Neurosurgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China

lNTRODUCTlON

The development of secondary brain injury in craniocerebral trauma is a key factor influencing the effects of clinical therapeutic strategies[1]. There are also multiple factors that regulate secondary brain injury[2]. The clinical significance of blood routine examination in craniocerebral trauma is frequently ignored by neurosurgeons. We previously confirmed close relationships between changes in leukocytes and their classification with secondary brain injury, as well as with patient variation and prognosis[3].

In the present study, we further examined the relationships between changes in platelet parameters and the variation and prognosis in acute craniocerebral trauma patients.

RESULTS

Quantitative analysis of participants

A total of 163 patients with craniocerebral trauma and 40 healthy adults were included in the final analysis.

Baseline data

Data from 163 patients and 40 controls are listed in Table 1.

Variance of platelet count (PLT), mean platelet volume (MPV), and platelet distribution width (PDW) in peripheral blood of craniocerebral trauma patients

The PLT count at 1 and 3 days after injury was significantly lower compared with the control group (P ＜ 0.05). There was no significant difference in PLT count between patient and control groups at 14 days (P ＞0.05). The MPV and PDW at 1 and 3 days after injury were significantly increased compared to controls (P ＜ 0.05). There was no difference in MPV and PDW at 14 days between patient and control groups (P ＞0.05; Table 2).

Table 1 Comparison of baseline data between patient and control groups

Correlation of PLT count, MPV, and PDW in peripheral blood at 1 day after injury to traumatic cerebral infarction

There was a range of degree of cerebral infarction in 16 cases in the patient group.

The PLT counts were lower, but MPV and PDW were higher, in patients with cerebral infarctions compared with patients without cerebral infarctions (P ＜ 0.01 and P ＜ 0.05,respectively; Table 3).

Table 2 Variance of platelet (PLT) count, mean platelet volume (MPV), and platelet distribution width (PDW) in peripheral blood at 1, 3, and 14 days after injury

Table 3 Variance of platelet (PLT) count, mean platelet volume (MPV), and platelet distribution width (PDW) in peripheral blood of patients with traumatic cerebral infarction

Correlation of PLT count, MPV, and PDW of peripheral blood to Glasgow Coma Scale (GCS)score during acute stage of craniocerebral trauma

At 1 day after injury, PLT counts were significantly lower,while MPV and PDW were significantly higher, in the patient group compared with the control group (P ＜ 0.01).

Further, PLT counts were lower, while MPV and PDW were higher, in the GCS score ＜ 8 group compared with the GCS score ≥ 8 group (P ＜ 0.05 and P ＜ 0.01,respectively; Table 4)[4].

Table 4 Variance of platelet (PLT) count, mean platelet volume (MPV), and platelet distribution width (PDW) of patients with different degrees of injury at 1 day after injury

There was positive correlation between PLT count and GCS score in peripheral blood of craniocerebral trauma patients (r = 0.605; P ＜ 0.05). There was negative correlation of MPV and PDW to GCS score (r = -0.541 and -0.615, respectively; P ＜ 0.05).

Variance in cerebral hemorrhage and volume of brain edema in craniocerebral trauma patients

There was a 5–30 mL intracerebral hematoma in all cases in the patient group on admission. The amount of hematoma was slightly increased at 1 day after injury,and obviously decreased at 7 days after injury. The size of edema around the hemorrhagic focus was increased with the development of the pathogenetic condition. The size of edema was largest at 7 days after injury compared with that on admission (P ＜ 0.05 and P ＜ 0.01;Table 5).

Table 5 Variance of the amount of cerebral hemorrhage and the size of edema of 163 patients at 1 and 7 days after injury (mL)

Brain edema was largest at 7 days after injury, where it most clearly reflected the degree of secondary brain injury. PLT values in blood routine examination at 1 day after injury reflected the changes in PLT value in the acute stage of craniocerebral injury. There was no difference in PLT at 1 day compared with 3 days after injury. Therefore, we chose the corresponding data at 1 and 3 days to study the relationship between the changes in PLT value and secondary brain injury. There was a negative correlation between the size of brain edema at 7 days after injury and the PLT count at 1 day after injury (r = -0.238; P ＜ 0.05). There was a positive correlation between brain edema and MPV or PDW (r =0.642 and 0.593, respectively; P ＜ 0.05).

Relationship between PLT count, MPV, and PDW of peripheral blood at 1 day after injury with Glasgow Outcome Scale (GOS)

A total of 64 cases were followed up for more than 6 months by call or return visit. The GOS after 6 months reflected the outcomes, as the larger the GOS score the better the outcome[5]. There was a positive correlation between PLT count of peripheral blood at 1 day after injury and GOS score (r = 0.883; P ＜ 0.05). There was a negative correlation between MPV and PDW with GOS score (r = -0.235 and -0.267, respectively; P ＜ 0.05).

DlSCUSSlON

The patterns of secondary brain injury observed by medical imaging after craniocerebral injury include expansion of intracerebral hemorrhage, change in low density around hemorrhagic focus, brain edema, and brain intumesce. There is a relationship between the formation of a low density area around the hemorrhagic focus after craniocerebral injury and the patients’pathogenetic condition and aggravation of neurological function. The center component element of secondary brain injury involves microcirculation disturbance around the injured focus. The factors regulating these microcirculation disturbances are complex.

Experimentally, there is evidence of marked white blood cells aggregation and infiltration in the damaged brain tissue or around it after brain trauma[6]. White blood cells can also produce microcirculation disturbances during secondary brain injury. As an important component of blood, PLTs have functions in cell adhesion, aggregation,and liberation. PLTs also play an important role in blood coagulation and thrombogenesis during hemostasis.

There is evidence that internal thrombogenesis can result from the combined actions of PLTs, fibrin ferment,and fibrinogen[7]. There are also strong relationships between abnormal changes in the amount, appearance,and function of PLTs with the occurrence and development of cerebral infarction, cerebral hemorrhage,hypoxic ischemic encephalopathy, and changes and prognosis of the pathogenetic condition[8-9]. The pathology and physiology of secondary brain injury after craniocerebral injury exhibit similar components as those diseases.

In the present study, the PLT count of peripheral blood decreased, while MPV and PDW increased, during the acute stage of the craniocerebral trauma. Furthermore,the PLT count was lower, while MPV and PDW were higher, in the GCS score ＜ 8 group than in the GCS score ≥ 8 group; i.e., PLT count decreased with increasing severity of traumatic condition, while MPV and PDW were increased. The potential causes of these relationships are: (1) Collagenous fibers and muscle fibers of the damaged location were exposed after craniocerebral trauma. PLTs were quickly adhered,aggregated, activated, and consumed in these areas in injury, and the blood PLTs were decreased. This phenomenon has also been reported in other types of brain injury[10]. (2) The decrease in PLTs stimulated the bone marrow to release more large PLTs, resulting in an increase in MPV. Potential factors contributing to the augmentation of MPV and the increase of organelles of PLTs include cytochondriome and a dense body. These organelles released more inflammatory substances,which were expressed on the surface of the plasmalemma of PLTs, which in turn mediated the damaging effects of endothelial cells and increased the aggregation and adhesion functions of PLTs. A thrombus was then formed which consumed more PLTs[11]. (3) The cytochondriomes of the vascular endothelial cells in the damaged location were shattered, and less blood vessel endothelium arachidonic acid was transformed into prostaglandin. Prostaglandin has an anti-aggregation function on PLTs[10]. (4) Platelet activating factor was increased more than 20-fold in the site of anoxic ischemic encephalopathy after injury compared with normal levels. At present, platelet activating factor is the strongest known anti-aggregating factor of PLTs[12]. (5)During the acute stage, the decrease in PLTs and the increase in MPV altered the clotting mechanism around the focus, inducing microvascular thrombosis in the focus and hyperviscosity syndrome, thus increasing the degree of injury following craniocerebral trauma. During the restorative period the microangiopathy gradually recovered, and PLT, MPV, and PDW also gradually returned to normal levels. Thus, dynamic changes in PLTs in craniocerebral trauma patients provide an important index for assessment of the degree of injury,and the change and turnover of the pathogenetic condition.

We found that the changes in PLT parameters regulated the pathogenetic condition of craniocerebral trauma patients by influencing secondary brain injury. For example, greater changes in PLT count, MPV, and PDW reflected more severe brain edema after injury, worse recovery, and lower GOS after six months. If the traumatic cerebral infarction occurred during the treatment process, there were more marked changes in PLT count, MPV, and PDW. The variance of PLT and its parameters were useful as indexes of the degree of brain edema after injury, and an important referenced index of the traumatic cerebral infarction. When the injury damaged the endotheliocyte of the endarterium, the basilemma under the endotheliocyte and the connective tissue under endothelium were exposed. PLTs adhered to the surface and were activated, resulting in aggregation and the release of α-granules and dense granules of the active substance, causing PLTs to further aggregate. By contrast, fibrin became sedimented, and the microthrombus formed. Blood around the focus was in a hypercoagulable state[8]. A previous study found a strong relationship between MPV and PLT function, with PLTs of different volumes and sizes exhibiting different aggregation adhesion parameters, as well as quantity of releasing particle[13]. Furthermore, MPV increased, PLT aggregation and adhesion function were strengthened,dense granules produced more thromboxane A, and PLTs were easily aggregated, resulting in thrombosis[13].

PDW best reflected the differences in the degree of PLT volume, especial the distribution of PLT volume. When the human body is abnormal, the PLT volume distribution curve may deviate from normal, resulting in a tight relationship between the changes of PDW, PLT, and MPV. When we analyzed the clinical significance of values of PLT, PDW, and PVM, we often considered them as a whole[7]. After craniocerebral trauma, PLTs were aggregated around the injured focus, which resulted in a reduction of PLTs in the peripheral blood and which stimulated the majority of megakaryocytes in bone marrow to change into a polyploidy form; PLTs with a larger volume were produced The volume distribution curve also deviated from normal levels. On the other hand, the large volume of PLTs caused more PLTs to aggregate around the injured focus, creating a vicious cycle. A large volume of PLTs then aggregated and gradually accumulated around the injured focus to form the microthrombus. The appearance of the injured brain by imaging showed cerebral edema, secondary brain injury aggravation, and deterioration of nervous system function. If cerebral edema could not be corrected in time,then traumatic cerebral infarction could occur, resulting in more severe pathogenetic condition.

In summary, our results indicate the clinical significance of blood routine examination in craniocerebral trauma patients. Changes in PLTs and white blood cell parameters reflected and predicted the levels of cerebral edema and secondary brain injury. A number of studies suggest that treatment of cerebral hemorrhage patients with anti-platelet drugs can improve recovery without increasing the risk of recurrence of cerebral hemorrhage[14]. The targeting of secondary brain injury after craniocerebral trauma by treatment with anti-platelet medicine requires further study.

SUBJECTS AND METHODS

Design

A retrospective case-control study.

Time and setting

Experiments were performed at the Affiliated Hospital of North Sichuan Medical College in March 2010.

Subjects

A total of 163 craniocerebral trauma patients were selected, with an age range from 9 to 73 years. There were 101 cases from car accident, 35 cases from crashes, and 27 cases from other causes. There were 42 cases of simple brain contusion and laceration, 36 cases of skull fracture, 43 cases of extensive contusion and laceration of the brain, 11 cases of contusion and laceration of brain combined with epidural mini-hematoma, 19 cases of contusion and laceration of brain combined with subdural mini-hematoma, 10 cases of contusion and laceration of brain combined with brain stem injury, and two cases of contusion and laceration of brain combined with intraventricular mini-hemorrhage. All patients were totally combined with inhomogeneous intracerebral hematoma. All cases were admitted within 24 hours after injury except for patients with heart and cerebral vessel damage, liver disease, hematologic disease, diabetes, hemorrhagic shock, or severe combined wounds at other regions. The patients who were operated on or who died during observation and therapy were excluded. Upon admission, 19 patients were conscious, 59 patients exhibited mild conscious disturbance, 49 patients exhibited medium conscious disturbance, and 36 patients exhibited severe conscious disturbance.

A total of 40 healthy adults (the workers of the hospital)were used as the control group. They did not have hematologic disease and the various blood indices were normal. The subjects (or the family) provided informed consent.

Methods

Patients with contusion and laceration of the brain or hematoma that were in a limited region often received general symptomatic treatment. If the patients were more severe, then an appropriate dehydrator (Mannitol;Sichuan Kelun Pharmaceutical Company, Chengdu,Sichuan Province, China) was used according to the pathogenetic condition. The most severe patients were placed in the intensive care unit with oxygen therapy,hibernotherapy, incision of trachea, and complication control. When a traumatic cerebral infarction was identified, fluid expansion and spasmolysis were used.

Observation data

(1) Patients were analyzed at 1, 3, and 14 days after hospitalization. A 2 mL volume of venous blood was collected. The PLT count, MPV, and PDW were analyzed by an automatic blood analyzer (Beckman Coulter, Inc.,Los Angeles, CA, USA). (2) The GCS score was evaluated on admission, and at 1 and 7 days[4]. (3) CT detection (Toshiba, Tokyo, Japan) was performed on admission, and at 1 and 7 days. The volume of hematoma and the size of brain edema were calculated by the Tada formula: the volume of hematoma = π/6 ×length × width × height, and the edema size around the hemorrhagic focus = volume of total focal zone displayed by CT image-volume of hematoma. If there were multiple focuses, the hematoma and edema volumes were calculated as the total of the multiple focuses[15]. (4) GOS was evaluated after 6 months[5].

The first three sets of observation data were detected in all 163 patients, while 64 cases were evaluated with GOS. In addition, PLT parameters of peripheral blood were determined in 40 healthy adults of control group.

Statistical analysis

Data were analyzed using SPSS 10.0 software (SPSS,Chicago, IL, USA). Data were expressed as mean ± SD.The analysis of variance (F test) and Student-Newman-Keuls-q test were applied between groups, and linear correlation analysis was performed in double-variance. A value of P ＜ 0.05 was considered statistically significant.

Author contributions:Xiaoping Tang participated in study concept and design, and manuscript writing. Chao You was in charge of manuscript authorization. Hua Peng ensured the integrity of the data and participated in statistical analyses. Tao Zhang, Wenguo Tang, Jian Qi, Renguo Luo, Yuanchuan Wang,Ling Feng, Zhangyang Gou, Junwei Duan, and Shun Li participated in data collection.

Conflicts of interest:None declared.

Funding:This study was supported by the Key Medical Construction Subject Foundation of Sichuan Province.

Ethical approval:This study was approved by the Ethics Committee, Affiliated Hospital of North Sichuan Medical College in China.

[1]Nimmo AJ, Cernak I, Heath DL, et al. Neurogenic inflammation is associated with development of edema and functional deficits following traumatic brain injury in rats. Neuropeptides. 2004;38(1):40-47.

[2]Sande A, West C. Traumatic brain injury: a review of pathophysiology and management. J Vet Emerg Crit Care (San Antonio). 2010;20(2):177-190.

[3]Tang XP, Wang YC, Peng H, et al. Changes in inflammatory cells of peripheral blood and its relationship with secondary brain insult in patients with cranlocerebral injury. Zhongguo Linchuang Shenjing Waike Zazhi. 2007;12(7):406-408.

[4]Zuercher M, Ummenhofer W, Baltussen A, et al. The use of Glasgow Coma Scale in injury assessment: a critical review. Brain Inj. 2009;23(5):371-384.

[5]Nichol AD, Higgins AM, Gabbe BJ, et al. Measuring functional and quality of life outcomes following major head injury: common scales and checklists. Injury. 2011;42(3):281-287.

[6]Clark RS, Schiding JK, Kaczorowski SL, et al. Neutrophil accumulation after traumatic brain injury in rats: comparison of weight drop and controlled cortical impact models. J Neurotrauma.1994;11(5):499-506.

[7]Deng SR, Liang T, Li HT, et al. The changes of parameter of platelet and its clinical signification in acute cerebrovascular disease. Guangxi Yike Daxue Xuebao. 2004;21(5):701-703.

[8]Feng YX. The changes of parameter of platelet of acute cerebrovascular disease patient. Wei Xunhuan Zazhi. 2006;6(2):76.

[9]Shan Y, Zheng CZ, Qin J, et al. Changes and significance of serum high-sensitivity C reactive protein and platelet parameter levels in newborns with hypoxic-ischemic encephalopathy.Shiyong Erke Linchuang Zazhi. 2006;21(12):751-752.

[10]Yang FM, Jia RH, Gao HB, et al. The changes of platelet parameters and its significance of neonatal hypoxic-ischemic encephalopathy. Xinsheng Erke Zazhi. 2004;19(1):4-6.

[11]Akisu M, Huseyinov A, Yalaz M, et al. Selective head cooling with hypothermia suppresses the generation of platelet-activating factor in cerebrospinal fluid of newborn infants with perinatal asphyxia. PLEFA. 2003;69(1):45-50.

[12]He JW, Zhao J, Liu J, et al. The correlation of changes in parameters of platelet with periventricular-intraventricular hemorrhages in premature infants. Guowai Yixue Fuyou Baojian Fence. 2005;16(1):7-8.

[13]Huang DS, Lu SG. The change of mean platelet volume and its clinical significance in certain diseases. Guowai Yixue Shexue yu Xueye Xue Fence. 1995;18(6):331-333.

[14]Qu DF. The anti-platelet therapy after cerebral hemorrhage. Guoji Nao Xueguan Bing Zazhi. 2006;14(3):196.

[15]Matteis M, Vernieri F, Troisi E, et al. Early cerebral hemodynamic changes during passive movements and motor recovery after stroke. J Neurol. 2003;250(7):810-817.