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.
"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 , as has ReoRox . Multiplate results have been shown to be affected by PLC  , but only weakly within the reference range . "
"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  "
[Show abstract][Hide abstract] 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.
Thrombosis Research 06/2014; 133(6). DOI:10.1016/j.thromres.2014.03.026 · 2.45 Impact Factor
"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
, high plasma fibrinogen levels over 300 mg/dL may even compensate for low platelet counts
. 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. "
[Show abstract][Hide abstract] 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.
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).
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.
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.
Journal of Cardiothoracic Surgery 05/2014; 9(1):90. DOI:10.1186/1749-8090-9-90 · 1.03 Impact Factor
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