Advances in Clinical and Experimental Medicine
2019, vol. 28, nr 2, February, p. 219–222
Publication type: original article
Fibrinogen concentrate replacement in ischemic stroke patients after recombinant tissue plasminogen activator treatment
1 Stroke Unit, Neurology Clinic, Department of Neuroscience, Nuovo Ospedale Civile S. Agostino-Estense, University of Modena and Reggio Emilia, Modena, Italy
2 Department of Oncology and Hematology, Polyclinic of Modena, University of Modena and Reggio Emilia, Modena, Italy
3 Clinical Pathology – Toxicology Department, Nuovo Ospedale Civile S. Agostino-Estense, Azienda Unita' Sanitaria Locale di Modena, Italy
Background. Post-thrombotic intracerebral hemorrhage (ICH) is experienced by 6–8% of stroke patients and is associated with multiple factors, including acquired coagulopathy induced by the thrombolytic drug.
Objectives. The objective of this study was to assess the outcome of the intravenous (IV) administration of fibrinogen concentrate in a series of acute stroke patients who developed iatrogenic fibrinogen critical depletion after IV thrombolysis.
Material and Methods. Of the 39 ischemic stroke patients treated with IV thrombolysis with a severe hypofibrinogenemia requiring infusion with IV fibrinogen concentrate, 30 patients were treated with 2 g of IV recombinant tissue plasminogen activator (rt-PA), followed by further doses until the fibrinogen level reached 200 mg/dL in hemorrhagic patients or 100 mg/dL in non-hemorrhagic patients, and 9 were treated with IV rt-PA followed by endovascular thrombectomy.
Results. Preand post-thrombolysis National Institutes of Health Stroke Scale (NIHSS) scores were statistically different for the Cochran-Mantel-Haenszel test overall (p = 0.0002), at 24-hour evaluation (p = 0.0455) and at 7-day assessment (p = 0.0006). Within the first 7 days post-thrombolysis, the brain computed tomography (CT) scans showed that 20/39 (51.28%) patients had ICH. Of the whole sample, 25.6% of the ICH patients had symptomatic intracerebral hemorrhage (SICH), according to National Institute of Neurological Disorders and Stroke (NINDS) classification. After rt-PA treatment, the median pre-thrombolysis fibrinogenemia of 332 mg/dL significantly dropped to 133 mg/dL (p < 0.0001). After the fibrinogen concentrate infusion, the median level of fibrinogenemia rose to 160 mg/dL, which was significantly higher than the median postthrombolysis levels (p < 0.0001). Recanalization was observed in 25/28 patients (89.29%): complete in 18 and partial in 7 patients. After fibrinogen IV infusion, no thrombotic complications were seen in 37 out of 39 patients (94.77%); 2/39 (0.05%) patients experienced a pulmonary embolism, 1 of them a segmental one.
Conclusion. This study showed the clinical safety of administering IV fibrinogen concentrate in order to increase plasma fibrinogen levels in a series of acute stroke patients with iatrogenic fibrinogen depletion after IV thrombolysis.
ischemic stroke, fibrinogen concentrate replacement, recombinant tissue plasminogen activator
- Powers WJ, Derdeyn CP, Biller J, et al; American Heart Association Stroke Council. 2015 American Heart Association / American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: A guideline for healthcare professionals from the American Heart Association / American Stroke Association. Stroke. 2015;46(10):3024–3039.
- Graham GD. Tissue plasminogen activator for acute ischemic stroke in clinical practice: A meta-analysis of safety data. Stroke. 2003;34(12):2847–2850.
- Wahlgren N, Ahmed N, Davalos A, et al; SITS-MOST Investigators. Thrombolysis with alteplase for acute ischemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): An observational study. Lancet. 2007;369(9558):275–282.
- Vandelli L, Marietta M, Gambini ME, et al. Fibrinogen decrease after intravenous thrombolysis in ischemic stroke patients is a risk factor for intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2015;24(2):394–400.
- Trouillas P, Derex L, Philippeau F, et al. Early fibrinogen degradation coagulopathy is predictive of parenchymal hematomas in cerebral rt-PA thrombolysis: A study of 157 cases. Stroke. 2004;35(6):1323–1328.
- Matosevic B, Knoflach M, Werner P, et al. Fibrinogen degradation coagulopathy and bleeding complications after stroke thrombolysis. Neurology. 2013;80(13):1216–1224.
- Danés AF, Cuenca LG, Bueno SR, Mendarte Barrenechea L, Ronsano JB. Efficacy and tolerability of human fibrinogen concentrate administration to patients with acquired fibrinogen deficiency and active or in high-risk severe bleeding. Vox Sang. 2008;94(3):221–226.
- Gollop ND, Chilcott J, Benton A, Rayment R, Jones J, Collins PW. National audit of the use of fibrinogen concentrate to correct hypofibrinogenemia. Transfus Med. 2012;22(5):350–355.
- Weiss G, Lison S, Glaser M, et al. Observational study of fibrinogen concentrate in massive hemorrhage: Evaluation of a multicenter register. Blood Coagul Fibrinolysis. 2011;22(8):727–734.
- Fenger-Eriksen C, Lindberg-Larsen M, Christensen AQ, Ingerslev J, Sørensen B. Fibrinogen concentrate substitution therapy in patients with massive hemorrhage and low plasma fibrinogen concentrations. Br J Anaesth. 2008;101(6):769–773.
- Hemphill JC, Greenberg SM, Anderson CS, et al; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology. Guidelines for the management of spontaneous intracerebral hemorrhage: A guideline for healthcare professionals from the American Heart Association / American Stroke Association. Stroke. 2015;46(7):2032–2060.
- De Silva DA, Brekenfeld C, Ebinger M, et al; Echoplanar Imaging Thrombolytic Evaluation trial (EPITHET) Investigators. The benefits of intravenous thrombolysis relate to the site of baseline arterial occlusion in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). Stroke. 2010;41(2):295–299.
- Fassl J, Lurati Buse G, Filipovic M, et al. Perioperative administration of fibrinogen does not increase adverse cardiac and thromboembolic events after cardiac surgery. Br J Anaesth. 2015;114(2):225–234.
- Wikkelsø A, Lunde J, Johansen M, et al. Fibrinogen concentrate in bleeding patients. Cochrane Database Syst Rev. 2013;8:CD008864.
- Skaf E, Stein PD, Beemath A, Sanchez J, Bustamante MA, Olson RE. Venous thromboembolism in patients with ischemic and hemorrhagic stroke. Am J Cardiol. 2005;96(12):1731–1733.