The role of monitoring platelet function perioperatively and platelet transfusion for operated spontaneous intracerebral hemorrhage patients with long-term oral antiplatelet therapy: A case report

Introduction and importance Spontaneous intracerebral hemorrhage (SICH) with long-term oral antiplatelet therapy (LOAPT) is known as a dilemma in balancing the risk of postoperative rebleeding and ischemic events because of confused coagulation function. We herein describe a report of perioperative management of spontaneous intracerebral hemorrhage patient on long-term oral antiplatelet therapy. Case presentation A 42-year-old male patient on long-term oral antiplatelet therapy presented with coma, and he was diagnosed with spontaneous intracerebral hemorrhage. Considering the patient's clinical condition, despite the thromboelastography suggested that the inhibition of platelet function was high preoperatively, an emergency craniectomy were underwent. After platelet transfusion during surgery and taking control of the clotting and platelet function postoperatively, the patient was stable without rebleeding and new ischemic events in perioperative period and recovered satisfactorily. Clinical discussion Rare studies have provided evidence for managing operated spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet therapy, and whether platelet transfusion is recommended was controversial. In this case, we presented monitoring and taking control of clotting and platelet function postoperatively would help in preventing rebleeding and ischemic events in such patients; moreover, platelet transfusion may quickly and safely reverse platelet dysfunction for emergency surgery. This case was the first to report platelet function and coagulation function management in spontaneous intracerebral hemorrhage patients with long-term oral antiplatelet therapy. Conclusion Monitoring and maintaining coagulation and platelet function perioperatively are essential to balance the risk of postoperative rebleeding and ischemic events.


Introduction
As the population ages, the number of spontaneous intracerebral hemorrhage with long-term oral antiplatelet therapy patients continues to increase [1]. In such patients, many people miss the optimal timing of surgery due to the high risk of postoperative bleeding complication [2], even though emergency surgery is an effective way to reduce mortality [3][4][5][6]. On the other hand, some studies have shown that non-selective platelet transfusion not only couldn't improve outcome, but also increase ischemic events [7][8][9]. This is a medical dilemma for every neurosurgeon to treat such patient. In our case, we described a spontaneous intracerebral hemorrhage (SICH) patient on long-term oral antiplatelet therapy (LOAPT) performed an emergency surgery under monitoring the platelet function in an academic hospital and shared our experience in treating such patients.

Methods
This work has been reported in line with the SCARE criteria [10].

Case presentation
A 42-year-old male patient presented with SICH to our medical institution (Being Tiantan Hospital/Beijing/China) in January 2020. The patient received two-month dual antiplatelet therapy for recent cerebellar infarction before SICH. Medication included aspirin (Bayas-pirin® 100 mg, Bayer S.p.A) 100 mg daily and clopidogrel (Plavix® 75 mg, Sanofi Winthrop Industrie) 75 mg daily. The patient had no alcohol or drug abuse history, surgery or any other noteworthy prior medical history, drug history, significant family history, and psychosocial history. Upon physical examination, the patient heart rate was regular at 50 bpm, blood pressure was 164/78 mmHg and body temperature was 37 • C. The Glasgow coma scale (GCS) [11] was 8 and modified Rankin scale (mRS) [12] was 5 at admission. An immediate computed tomography (CT) revealed a right frontotemporal hematoma with cerebral herniation. The preoperative laboratory examination demonstrated the routine blood tests and coagulation test as normal; However, the thromboelastography showed that platelet function was inhibited completely (citric acid kaolin (CK)-maximum amplitude (MA): 42 mm; the inhibition rate of arachidonic acid (AA%): 78%; and the inhibition rate of adenosine diphosphate (ADP%): 100%). Nine hours after SICH, an emergency craniectomy was performed to evacuate hematoma and decompress, with consent from the patients' family members and neurosurgeons. A ten-year experience neurosurgeon performed the procedure, and the corresponding author supervised this surgery. Ten hours after SICH, to improve the coagulation function, the platelet and plasma transfusion was performed during the surgery. Postoperatively, the patient was transferred to the intensive care unit (ICU). On the third day after the surgery, the thromboelastography showed that the ADP% decreased by 40% the AA% decreased by 24.8% and the CK-MA increased to 52 mm; and the routine CTs, which were performed postoperatively and on third and sixth day after surgery, didn't find the sign of rebleeding (Fig. 1). Platelet count declined continuously after surgery and reached a minimum of 51*10 9 /L on the fourth day after surgery but increased subsequently ( Fig. 2A). Moreover, although activated partial thromboplastin time (APTT) and prothrombin time (PT) was acceptable (Fig. 2B), the significantly decreased fibrinogen (Fig. 2C) was found on the fifth day after surgery. However, because the fibrinogen and platelet count recovered shortly afterwards and there was no sign of rebleeding or new ischemic stroke in CT (Fig. 1), we didn't admit any special treatment. Notably, although the patient didn't restart antiplatelet therapy, there was no occurrence of special events later, and the patient was stable and recovered satisfactorily. Finally, the patient was discharged with GCS as 4 T6 and mRS as 4. The patient was followed up routinely three months after SICH via telephone, and the result suggested that the patient detached from respirator and the GCS was 15. Six months after SICH, telephone follow-up revealed that the patient's condition was further improved and the mRS was 3. The patient's family was satisfied with the treatment outcome and had good compliance with follow-up.
The work was approved by the Institutional Review Board of Tiantan Hospital, and the ethics committee number is KY2019-096-02. Informed consent was obtained for the case report, and privacy of patient has been effectively protected.
As described in previous similar studies, the high AA% or ADP% suggested an increased risk of preoperative hematoma expansion and postoperative bleeding [14,27,28]. In this case, we also found that both of preoperative AA% and ADP% were quite high, which suggested that the patient was under a high risk of bleeding complication. After giving platelet transfusion, the AA% and ADP% were significantly safely declined on the third day after surgery without sign of rebleeding or ischemic events; and, by continually monitoring, although the platelet count was significantly decreased on the fourth day after surgery, the platelet function recovered to the normal, which might prevent from rebleeding. Based on these facts, our experience was that it's usually not clotting dysfunction in patients on LOAPT, and a neurosurgeon should pay more attention to platelet function rather than platelet count. Sometimes, the platelet count might be acceptable, but the inhibited proportion was high; thus, the patient is still not in normal hemostasis [29]. Moreover, although there would be a massive consumption of platelet within 4 days after surgery, we thought that as long as the remaining platelet worked normally, which presented as CK-MA > 40 mm and AA%/ADP% <60% in our experience, it could maintain the normal coagulation; however, if the platelet count was less than 50*10 9 / L, we still recommended platelet transfusion to prevent rebleeding (our experience was presented as Fig. 3).
Although there was still controversy about whether platelet transfusion should be considered for SICH patients on LOAPT [7][8][9][22][23][24][25][26], some studies have shown that platelet transfusion can improve the platelet activity [26,28]. Physiologically, it usually takes at least seven days for platelet function to recover after stopping antiplatelet therapy [30][31][32]. However, several studies reported that platelet transfusion could improve the platelet function in a short period [25,26,28]. We found the similar fact, that both of AA% and ADP% decreased significantly within three days after platelet transfusion and recovered to a normal level at third day after surgery. Our case also supports the conclusion that platelet transfusion can improve platelet function. Therefore, we believe that if the patient had a platelet dysfunction caused by LOAPT, platelet transfusion should be considered intraoperatively or within 24 h after surgery.
The effect of platelet transfusion was another concern in clinical work [7][8][9]27]. The PATCH study and other similar studies demonstrated that platelet transfusion not only couldn't improve the outcome, but also caused a higher mortality and rate of ischemic events [7][8][9]. However, considering the coagulation was more critical for operated patients, we thought that the importance of platelet transfusion is to prevent postoperative rebleeding [27]. In addition, for the patients with resistance of antiplatelet agent, non-selective platelet transfusion would increase the risk of thromboembolic events unnecessarily. Therefore, we recommended platelet transfusion for patients with significant platelet dysfunction. However, further studies were still needed to investigate the quickly and safely method to reverse the platelet function of patients on LOAPT for emergency surgery.

Conclusion
We report the first case that management of platelet function and coagulation function in SICH patients on LOAPT. Postoperatively, monitoring and taking control of clotting and platelet function would help in preventing rebleeding and ischemic events in such patients; moreover, platelet transfusion may quickly and safely reverse platelet dysfunction for emergency surgery.

Ethics approval
The work was approved by the Institutional Review Board of Tiantan Hospital, and the ethics committee number is KY2019-096-02. Written informed consents will be obtained from their legally authorized representatives. Privacy of patient has been effectively protected.

Sources of funding
This work was supported by "Major special projects in the 13th fiveyear plan" (Grant No.2016YFC1301800). The sponsors had no role in the design or conduct of this research.

CRediT authorship contribution statement
Author contributions to the study and manuscript preparation include the following.

Guarantor
The Guarantor is Shuo Wang.

Research registration
None.

Consent
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Provenance and peer review
Not commissioned, externally peer-reviewed.

Declaration of competing interest
All authors certify that we have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.