The effect of fibrinogen concentrate on thrombocytopenia

Department of Anaesthesiology and Intensive Care Medicine, Innsbruck Medical University, Innsbruck, Austria.
Journal of Thrombosis and Haemostasis (Impact Factor: 5.72). 05/2007; 5(5):1019-25. DOI: 10.1111/j.1538-7836.2007.02481.x
Source: PubMed


The hypothesis that the administration of fibrinogen concentrate enables restoration of impaired clot formation and increased bleeding in severe thrombocytopenia was tested.
Thirty pigs were anesthetized, instrumented for blood sampling (routine coagulation tests, modified thrombelastography ROTEM, hemodynamic monitoring and platelet apheresis to a target below 30 x 10(9) L(-1) after splenectomy. Thereafter 10 each of the animals randomly received two apheresis platelet concentrates, 250 mg kg(-1) fibrinogen concentrate or normal saline solution. A standardized liver injury was subsequently inflicted to induce uncontrolled hemorrhage.
Median (Q1, Q3) clot firmness increased significantly more in thrombocytopenic pigs after fibrinogen administration (42 mm (41, 43) to 60 mm (57, 63)) than following platelet transfusion (40 mm (37, 45) to 52 mm (48, 55), P = 0.0004) or placebo (45 mm (41, 48) to 45 mm (43, 46), P = 0.0002). Median blood loss velocity after liver injury was significantly less with fibrinogen (33 mL min(-1), P = 0.005) than with platelets (62 mL min(-1), P = 0.037) or saline (84 mL min(-1), P = 0.005), and median survival time after liver injury was 55 min in the fibrinogen, 26 min in the platelet (P = 0.035) and 19 min in the saline group (P = < 0.0001).
These data show for the first time that impaired clot formation during thrombocytopenia improves with administration of fibrinogen concentrate, which results in a slowdown of blood loss and prolonged survival.

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Available from: Uri Martinowitz (Martonovich), Oct 03, 2014
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    • "This protein is required for both platelet aggregation and fibrin formation [7]. Fibrinogen supplementation may also compensate for dilutional coagulopathy or impaired haemostasis due to thrombocytopenia [8,9] Low plasma fibrinogen concentration is common among major trauma patients and associated with poor clinical outcomes [10-13]. Importantly, FFP and solvent/detergent-treated plasma (SD-plasma) contain only low levels of fibrinogen [14]. "
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    ABSTRACT: Low plasma fibrinogen concentration is a predictor of poor outcome in major trauma patients. The role of fibrinogen concentrate for rapidly increasing fibrinogen plasma levels in severe trauma is not well defined. In this retrospective study we included severe trauma patients treated with fibrinogen concentrate alone (FC group), fibrinogen concentrate with prothrombin complex concentrate (FC--PCC group) or fibrinogen concentrate with PCC and fresh frozen plasma (FC--PCC--FFP group). PCC was generally administered as the second step of intraoperative therapy, while FFP was only administered as a third step. All patients received >=1 g fibrinogen concentrate within 24 hours. Plasma fibrinogen concentration and ROTEM parameters upon emergency room (ER) admission, intensive care unit (ICU) admission, and after 24 hours were analysed. Among 157 patients fulfilling the inclusion criteria, 83% were male; mean age was 44 years and median injury severity score (ISS) was 29. Standard coagulation tests reflected increasing severity of coagulopathy with increasing complexity of haemostatic therapy (highest severity in the FC--PCC--FFP group; p < 0.0001). Total 24-hour fibrinogen concentrate dose also increased with complexity of haemostatic therapy. Plasma fibrinogen concentration was maintained, with no significant difference between ER admission and ICU admission in all patient groups. FIBTEM clot firmness at 10 minutes (CA10) was similarly maintained, albeit with a small increase in the FC--PCC group. Fibrinogen concentration and FIBTEM CA10 were within the normal range in all groups at 24 hours. The ratio of fibrinogen concentrate to red blood cells (g:U) ranged between 0.7:1.0 and 1.0:1.0. Fibrinogen concentrate therapy maintained fibrinogen concentration and FIBTEM CA10 during the initial phase of trauma care until ICU admission. After 24 hours, these parameters were comparable between the three groups and within the normal range for each of them. Further studies are warranted to investigate the effect of fibrinogen concentrate on clinical outcomes.
    Full-text · Article · Oct 2013 · Scandinavian Journal of Trauma Resuscitation and Emergency Medicine
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    • "It may also be considered as a strategy for reducing transfusion of allogeneic blood products: the need for FFP may be reduced by the administration of coagulation factors: fibrinogen, contained in fibrinogen concentrate, and factors II, VII, IX and X, contained in most PCCs. Furthermore, clinical and experimental data suggest that fibrinogen supplementation may also compensate for reduced platelet count [13,14]. Supplementation of fibrinogen may support primary haemostasis, because fibrinogen facilitates platelet aggregation by bridging platelet glycoprotein IIb/IIIa receptors [15]. "
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    ABSTRACT: Thromboelastometry (TEM)-guided haemostatic therapy with fibrinogen concentrate and prothrombin complex concentrate (PCC) in trauma patients may reduce the need for transfusion of red blood cells (RBC) or platelet concentrate, compared with fresh frozen plasma (FFP)-based haemostatic therapy. This retrospective analysis compared patients from the Salzburg Trauma Centre (Salzburg, Austria) treated with fibrinogen concentrate and/or PCC, but no FFP (fibrinogen-PCC group, n = 80), and patients from the TraumaRegister DGU receiving ≥ 2 units of FFP, but no fibrinogen concentrate/PCC (FFP group, n = 601). Inclusion criteria were: age 18-70 years, base deficit at admission ≥ 2 mmol/L, injury severity score (ISS) ≥ 16, abbreviated injury scale for thorax and/or abdomen and/or extremity ≥ 3, and for head/neck < 5. For haemostatic therapy in the emergency room and during surgery, the FFP group (ISS 35.5 ± 10.5) received a median of 6 units of FFP (range: 2, 51), while the fibrinogen-PCC group (ISS 35.2 ± 12.5) received medians of 6 g of fibrinogen concentrate (range: 0, 15) and 1200 U of PCC (range: 0, 6600). RBC transfusion was avoided in 29% of patients in the fibrinogen-PCC group compared with only 3% in the FFP group (P< 0.001). Transfusion of platelet concentrate was avoided in 91% of patients in the fibrinogen-PCC group, compared with 56% in the FFP group (P< 0.001). Mortality was comparable between groups: 7.5% in the fibrinogen-PCC group and 10.0% in the FFP group (P = 0.69). TEM-guided haemostatic therapy with fibrinogen concentrate and PCC reduced the exposure of trauma patients to allogeneic blood products.
    Full-text · Article · Mar 2011 · Critical care (London, England)
    • "In addition, a high fibrinogen concentration has been suggested to have a compensatory effect for decreased platelet count in a recent retrospective clinical study [19]. Furthermore, treatment with high dosage fibrinogen concentrate has been shown to control traumatic bleeding more effectively than the addition of platelet concentrates in an animal model of thrombocytopenia [25]. The use of fibrinogen is encouraging, however it is important to remain critical and sceptical regarding the best-suited clinical scenarios. "

    No preview · Article · Jun 2010 · European Journal of Anaesthesiology
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