Abstract
Background
Optimal hemostasis provides safety and reliability during neurosurgery which improves surgical outcomes. Previously, artificial cerebrospinal fluid (aCSF) and its component sodium bicarbonate were found to facilitate physiological hemostasis by amplifying platelet aggregation. This study aimed to verify whether aCSF amplifies platelet-dependent hemostasis in the presence of antiplatelet agents.
Methods
We prepared platelet-rich plasma (PRP) or washed platelets using aspirin (acetylsalicylic acid, (ASA)) or normal saline (NS). We evaluated samples treated with a commercially available aCSF solution or NS for amplification of aggregation, activation of integrin αIIbβ3, phosphatidylserine (PS) exposure, P-selectin (CD62P) expression, and formation of microparticles (MPs). We assessed the effect of aCSF on in vivo hemostasis in the presence of ASA by measuring the tail bleeding time in ASA-or NS-injected C57BL/6 N mice.
Results
Compared with NS, aCSF amplified ASA-inhibited platelet aggregation by recovering platelet activation including PS exposure, MP release, CD62P expression, and integrin αIIbβ3 activation. When using washed platelets, aCSF almost completely counteracted the inhibition of platelet aggregation by ASA. Prolonged bleeding time from the amputated tail of ASA-injected mice was significantly shortened by the treatment with aCSF compared to NS. Sodium bicarbonate also directly amplified ASA-inhibited platelet aggregation.
Conclusions
aCSF and sodium bicarbonate facilitate physiological hemostasis through the recovery of inhibited platelet aggregation even in the presence of ASA. The utilization of aCSF in the operative field may be advantageous for facilitating hemostasis in patients with impaired platelet function and contribute to improving outcomes of neurosurgery.
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Data availability
The raw data supporting the conclusions of this article will be made available by the authors without undue reservation.
Abbreviations
- ACD:
-
Acid–citrate–dextrose
- aCSF:
-
Artificial cerebrospinal fluid
- ADP:
-
Adenosine diphosphate
- ASA:
-
Acetylsalicylic acid
- CD62P:
-
P-selectin
- Cy5:
-
Cyanine-5
- DAG:
-
Diacylglycerol
- FITC:
-
Fluorescein isothiocyanate
- GP:
-
Glycoprotein
- IP3:
-
Inositol 1,4,5-trisphosphate
- mAb:
-
Monoclonal antibody
- MAPK:
-
Mitogen-activated protein kinase
- MP:
-
Microparticle
- NS:
-
Normal saline
- PE:
-
Phycoerythrin
- PRP:
-
Platelet-rich plasma
- PS:
-
Phosphatidylserine
- RT:
-
Room temperature
- SD:
-
Standard deviation
- TXA2 :
-
Thromboxane A2
References
Bevers EM, Comfurius P, van Rijn JL, Hemker HC, Zwaal RF (1982) Generation of prothrombin-converting activity and the exposure of phosphatidylserine at the outer surface of platelets. Eur J Biochem 122:429–436
Bledzka K, Smyth SS, Plow EF (2013) Integrin αIIbβ3: from discovery to efficacious therapeutic target. Circ Res 112:1189–1200
Doi K, Kawano T, Morioka Y, Fujita Y, Nishimura M (2006) Various irrigation fluids affect postoperative brain edema and cellular damage during experimental neurosurgery in rats. Surg Neurol 66(6):565–571
Enomoto R, Tatsuoka H, Komai T, Sugahara C, Takemura K, Yamauchi A, Nishimura M, Naito S, Matsuda T, Lee E (2004) Involvement of histone phosphorylation in apoptosis of human astrocytes after exposure to saline solution. Neurochem Int 44:459–467
Ferraris VA, Ferraris SP, Lough FC, Berry WR (1988) Preoperative aspirin ingestion increases operative blood loss after coronary artery bypass grafting. Ann Thorac Surg 45:71–74
Fujita Y, Doi K, Harada D, Kamikawa S (2010) Modulation of physiological hemostasis by irrigation solution: comparison of various irrigation solutions using a mouse brain surface bleeding model. J Neurosurg 112(4):824–828
Gilbert GE, Drinkwater D, Barter S, Clouse SB (1992) Specificity of phosphatidylserine-containing membrane binding sites for factor VIII. Studies with model membranes supported by glass microspheres (lipospheres). J Biol Chem 22:15861–15868
Hashizume T, Sato T (1999) Influence of cytoplasmic pH on the aggregation and Ca2+ mobilization in rabbit platelets. Biol Pharm Bull 22:663–666
Huang J, Li X, Shi X, Zhu M, Wang J, Huang S, Huang X, Wang H, Li L, Deng H, Zhou Y, Mao J, Long Z, Ma Z, Ye W, Pan J, Xi X, Jin J (2019) Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting. J Hematol Oncol 12:26
Italiano JE Jr, Mairuhu AT, Flaumenhaft R (2010) Clinical relevance of microparticles from platelets and megakaryocytes. Curr Opin Hematol 17:578–584
Kozuma Y, Yamamoto T, Ishikawa E, Yoshida F, Akutsu H, Matsuda M, Nakai K, Tsuruta W, Takano S, Matsumura A, Ninomiya H (2016) Sodium bicarbonate facilitates hemostasis in the presence of cerebrospinal fluid through amplification of platelet aggregation. Neurosurgery 78:274–284
Lewis RC, Elliott KAC (1950) Clinical uses of an artificial cerebrospinal fluid. J Neurosurg 7:256–260
Lin LL, Wartmann M, Lin AY, Knopf JL, Seth A, Davis RJ (1993) cPLA2 is phosphorylated and activated by MAP kinase. Cell 72:269–278
Marumo M, Suehiro A, Kakishita E, Wakabayashi I (2002) Intracellular alkalinization augments platelet aggregation due to increase in cytosolic free-Ca2+. Platelets 13:159–165
Nomura S, Shimizu M (2015) Clinical significance of procoagulant microparticles. J Intensive Care 3:2
Oka K, Yamamoto M, Nonaka T, Tomonaga M (1996) The significance of artificial cerebrospinal fluid as perfusate and endoneurosurgery. Neurosurgery 38:733–736
Ozaki Y, Yatomi Y, Kariya T, Kume S (1989) Anion channels contribute to the regulation of intracellular pH in human platelets. Thromb Res 53:221–230
Palmer JD, Sparrow OC, Iannotti F (1994) Postoperative hematoma: a 5-year survey and identification of avoidable risk factors. Neurosurgery 35:1061–1065
Rhee SG (2001) Regulation of phosphoinositide-specific phospholipase C. Annu Rev Biochem 70:281–312
Shattil SJ, Newman PJ (2004) Integrins: dynamic scaffolds for adhesion and signaling in platelets. Blood 104:1606–1615
Sinauridze EI, Kireev DA, Popenko NY, Pichugin AV, Panteleev MA, Krymskaya OV, Ataullakhanov FI (2007) Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. Thromb Haemost 97:425–434
Stegner D, Nieswandt B (2011) Platelet receptor signaling in thrombus formation. J Mol Med (Berl) 89:109–121
Wiedmer T, Shattil SJ, Cunningham M, Sims PJ (1990) Role of calcium and calpain in complement-induced vesiculation of the platelet plasma membrane and in the exposure of the platelet factor va receptor. Biochemistry 29:623–632
Acknowledgements
We are grateful to Akemi Matsubara, PhD, for statistical consultation, and to Editage (www.editage.com) for English language editing.
Funding
This work was supported by JSPS KAKENHI (grant numbers JP18K08587 and JP21K08608), and Kumamoto Health Science University special fellowship (grant number 2018-D-03).
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YK and TY contributed to the conception and design of this study. YK, CI, KT, IN, and HA acquired and analyzed the data. YK and RS interpreted the data. RS and YK wrote the draft of this article, and TY contributed to the revision. All authors contributed to the study and approved the manuscript as submitted.
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This study was approved by the ethics committee of the University of Tsukuba (approval number: 795) and Kumamoto Health Science University (approval number: 18055).
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Suzuki, R., Kozuma, Y., Inoue, C. et al. Artificial cerebrospinal fluid restores aspirin-inhibited physiological hemostasis through recovery of platelet aggregation function. Acta Neurochir 165, 1269–1276 (2023). https://doi.org/10.1007/s00701-022-05471-9
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DOI: https://doi.org/10.1007/s00701-022-05471-9