Impact of fibrinogen concentration in severely ill patients on mechanical properties of whole blood clots
Fibrinogen concentration influences mechanical and functional properties of the clot. The purpose of the present study was to identify threshold concentrations of fibrinogen resulting in relevant changes in whole blood clot elastic modulus and platelet contractile force, as well as plasma prothrombin time and activated partial thromboplastin time. We measured clot elastic modulus, platelet contractile force, and other hemostasis parameters in whole blood samples from 552 patients admitted to a surgical intensive care unit. Platelet contractile force and clot elastic modulus were measured using the Hemodyne apparatus. Fibrinogen levels were between less than 0.10 and 9.44 g/l, with a mean of 2.41 g/l. Mean platelet count was 203 x 10(9) l(-1), with a range of 16 x 10(9) l(-1) to 682 x 10(9) l(-1). High levels of fibrinogen result in improved mechanical stability and improved interaction of platelets with the fibrin network. Clot elastic modulus and platelet contractile force are correlated positively with plasma fibrinogen concentration. However, there was no threshold concentration or ceiling effect concerning the mechanical properties of the clots. In contrast, clotting time assays such as prothrombin time, thrombin time, or activated partial thromboplastin time are influenced by the fibrinogen concentration only at levels below 1 g/l. In linear regression analysis, clot elastic modulus was mainly influenced by fibrinogen concentration (F = 185.4, P < 0.0001), whereas platelet contractile force was influenced by fibrinogen (F = 197.0, P < 0.0001) and platelet count (F = 104.7, P < 0.0001). The present data show that 1 g/l is a threshold fibrinogen concentration for an effect on coagulation assays such as prothrombin time, thrombin time, or activated partial thromboplastin time, but increasing fibrinogen concentrations above this level results in further continuous improvement of mechanical properties of the whole blood clot.
Available from: Donald F Brophy
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ABSTRACT: Identifying early changes in hemostatic clot function as a result of tissue injury and hypoperfusion may provide important information regarding the mechanisms of traumatic coagulopathy. A combat-relevant swine model was used to investigate the development of coagulopathy during trauma by monitoring hemostatic function during increasing severity of shock.
Swine were injured (soft tissue+femur fracture) and hemorrhaged while continuously monitoring Oxygen Debt (OD) by indirect calorimetry at the airway. Hemostatic function was assessed by Thrombelastography (TEG), Prothrombin Time (PT), Partial Thromboplastin Time (PTT), and fibrinogen concentration and compared before hemorrhage (D0) and during shock when OD=40 and 80 ml/kg. An instrumented sham group was used for comparison.
N=23 swine (N=18 hemorrhage, N=5 sham) weighing 45+/-6 kg were studied after removing an average of 34+/-14% of blood volume during hemorrhage. Hgb, Hct, platelet counts, PT and PTT did not change with increasing OD (p<0.05). Fibrinogen was reduced significantly by OD=40 ml/kg (mean diff.=-59.9 mg/dl, 95% CI diff. [-95.1, -24.6]). TEG parameters representing clot initiation (R) and polymerization (K and Alpha Angle) did not change with increasing OD during shock (p>0.053). Clot strength (MA) was reduced in the hemorrhage group by OD=80 ml/kg (mean diff.=-4.1mm, 95% CI diff. [-7.4, -0.8]).
In this swine model of traumatic shock, fibrinogen was significantly reduced and an isolated reduction in clot strength (MA) was found with increasing OD. Fibrinogen consumption and altered platelet function may account for the earliest changes in hemostatic function during traumatic shock.
Resuscitation 10/2009; 81(1):111-6. DOI:10.1016/j.resuscitation.2009.09.017 · 4.17 Impact Factor
Available from: M. R. Falvo
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ABSTRACT: When normal blood circulation is compromised by damage to vessel walls, clots are formed at the site of injury. These clots prevent bleeding and support wound healing. To sustain such physiological functions, clots are remarkably extensible and elastic. Fibrin fibers provide the supporting framework of blood clots, and the properties of these fibers underlie the mechanical properties of clots. Recent studies, which examined individual fibrin fibers or cylindrical fibrin clots, have shown that the mechanical properties of fibrin depend on the mechanical properties of the individual fibrin monomers. Within the fibrin monomer, three structures could contribute to these properties: the coiled-coil connectors the folded globular nodules and the relatively unstructured αC regions. Experimental data suggest that each of these structures contributes. Here we review the recent work with a focus on the molecular origins of the remarkable biomechanical properties of fibrin clots.
Biophysical chemistry 09/2010; 152(1-3):15-20. DOI:10.1016/j.bpc.2010.08.009 · 1.99 Impact Factor
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ABSTRACT: Coagulation management requires the balancing of different components that contribute to clot formation. These components include the interactions between platelets, procoagulant, anticoagulant, and fibrinolytic factors. The cause of bleeding or thrombotic events is often multifactorial; however, the tests clinicians most frequently use to assess hemostasis do not reflect the complexity of the coagulation system. The paucity of global measurements of hemostasis has resulted in either an empirical or a one-size-fits-all approach to treatment. In contrast, thromboelastography is a test that monitors the different phases of clot formation and lysis, providing the clinician with a tool for making informed therapeutic decisions. This review provides an overview of thromboelastography in the management of hypocoagulable and hypercoagulable conditions.
Seminars in Thrombosis and Hemostasis 10/2010; 36(7):699-706. DOI:10.1055/s-0030-1265286 · 3.88 Impact Factor
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