The Effects of Fibrinogen Levels on Thromboelastometric Variables in the Presence of Thrombocytopenia

Department of Anesthesiology, Medical School, Hannover, Germany.
Anesthesia and analgesia (Impact Factor: 3.47). 04/2009; 108(3):751-8. DOI: 10.1213/ane.0b013e3181966675
Source: PubMed


The binding of fibrinogen and fibrin to platelets is important in normal hemostasis. The extent of platelet-fibrin interaction can be measured as the viscoelastic strength of clot by rotational thromboelastometry (ROTEM). In this study, we investigated the effect of fibrinogen concentration and its relative contribution to overall clot strength using ROTEM.
Blood samples were collected from healthy volunteers. The effects of platelet count on clot strength, determined by maximum clot elasticity (MCE), were evaluated on ROTEM using platelet-rich plasma (PRP) adjusted with autologous plasma to generate a range of platelet counts. PRPs were adjusted to 10 x 10(3) mm(-3), 50 x 10(3) mm(-3), and 100 x 10(3) mm(-3) and spiked with fibrinogen concentrates at 550 and 780 mg/dL. The effect of fibrin polymerization on clot strength, independent of platelet attachment, was analyzed by the cytochalasin D-modified thromboelastometry (FIBTEM) method. Additional retrospective analysis of clot strength (MCE) in two groups of thrombocytopenic patients was conducted.
Clot strength (MCE) decreased at a platelet count below 100 x 10(3) mm(-3), whereas increases in MCE peaked and reached a plateau at platelet counts from 400 x 10(3) mm(-3). Increasing fibrinogen concentrations in PRP increased clot strength in a concentration-dependent manner, even at low platelet counts (10 x 10(3) mm(-3)). The positive correlation between clot strength and plasma fibrinogen level was also confirmed in the analysis of the data obtained from 904 thrombocytopenic patients.
These in vitro and clinical data indicate that the clot strength increases in a fibrinogen concentration-dependent manner independent of platelet count, when analyzed by ROTEM. The maintenance of fibrinogen concentration is critical in the presence of thrombocytopenia. EXTEM (extrinsic activation) and FIBTEM may be useful in guiding fibrinogen repletion therapy.

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    • "Both ROTEM and ReoRox clot elasticity variables were shown to correlate with the fibrinogen concentration with the highest correlations in the assays where platelets were inhibited. The elasticity detected by ROTEM has also previously been shown to increase with increasing fibrinogen concentrations [29], as has ReoRox [16]. Multiplate results have been shown to be affected by PLC [28] [30], but only weakly within the reference range [31]. "
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    ABSTRACT: The purposes of the study are to compare point-of-care (POC) hemostatic devices in critically ill patients with routine laboratory tests and intensive care unit (ICU) outcome scoring assessments and to describe the time course of these variables in relation to mortality rate. Patients admitted to the ICU with a prognosis of more than 3 days of stay were included. The POC devices, Multiplate platelet aggregometry, rotational thromboelastometry, and ReoRox viscoelastic tests, were used. All variables were compared between survivors and nonsurvivors. Point-of-care results were compared to prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen concentration, and Sequential Organ Failure Assessment score and Simplified Acute Physiology Score 3. Blood was sampled on days 0 to 1, 2 to 3, and 4 to 10 from 114 patients with mixed diagnoses during 237 sampling events. Nonsurvivors showed POC and laboratory signs of hypocoagulation and decreased fibrinolysis over time compared to survivors. ReoRox detected differences between survivors and nonsurvivors better than ROTEM and Multiplate. All POC and routine laboratory tests showed a hypocoagulative response in nonsurvivors compared to survivors. ReoRox was better than ROTEM and Multiplate at detecting differences between surviving and nonsurviving ICU patients. However, Simplified Acute Physiology Score 3 showed the best association to mortality outcome. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jun 2015 · Journal of critical care
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    • "The smaller extent of these increments is attributable to their progressively close proximity to the upper limits of the MA signal. These results are in general agreement with those reported in plasma studies [24] "
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    ABSTRACT: Introduction Thromboelastography (TEG), a widely used clinical point of care coagulation test, is poorly understood. To investigate its fibrin determinants we used normal and variant fibrinogen isolates. Materials and Methods We focused mainly on the TEG maximum signal amplitude (MA), a shear modulus and clot stiffness indicator. Isolates included normal des-αC, cord, and abnormal congenital variants with amino acid substitutions or deletions that impaired fibrin polymerization. Heterophenotypic congenital isolates were from cryoprecipitate-depleted plasma owing to their more diminished clot MA than their cryoprecipitate counterparts. By colorimetric assay, the amount of fibrinogen adsorbed by untreated TEG cups was 83.5 ± 12.4 pM/cm2, n = 18. Thrombin-induced clots were obtained at pH 6.4 or 7.4, the latter containing 8 mM CaCl2, and 14% afibrinogenemic plasma with and without gel-sieved platelets. Results and Conclusions Measured by the water droplet contact angle, > 90% reduction of surface hydrophobicity by exposure of TEG cup and pin to ozone plasma decreased MA by 74%. Increasing normal fibrinogen or thrombin concentrations progressively increased MA. Platelets increased MA further ~ 2 fold, except for ≥ 10 fold for des-αC clots. Examined in the absence of platelets, MA of heterophenotypic fibrin variants averaged 21%, n = 15. The results imply that essential MA determinants include hydrophobic fibrinogen/fibrin adsorption and each polymerization contact site, with substantial enhancement by platelets. Also, cryoprecipitate-harvested soluble fibrinogen/fibrin complexes contained mostly normal molecules, while cryoprecipitate-depleted plasma contained mostly variant molecules. Moreover, significantly decreased MA by fibrinogen anomalies and/or low level thrombin generation can potentially impact clinical interpretation of MA.
    Preview · Article · Jun 2014 · Thrombosis Research
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    • "Because fibrinogen seems to be the coagulation factor first reaching a critically low level (100 mg/dL) even before thrombocytopenia develops during massive hemorrhage, the hemostatic therapy in this setting should be focused upon quick and enough supplementation of fibrinogen. Although, the target plasma concentration for fibrinogen replacement was predicted by in vitro study to be higher than 200 mg/dL as only these concentrations optimized the rate of clot formation [23], high plasma fibrinogen levels over 300 mg/dL may even compensate for low platelet counts [24]. We have conventionally used FFP for the purpose of fibrinogen replacement in intraoperative massive hemorrhage because neither cryoprecipitate nor fibrinogen concentrate has been available for decades in Japan. "
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    ABSTRACT: Background Repair of thoracic aortic aneurysm (TAA) is often associated with massive hemorrhage aggravated by dilutional coagulopathy with severe hypofibrinogenemia. Although only fresh frozen plasma (FFP) is available for acquired hypofibrinogenemia in Japan, the hemostatic effect of FFP has not been enough for dilutional coagulopathy in TAA surgery. There are increasing reports suggesting that fibrinogen concentrate may be effective in controlling perioperative bleeding and reducing transfusion requirements. Methods We retrospectively analyzed the hemostatic effect of fibrinogen concentrate compared with FFP in total 49 cases of elective TAA surgery. In 25 patients, fibrinogen concentrate was administered when the fibrinogen level was below 150 mg/dL at the cardiopulmonary bypass (CPB) termination. The recovery of fibrinogen level, blood loss, and transfused units during surgery were compared between cases of this agent and FFP (n = 24). Results We observed rapid increases in plasma fibrinogen level and subsequent improvement in hemostasis by administration of fibrinogen concentrate after CPB termination. The average volume of total blood loss decreased by 64% and the average number of transfused units was reduced by 58% in cases of fibrinogen concentrate given, in comparison with cases of only FFP transfused for fibrinogen supplementation. Conclusions In patients showing severe hypofibrinogenemia during TAA surgery, timely administration of fibrinogen concentrate just after removal from CPB is effective for hemostasis, and therefore in reducing blood loss and transfused volumes.
    Full-text · Article · May 2014 · Journal of Cardiothoracic Surgery
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