Hemostasis and Fibrinolysis following Aneurysmal Subarachnoid Hemorrhage: A Systematic Review on Additional Knowledge from Dynamic Assays and Potential Treatment Targets

Abstract

Mortality after aneurysmal subarachnoid hemorrhage (aSAH) is augmented by rebleeding and delayed cerebral ischemia (DCI). A range of assays evaluating the dynamic process of blood coagulation, from activation of clotting factors to fibrinolysis, has emerged and a comprehensive review of hemostasis and fibrinolysis following aSAH may reveal targets of treatment. We conducted a systematic review of existing literature assessing coagulation and fibrinolysis following aSAH, but prior to treatment. PubMed, Embase, and Web of Science were searched on November 18, 2020, without time boundaries. In total, 45 original studies were eventually incorporated into this systematic review, divided into studies presenting data only from conventional or quantitative assays (n = 22) and studies employing dynamic assays (n = 23). Data from conventional or quantitative assays indicated increased platelet activation, whereas dynamic assays detected platelet dysfunction possibly related to an increased risk of rebleeding. Secondary hemostasis was activated in conventional, quantitative, and dynamic assays and this was related to poor neurological outcome and mortality. Studies systematically investigating fibrinolysis were sparse. Measurements from conventional or quantitative assays, as well as dynamic fibrinolysis assays, revealed conflicting results with normal or increased lysis and changes were not associated with outcome. In conclusion, dynamic assays were able to detect reduced platelet function, not revealed by conventional or quantitative assays. Activation of secondary hemostasis was found in both dynamic and nondynamic assays, while changes in fibrinolysis were not convincingly demonstrable in either dynamic or conventional or quantitative assays. Hence, from a mechanistic point of view, desmopressin to prevent rebleeding and heparin to prevent DCI may hold potential as therapeutic options. As changes in fibrinolysis were not convincingly demonstrated and not related to outcome, the use of tranexamic acid prior to aneurysm closure is not supported by this review.

The Efficacy of Antifibrinolytic Therapy in Aneurysmal Subarachnoid Hemorrhage: a Systematic Review and meta-analysis

“…Rebleeding is the most feared complication after SAH as it carries a high mortality [ 23 ]. The role of TXA in clot stabilization and its antifibrinolytic properties initially nurtured the idea of using it in SAH, and the results of various clinical trials supported it as well [ 24 ].…”

“…Thus, while TXA may have some role in clot stabilization (especially when used long-term), there is little to no evidence to support its use at present. Recent studies have also suggested exploring alternative agents such as desmopressin to prevent rebleeding [ 23 ].…”

Hemostasis and Neuroscience—Hemostasis and Fibrinolysis Involved in Brain Pathology and Brain Disorders

“…The last review of this section is written by the co-editors Hvas and Hvas and is a systematic review on hemostasis and fibrinolysis following subarachnoid hemorrhage. 12 Rebleeding and delayed cerebral ischemia increase mortality after subarachnoid hemorrhage, and hemostatic or antifibrinolytic therapy has not been able to decrease mortality. Gathering current knowledge on changes in hemostasis and fibrinolysis, evaluated by both conventional, quantitative, and dynamic assays may reveal potential treatment targets.…”

Viscoelastic Testing in the Clinical Management of Subarachnoid Hemorrhage and Intracerebral Hemorrhage

“…10 11 A high incidence of changes in coagulation and fibrinolysis has been reported following SAH involving both primary and secondary hemostasis. 12 Measurements of increased platelet-activating factors and a hypercoagulable state with increased coagulation factors and von Willebrand factor suggest the presence of a systemically disturbed coagulation system. 13 14 15…”

“…10,11 A high incidence of changes in coagulation and fibrinolysis has been reported following SAH involving both primary and secondary hemostasis. 12 Measurements of increased platelet-activating factors and a hypercoagulable state with increased coagulation factors and von Willebrand factor suggest the presence of a systemically disturbed coagulation system. [13][14][15] Development of spontaneous ICH is closely linked to the presence of hypertension and constitutes 10 to 15% of annual 700,000 strokes in the United States, 16 with an ICH incidence of 12 to 15 cases per 100,000.…”